WorldWideScience

Sample records for autologous mesenchymal stem

  1. Importance of mesenchymal stem cells in autologous fat grafting

    DEFF Research Database (Denmark)

    Trojahn Kølle, Stig-Frederik; Oliveri, Roberto S; Glovinski, Peter Viktor;

    2012-01-01

    the fat graft with adipose tissue-derived mesenchymal stem cells (ASC) before transplantation. We have reviewed original studies published on fat transplantation enriched with ASC. We found four murine and three human studies that investigated the subject after a sensitive search of publications. In...... the human studies, so-called cell assisted lipotransfer (CAL) increased the ASC concentration 2-5 times compared with non-manipulated fat grafts, which caused a questionable improvement in survival of fat grafts, compared with that of traditional lipofilling. In contrast, in two of the murine studies......Autologous fat grafting (lipofilling) enables repair and augmentation of soft tissues and is increasingly used both in aesthetic and reconstructive surgery. Autologous fat has several advantages, including biocompatibility, versatility, natural appearance, and low donor site morbidity. The main...

  2. Immunological aspects of allogeneic and autologous mesenchymal stem cell therapies.

    Science.gov (United States)

    Hoogduijn, M J; Roemeling-van Rhijn, M; Korevaar, S S; Engela, A U; Weimar, W; Baan, C C

    2011-12-01

    Mesenchymal stem cells (MSCs) have potential for therapeutic application as an immunomodulatory and regenerative agent. The immunogenicity and survival of MSCs after infusion are, however, not clear and evidence suggests that allogeneic but also autologous MSCs disappear rapidly after infusion. This may be associated with the susceptibility of MSCs to lysis by natural killer (NK) cells, possibly a result of culture-induced stress. In the present study we examined whether NK cell-mediated lysis of MSCs could be inhibited by immunosuppressive drugs. Human MSCs were isolated from adipose tissue and expanded in culture. Peripheral blood mononuclear cells were activated with interleukin (IL)-2 (200 U/ml) and IL-15 (10 ng/ml) for 7 days. CD3(-)CD16(+)CD56(+) NK cells were then isolated by fluorescence-activated cell sorting and added to europium-labeled MSCs for 4 hr in the presence or absence of immunosuppressive drugs. Lysis of MSCs was determined by spectrophotometric measurement of europium release. Nonactivated NK cells were not capable of lysing MSCs. Cytokine-activated NK cells showed upregulated levels of granzyme B and perforin and efficiently lysed allogeneic and autologous MSCs. Addition of tacrolimus, rapamycin or sotrastaurin to the lysis assay did not inhibit MSC killing. Furthermore, preincubation of activated NK cells with the immunosuppressive drugs for 24 hr before exposure to MSCs had no effect on MSC lysis. Last, addition of the immunosuppressants before and during the activation of NK cells, reduced NK cell numbers but did not affect their capacity to lyse MSCs. We conclude that the immunosuppressive drugs tacrolimus, rapamycin, and sotrastaurin are not capable of inhibiting the lysis of allogeneic and autologous MSCs by activated NK cells. Other approaches to controlling lysis of MSCs should be investigated, as controlling lysis may determine the efficacy of MSC therapy. PMID:21732766

  3. Autologous transplantation of amniotic fluid-derived mesenchymal stem cells into sheep fetuses

    OpenAIRE

    Shaw, S. W. Steven; Bollini, Sveva; Nader, Khalil Abi; Gastadello, Annalisa; Mehta, Vedanta; Filppi, Elisa; Cananzi, Mara; Gaspar, H. Bobby; Qasim, Waseem; Coppi, Paolo; David, Anna L.

    2011-01-01

    Long-term engraftment and phenotype correction has been difficult to achieve in humans after in utero stem cell transplantation mainly because of allogeneic rejection. Autologous cells could be obtained during gestation from the amniotic fluid with minimal risk for the fetus and the mother. Using a sheep model, we explored the possibility of using amniotic fluid mesenchymal stem cells (AFMSCs) for autologous in utero stem cell/gene therapy. We collected amniotic fluid (AF) under ultrasound-gu...

  4. A Biological Pacemaker Restored by Autologous Transplantation of Bone Marrow Mesenchymal Stem Cells

    Institute of Scientific and Technical Information of China (English)

    REN Xiao-qing; PU Jie-lin; ZHANG Shu; MENG Liang; WANG Fang-zheng

    2008-01-01

    Objective:To restore cardiac autonomic pace function by autologous transplantation and committed differentiation of bone marrow mesenchymal stem cells, and explore the technique for the treatment of sick sinus syndrome. Methods:Mesenchymal stem cells isolated from canine bone marrow were culture-expanded and differentiated in vitro by 5-azacytidine. The models of sick sinus syndrome in canines were established by ablating sinus node with radio-frequency technique. Differentiated mesenchymal stem cells labeled by BrdU were autologously transplanted into sinus node area through direct injection. The effects of autologous transplantation of mesenchymal stem cells on cardiac autonomic pace function in sick sinus syndrome models were evaluated by electrocardiography, pathologic and immunohistochemical staining technique.Results:There was distinct improvement on pace function of sick sinus syndrome animal models while differentiated mesenchymal stem cells were auto-transplanted into sinus node area. Mesenchymal stem cells transplanted in sinus node area were differentiated into similar sinus node cells and endothelial cells in vivo, and established gap junction with native cardiomyocytes. Conclusion:The committed-induced mesenchymal stem cells transplanted into sinus node area can differentiate into analogous sinus node cells and improve pace function in canine sick sinus syndrome models.

  5. Transplantation of autologous bone marrow-derived mesenchymal stem cells for traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Jindou Jiang; Xingyao Bu; Meng Liu; Peixun Cheng

    2012-01-01

    Results from the present study demonstrated that transplantation of autologous bone marrow-derived mesenchymal stem cells into the lesion site in rat brain significantly ameliorated brain tissue pathological changes and brain edema, attenuated glial cell proliferation, and increased brain-derived neurotrophic factor expression. In addition, the number of cells double-labeled for 5-bromodeoxyuridine/glial fibrillary acidic protein and cells expressing nestin increased. Finally, blood vessels were newly generated, and the rats exhibited improved motor and cognitive functions. These results suggested that transplantation of autologous bone marrow-derived mesenchymal stem cells promoted brain remodeling and improved neurological functions following traumatic brain injury.

  6. Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Puente, Pilar de la, E-mail: pilardelapuentegarcia@gmail.com [Tissue Bank, San Francisco Clinic Foundation, Av./Facultad 51, 5°, 24004 León (Spain); Ludeña, Dolores [Pathology Service, University Hospital of Salamanca, P/San Vicente 58-182, 37007 Salamanca (Spain); López, Marta; Ramos, Jennifer; Iglesias, Javier [Tissue Bank, San Francisco Clinic Foundation, Av./Facultad 51, 5°, 24004 León (Spain)

    2013-02-01

    Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12 pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering. -- Highlights: ► Low fibrinogen concentration provides a suitable matrix for cell migration and differentiation. ► Autologous fibrin scaffolds is a promising technique in tissue engineering. ► Dermal cells are an easily accessible mesenchymal stem cell source. ► Fibrin scaffolds afforded adipogenic, osteogenic and chondrogenic differentiation.

  7. Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype

    International Nuclear Information System (INIS)

    Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12 pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering. -- Highlights: ► Low fibrinogen concentration provides a suitable matrix for cell migration and differentiation. ► Autologous fibrin scaffolds is a promising technique in tissue engineering. ► Dermal cells are an easily accessible mesenchymal stem cell source. ► Fibrin scaffolds afforded adipogenic, osteogenic and chondrogenic differentiation.

  8. Autologous transplantation of bone marrow mesenchymal stem cells on diabetic patients with lower limb ischemia

    Institute of Scientific and Technical Information of China (English)

    Lu Debin; Jiang Youzhao; Liang Ziwen; Li Xiaoyan; Zhang Zhonghui; Chen Bing

    2008-01-01

    Objective: To study the efficacy and safety of autologous transplantation of bone marrow mesenchymal stem cells on diabetic patients with lower limb ischemia. Methods: Fifty Type 2 diabetic patients with lower limb ischemia were enrolled and randomized to either transplanted group or control group. Patients in both group received the same conventional treatment. Meanwhile, 20 ml bone marrow from each transplanted patient were collected, and the mesenchymal stem cells were separated by density gradient centrifugation and cultured in the medium with autologous serum. After three-weeks adherent culture in vitro, 7.32×108-5.61×109 mesenchymal stern cells were harvested and transplanted by multiple intramuscular and hypodermic injections into the impaired lower limbs. Results: At the end of 12-week follow-up, 5 patients were excluded from this study because of clinical worsening or failure of cell culture. Main ischemic symptoms, including rest pain and intermittent claudication, were improved significantly in transplanted patients. The ulcer healing rate of the transplanted group (15 of 18, 83.33%) was significantly higher than that of the control group (9 of 20, 45.00%, P=0.012).The mean of resting ankle-brachial index (ABI) in transplanted group significantly was increased from 0.61±0.09 to 0.74±0.11 (P<0.001). Magnetic resonance angiography (MRA) demonstrated that there were more patients whose score of new vessels exceeded or equaled to 2 in the transplant patients (11 of 15) than in control patients (2 of 14, P=0.001). Lower limb amputation rate was significantly lower in transplanted group than in the control group (P=0.040). No adverse effects was observed in transplanted group. Conclusion: These results indicate that the autologous transplantation of bone marrow mesenehymal stem cells relieves critical lower limb ischemia and promotes ulcers healing in Type 2 diabetic patients.

  9. Autologous adipose tissue-derived mesenchymal stem cells are involved in rat liver regeneration following repeat partial hepatectomy

    OpenAIRE

    Liu, Tao; Mu, Hong; SHEN, ZHONGYANG; Song, Zhuolun; CHEN, XIAOBO; Wang, Yuliang

    2016-01-01

    Adipose tissue-derived mesenchymal stem cells (ADSCs) have been considered to be attractive and readily available adult mesenchymal stem cells, and they are becoming increasingly popular for use in regenerative cell therapy, as they are readily accessible through minimally invasive techniques. The present study investigated whether autologous ADSC transplantation promoted liver regeneration following a repeat partial hepatectomy in rats. The rats were divided into three groups as follows: 70%...

  10. Use of Autologous Mesenchymal Stem Cells Derived from Bone Marrow for the Treatment of Naturally Injured Spinal Cord in Dogs

    OpenAIRE

    Euler Moraes Penha; Cássio Santana Meira; Elisalva Teixeira Guimarães; Marcus Vinícius Pinheiro Mendonça; Faye Alice Gravely; Cláudia Maria Bahia Pinheiro; Taiana Maria Bahia Pinheiro; Stella Maria Barrouin-Melo; Ricardo Ribeiro-dos-Santos; Milena Botelho Pereira Soares

    2014-01-01

    The use of stem cells in injury repair has been extensively investigated. Here, we examined the therapeutic effects of autologous bone marrow mesenchymal stem cells (MSC) transplantation in four dogs with natural traumatic spinal cord injuries. MSC were cultured in vitro, and proliferation rate and cell viability were evaluated. Cell suspensions were prepared and surgically administered into the spinal cord. The animals were clinically evaluated and examined by nuclear magnetic resonance. Ten...

  11. Platelet-rich plasma-induced bone marrow mesenchymal stem cells versus autologous nerve grafting for sciatic nerve repair

    Institute of Scientific and Technical Information of China (English)

    Changsuo Xia; Yajuan Li; Wen Cao; Zhaohua Yu

    2010-01-01

    Autologous nerve grafting is the gold standard of peripheral nerve repair.We previously showed that autologous platelet-rich plasma(PRP)contains high concentrations of growth factors and can induce in vitro cultured bone marrow mesenchymal stem cells(BMSCs)to differentiate into Schwann cells.Here we used PRP-induced BMSCs combined with chemically extracted acellular nerves to repair sciatic nerve defects and compared the effect with autologous nerve grafting.The BMSCs and chemically extracted acellular nerve promoted target muscle wet weight restoration,motor nerve conduction velocity,and axonal and myelin sheath regeneration,with similar effectiveness to autologous nerve grafting.This finding suggests that PRP induced BMSCs can be used to repair peripheral nerve defects.

  12. Treatment of one case of cerebral palsy combined with posterior visual pathway injury using autologous bone marrow mesenchymal stem cells

    OpenAIRE

    Li Min; Yu Aixue; Zhang Fangfang; Dai GuangHui; Cheng Hongbin; Wang Xiaodong; An Yihua

    2012-01-01

    Abstract Background Cerebral palsy is currently one of the major diseases that cause severe paralysis of the nervous system in children; approximately 9–30% of cerebral palsy patients are also visually impaired, for which no effective treatment is available. Bone marrow mesenchymal stem cells (BMSCs) have very strong self-renewal, proliferation, and pluripotent differentiation potentials. Therefore, autologous BMSC transplantation has become a novel method for treating cerebral palsy. Methods...

  13. Beneficial effects of autologous bone marrow-derived mesenchymal stem cells in naturally occurring tendinopathy.

    Directory of Open Access Journals (Sweden)

    Roger Kenneth Whealands Smith

    Full Text Available Tendon injuries are a common age-related degenerative condition where current treatment strategies fail to restore functionality and normal quality of life. This disease also occurs naturally in horses, with many similarities to human tendinopathy making it an ideal large animal model for human disease. Regenerative approaches are increasingly used to improve outcome involving mesenchymal stem cells (MSCs, supported by clinical data where injection of autologous bone marrow derived MSCs (BM-MSCs suspended in marrow supernatant into injured tendons has halved the re-injury rate in racehorses. We hypothesized that stem cell therapy induces a matrix more closely resembling normal tendon than the fibrous scar tissue formed by natural repair. Twelve horses with career-ending naturally-occurring superficial digital flexor tendon injury were allocated randomly to treatment and control groups. 1X10(7 autologous BM-MSCs suspended in 2 ml of marrow supernatant were implanted into the damaged tendon of the treated group. The control group received the same volume of saline. Following a 6 month exercise programme horses were euthanized and tendons assessed for structural stiffness by non-destructive mechanical testing and for morphological and molecular composition. BM-MSC treated tendons exhibited statistically significant improvements in key parameters compared to saline-injected control tendons towards that of normal tendons and those in the contralateral limbs. Specifically, treated tendons had lower structural stiffness (p<0.05 although no significant difference in calculated modulus of elasticity, lower (improved histological scoring of organisation (p<0.003 and crimp pattern (p<0.05, lower cellularity (p<0.007, DNA content (p<0.05, vascularity (p<0.03, water content (p<0.05, GAG content (p<0.05, and MMP-13 activity (p<0.02. Treatment with autologous MSCs in marrow supernatant therefore provides significant benefits compared to untreated tendon repair

  14. Cardiac atrioventricular conduction improved by autologous transplantation of mesenchymal stem cells in canine atrioventricular block models

    Institute of Scientific and Technical Information of China (English)

    Xiaoqing Ren; Jielin Pu; Shu Zhang; Liang Meng; Fangzheng Wang

    2007-01-01

    Objective Atrioventricular block (AVB) is a common and serious arrhythmia. At present, there is no perfect method of treatment for this kind of arrhythmia. The purpose of this study was to regenerate cardiac atrioventricular conduction by autologous transplantation of bone marrow mesenchymal stem cells (MSCs), and explore new methods for therapy of atrioventricular block. Methods Eleven Mongrel canines were randomized to MSCs transplantation (n=6) or control (n=5) group. The models of permanent and complete AVB in 11 canines were established by ablating His bundle with radiofrequency technique. At 4 weeks after AVB, bone marrow was aspirated from the iliac crest. MSCs were isolated and culture-expanded by means of gradient centrifugal and adherence to growth technique, and differentiated by 5-azacytidine in vitro. Differentiated MSCs (1ml, 1.5×107cells) labeled with BrdU were autotransplanted into His bundle area of canines by direct injection in the experimental group, and 1ml DMEM in the control group. At 1-12 weeks after operation,the effects of autologous MSCs transplantation on AVB models were evaluated by electrocardiogram, pathologic and immunohistochemical staining technique. Results Compared with the control group, there was a distinct improvement in atrioventricular conduction function in the experimental group. MSCs transplanted in His bundle were differentiated into analogous conduction system cells and endothelial cells in vivo, and established gap junction with host cardiomyocytes. Conclusions The committed-induced MSCs transplanted into His bundle area could differentiate into analogous conduction system cells and improve His conduction function in canine AVB models.

  15. Autologous adipose tissue‑derived mesenchymal stem cells are involved in rat liver regeneration following repeat partial hepatectomy.

    Science.gov (United States)

    Liu, Tao; Mu, Hong; Shen, Zhongyang; Song, Zhuolun; Chen, Xiaobo; Wang, Yuliang

    2016-03-01

    Adipose tissue‑derived mesenchymal stem cells (ADSCs) have been considered to be attractive and readily available adult mesenchymal stem cells, and they are becoming increasingly popular for use in regenerative cell therapy, as they are readily accessible through minimally invasive techniques. The present study investigated whether autologous ADSC transplantation promoted liver regeneration following a repeat partial hepatectomy in rats. The rats were divided into three groups as follows: 70% partial hepatectomy (PH) group; repeat PH (R‑PH) group and R‑PH/ADSC group, subjected to R‑PH and treated with autologous ADSCs via portal vein injection. In each group, the rats were sacrificed at different time points postoperatively in order to evaluate the changes in liver function and to estimate the liver regenerative response. The expression of proliferating cell nuclear antigen (PCNA) labeling index in the liver was measured using immunohistochemistry. The expression levels of hepatocyte growth factor (HGF) mRNA were measured using reverse transcription polymerase chain reaction. The results showed that regeneration of the remaining liver following R‑PH was significantly promoted by ADSC transplantation, as shown by a significant increase in liver to body weight ratio and the PCNA labeling index at 24 h post‑hepatectomy. Additionally, ADSC transplantation markedly inhibited the elevation of serum levels of alanine aminotransferase, aspartate aminotransferase and total bilirubin, increased HGF content and also attenuated hepatic vacuolar degeneration 24 h postoperatively. Furthermore, the liver was found to almost fully recover from hepatocellular damage due to hepatectomy among the three groups at 168 h postoperatively. These results indicated that autologous ADSC transplantation enhanced the regenerative capacity of the remnant liver tissues in the early phase following R‑PH. PMID:26783183

  16. AKT-modified autologous intracoronary mesenchymal stem cells prevent remodeling and repair in swine infarcted myocardium

    Institute of Scientific and Technical Information of China (English)

    YU Yun-sheng; SHEN Zhen-ya; YE Wen-xue; HUANG Hao-yue; HUA Fei; CHEN Yi-huan; CHEN Ke; LAO Wei-jie; TAO Li

    2010-01-01

    Background Transplantation of adult bone marrow-derived mesenchymal stem cells (MSCs) has been proposed as a strategy for cardiac repair following myocardial damage. However cell transplantation strategies to replace lost myocardium are limited by the inability to deliver large numbers of cells that resist peritransplantation graft cell death. Accordingly, we set out to isolate and expand adult swine bone marrow-derived MSCs, and to engineer these cells to overexpress AKT1 (protein kinase B), to test the hypothesis that AKT1 -engineered MSCs are more resistant to apoptosis and can enhance cardiac repair after transplantation into the ischemic swine heart.Methods The CDS (regulation domain of AKT1) AKT1-cDNA fragment was amplified, and MSCs were transfected following synthesis with a pCDH1-AKT1 shuttling plasmid. Western blotting analysis and real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed. Myocardial infarction (Ml) models were constructed in Meishan pigs, and cardiac function was evaluated by magnetic resonance imaging (MRI) measurements and echocardiography 4 weeks later. All pigs were assigned to four groups: control (A), DMEM (B), MSC (C), and AKT-transfected (D). MSCs were transfected with the AKT1 gene, and autologous BrdU-labeled stem cells (1 × 107/5 ml) were injected into left anterior descending coronary atery (LAD) of the infarct heart in groups C and D. In group B, DMEM was injected using the same approach. In group A, there was no injection following LAD occlusion. After 4 weeks, cardiac function and regional perfusion measurements were repeated by MRI and echocardiography, and histological characteristics of the hearts were assessed. Connecxin-43 (CX-43), BrdU, and von Willebrand factor (VWF) immunoreactivity was tested using enzyme linked immunosorbent assay (ELISA). Vascular endothelial growth factor (VEGF), transforming growth factor-(31 (TGF-p1) were analyzed at the same time.Results AKT1-cDNA was cloned into p

  17. MRI assessment of acute myocardial infarction with transplantation of autologous mesenchymal stem cells in swine: an experimental study

    International Nuclear Information System (INIS)

    Objective: To investigate the effects of autologous bone marrow-derived mesenchymal stem cells (MSCs) transplantation on acute myocardial infarction in swine models using MRI. Methods: Fourteen Chinese mini-pigs (27 ± 3 kg) were divided into control group (n=7) and transplantation group (n=7). Acute myocardial infarction (AMI) model was made by occlusion of the left anterior descending coronary artery for 90 minutes, and then 10 ml autologous MSCs (3 x 106 cell/ml) were injected into LAD by over-wire-balloon catheter after one week. MRI was performed to assess the cardiac function and myocardial perfusion 1 week after AMI and 6 weeks after transplantation. The implanted cells in vitro were analyzed by immunofluorescence. Results: The left ventricular ejection fraction (LVEF) in transplantation group was increased from (42.7±7.5)% to (50.1±10.1)%, which was significantly different from that in control group (P2 respectively (P2 in transplantation group (P<0.05) compared with control group. The DAPI-labeled cells in infarcted and peri-infarcted region indicated the survived MSCs. Immunofluorescence also confirmed that those cells expressed cardiomyocyte-specific troponin T, connexin 43 and vessel-specific smooth muscle actin. Capillary density in both infarcted and peri-infarcted region were higher in transplantation group than the control group (P<0.01). Conclusion: MRI is a reliable imaging method for assessing the effects of stem cell transplantation in acute myocardial infartion of swine models. (authors)

  18. Mesenchymal properties of SJL mice-stem cells and their efficacy as autologous therapy in a relapsing–remitting multiple sclerosis model

    OpenAIRE

    Marin-Bañasco, Carmen; García, Margarita Suardíaz; Guerrero, Issac Hurtado; Sánchez, Rafael Maldonado; Estivill-Torrús, Guillermo; Fernández, Laura Leyva; Fernández, Oscar Fernández

    2014-01-01

    Introduction Mesenchymal stem cells (MSCs) are a multipotent population of adult stem cells, which may represent a promising therapeutic approach for neurological autoimmune diseases such as multiple sclerosis. The mouse is the most used species for obtaining and studying the characteristics of MSC and their potential as autologous transplants in pre-clinical models. However, conflicting data have been published disclosing intraspecies variations. The choice of the mouse strain and the tissue...

  19. Science Letters: Brain natriuretic peptide: A potential indicator of cardiomyogenesis after autologous mesenchymal stem cell transplantation?

    Institute of Scientific and Technical Information of China (English)

    LI Nan; WANG Jian-an

    2006-01-01

    We observed in a pilot study that there was a transient elevation of brain natriuretic peptide (BNP) level shortly after the transplantation in the patient with ischemic heart failure, which is unexplainable by the simultaneous increase of the cardiac output and six-minute walk distance. Similar findings were observed in the phase I trial. We postulated on the basis of the finding of Fukuda in vitro that this transient elevation of BNP level against the improvement of cardiac function and exercise capacity might indicate cardiomyogenesis in patients after mesenchymal stem cell transplantation. Further study is warranted to verify the hypothesis.

  20. Treatment of one case of cerebral palsy combined with posterior visual pathway injury using autologous bone marrow mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Li Min

    2012-05-01

    Full Text Available Abstract Background Cerebral palsy is currently one of the major diseases that cause severe paralysis of the nervous system in children; approximately 9–30% of cerebral palsy patients are also visually impaired, for which no effective treatment is available. Bone marrow mesenchymal stem cells (BMSCs have very strong self-renewal, proliferation, and pluripotent differentiation potentials. Therefore, autologous BMSC transplantation has become a novel method for treating cerebral palsy. Methods An 11-year-old boy had a clear history of dystocia and asphyxia after birth; at the age of 6 months, the family members observed that his gaze roamed and noted that he displayed a lack of attention. A brain MRI examination at the age of 7 years showed that the child had cerebral palsy with visual impairment (i.e., posterior visual pathway injury. The patient was hospitalized for 20 days and was given four infusions of intravenous autologous BMSCs. Before transplantation and 1, 6, and 12 months after transplantation, a visual evoked potential test, an electrocardiogram, routine blood tests, and liver and kidney function tests were performed. Results The patient did not have any adverse reactions during hospitalization or postoperative follow-up. After discharge, the patient could walk more smoothly than he could before transplantation; furthermore, his vision significantly improved 6 months after transplantation, which was also supported by the electrophysiological examinations. Conclusions The clinical application of BMSCs is effective for improving vision in a patient with cerebral palsy combined with visual impairment.

  1. Bone tissue engineering using polyetherketoneketone scaffolds combined with autologous mesenchymal stem cells in a sheep calvarial defect model.

    Science.gov (United States)

    Adamzyk, Carina; Kachel, Paul; Hoss, Mareike; Gremse, Felix; Modabber, Ali; Hölzle, Frank; Tolba, Rene; Neuss, Sabine; Lethaus, Bernd

    2016-08-01

    Polyetherketoneketone (PEKK) a high performance thermoplastic polymer that is FDA-approved for cranio- and maxillo-facial as well as spineal surgery. We studied the viability, growth and osteogenic differentiation of bone marrow-derived human and sheep mesenchymal stem cells (MSC) in combination with a 3D scaffold made of PEKK using different cell-based assays. To investigate if autologous MSC, either undifferentiated or osteogenically pre-differentiated, augmented bone formation after implantation, we implanted cell-seeded 3D PEKK scaffolds into calvarial defects in sheep for 12 weeks. The volume and quality of newly formed bone were investigated using micro-computer tomography (micro-CT) and histological stainings. Our results show that the 3D PEKK scaffolds were cyto- and bio-compatible. They allowed for adherence, growth and osteogenic differentiation of human and ovine MSC. However, bone healing seemed unaffected by whether the scaffolds were seeded with MSC. Considerable amounts of newly formed bone were found in all PEKK treated groups, but a fibrous capsule was formed around the implants regardless of cell seeding with MSC. PMID:27328894

  2. Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Sara Llufriu

    Full Text Available Uncontrolled studies of mesenchymal stem cells (MSCs in multiple sclerosis suggested some beneficial effect. In this randomized, double-blind, placebo-controlled, crossover phase II study we investigated their safety and efficacy in relapsing-remitting multiple sclerosis patients. Efficacy was evaluated in terms of cumulative number of gadolinium-enhancing lesions (GEL on magnetic resonance imaging (MRI at 6 months and at the end of the study.Patients unresponsive to conventional therapy, defined by at least 1 relapse and/or GEL on MRI scan in past 12 months, disease duration 2 to 10 years and Expanded Disability Status Scale (EDSS 3.0-6.5 were randomized to receive IV 1-2×10(6 bone-marrow-derived-MSCs/Kg or placebo. After 6 months, the treatment was reversed and patients were followed-up for another 6 months. Secondary endpoints were clinical outcomes (relapses and disability by EDSS and MS Functional Composite, and several brain MRI and optical coherence tomography measures. Immunological tests were explored to assess the immunomodulatory effects.At baseline 9 patients were randomized to receive MSCs (n = 5 or placebo (n = 4. One patient on placebo withdrew after having 3 relapses in the first 5 months. We did not identify any serious adverse events. At 6 months, patients treated with MSCs had a trend to lower mean cumulative number of GEL (3.1, 95% CI = 1.1-8.8 vs 12.3, 95% CI = 4.4-34.5, p = 0.064, and at the end of study to reduced mean GEL (-2.8±5.9 vs 3±5.4, p = 0.075. No significant treatment differences were detected in the secondary endpoints. We observed a non-significant decrease of the frequency of Th1 (CD4+ IFN-γ+ cells in blood of MSCs treated patients.Bone-marrow-MSCs are safe and may reduce inflammatory MRI parameters supporting their immunomodulatory properties. ClinicalTrials.gov NCT01228266.

  3. Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Ra Jeong Chan

    2011-10-01

    Full Text Available Abstract Prolonged life expectancy, life style and environmental changes have caused a changing disease pattern in developed countries towards an increase of degenerative and autoimmune diseases. Stem cells have become a promising tool for their treatment by promoting tissue repair and protection from immune-attack associated damage. Patient-derived autologous stem cells present a safe option for this treatment since these will not induce immune rejection and thus multiple treatments are possible without any risk for allogenic sensitization, which may arise from allogenic stem cell transplantations. Here we report the outcome of treatments with culture expanded human adipose-derived mesenchymal stem cells (hAdMSCs of 10 patients with autoimmune associated tissue damage and exhausted therapeutic options, including autoimmune hearing loss, multiple sclerosis, polymyotitis, atopic dermatitis and rheumatoid arthritis. For treatment, we developed a standardized culture-expansion protocol for hAdMSCs from minimal amounts of fat tissue, providing sufficient number of cells for repetitive injections. High expansion efficiencies were routinely achieved from autoimmune patients and from elderly donors without measurable loss in safety profile, genetic stability, vitality and differentiation potency, migration and homing characteristics. Although the conclusions that can be drawn from the compassionate use treatments in terms of therapeutic efficacy are only preliminary, the data provide convincing evidence for safety and therapeutic properties of systemically administered AdMSC in human patients with no other treatment options. The authors believe that ex-vivo-expanded autologous AdMSCs provide a promising alternative for treating autoimmune diseases. Further clinical studies are needed that take into account the results obtained from case studies as those presented here.

  4. Autologous Bone Marrow-Derived Mesenchymal Stem Cells Modulate Molecular Markers of Inflammation in Dogs with Cruciate Ligament Rupture.

    Science.gov (United States)

    Muir, Peter; Hans, Eric C; Racette, Molly; Volstad, Nicola; Sample, Susannah J; Heaton, Caitlin; Holzman, Gerianne; Schaefer, Susan L; Bloom, Debra D; Bleedorn, Jason A; Hao, Zhengling; Amene, Ermias; Suresh, M; Hematti, Peiman

    2016-01-01

    Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated stifle osteoarthritis (OA) is an important veterinary health problem. CR causes stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common. This suggests that both genetic and environmental factors may increase ligament rupture risk. We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and stifle joint inflammatory responses in dogs with CR. Twelve dogs with unilateral CR and contralateral stable partial CR were enrolled prospectively. BM-MSCs were collected during surgical treatment of the unstable CR stifle and culture-expanded. BM-MSCs were subsequently injected at a dose of 2x106 BM-MSCs/kg intravenously and 5x106 BM-MSCs by intra-articular injection of the partial CR stifle. Blood (entry, 4 and 8 weeks) and stifle synovial fluid (entry and 8 weeks) were obtained after BM-MSC injection. No adverse events after BM-MSC treatment were detected. Circulating CD8+ T lymphocytes were lower after BM-MSC injection. Serum C-reactive protein (CRP) was decreased at 4 weeks and serum CXCL8 was increased at 8 weeks. Synovial CRP in the complete CR stifle was decreased at 8 weeks. Synovial IFNγ was also lower in both stifles after BM-MSC injection. Synovial/serum CRP ratio at diagnosis in the partial CR stifle was significantly correlated with development of a second CR. Systemic and intra-articular injection of autologous BM-MSCs in dogs with partial CR suppresses systemic and stifle joint inflammation, including CRP concentrations. Intra-articular injection of autologous BM-MSCs had profound effects on the correlation and conditional dependencies of cytokines using causal networks. Such treatment effects could ameliorate risk of a second CR by modifying the stifle joint inflammatory response

  5. Neural stem cell-like cells derived from autologous bone mesenchymal stem cells for the treatment of patients with cerebral palsy

    Directory of Open Access Journals (Sweden)

    Chen Guojun

    2013-01-01

    Full Text Available Abstract Background Stem cell therapy is a promising treatment for cerebral palsy, which refers to a category of brain diseases that are associated with chronic motor disability in children. Autologous MSCs may be a better cell source and have been studied for the treatment of cerebral palsy because of their functions in tissue repair and the regulation of immunological processes. Methods To assess neural stem cell–like (NSC-like cells derived from autologous marrow mesenchymal stem cells as a novel treatment for patients with moderate-to-severe cerebral palsy, a total of 60 cerebral palsy patients were enrolled in this open-label, non-randomised, observer-blinded controlled clinical study with a 6-months follow-up. For the transplantation group, a total of 30 cerebral palsy patients received an autologous NSC-like cells transplantation (1-2 × 107 cells into the subarachnoid cavity and rehabilitation treatments whereas 30 patients in the control group only received rehabilitation treatment. Results We recorded the gross motor function measurement scores, language quotients, and adverse events up to 6 months post-treatment. The gross motor function measurement scores in the transplantation group were significantly higher at month 3 (the score increase was 42.6, 95% CI: 9.8–75.3, P=.011 and month 6 (the score increase was 58.6, 95% CI: 25.8–91.4, P=.001 post-treatment compared with the baseline scores. The increase in the Gross Motor Function Measurement scores in the control group was not significant. The increases in the language quotients at months 1, 3, and 6 post-treatment were not statistically significant when compared with the baseline quotients in both groups. All the 60 patients survived, and none of the patients experienced serious adverse events or complications. Conclusion Our results indicated that NSC-like cells are safe and effective for the treatment of motor deficits related to cerebral palsy. Further randomised clinical

  6. Autologous mesenchymal stem cells applied on the pressure ulcers had produced a surprising outcome in a severe case of neuromyelitis optica.

    Science.gov (United States)

    Dulamea, Adriana Octaviana; Sirbu-Boeti, Mirela-Patricia; Bleotu, Coralia; Dragu, Denisa; Moldovan, Lucia; Lupescu, Ioana; Comi, Giancarlo

    2015-11-01

    Recent studies provided evidence that mesenchymal stem cells (MSCs) have regenerative potential in cutaneous repair and profound immunomodulatory properties making them a candidate for therapy of neuroimmunologic diseases. Neuromyelitis optica (NMO) is an autoimmune, demyelinating central nervous system disorder characterized by a longitudinally extensive spinal cord lesion. A 46-year-old male diagnosed with NMO had relapses with paraplegia despite treatment and developed two stage IV pressure ulcers (PUs) on his legs. The patient consented for local application of autologous MSCs on PUs. MSCs isolated from the patient's bone marrow aspirate were multiplied in vitro during three passages and embedded in a tridimensional collagen-rich matrix which was applied on the PUs. Eight days after MSCs application the patient showed a progressive healing of PUs and improvement of disability. Two months later the patient was able to walk 20 m with bilateral assistance and one year later he started to walk without assistance. For 76 months the patient had no relapse and no adverse event was reported. The original method of local application of autologous BM-MSCs contributed to healing of PUs. For 6 years the patient was free of relapses and showed an improvement of disability. The association of cutaneous repair, sustained remission of NMO and improvement of disability might be explained by a promotion/optimization of recovery mechanisms in the central nervous system even if alternative hypothesis should be considered. Further studies are needed to assess the safety and efficacy of mesenchymal stem cells in NMO treatment. PMID:26807122

  7. Autologous mesenchymal stem cells applied on the pressure ulcers had produced a surprising outcome in a severe case of neuromyelitis optica

    Directory of Open Access Journals (Sweden)

    Adriana Octaviana Dulamea

    2015-01-01

    Full Text Available Recent studies provided evidence that mesenchymal stem cells (MSCs have regenerative potential in cutaneous repair and profound immunomodulatory properties making them a candidate for therapy of neuroimmunologic diseases. Neuromyelitis optica (NMO is an autoimmune, demyelinating central nervous system disorder characterized by a longitudinally extensive spinal cord lesion. A 46-year-old male diagnosed with NMO had relapses with paraplegia despite treatment and developed two stage IV pressure ulcers (PUs on his legs. The patient consented for local application of autologous MSCs on PUs. MSCs isolated from the patient′s bone marrow aspirate were multiplied in vitro during three passages and embedded in a tridimensional collagen-rich matrix which was applied on the PUs. Eight days after MSCs application the patient showed a progressive healing of PUs and improvement of disability. Two months later the patient was able to walk 20 m with bilateral assistance and one year later he started to walk without assistance. For 76 months the patient had no relapse and no adverse event was reported. The original method of local application of autologous BM-MSCs contributed to healing of PUs. For 6 years the patient was free of relapses and showed an improvement of disability. The association of cutaneous repair, sustained remission of NMO and improvement of disability might be explained by a promotion/optimization of recovery mechanisms in the central nervous system even if alternative hypothesis should be considered. Further studies are needed to assess the safety and efficacy of mesenchymal stem cells in NMO treatment.

  8. Combination of autologous bone marrow mesenchymal stem cells and cord blood mononuclear cells in the treatment of chronic thoracic spinal cord injury in 27 cases

    Directory of Open Access Journals (Sweden)

    Lian-zhong WANG

    2012-08-01

    Full Text Available Objective To investigate and evaluate therapeutic effects of transplantation of autologous bone marrow mesenchymal stem cells in conjunction with cord blood mononuclear cells for late thoracic spinal cord injury. Methods Data from 27 patients with late thoracic spinal cord injury who received transplantation of autologous bone marrow mesenchymal stem cells in conjunction with cord blood mononuclear cells in Neurosurgery Department of 463rd Hospital of PLA between July 2006 and July 2008 were collected and analyzed. The full treatment course consisted of 4 consecutive injections at one week apart. Indicators for evaluation followed that of the American Spiral Injury Association (ASIA Impairment Scale (AIS grade, ASIA motor and sensory scores, ASIA visual analog score, and the Ashworth score. The follow-up period was 6 months. Evaluations were made 6 weeks and 6 months after the treatment. Results Improvement from AIS A to AIS B was found in 4 patients. In one patient, improvement from AIS A to AIS C and in one patient from AIS B to AIS C was found 6 weeks after the treatment. The AIS improvement rate was 22.2%. In one patient improvement from AIS A to AIS B was found after 6 months. The overall AIS improvement rate was 25.9%. ASIA baseline motor scores of lower extremties were 0.5±1.5, 1.7±2.9, 3.1±3.6 before the treatment, 6 weeks and 6 months after the treatment, respectively, and showed a statistically significant improvement (P < 0.05. ASIA sensory scores including light touch and pinprick were 66.6±13.7 and 67.0±13.6 respectively before treatment, and they became 68.8±14.4, 68.4±14.7 and 70.5±14.4, 70.2±14.4 six weeks and six months after the treatment. The changes were statistically significant (P < 0.05; Modified Ashworth Scale scores were 1.8±1.5, 1.6±1.2,1.1±0.8 respectively at baseline, 6 weeks and 6months after the treatment, and showed a statistically significant descending trend (P < 0.05. Conclusion Transplantation of

  9. Local transplantation of osteogenic pre-differentiated autologous adipose-derived mesenchymal stem cells may accelerate non-union fracture healing with limited pro-metastatic potency.

    Science.gov (United States)

    Han, Duanyang; Han, Na; Zhang, Peixun; Jiang, Baoguo

    2015-01-01

    Fracture non-union is a serious complication in orthopedic clinical practice. Mesenchymal stem cells are believed to play a vital role in fracture healing process. Among various origins of mesenchymal stem cell, adipose derived stem cells hold great promise especially in clinical milieu. However, the wide spread application of mesenchymal stem cell based therapy is impeded by the pro-metastasis nature of the mesenchymal stem cell itself. Based on the findings from previous studies, we hypothesize that local transplanted osteogenic pre-differentiatiated adipose stem cell may promote the non-union fracture healing. Moreover, the pre-differnetiation stem cells by down-regulating the expression of CCL5 and CCL2. This novel osteogenic pre-differnetiation technique may help clinical orthopedists to resolve the refractory non-union cases and shed new light on other stem cell based therapies to counteract to avoid the pro-metastasis nature of the mesenchymal stem cells. PMID:25785146

  10. Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model

    Directory of Open Access Journals (Sweden)

    Boos AM

    2014-11-01

    Full Text Available Anja M Boos,1,* Annika Weigand,1,* Gloria Deschler,1 Thomas Gerber,2 Andreas Arkudas,1 Ulrich Kneser,1 Raymund E Horch,1 Justus P Beier11Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg FAU, Erlangen, 2Institute of Physics, University of Rostock, Rostock, Germany *These authors contributed equally to this work Abstract: New therapeutic strategies are required for critical size bone defects, because the gold standard of transplanting autologous bone from an unharmed area of the body often leads to several severe side effects and disadvantages for the patient. For years, tissue engineering approaches have been seeking a stable, axially vascularized transplantable bone replacement suitable for transplantation into the recipient bed with pre-existing insufficient conditions. For this reason, the arteriovenous loop model was developed and various bone substitutes have been vascularized. However, it has not been possible thus far to engineer a primary stable and axially vascularized transplantable bone substitute. For that purpose, a primary stable silica-embedded nanohydroxyapatite (HA bone substitute in combination with blood, bone marrow, expanded, or directly retransplanted mesenchymal stem cells, recombinant human bone morphogenetic protein 2 (rhBMP-2, and different carrier materials (fibrin, cell culture medium, autologous serum was tested subcutaneously for 4 or 12 weeks in the sheep model. Autologous serum lead to an early matrix change during degradation of the bone substitute and formation of new bone tissue. The best results were achieved in the group combining mesenchymal stem cells expanded with 60 µg/mL rhBMP-2 in autologous serum. Better ingrowth of fibrovascular tissue could be detected in the autologous serum group compared with the control (fibrin. Osteoclastic activity indicating an active bone remodeling process was observed after 4 weeks, particularly

  11. A Patient-Inspired Ex Vivo Liver Tissue Engineering Approach with Autologous Mesenchymal Stem Cells and Hepatogenic Serum.

    Science.gov (United States)

    Bishi, Dillip K; Mathapati, Santosh; Venugopal, Jayarama R; Guhathakurta, Soma; Cherian, Kotturathu M; Verma, Rama S; Ramakrishna, Seeram

    2016-05-01

    Design and development of ex vivo bioengineered liver tissue substitutes intended for subsequent in vivo implantation has been considered therapeutically relevant to treat many liver diseases that require whole-organ replacement on a long-term basis. The present study focus on patient-inspired ex vivo liver tissue engineering strategy to generate hepatocyte-scaffold composite by combining bone marrow mesenchymal stem cells (BMSCs) derived from cardiac failure patients with secondary hyperbilirubinemia as primers of hepatic differentiation and hepatocyte growth factor (HGF)-enriched sera from same individuals as hepatic inducer. A biodegradable and implantable electrospun fibrous mesh of poly-l-lactic acid (PLLA) and gelatin is used as supporting matrix (average fiber diameter = 285 ± 64 nm, porosity = 81 ± 4%, and average pore size = 1.65 ± 0.77 μm). The fibrous mesh supports adhesion, proliferation, and hepatic commitment of patient-derived BMSCs of adequate stemness using HGF-enriched sera generating metabolically competent hepatocyte-like cells, which is comparable to the hepatic induction with defined recombinant growth factor cocktail. The observed results confirm the combinatorial effects of nanofiber topography and biochemical cues in guiding hepatic specification of BMSCs. The fibrous mesh-hepatocyte construct developed in this study using natural growth factors and BMSCs of same individual is promising for future therapeutic applications in treating damaged livers. PMID:26890619

  12. Evaluation of autologous bone marrow-derived mesenchymal stem cells on renal regeneration after experimentally induced acute kidney injury in dogs.

    Science.gov (United States)

    Lim, Chae-Young; Han, Jae-Ik; Kim, Seung-Gon; Lee, Chang-Min; Park, Hee-Myung

    2016-02-01

    OBJECTIVE To evaluate the usefulness of autologous bone marrow-derived mesenchymal stem cell (BM-MSC) therapy for the treatment of dogs with experimentally induced acute kidney injury. ANIMALS 6 healthy dogs. PROCEDURES After induction of kidney injury (day 0) with cisplatin (5 mg/kg, IV), dogs immediately received saline (0.9% NaCl) solution (10 mL; n = 3) or BM-MSCs (1 × 10(6) cells/kg in 10 mL of saline solution; 3) IV. A CBC, serum biochemical analysis, and urinalysis were performed for each dog before administration of cisplatin and on days 1 through 4. Glomerular filtration rate was determined for all dogs on days -7 and 2; BM-MSC tracking by MRI was performed on BM-MSC-treated dogs on days -14 and 4. After sample collection and BM-MSC tracking on day 4, all dogs were euthanized; kidney tissue samples underwent histologic evaluation, immunohistochemical analysis, and cytokine profiling via reverse transcriptase PCR assays. RESULTS Kidney tissue from both groups had mononuclear inflammatory cell infiltration, tubular necrosis, dilated tubules, and glomerular damage. However, there was less fibrotic change and increased proliferation of renal tubular epithelial cells in the BM-MSC-treated dogs, compared with findings for the control dogs. Expressions of tumor necrosis factor-α and transforming growth factor-β were lower in the BM-MSC-treated group, compared with findings for the control group. Laboratory data revealed no improvement in the renal function in BM-MSC-treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results of this study suggested that autologous BM-MSCs may accelerate renal regeneration after experimentally induced acute kidney injury in dogs. (Am J Vet Res 2016;77:208-217). PMID:27027716

  13. Autologous mesenchymal stem cell (MSCs transplantation for critical-sized bone defect following a wide excision of osteofibrous dysplasia

    Directory of Open Access Journals (Sweden)

    Ismail Hadisoebroto Dilogo

    2015-01-01

    Conclusion: Osteofibrous dysplasia was successfully excised without signs of recurrence after 84-week follow-up. Autologous transplantation of augmented BM-MSCs has successfully created new normal bone tissue without causing any side effect and had significantly improved the patient’s quality of life.

  14. Dental mesenchymal stem cells

    OpenAIRE

    Kaukua, Nina

    2014-01-01

    Mesenchymal stem cells have been found in various tissues and act as source for renewal and repair. The mouse incisor tooth continuously grows throughout life, implicating that there are stem cell niches constantly contributing with cells. The composition of these stem cell niches is not fully understood. Here, we show that Schwann cells on the peripheral nerves in the close proximity to the incisor tooth constitute a stem cell niche. Transgenic mouse models were used to label ...

  15. Chronic spinal cord injury treated with transplanted autologous bone marrow-derived mesenchymal stem cells tracked by magnetic resonance imaging: a case report

    OpenAIRE

    Chotivichit, Areesak; Ruangchainikom, Monchai; Chiewvit, Pipat; Wongkajornsilp, Adisak; Sujirattanawimol, Kittipong

    2015-01-01

    Introduction Intrathecal transplantation is a minimally invasive method for the delivery of stem cells, however, whether the cells migrate from the lumbar to the injured cervical spinal cord has not been proved in humans. We describe an attempt to track bone marrow-derived mesenchymal stem cells in a patient with a chronic cervical spinal cord injury. Case presentation A 33-year-old Thai man who sustained an incomplete spinal cord injury from the atlanto-axial subluxation was enrolled into a ...

  16. Co-infusion of autologous adipose tissue derived insulin-secreting mesenchymal stem cells and bone marrow derived hematopoietic stem cells: Viable therapy for type III.C. a diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Umang G Thakkar

    2014-12-01

    Full Text Available Transition from acute pancreatitis to insulin-dependent diabetes mellitus (IDDM is a rare manifestation of primary hyperparathyroidism caused by parathyroid adenoma because of impaired glucose tolerance and suppresses insulin secretion. We report the case of a 26-year-old male with pancreatic diabetes caused by parathyroid adenoma induced chronic pancreatitis. He had serum C-peptide 0.12 ng/ml, glutamic acid decarboxylase antibody 5.0 IU/ml, and glycosylated hemoglobin (HbA1C 8.9%, and required 72 IU/day of biphasic-isophane insulin injection for uncontrolled hyperglycemia. We treated him with his own adipose tissue derived insulin-secreting mesenchymal stem-cells (IS-ADMSC along with his bone marrow derived hematopoietic stem cells (BM-HSC. Autologous IS-ADMSC + BM-HSC were infused into subcutaneous tissue, portal and thymic circulation without any conditioning. Over a follow-up of 27 months, the patient is maintaining fasting and postprandial blood sugar levels of 132 and 165 mg/dl, respectively, with HbA1C 6.8% and requiring 36 IU/day of biphasic-isophane insulin. Co-infusion of IS-ADMSC + BM-HSC offers a safe and viable therapy for type III.C.a Diabetes Mellitus.

  17. Co-infusion of autologous adipose tissue derived insulin-secreting mesenchymal stem cells and bone marrow derived hematopoietic stem cells: viable therapy for type III.C. a diabetes mellitus.

    Science.gov (United States)

    Thakkar, Umang G; Vanikar, Aruna V; Trivedi, Hargovind L

    2013-01-01

    Transition from acute pancreatitis to insulin-dependent diabetes mellitus (IDDM) is a rare manifestation of primary hyperparathyroidism caused by parathyroid adenoma because of impaired glucose tolerance and suppresses insulin secretion. We report the case of a 26-year-old male with pancreatic diabetes caused by parathyroid adenoma induced chronic pancreatitis. He had serum C-peptide 0.12 ng/ml, glutamic acid decarboxylase antibody 5.0 IU/ml, and glycosylated hemoglobin (HbA1C) 8.9%, and required 72 IU/day of biphasic-isophane insulin injection for uncontrolled hyperglycemia. We treated him with his own adipose tissue derived insulin-secreting mesenchymal stem-cells (IS-ADMSC) along with his bone marrow derived hematopoietic stem cells (BM-HSC). Autologous IS-ADMSC + BM-HSC were infused into subcutaneous tissue, portal and thymic circulation without any conditioning. Over a follow-up of 27 months, the patient is maintaining fasting and postprandial blood sugar levels of 132 and 165 mg/dl, respectively, with HbA1C 6.8% and requiring 36 IU/day of biphasic-isophane insulin. Co-infusion of IS-ADMSC + BM-HSC offers a safe and viable therapy for type III.C.a Diabetes Mellitus. PMID:24385073

  18. Mesenchymal stem cells.

    Science.gov (United States)

    Ding, Dah-Ching; Shyu, Woei-Cherng; Lin, Shinn-Zong

    2011-01-01

    Stem cells have two features: the ability to differentiate along different lineages and the ability of self-renewal. Two major types of stem cells have been described, namely, embryonic stem cells and adult stem cells. Embryonic stem cells (ESC) are obtained from the inner cell mass of the blastocyst and are associated with tumorigenesis, and the use of human ESCs involves ethical and legal considerations. The use of adult mesenchymal stem cells is less problematic with regard to these issues. Mesenchymal stem cells (MSCs) are stromal cells that have the ability to self-renew and also exhibit multilineage differentiation. MSCs can be isolated from a variety of tissues, such as umbilical cord, endometrial polyps, menses blood, bone marrow, adipose tissue, etc. This is because the ease of harvest and quantity obtained make these sources most practical for experimental and possible clinical applications. Recently, MSCs have been found in new sources, such as menstrual blood and endometrium. There are likely more sources of MSCs waiting to be discovered, and MSCs may be a good candidate for future experimental or clinical applications. One of the major challenges is to elucidate the mechanisms of differentiation, mobilization, and homing of MSCs, which are highly complex. The multipotent properties of MSCs make them an attractive choice for possible development of clinical applications. Future studies should explore the role of MSCs in differentiation, transplantation, and immune response in various diseases. PMID:21396235

  19. Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC).

    Science.gov (United States)

    Huh, Sung Woo; Shetty, Asode Ananthram; Ahmed, Saif; Lee, Dong Hwan; Kim, Seok Jung

    2016-01-01

    Degenerative and traumatic articular cartilage defects are common, difficult to treat, and progressive lesions that cause significant morbidity in the general population. There have been multiple approaches to treat such lesions, including arthroscopic debridement, microfracture, multiple drilling, osteochondral transplantation and autologous chondrocyte implantation (ACI) that are currently being used in clinical practice. Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC) is a single-staged arthroscopic procedure. This method combines a modified microfracture technique with the application of a bone marrow aspirate concentrate (BMAC), hyaluronic acid and fibrin gel to treat articular cartilage defects. We reviewed the current literatures and surgical techniques for mesenchymal cell induced chondrogenesis. PMID:27489409

  20. Sweet Syndrome After Autologous Stem Cell Transplant.

    Science.gov (United States)

    Alkan, Ali; İdemen, Celal; Okçu Heper, Aylin; Utkan, Güngör

    2016-02-01

    Sweet syndrome (acute febrile neutrophilic dermatosis) is a rare clinical entity characterized by skin lesions, neutrophilia, fever, and neutrophilic infiltration of the dermis. It may be a consequence of malignant disease, comorbidities, or drugs. We present a case of acute febrile neutrophilic dermatosis in a patient after autologous stem cell transplant. PMID:25748978

  1. Uses of mesenchymal stem cells

    OpenAIRE

    M. Delgado; González-Rey, Elena; Büscher, Dirk

    2008-01-01

    The invention relates to the use of mesenchymal stem cells (MSCs) for treating systemic infiammatory response syndrome (SIRS) in a subject. The invention provides compositions, uses and methods for the treatment of SIRS.

  2. Lymphoscintigraphy and autologous stem cell implantation

    International Nuclear Information System (INIS)

    Lymphoscintigraphy is the criterion standard technique for the diagnosis of lymphedema. Advances of the application of autologous hematopoietic stem cells in ischemic disorders of lower limbs have increased the attention of researchers in this field. Aim: To determine the usefulness of lymphoscintigraphy for the assessment the efficacy of autologous stem cell implantation in patients with chronic lymphedema of the upper and lower limbs. Methods: Sixty-five patients were included. Clinical evaluation and lymphoscintigraphy were performed before and six months after stem cells implantation. The stem cells implantations were carried out by multiple superficial and deep injections in the trajectory of the lymphatic vessels and also in the inguinal region. A volume of 0.75 to 1.00 mL of cell suspension (1.0-2.2 x 109 stem cells) was administered in each injection site. Lymphoscintigraphy: Whole-body scans were acquired at 20 minutes, 1 hour, and 3 hours after administration of 185 to 259 MBq (5–7mCi) of 99mTc-albumin nanocolloids in the interdigital space of both limbs. The anatomy and function of the lymphatic system were evaluated. Results: Functional assessment before implantation of stem cells showed that 69.2% of the patients had severe lymphatic insufficiency. The 61.5% of patients showed clinical improvement, confirmed by the results of the lymphoscintigraphy. The 46.1% of the cases evaluated showed a clear improvement. The study showed that the isotopic lymphography can evaluate the therapeutic response and its intensity. Conclusion: Lymphoscintigraphy is a useful technique for the evaluation and monitoring of autologous stem cell transplantation in patients with chronic lymphedema. (author)

  3. Cryptococcal meningitis post autologous stem cell transplantation.

    Science.gov (United States)

    Chaaban, S; Wheat, L J; Assi, M

    2014-06-01

    Disseminated Cryptococcus disease occurs in patients with defective T-cell immunity. Cryptococcal meningitis following autologous stem cell transplant (SCT) has been described previously in only 1 patient, 4 months post SCT and while off antifungal prophylaxis. We present a unique case of Cryptococcus meningitis pre-engraftment after autologous SCT, while the patient was receiving fluconazole prophylaxis. A 41-year-old man with non-Hodgkin's lymphoma underwent autologous SCT. Post-transplant prophylaxis consisted of fluconazole 400 mg daily, levofloxacin 500 mg daily, and acyclovir 800 mg twice daily. On day 9 post transplant, he developed fever and headache. Peripheral white blood cell count (WBC) was 700/μL. Magnetic resonance imaging of the brain showed lesions consistent with meningoencephalitis. Cerebrospinal fluid (CSF) analysis revealed a WBC of 39 with 77% lymphocytes, protein 63, glucose 38, CSF pressure 20.5 cmH2 O, and a positive cryptococcal antigen. CSF culture confirmed Cryptococcus neoformans. The patient was treated with liposomal amphotericin B 5 mg/kg intravenously daily, and flucytosine 37.5 mg/kg orally every 6 h. He was switched to fluconazole 400 mg daily after 3 weeks of amphotericin therapy, with sterilization of the CSF with negative CSFCryptococcus antigen and negative CSF culture. Review of the literature revealed 9 cases of cryptococcal disease in recipients of SCT. Median time of onset was 64 days post transplant. Only 3 meningitis cases were described; 2 of them after allogeneic SCT. Fungal prophylaxis with fluconazole post autologous SCT is recommended at least through engraftment, and for up to 100 days in high-risk patients. A high index of suspicion is needed to diagnose and treat opportunistic infections, especially in the face of immunosuppression and despite adequate prophylaxis. Infection is usually fatal without treatment, thus prompt diagnosis and therapy might be life saving. PMID:24750320

  4. Mesenchymal stem cells (MSCs) as skeletal therapeutics–an update

    OpenAIRE

    Saeed, Hamid; Ahsan, Muhammad; Saleem, Zikria; Iqtedar, Mehwish; Islam, Muhammad; Danish, Zeeshan; Khan, Asif Manzoor

    2016-01-01

    Mesenchymal stem cells hold the promise to treat not only several congenital and acquired bone degenerative diseases but also to repair and regenerate morbid bone tissues. Utilizing MSCs, several lines of evidences advocate promising clinical outcomes in skeletal diseases and skeletal tissue repair/regeneration. In this context, both, autologous and allogeneic cell transfer options have been utilized. Studies suggest that MSCs are transplanted either alone by mixing with autogenous plasma/ser...

  5. Generation of induced pluripotent stem cells from human mesenchymal stem cells of parotid gland origin

    OpenAIRE

    Yan, Xing; Xu, Nuo; Meng, Cen; Wang, Bianhong; Yuan, Jinghong; Wang, Caiyun; Li, Yang

    2016-01-01

    The technology to reprogram human somatic cells to pluripotent state allows the generation of patient-specific induced pluripotent stem cells (iPSCs) and holds a great promise for regenerative medicine and autologous transplantation. Here we, for the first time, identified mesenchymal stem cells isolated from parotid gland (hPMSCs) as a suitable candidate for iPSC production. In the present study, hPMSCs were isolated from parotid gland specimens in patients with squamous cell carcinoma of th...

  6. In Vivo Study of Ligament-Bone Healing after Anterior Cruciate Ligament Reconstruction Using Autologous Tendons with Mesenchymal Stem Cells Affinity Peptide Conjugated Electrospun Nanofibrous Scaffold

    Directory of Open Access Journals (Sweden)

    Jingxian Zhu

    2013-01-01

    Full Text Available Electrospinning nanofibrous scaffold was commonly used in tissue regeneration recently. Nanofibers with specific topological characteristics were reported to be able to induce osteogenic differentiation of MSCs. In this in vivo study, autologous tendon grafts with lattice-like nanofibrous scaffold wrapping at two ends of autologous tendon were used to promote early stage of ligament-bone healing after rabbit ACL reconstruction. To utilize native MSCs from bone marrow, an MSCs specific affinity peptide E7 was conjugated to nanofibrous meshes. After 3 months, H-E assessment and specific staining of collagen type I, II, and III showed direct ligament-bone insertion with typical four zones (bone, calcified fibrocartilage, fibrocartilage, and ligament in bioactive scaffold reconstruction group. Diameters of bone tunnel were smaller in nanofibrous scaffold conjugated E7 peptide group than those in control group. The failure load of substitution complex also indicated a stronger ligament-bone insertion healing using bioactive scaffold. In conclusion, lattice-like nanofibrous scaffold with specific MSCs affinity peptide has great potential in promoting early stage of ligament-bone healing after ACL reconstruction.

  7. Co-infusion of autologous adipose tissue derived neuronal differentiated mesenchymal stem cells and bone marrow derived hematopoietic stem cells, a viable therapy for post-traumatic brachial plexus injury: A case report

    Directory of Open Access Journals (Sweden)

    Umang G Thakkar

    2014-08-01

    Full Text Available Stem cell therapy is emerging as a viable approach in regenerative medicine. A 31-year-old male with brachial plexus injury had complete sensory-motor loss since 16 years with right pseudo-meningocele at C5-D1 levels and extra-spinal extension up to C7-D1, with avulsion on magnetic resonance imaging and irreversible damage. We generated adipose tissue derived neuronal differentiated mesenchymal stem cells (N-AD-MSC and bone marrow derived hematopoietic stem cells (HSC-BM. Neuronal stem cells expressed β-3 tubulin and glial fibrillary acid protein which was confirmed on immunofluorescence. On day 14, 2.8 ml stem cell inoculum was infused under local anesthesia in right brachial plexus sheath by brachial block technique under ultrasonography guidance with a 1.5-inch-long 23 gauge needle. Nucleated cell count was 2 × 10 4 /μl, CD34+ was 0.06%, and CD45-/90+ and CD45-/73+ were 41.63% and 20.36%, respectively. No untoward effects were noted. He has sustained recovery with re-innervation over a follow-up of 4 years documented on electromyography-nerve conduction velocity study.

  8. 骨髓间充质干细胞移植治疗杜氏型进行性肌营养不良症344例临床疗效分析%Clinical study of concurrent transplantation of autologous mesenchymal stem cells and umbilical cord mesenchymal stem cells in patients with Duchenne muscular dystrophy

    Institute of Scientific and Technical Information of China (English)

    崔激平; 杨晓凤; 王红梅; 吴雁翔; 吕乃武; 张轶斌; 许忆峰; 单鸿; 周金旭

    2011-01-01

    [ Objective ] To discuss the clinical effect of transplantation of autologous mesenchymal stem cells and umbilical cord mesenchymal stem cells (CMSC) with in patients with Duchenne muscular dystrophy. [Methods ]Totally 344 patients who were diagnosed with Duchenne muscular dystrophy received a whole year treatment with autologous MSCs and cord blood mesenchymal stem cells transplantation from June 2007 to June 2008 in our center.Parameters before and after treatment were compared. Granulocyte-colony stimulating factor (G-CSF) was infused into all patients, and bone marrow was collected following 4 days of mobilization. Bone marrow mononuclear cells (MNC) were isolated by Percoll gradient centrifugation. The amount of MNC was (5.72±1.89) ×l08, the content of CD34+ cells was (2.67±1.22)%, and the content of CD133+ cells was (1.79±0.73)%. The MNC was cultured for 7~10 days and MSCs were got at last. The amount of MSCs was (1.90±0.96) ×108. MSCs were transplanted into all the limbs by intramuscular injection.[Results] One year after transplantation, increased rate of muscle force of the patients was 85% of the patients. [ Conclusion] It was indicated that transplantation of autologous bone marrow stem cells for Duchenne muscular dystrophy can enhance the bare-handed muscle force and activities of daily living and improve values of serum creatine kinase, lactic acid dehydrogenase and creatinine.%目的 探讨自体骨髓间充质干细胞(MSCs)及脐带间充质干细胞移植治疗杜氏型进行性肌营养不良症的临床疗效.方法 2007年6月~2008年6月该科室应用自体MSCs移植对344例杜氏型肌营养不良症患者进行治疗,采用治疗前后对照方法进行研究.骨髓间充质干细胞制备:对344例患者皮下注射粒细胞集落刺激因子,剂量为每日每公斤体重5~10μg,动员骨髓干细胞,共4 d,4 d后采集骨髓,将采集的骨髓通过Percoll梯度离心,提取单个核细胞(MNC),总量为(5.72±1.89)X108

  9. The short-term curative effects of autologous bone marrow mesenchymal stem cells transplantation on patients with primary brain stem injury%自体骨髓间充质干细胞移植治疗原发性脑干损伤的近期效果观察

    Institute of Scientific and Technical Information of China (English)

    肖以磊; 李忠民; 朱建新; 耿凤阳; 郭传军; 庞月玖; 陈秋兰; 张志逖; 种宗雷

    2012-01-01

    目的 观察自体骨髓间充质干细胞移植治疗原发性脑干损伤的近期有效性和安全性.方法 2007年7月至2010年7月我院收治原发性脑干损伤患者54例.移植组30例患者通过蛛网膜下腔注射方式行自体骨髓间充质干细胞移植,选择同时期入院但未行干细胞移植患者24例作为对照组.两组患者移植后1个月进行NIHSS评分,移植后6个月进行疗效比较.同期检测血常规、凝血机制、生化全项、肿瘤标记物.结果 移植后1个月,移植组患者NIHSS评分与对照组比较差异有统计学意义[分别为(10.86 ±7.48)、(18.26±8.74)分,t=2.681,P<0.05];移植后6个月进行疗效比较差异有统计学意义(Z=2.306,P <0.05).随访各项血液检查结果未出现明显异常.结论 自体骨髓间充质干细胞移植治疗原发性脑干损伤安全且近期疗效确定,远期疗效尚待进一步观察.%Objective To explore the short-term curative effect and safety of autologous bone marrow mesenchymal stem cells transplantation in patients with primary brain stem injury.Methods Fifty-four cases with primary brain stem injury were hospitalized during Jul.2007 to Jul.2010 at Liaocheng Brain Hospital,Shandong Province.All cases were randomized into transplantation group( n =30)or control group( n =24 ).The transplantation group was treated with autologous bone marrow mesenchymal stem cell transplantation by subarachnoid space injection (n =30).The control group were selected from primary brain stem injury patients without stem cell transplantation who were hospitalized at the same period with patients from the transplantation group.Respectively,National Institutes of Health Stroke Scale (NIHSS) score was employed to evaluate the condition of patients in the two groups one month after treatment,and Glasgow Outcome Scale (GOS) score was used to evaluate curative effects of the two groups at sixth months after treatment.Meanwhile,some other parameters were observed

  10. Mesenchymal Stem Cell Therapy in Diabetes Mellitus: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Nagwa El-Badri

    2013-01-01

    Full Text Available Advanced type 2 diabetes mellitus is associated with significant morbidity and mortality due to cardiovascular, nervous, and renal complications. Attempts to cure diabetes mellitus using islet transplantation have been successful in providing a source for insulin secreting cells. However, limited donors, graft rejection, the need for continued immune suppression, and exhaustion of the donor cell pool prompted the search for a more sustained source of insulin secreting cells. Stem cell therapy is a promising alternative for islet transplantation in type 2 diabetic patients who fail to control hyperglycemia even with insulin injection. Autologous stem cell transplantation may provide the best outcome for those patients, since autologous cells are readily available and do not entail prolonged hospital stays or sustained immunotoxic therapy. Among autologous adult stem cells, mesenchymal stem cells (MSCs therapy has been applied with varying degrees of success in both animal models and in clinical trials. This review will focus on the advantages of MSCs over other types of stem cells and the possible mechanisms by which MSCs transplant restores normoglycemia in type 2 diabetic patients. Sources of MSCs including autologous cells from diabetic patients and the use of various differentiation protocols in relation to best transplant outcome will be discussed.

  11. Isolation of mesenchymal stem cells from equine umbilical cord blood

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Heerkens, Tammy; Thomsen, Preben Dybdahl;

    2007-01-01

    Background: There are no published studies on stem cells from equine cord blood although commercial storage of equine cord blood for future autologous stem cell transplantations is available. Mesenchymal stem cells (MSC) have been isolated from fresh umbilical cord blood of humans collected non......-invasively at the time of birth and from sheep cord blood collected invasively by a surgical intrauterine approach. Mesenchymal stem cells isolation percentage from frozen-thawed human cord blood is low and the future isolation percentage of MSCs from cryopreserved equine cord blood is therefore expectedly low....... The hypothesis of this study was that equine MSCs could be isolated from fresh whole equine cord blood. Results: Cord blood was collected from 7 foals immediately after foaling. The mononuclear cell fraction was isolated by Ficoll density centrifugation and cultured in a DMEM low glucose based media...

  12. Human stromal (mesenchymal) stem cells

    DEFF Research Database (Denmark)

    Aldahmash, Abdullah; Zaher, Walid; Al-Nbaheen, May;

    2012-01-01

    Human stromal (mesenchymal) stem cells (hMSC) represent a group of non-hematopoietic stem cells present in the bone marrow stroma and the stroma of other organs including subcutaneous adipose tissue, placenta, and muscles. They exhibit the characteristics of somatic stem cells of self......-renewal and multi-lineage differentiation into mesoderm-type of cells, e.g., to osteoblasts, adipocytes, chondrocytes and possibly other cell types including hepatocytes and astrocytes. Due to their ease of culture and multipotentiality, hMSC are increasingly employed as a source for cells suitable for a number...

  13. Autologous Stem Cell Transplant for AL Amyloidosis

    Directory of Open Access Journals (Sweden)

    Vivek Roy

    2012-01-01

    Full Text Available AL amyloidosis is caused by clonal plasma cells that produce immunoglobulin light chains which misfold and get deposited as amyloid fibrils. Therapy directed against the plasma cell clone leads to clinical benefit. Melphalan and corticosteroids have been the mainstay of treatment for a number of years and the recent availability of other effective agents (IMiDs and proteasome inhibitors has increased treatment options. Autologous stem cell transplant (ASCT has been used in the treatment of AL amyloidosis for many years. It is associated with high rates of hematologic response and improvement in organ function. However, transplant carries considerable risks. Careful patient selection is important to minimize transplant related morbidity and mortality and ensure optimal patient outcomes. As newer more affective therapies become available the role and timing of ASCT in the overall treatment strategy of AL amyloidosis will need to be continually reassessed.

  14. Biological conduits combining bone marrow mesenchymal stem cells and extracellular matrix to treat long-segment sciatic nerve defects

    Directory of Open Access Journals (Sweden)

    Yang Wang

    2015-01-01

    Full Text Available The transplantation of polylactic glycolic acid conduits combining bone marrow mesenchymal stem cells and extracellular matrix gel for the repair of sciatic nerve injury is effective in some respects, but few data comparing the biomechanical factors related to the sciatic nerve are available. In the present study, rabbit models of 10-mm sciatic nerve defects were prepared. The rabbit models were repaired with autologous nerve, a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells, or a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel. After 24 weeks, mechanical testing was performed to determine the stress relaxation and creep parameters. Following sciatic nerve injury, the magnitudes of the stress decrease and strain increase at 7,200 seconds were largest in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group, followed by the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group, and then the autologous nerve group. Hematoxylin-eosin staining demonstrated that compared with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group and the autologous nerve group, a more complete sciatic nerve regeneration was found, including good myelination, regularly arranged nerve fibers, and a completely degraded and resorbed conduit, in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group. These results indicate that bridging 10-mm sciatic nerve defects with a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel construct increases the stress relaxation under a constant strain, reducing anastomotic tension. Large elongations under a constant physiological load can limit the anastomotic opening and shift, which is beneficial for the regeneration and functional reconstruction of sciatic nerve. Better

  15. Research Advancements in Porcine Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Bharti, Dinesh; Shivakumar, Sharath Belame; Subbarao, Raghavendra Baregundi; Rho, Gyu-Jin

    2016-01-01

    In the present era of stem cell biology, various animals such as Mouse, Bovine, Rabbit and Porcine have been tested for the efficiency of their mesenchymal stem cells (MSCs before their actual use for stem cell based application in humans. Among them pigs have many similarities to humans in the form of organ size, physiology and their functioning, therefore they have been considered as a valuable model system for in vitro studies and preclinical assessments. Easy assessability, few ethical issues, successful MSC isolation from different origins like bone marrow, skin, umbilical cord blood, Wharton's jelly, endometrium, amniotic fluid and peripheral blood make porcine a good model for stem cell therapy. Porcine derived MSCs (pMSCs have shown greater in vitro differentiation and transdifferention potential towards mesenchymal lineages and specialized lineages such as cardiomyocytes, neurons, hepatocytes and pancreatic beta cells. Immunomodulatory and low immunogenic profiles as shown by autologous and heterologous MSCs proves them safe and appropriate models for xenotransplantation purposes. Furthermore, tissue engineered stem cell constructs can be of immense importance in relation to various osteochondral defects which are difficult to treat otherwise. Using pMSCs successful treatment of various disorders like Parkinson's disease, cardiac ischemia, hepatic failure, has been reported by many studies. Here, in this review we highlight current research findings in the area of porcine mesenchymal stem cells dealing with their isolation methods, differentiation ability, transplantation applications and their therapeutic potential towards various diseases. PMID:26201864

  16. Mesenchymal Stem Cells and Tooth Engineering

    Institute of Scientific and Technical Information of China (English)

    Li Peng; Ling Ye; Xue-dong Zhou

    2009-01-01

    Tooth loss compromises human oral health. Although several prosthetic methods, such as artificial denture and dental implants, are clinical therapies to tooth loss problems, they are thought to have safety and usage time issues. Recently, tooth tissue engineering has attracted more and more attention. Stem cell based tissue engineering is thought to be a promising way to replace the missing tooth. Mesenchymal stem cells (MSCs) are multipotent stem cells which can differentiate into a variety of cell types. The potential MSCs for tooth regeneration mainly include stem cells from human exfoliated deciduous teeth (SHEDs), adult dental pulp stem cells (DPSCs), stem cells from the apical part of the papilla (SCAPs), stem cells from the dental follicle (DFSCs), periodontal ligament stem cells (PDLSCs) and bone marrow derived mesenchymal stem cells (BMSCs). This review outlines the recent progress in the mesenchymal stem cells used in tooth regeneration.

  17. Autologous stem cell transplantation in the treatment of Hodgkin's disease

    OpenAIRE

    Tarabar Olivera; Tukić Ljiljana; Stamatović Dragana; Balint Bela; Elez Marija; Ostojić Gordana; Tatomirović Željka; Marjanović Slobodan

    2009-01-01

    Background/Aim. High-dose chemotherapy with autologous stem cell transplantacion (ASCT) has shown to produce long-term disease-free survival in patients with chemotherapysensitive Hodgkin disease. The aim of the study was to evaluate efficacy of ASCT in the treatment of Hodgkin's disease. Methods. Between May 1997 and September 2008, 34 patients with Hodgkin's disease in median age of 25 (range 16-60) years, underwent ASCT. Autologous SCT were performed as consolidation therapy in one poor-ri...

  18. Cultura autóloga de células-tronco mesenquimais de tecido adiposo para o tratamento de rítides faciais Autologous mesenchymal stem cells culture from adipose tissue for treatment of facial rhytids

    Directory of Open Access Journals (Sweden)

    César Claudio-da-Silva

    2009-08-01

    Full Text Available OBJETIVO: Testar o efeito das c élulas tronco mesenquimais (CTM de tecido adiposo no preenchimento cutâneo de rítides na região naso-labial. MÉTODOS: Foram coletados 50 cc de gordura da região infra-umbilical e 20 mL de sangue periférico de 15 voluntárias do sexo feminino para obtenção das CTM e de plasma autólogo, respectivamente. As voluntárias foram agrupadas de acordo com as estratégias de injeções intra-dérmicas: grupo (1 somente o ácido hialurônico; grupo (2 somente as CTM; grupo (3 CTM associadas ao ácido hialurônico. Tratando-se de um estudo prospectivo e qualitativo o acompanhamento das voluntárias era mensal através de fotografias. RESULTADOS: No grupo (1 foi observado um efeito de preenchimento imediato ao contrário do grupo (2 onde o efeito de preenchimento pleno foi alcançado aproximadamente após dois meses. No grupo (3 o preenchimento ocorreu de maneira mais efetiva e também progressiva, devido à combinação dos efeitos de curto e de longo prazo gerados pelo ácido hialurônico e pelas CTM, respectivamente. CONCLUSÃO: As CTM quando associadas ao ácido hialurônico foram capazes de promover o preenchimento de sulcos profundos, com melhora progressiva do tônus da pele e diminuição das linhas de expressão.OBJECTIVE: To test the effect of mesenchymal stem cells (MSC from adipose tissue on the dermal filling for nasolabial rhytids correction. MEHTODS: 50 cc of infraumbilical fat and 20 ml of peripheral blood were harvested to isolate MSC and autologous plasma from 15 female volunteers, respectively. The volunteers were grouped in according to the following strategies of intra-dermal injection: Group (I only hyaluronic acid; Group (II only MSC; Group (III MSC combined with hyaluronic acid. For this qualitative and prospective study photographic monitoring was done monthly. RESULTS: In the group (I we observed an immediate effect of filling; in the group (II the effect of filling was reached after

  19. Biological conduits combining bone marrow mesenchymal stem cells and extracellular matrix to treat long-segment sciatic nerve defects

    OpenAIRE

    Yang Wang; Zheng-wei Li; Min Luo; Ya-jun Li; Ke-qiang Zhang

    2015-01-01

    The transplantation of polylactic glycolic acid conduits combining bone marrow mesenchymal stem cells and extracellular matrix gel for the repair of sciatic nerve injury is effective in some respects, but few data comparing the biomechanical factors related to the sciatic nerve are available. In the present study, rabbit models of 10-mm sciatic nerve defects were prepared. The rabbit models were repaired with autologous nerve, a polylactic glycolic acid conduit + bone marrow mesenchymal stem ...

  20. Mesenchymal Stem Cell-Based Therapy

    OpenAIRE

    Mundra, Vaibhav; Gerling, Ivan C.; Mahato, Ram I.

    2012-01-01

    Mesenchymal stem cells (MSCs) are multipotent adult stem cells which have self-renewal capacity and differentiation potential into several mesenchymal lineages including bones, cartilages, adipose tissues and tendons. MSCs may repair tissue injuries and prevent immune cell activation and proliferation. Immunomodulation and secretion of growth factors by MSCs have led to realizing the true potential of MSC-based cell therapy. The use of MSCs as immunomdulators has been explored in cell/organ t...

  1. Mesenchymal stem cells in regenerative rehabilitation

    OpenAIRE

    Nurkovic, Jasmin; Dolicanin, Zana; Mustafic, Fahrudin; Mujanovic, Rifat; Memic, Mensur; Grbovic, Vesna; Skevin, Aleksandra Jurisic; Nurkovic, Selmina

    2016-01-01

    [Purpose] Regenerative medicine and rehabilitation contribute in many ways to a specific plan of care based on a patient’s medical status. The intrinsic self-renewing, multipotent, regenerative, and immunosuppressive properties of mesenchymal stem cells offer great promise in the treatment of numerous autoimmune, degenerative, and graft-versus-host diseases, as well as tissue injuries. As such, mesenchymal stem cells represent a therapeutic fortune in regenerative medicine. The aim of this re...

  2. Mesenchymal Stem Cells in Cardiology.

    Science.gov (United States)

    White, Ian A; Sanina, Cristina; Balkan, Wayne; Hare, Joshua M

    2016-01-01

    Cardiovascular disease (CVD) accounts for more deaths globally than any other single disease. There are on average 1.5 million episodes of myocardial infarction (heart attack) each year in the United States alone with roughly one-third resulting in death. There is therefore a major need for developing new and effective strategies to promote cardiac repair. Intramyocardial transplantation of mesenchymal stem cells (MSCs) has emerged as a leading contender in the pursuit of clinical intervention and therapy. MSCs are potent mediators of cardiac repair and are therefore an attractive tool in the development of preclinical and clinical trials. MSCs are capable of secreting a large array of soluble factors, which have had demonstrated effects on pathogenic cardiac remolding, fibrosis, immune activation, and cardiac stem cell proliferation within the damaged heart. MSCs are also capable of differentiation into cardiomyocytes, endothelial cells, and vascular smooth muscle cells, although the relative contribution of trilineage differentiation and paracrine effectors on cardiac repair remains the subject of active investigation. PMID:27236666

  3. Mesenchymal stem cells in regenerative rehabilitation

    Science.gov (United States)

    Nurkovic, Jasmin; Dolicanin, Zana; Mustafic, Fahrudin; Mujanovic, Rifat; Memic, Mensur; Grbovic, Vesna; Skevin, Aleksandra Jurisic; Nurkovic, Selmina

    2016-01-01

    [Purpose] Regenerative medicine and rehabilitation contribute in many ways to a specific plan of care based on a patient’s medical status. The intrinsic self-renewing, multipotent, regenerative, and immunosuppressive properties of mesenchymal stem cells offer great promise in the treatment of numerous autoimmune, degenerative, and graft-versus-host diseases, as well as tissue injuries. As such, mesenchymal stem cells represent a therapeutic fortune in regenerative medicine. The aim of this review is to discuss possibilities, limitations, and future clinical applications of mesenchymal stem cells. [Subjects and Methods] The authors have identified and discussed clinically and scientifically relevant articles from PubMed that have met the inclusion criteria. [Results] Direct treatment of muscle injuries, stroke, damaged peripheral nerves, and cartilage with mesenchymal stem cells has been demonstrated to be effective, with synergies seen between cellular and physical therapies. Over the past few years, several researchers, including us, have shown that there are certain limitations in the use of mesenchymal stem cells. Aging and spontaneous malignant transformation of mesenchymal stem cells significantly affect the functionality of these cells. [Conclusion] Definitive conclusions cannot be made by these studies because limited numbers of patients were included. Studies clarifying these results are expected in the near future. PMID:27390452

  4. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma

    DEFF Research Database (Denmark)

    Mellqvist, Ulf-Henrik; Gimsing, Peter; Hjertner, Oyvind;

    2013-01-01

    The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370...

  5. Autologous bone marrow mesenchymal stem cells combined with hydroxyapatite/tricalcium phosphate complex in the spinal fusion%自体骨髓富集间质干细胞与羟基磷灰石磷酸三钙材料复合在脊柱融合中的应用

    Institute of Scientific and Technical Information of China (English)

    闫伟; 杨莉; 凌梅; 甘嘉亮

    2016-01-01

    背景:脊柱融合过程中使用一定的骨移植材料可以达到促进骨融合、增强脊柱稳定性的效果。目的:探讨自体骨髓富集的间质干细胞复合羟基磷灰石磷酸三钙在脊柱融合中的应用效果。方法:回顾性分析64例行脊柱融合患者的临床资料,按照植骨融合材料的不同分为对照组(32例)和观察组(32例),分别予以自体髂骨移植和自体骨髓富集的间质干细胞复合羟基磷灰石磷酸三钙移植。治疗后随访12个月,对两组患者腰背疼痛、脊柱融合、伤椎复位情况等进行评估。结果与结论:治疗后两组患者 LBOS 评分、LBOS 评分优良率、脊柱融合 Lenke 分级、Cobb 角经比较差异无显著性意义(P >0.05)。两组患者均未出现感染和炎症表现,内固定物对皮肤无刺激现象。两组患者凝血功能、肾功能、炎性因子相关指标均处于正常水平,差异无显著性意义(P >0.05)。试验结果表明,自体骨髓富集的间质干细胞复合羟基磷灰石磷酸三钙应用于脊柱融合可以获得与自体髂骨移植基本相当的临床效果。%BACKGROUND: The use of bone graft materials can promote bone fusion and enhance the stability of the spine during the spinal fusion. OBJECTIVE: To investigate the effect of autologous bone marrow mesenchymal stem cel s with hydroxyapatite/ tricalcium phosphate in the spinal fusion. METHODS: A retrospective analysis of clinical data of 64 patients with spinal fusion was carried out, and these patients were divided into two groups (n=32 per group): control group undergoing autogenous iliac bone grafting and observation group undergoing autologous bone marrow mesenchymal stem cel s combined with hydroxyapatite/tricalcium phosphate. Al patients were fol owed up for 12 months, and their recovery conditions about low back pain, spinal fusion and vertebral reset were assessed. RESULTS AND CONCLUSION: The low-back outcome scale scores and excel

  6. Mesenchymal stem cells in oral reconstructive surgery

    DEFF Research Database (Denmark)

    Jakobsen, C; Sørensen, J A; Kassem, M;

    2013-01-01

    This study evaluated clinical outcomes following intraoperative use of adult mesenchymal stem cells (MSCs) in various oral reconstructive procedures. PubMed was searched without language restrictions from 2000 to 2011 using the search words stem cell, oral surgery, tissue engineering, sinus lift...

  7. Mesenchymal stem cells as a therapeutic tool in tissue and organ regeneration

    Directory of Open Access Journals (Sweden)

    Anna Bajek

    2011-01-01

    Full Text Available Tissue engineering is an interdisciplinary field that offers new opportunities for regeneration of diseased and damaged tissue with the use of many different cell types,including adult stem cells. In tissue engineering and regenerative medicine the most popular are mesenchymal stem cells (MSCs isolated from bone marrow. Bone marrow mesenchymal stem cells are a potential source of progenitor cells for osteoblasts, chondroblasts, adipocytes, skeletal muscles and cardiomyocytes. It has also been shown that these cells can differentiate into ecto- and endodermal cells, e.g. neuronal cells, glial cells, keratinocytes and hepatocytes. The availability of autologous MSCs, their proliferative potential and multilineage differentiation capacity make them an excellent tool for tissue engineering and regenerative medicine. The aim of this publication is to present characteristic and biological properties of mesenchymal stem cells isolated from bone marrow.

  8. Isolation of mesenchymal stem cells from equine umbilical cord blood

    Directory of Open Access Journals (Sweden)

    Thomsen Preben D

    2007-05-01

    Full Text Available Abstract Background There are no published studies on stem cells from equine cord blood although commercial storage of equine cord blood for future autologous stem cell transplantations is available. Mesenchymal stem cells (MSC have been isolated from fresh umbilical cord blood of humans collected non-invasively at the time of birth and from sheep cord blood collected invasively by a surgical intrauterine approach. Mesenchymal stem cells isolation percentage from frozen-thawed human cord blood is low and the future isolation percentage of MSCs from cryopreserved equine cord blood is therefore expectedly low. The hypothesis of this study was that equine MSCs could be isolated from fresh whole equine cord blood. Results Cord blood was collected from 7 foals immediately after foaling. The mononuclear cell fraction was isolated by Ficoll density centrifugation and cultured in a DMEM low glucose based media at 38.5°C in humidified atmosphere containing 5% CO2. In 4 out of 7 samples colonies with MSC morphology were observed. Cellular morphology varied between monolayers of elongated spindle-shaped cells to layered cell clusters of cuboidal cells with shorter cytoplasmic extensions. Positive Alizarin Red and von Kossa staining as well as significant calcium deposition and alkaline phosphatase activity confirmed osteogenesis. Histology and positive Safranin O staining of matrix glycosaminoglycans illustrated chondrogenesis. Oil Red O staining of lipid droplets confirmed adipogenesis. Conclusion We here report, for the first time, the isolation of mesenchymal-like stem cells from fresh equine cord blood and their differentiation into osteocytes, chondrocytes and adipocytes. This novel isolation of equine cord blood MSCs and their preliminary in vitro differentiation positions the horse as the ideal pre-clinical animal model for proof-of-principle studies of cord blood derived MSCs.

  9. Immunological characteristics of mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Cíntia de Vasconcellos Machado

    2013-01-01

    Full Text Available Although bone marrow is the main source, mesenchymal stem cells have already been isolated from various other tissues, such as the liver, pancreas, adipose tissue, peripheral blood and dental pulp. These plastic adherent cells are morphologically similar to fibroblasts and have a high proliferative potential. This special group of cells possesses two essential characteristics: self-renewal and differentiation, with appropriate stimuli, into various cell types. Mesenchymal stem cells are considered immunologically privileged, since they do not express costimulatory molecules, required for complete T cell activation, on their surface. Several studies have shown that these cells exert an immunosuppressive effect on cells from both innate and acquired immunity systems. Mesenchymal stem cells can regulate the immune response in vitro by inhibiting the maturation of dendritic cells, as well as by suppressing the proliferation and function of T and B lymphocytes and natural killer cells. These special properties of mesenchymal stem cells make them a promising strategy in the treatment of immune mediated disorders, such as graft-versus-host disease and autoimmune diseases, as well as in regenerative medicine. The understanding of immune regulation mechanisms of mesenchymal stem cells, and also those involved in the differentiation of these cells in various lineages is primordial for their successful and safe application in different areas of medicine.

  10. Turning Stem Cells into Mesenchymal Tissues

    OpenAIRE

    Tiziano Barberi; Willis, Lucy M.; Socci, Nicholas D.; Lorenz Studer

    2005-01-01

    BACKGROUND: Human embryonic stem cells provide access to the earliest stages of human development and may serve as a source of specialized cells for regenerative medicine. Thus, it becomes crucial to develop protocols for the directed differentiation of embryonic stem cells into tissue-restricted precursors. METHODS AND FINDINGS: Here, we present culture conditions for the derivation of unlimited numbers of pure mesenchymal precursors from human embryonic stem cells and demonstrate multilinea...

  11. 钽棒植入联合自体骨髓间充质干细胞移植治疗早期股骨头缺血性坏死%Early Clinical Results of Implantation of Tantalum Rod Combined Transplantation of Autologous Bone Marrow Mesenchy-mal Stem Cells for Early Stage of Avascular Necrosis of Femoral Head

    Institute of Scientific and Technical Information of China (English)

    梁红锁; 黄克; 李林; 张波; 韦程寿

    2014-01-01

    Objective:To study the effects of implantation of tantalum rod and transplantation of autologous bone mar-row mesenchymal stem cells for early stage of avascular necrosis of femoral head .Methods:27 patients with avascular necrosis of femoral head in the early stage were treated with implantation of tantalum rod and transplantation of autolo-gous bone marrow mesenchymal stem cells .Results:The average period of follow-up was thirteen months (7 ~ 24 months) .Pain of all patients disappeared .The movement range of the hip joint was normal or approximate to normal . Except two cases evolved to stage of ARCOⅢ ,X-ray showed that cystic degeneration disappeared .The Harris score was 54 .2 ± 7 .1 before operation and it increased significantly to 83 .9 ± 8 .6 after operation .Conclusion:It has the ad-vantage to minimal damage of implantation of tantalum rod and transplantation of autologous bone marrow mesenchy-mal stem cells for early stage of avascular necrosis of femoral head .It is an effective way for the treatment of femoral head necrosis .The short-term efficacy is good .%目的:观察钽棒植入联合自体骨髓间充质干细胞移植治疗早期股骨头缺血性坏死的临床疗效。方法:对27例ARCOⅠ、Ⅱ期的ANFH患者采用股骨头髓芯减压后植入钽棒并联合自体骨髓间充质干细胞移植。结果:所有患者经过7~24个月(平均13个月)的随访,关节疼痛基本消失,活动范围接近或恢复正常,除2例患者进展为ARCOⅢ期外,其余股骨头均无塌陷,影像学检查结果示股骨头囊性变消失,Harris评分由术前的(54.2±7.1)分提高到术后(83.9±8.6)分。结论:钽棒植入联合自体骨髓间充质干细胞移植治疗早期股骨头缺血性坏死,具有创伤小、疗效确切等优点,近期临床疗效良好。

  12. Reengineering autologous bone grafts with the stem cell activator WNT3A.

    Science.gov (United States)

    Jing, Wei; Smith, Andrew A; Liu, Bo; Li, Jingtao; Hunter, Daniel J; Dhamdhere, Girija; Salmon, Benjamin; Jiang, Jie; Cheng, Du; Johnson, Chelsey A; Chen, Serafine; Lee, Katherine; Singh, Gurpreet; Helms, Jill A

    2015-04-01

    Autologous bone grafting represents the standard of care for treating bone defects but this biomaterial is unreliable in older patients. The efficacy of an autograft can be traced back to multipotent stem cells residing within the bone graft. Aging attenuates the viability and function of these stem cells, leading to inconsistent rates of bony union. We show that age-related changes in autograft efficacy are caused by a loss in endogenous Wnt signaling. Blocking this endogenous Wnt signal using Dkk1 abrogates autograft efficacy whereas providing a Wnt signal in the form of liposome-reconstituted WNT3A protein (L-WNT3A) restores bone forming potential to autografts from aged animals. The bioengineered autograft exhibits significantly better survival in the hosting site. Mesenchymal and skeletal stem cell populations in the autograft are activated by L-WNT3A and mitotic activity and osteogenic differentiation are significantly enhanced. In a spinal fusion model, aged autografts treated with L-WNT3A demonstrate superior bone forming capacity compared to the standard of care. Thus, a brief incubation in L-WNT3A reliably improves autologous bone grafting efficacy, which has the potential to significantly improve patient care in the elderly. PMID:25682158

  13. Genetically modified mesenchymal stem cells induce mechanically stable posterior spine fusion

    OpenAIRE

    Sheyn, D; Rüthemann, M; Mizrahi, O; Kallai, I; Zilberman, Y.; Tawackoli, W; Kanim, L E A; Zhao, L; Bae, H; Pelled, G.; Snedeker, J G; Gazit, D.

    2010-01-01

    Most spine fusion procedures involve the use of prosthetic fixation devices combined with autologous bone grafts rather than biological treatment. We had shown that spine fusion could be achieved by injection of bone morphogenetic protein-2 (BMP-2)-expressing mesenchymal stem cells (MSCs) into the paraspinal muscle. In this study, we hypothesized that posterior spinal fusion achieved using genetically modified MSCs would be mechanically comparable to that realized using a mechanical fixation....

  14. Biological conduits combining bone marrow mesenchymal stem cells and extracellular matrix to treat long-segment sciatic nerve defects

    Institute of Scientific and Technical Information of China (English)

    Yang Wang; Zheng-wei Li; Min Luo; Ya-jun Li; Ke-qiang Zhang

    2015-01-01

    The transplantation of polylactic glycolic acid conduits combining bone marrow mesenchymal stem cells and extracellular matrix gel for the repair of sciatic nerve injury is effective in some re-spects, but few data comparing the biomechanical factors related to the sciatic nerve are available. In the present study, rabbit models of 10-mm sciatic nerve defects were prepared. The rabbit models were repaired with autologous nerve, a polylactic glycolic acid conduit+bone marrow mesenchymal stem cells, or a polylactic glycolic acid conduit+bone marrow mesenchymal stem cells+extracellular matrix gel. After 24 weeks, mechanical testing was performed to determine the stress relaxation and creep parameters. Following sciatic nerve injury, the magnitudes of the stress decrease and strain increase at 7,200 seconds were largest in the polylactic glycolic acid conduit+bone marrow mesenchymal stem cells+extracellular matrix gel group, followed by the polylactic glycolic acid conduit+bone marrow mesenchymal stem cells group, and then the autologous nerve group. Hematoxylin-eosin staining demonstrated that compared with the poly-lactic glycolic acid conduit+bone marrow mesenchymal stem cells group and the autologous nerve group, a more complete sciatic nerve regeneration was found, including good myelination, regularly arranged nerve ifbers, and a completely degraded and resorbed conduit, in the polylac-tic glycolic acid conduit+bone marrow mesenchymal stem cells+extracellular matrix gel group. These results indicate that bridging 10-mm sciatic nerve defects with a polylactic glycolic acid conduit+bone marrow mesenchymal stem cells+extracellular matrix gel construct increases the stress relaxation under a constant strain, reducing anastomotic tension. Large elongations under a constant physiological load can limit the anastomotic opening and shift, which is ben-eifcial for the regeneration and functional reconstruction of sciatic nerve. Better regeneration was found with the

  15. Mesenchymal stem cells targeting the GVHD

    Institute of Scientific and Technical Information of China (English)

    WANG Liang; ZHAO Robert ChunHua

    2009-01-01

    Acute graft-versus-host disease (GVHD) occurs after allogeneic hematopoietic stem cell transplant and is a reaction of donor immune cells against host tissues. About 35% -5% of hematopoietic stem cell transplant (HSCT) recipients will develop acute GVHD. It is associated with considerable morbidity and mortality, particularly in patients who do not respond to primary therapy, which usually consists of glucocorticoids(steroids). Most of the available second-line and third-line treatments for sterold-refractory acute GVHD induce severe immunodeficiency, which is commonly accompanied by lethal infectious complications. Mesenchymal stem cells (MSCs) have been shown to mediate immunomodulatory effects. The recently elucidated immunosuppreseive potential of mesenchymal stem cells has set the stage for their clinical testing as cellular immunosuppressants, MSCs have been used in patients with steroid-refractory acute GVHD, and encouraging responses have been obtained in many studies. The utility of MSCs for the treatment of GVHD is becoming clear.

  16. Autologous Stem Cell Transplantation in Patient with Critical Limb Ischemia

    International Nuclear Information System (INIS)

    Critical limb ischemia (CLI) is clinical manifestation of an end-stage peripheral arterial obstruction disease. Progressive ischemia leads to development of ischemic rest pain and skin defects. Early recognition, medicamentous treatment and revascularisation are standard treatment practise in these patients. However, up to 30% of patients are not eligible for endovascular or surgical revascularisation. Remaining patients are threatened with disease progression and high risk for leg amputation. Some clinical studies demonstrated, that therapeutic angio genesis with autologous stem cells therapy may be effective in ulcer healing and prevention of limb amputation. This case report describes a 47-year old male with history of one year non-healing ulcer after the third and fifth finger amputation without option of endovascular or surgical revascularisation. Patient was successfully treated with intramuscular autologous bone marrow therapy with ulcer healing and limb salvage after 12-month follow-up. (author)

  17. Autologous Bone Marrow Stem Cells combined with Allograft Cancellous Bone in Treatment of Nonunion

    OpenAIRE

    Le Thua Trung Hau; Duc Phu Bui; Nguyen Duy Thang; Pham Dang Nhat; Le Quy Bao; Nguyen Phan Huy; Tran Ngoc Vu; Le Phuoc Quang; Boeckx willy Denis; Mey Albert De

    2015-01-01

    Autologous cancellous bone graft is currently used as a gold standard method for treatment of bone nonunion. However, there is a limit to the amount of autologous cancellous bone that can be harvested and the donor site morbidity presents a major disadvantage to autologous bone grafting. Embedding viable cells within biological scaffolds appears to be extremely promising. The purpose of this study was to assess the outcome of autologous bone marrow stem cells combined with a cancellous bone a...

  18. Glioma treatment strategies using mesenchymal stem cells

    International Nuclear Information System (INIS)

    Because of the growth characteristics of malignant gliomas that are highly invasive and deeply infiltrate the surrounding brain area; the surgical resection of these gliomas with preservation of neural functions is almost always noncurative. The residual tumor cells are usually resistant to standard adjuvant radio-chemotherapy, and therefore, the tumors inevitably recur after a certain period and finally cause the death of the patients. Neural and mesenchymal stem cells have been extensively studied for the development of new strategies for treating malignant gliomas because of these cells possess the intrinsic property of homing toward tumor cells. By using neural and mesenchymal stem cells as vehicles for drug carriers, it is possible to deliver anticancer drugs to the tumor cells that infiltrate functioning normal brain tissue and are difficult to remove. Several cytokines and suicide genes have been tested, and promising results have been reported in animal brain tumor models. However, further studies involving safety issues such as secondary cancer formation are required before human trials of stem cell therapies. In the present paper, the author has reviewed the recent concepts involved in the treatment of malignant gliomas with stem cells, especially mesenchymal stem cells that are much easier to obtain from the patients themselves. (author)

  19. Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Raquel Taléns-Visconti; Ana Bonora; Ramiro Jover; Vicente Mirabet; Francisco Carbonell; José Vicente Castell; María José Gómez-Lechón

    2006-01-01

    AIM: To investigate and compare the hepatogenic transdifferentiation of adipose tissue-derived stem cells (ADSC) and bone marrow-derived mesenchymal stem cells (BMSC) in vitro. Transdifferentiation of BMSC into hepatic cells in vivo has been described. Adipose tissue represents an accessible source of ADSC, with similar characteristics to BMSC.METHODS: BMSCs were obtained from patients undergoing total hip arthroplasty and ADSC from human adipose tissue obtained from lipectomy. Cells were grown in medium containing 15% human serum. Cultures were serum deprived for 2 d before cultivating under similar pro-hepatogenic conditions to those of liver development using a 2-step protocol with sequential addition of growth factors, cytokines and hormones. Hepatic differentiation was RT-PCR-assessed and liver-marker genes were immunohistochemically analysed.RESULTS: BMSC and ADSC exhibited a fibroblastic morphology that changed to a polygonal shape when cells differentiated. Expression of stem cell marker Thy1 decreased in differentiated ADSC and BMSC. However, the expression of the hepatic markers, albumin and CYPs increased to a similar extent in differentiated BMSC and ADSC. Hepatic gene activation could be attributed to increased liver-enriched transcription factors (C/EBPβ and HNF4α), as demonstrated by adenoviral expression vectors.CONCLUSION: Mesenchymal stem cells can be induced to hepatogenic transdifferentiation in vitro. ADSCs have a similar hepatogenic differentiation potential to BMSC,but a longer culture period and higher proliferation capacity. Therefore, adipose tissue may be an ideal source of large amounts of autologous stem cells, and may become an alternative for hepatocyte regeneration, liver cell transplantation or preclinical drug testing.

  20. Defining Molecular Phenotypes of Mesenchymal and hematopoietic Stem Cells derived from Peripheral blood of Acute Lymphocytic Leukemia patients for regenerative stem cell therapy

    OpenAIRE

    Pravin D. Potdar; Rambhadur P Subedi

    2011-01-01

    Acute Lymphocytic Leukemia (ALL) is a clonal myeloid disorder affecting all age groups, characterized by accumulation of immature blast cells in bone marrow and in peripheral blood. Autologous Bone Marrow Transplantation is a present treatment for cure of ALL patients, which is very expensive, invasive process and may have possibility of transplantation of malignant stem cells to patients. In the present study, we hypothesized to isolate large number of normal Mesenchymal & Hematopoietic stem...

  1. Tenogenically Induced Allogeneic Mesenchymal Stem Cells for the Treatment of Proximal Suspensory Ligament Desmitis in a Horse

    OpenAIRE

    Vandenberghe, Aurélie; Broeckx, Sarah Y; Beerts, Charlotte; Seys, Bert; Zimmerman, Marieke; Verweire, Ineke; Suls, Marc; Spaas, Jan H.

    2015-01-01

    Suspensory ligament injuries are a common injury in sport horses, especially in competing dressage horses. Because of the poor healing of chronic recalcitrant tendon injuries, this represents a major problem in the rehabilitation of sport horses and often compromises the return to the initial performance level. Stem cells are considered as a novel treatment for different pathologies in horses and humans. Autologous mesenchymal stem cells (MSCs) are well known for their use in the treatment of...

  2. Clinical observation of ameliorating motor function in 332 cases with Duchenne muscular dystrophies by autologous bone marrow mesenchymal stem cells transplantation%自体骨髓间充质干细胞移植改善进行性肌营养不良症患者运动功能的研究

    Institute of Scientific and Technical Information of China (English)

    许忆峰; 杨晓凤; 吴雁翔; 王红梅; 张轶斌; 吕乃武; 单鸿; 崔激平; 周金旭

    2011-01-01

    Objective To investigate whether treatment with autologous bone marrow mesenchymal stem cells transplantation can ameliorate the motor function in patients with Duchenne muscular dystrophies.Method Following the agreement of Ethics Committee of the 463 Hospital of Chinese PLA , a total of 332 cases with Duchenne muscular dystrophy (DMD) (all were male) , aged 6-18 years , with the course of disease of 2-18 years were enrolled from the Department of Cell treatment Center of the 463 Hospital of Chinese PLA from December 2007 to May 2009. Granulocyte-colony stimulating factor ( G-CSF) was injected subcutaneously , and bone marrow was collected 4 days later.Bone marrow mononuclear cells were isolated and cultured for 10-14 davs by Percoll gradient centrifugation. Cell suspension [ (2-3) x 1010/L] was prepared and transplanted into all over the body by intravenous injection and intramuscular injection in the four extremities. The amount of mononuclear cells was ( 1.99 ±1.18) x 108 and the amount of mesenchymal cells was (1.77 ± 0.84) x 108. Result Twelve months after transplantation, the improvement rates of bare-handed muscle force and activities of daily living (ADL) were 46.1% and 81.8% respectively. Motor function was ameliorated by 70.8%. Conclusion Transplantation of autologous bone marrow mesenchymal stem cells treated for DMD can enhance the hare-handed muscle force and activities of daily living and ameliorate motor function.%目的:探讨自体骨髓间充质干细胞移植临床治疗进行性肌营养不良症能否改善患者运动功能.方法:经解放军第四六三医院伦理委员会同意,纳入2007年12月至2009年5月在细胞治疗中心住院的具有完整随访资料的杜氏型肌营养不良症患者332例,均为男性,年龄6~18岁,平均(9.4±6.1)岁;病程2~ 18年,平均(6.9±5.7)年.患者皮下注射粒细胞集落刺激因子,动员4 d后采集骨髓,Percoll梯度离心培养骨髓单个核细胞10~14 d.配制浓度为(2

  3. Persistent seropositivity for yellow fever in a previously vaccinated autologous hematopoietic stem cell transplantation recipient

    OpenAIRE

    Kayoko Hayakawa; Tomohiko Takasaki; Hiroko Tsunemine; Shuzo Kanagawa; Satoshi Kutsuna; Nozomi Takeshita; Momoko Mawatari; Yoshihiro Fujiya; Kei Yamamoto; Norio Ohmagari; Yasuyuki Kato

    2015-01-01

    The duration of a protective level of yellow fever antibodies after autologous hematopoietic stem cell transplantation in a previously vaccinated person is unclear. The case of a patient who had previously been vaccinated for yellow fever and who remained seropositive for 22 months after autologous peripheral blood stem cell transplantation for malignant lymphoma is described herein.

  4. Pulmonary heart valve replacement using stabilized acellular xenogeneic scaffolds; effects of seeding with autologous stem cells

    Directory of Open Access Journals (Sweden)

    Harpa Marius Mihai

    2015-12-01

    Full Text Available Background: We hypothesized that an ideal heart valve replacement would be acellular valve root scaffolds seeded with autologous stem cells. To test this hypothesis, we prepared porcine acellular pulmonary valves, seeded them with autologous adipose derived stem cells (ADSCs and implanted them in sheep and compared them to acellular valves.

  5. Therapeutic Potential of Mesenchymal Stem Cells in Regenerative Medicine

    Directory of Open Access Journals (Sweden)

    Devang M. Patel

    2013-01-01

    Full Text Available Mesenchymal stem cells (MSCs are stromal cells that have the ability to self-renew and also exhibit multilineage differentiation into both mesenchymal and nonmesenchymal lineages. The intrinsic properties of these cells make them an attractive candidate for clinical applications. MSCs are of keen interest because they can be isolated from a small aspirate of bone marrow or adipose tissues and can be easily expanded in vitro. Moreover, their ability to modulate immune responses makes them an even more attractive candidate for regenerative medicine as allogeneic transplant of these cells is feasible without a substantial risk of immune rejection. MSCs secrete various immunomodulatory molecules which provide a regenerative microenvironment for a variety of injured tissues or organ to limit the damage and to increase self-regulated tissue regeneration. Autologous/allogeneic MSCs delivered via the bloodstream augment the titers of MSCs that are drawn to sites of tissue injury and can accelerate the tissue repair process. MSCs are currently being tested for their potential use in cell and gene therapy for a number of human debilitating diseases and genetic disorders. This paper summarizes the current clinical and nonclinical data for the use of MSCs in tissue repair and potential therapeutic role in various diseases.

  6. SHIPi Enhances Autologous and Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Sandra Fernandes

    2015-03-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is a highly effective procedure enabling long-term survival for patients with hematologic malignancy or heritable defects. Although there has been a dramatic increase in the success rate of HSCT over the last two decades, HSCT can result in serious, sometimes untreatable disease due to toxic conditioning regimens and Graft-versus-Host-Disease. Studies utilizing germline knockout mice have discovered several candidate genes that could be targeted pharmacologically to create a more favorable environment for transplant success. SHIP1 deficiency permits improved engraftment of hematopoietic stem-progenitor cells (HS-PCs and produces an immunosuppressive microenvironment ideal for incoming allogeneic grafts. The recent development of small molecule SHIP1 inhibitors has opened a different therapeutic approach by creating transient SHIP1-deficiency. Here we show that SHIP1 inhibition (SHIPi mobilizes functional HS-PC, accelerates hematologic recovery, and enhances donor HS-PC engraftment in both allogeneic and autologous transplant settings. We also observed the expansion of key cell populations known to suppress host-reactive cells formed during engraftment. Therefore, SHIPi represents a non-toxic, new therapeutic that has significant potential to improve the success and safety of therapies that utilize autologous and allogeneic HSCT.

  7. A SAGE View of Mesenchymal Stem Cells

    OpenAIRE

    Phinney, Donald G.

    2009-01-01

    Mesenchymal stem cells (MSCs) were initially defined by their capacity to differentiate into connective tissue cell lineages and support hematopoiesis. More recently, MSCs have demonstrated some degree of therapeutic efficacy in a broad range of diseases including neurological and auto-immune disorders, stroke, diabetes, and chronic inflammatory conditions. An emerging paradigm suggests that MSCs alter the tissue microenvironment via paracrine signaling to induce angiogenesis, alter immune ce...

  8. Osteogenic potential of sorted equine mesenchymal stem cell subpopulations

    OpenAIRE

    Radtke, Catherine L.; Nino-Fong, Rodolfo; Rodriguez-Lecompte, Juan Carlos; Esparza Gonzalez, Blanca P.; Stryhn, Henrik; McDuffee, Laurie A.

    2015-01-01

    The objectives of this study were to use non-equilibrium gravitational field-flow fractionation (GrFFF), an immunotag-less method of sorting mesenchymal stem cells (MSCs), to sort equine muscle tissue-derived mesenchymal stem cells (MMSCs) and bone marrow-derived mesenchymal stem cells (BMSC) into subpopulations and to carry out assays in order to compare their osteogenic capabilities. Cells from 1 young adult horse were isolated from left semitendinosus muscle tissue and from bone marrow asp...

  9. Safety in mesenchymal stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Matthie Robert

    2014-01-01

    Full Text Available To date, adult stem cell therapy has some achievements in the treatment of chronic disease. However, some risks in stem cell transplantation still serve as high barriers obstructing the pulling of these therapies into clinical use. Tumorigenecity is of almost concern after it is injected into patients. However, all clinical studies indexed in PubMed showed that there were no cases of tumor after transplantation. Especially in recent study published in Cell Death and Disease, Wang et al. (2013 showed that long-term cultured mesenchymal stem cells could develop the genomic mutations but cannot undergo malignant transformation. Moreover, the study also revealed these stem cells as capable of forming tumors. This commentary assesses the data generated to date, and discusses the conclusions drawn from various studies. [Biomed Res Ther 2014; 1(1.000: 21-24

  10. Human induced pluripotent stem cells on autologous feeders.

    Directory of Open Access Journals (Sweden)

    Kazutoshi Takahashi

    Full Text Available BACKGROUND: For therapeutic usage of induced Pluripotent Stem (iPS cells, to accomplish xeno-free culture is critical. Previous reports have shown that human embryonic stem (ES cells can be maintained in feeder-free condition. However, absence of feeder cells can be a hostile environment for pluripotent cells and often results in karyotype abnormalities. Instead of animal feeders, human fibroblasts can be used as feeder cells of human ES cells. However, one still has to be concerned about the existence of unidentified pathogens, such as viruses and prions in these non-autologous feeders. METHODOLOGY/PRINCIPAL FINDINGS: This report demonstrates that human induced Pluripotent Stem (iPS cells can be established and maintained on isogenic parental feeder cells. We tested four independent human skin fibroblasts for the potential to maintain self-renewal of iPS cells. All the fibroblasts tested, as well as their conditioned medium, were capable of maintaining the undifferentiated state and normal karyotypes of iPS cells. Furthermore, human iPS cells can be generated on isogenic parental fibroblasts as feeders. These iPS cells carried on proliferation over 19 passages with undifferentiated morphologies. They expressed undifferentiated pluripotent cell markers, and could differentiate into all three germ layers via embryoid body and teratoma formation. CONCLUSIONS/SIGNIFICANCE: These results suggest that autologous fibroblasts can be not only a source for iPS cells but also be feeder layers. Our results provide a possibility to solve the dilemma by using isogenic fibroblasts as feeder layers of iPS cells. This is an important step toward the establishment of clinical grade iPS cells.

  11. Mesenchymal stem cells targeting the GVHD

    Institute of Scientific and Technical Information of China (English)

    ZHAO; Robert; ChunHua

    2009-01-01

    Acute graft-versus-host disease(GVHD) occurs after allogeneic hematopoietic stem cell transplant and is a reaction of donor immune cells against host tissues.About 35%-50% of hematopoietic stem cell transplant(HSCT) recipients will develop acute GVHD.It is associated with considerable morbidity and mortality,particularly in patients who do not respond to primary therapy,which usually consists of glucocorticoids(steroids).Most of the available second-line and third-line treatments for steroid-refractory acute GVHD induce severe immunodeficiency,which is commonly accompanied by lethal infectious complications.Mesenchymal stem cells(MSCs) have been shown to mediate immunomodulatory effects.The recently elucidated immunosuppressive potential of mesenchymal stem cells has set the stage for their clinical testing as cellular immunosuppressants,MSCs have been used in patients with steroid-refractory acute GVHD,and encouraging responses have been obtained in many studies.The utility of MSCs for the treatment of GVHD is becoming clear.

  12. An ethical framework for the disposal of autologous stem cells.

    Science.gov (United States)

    Petrini, Carlo

    2013-01-01

    The disposal of haematopoietic stem cells stored for autologous transplantation purposes becomes a problem for hospitals when the conditions for their preservation cease to exist. When these cells have been stored for a considerable time the problem often becomes an ethical one involving informed consent and is linked to at least two simultaneous circumstances: (i) the indications regarding disposal contained in available informed consent papers are either absent or too generic; (ii) the person who provided the sample can no longer be traced. This article proposes and discusses some of the ethical criteria for addressing this problem on the basis of the so-called "principles" of North American bioethics, and compares them with some of the principles and values proposed in other models of bioethics. PMID:23412868

  13. Adult Mesenchymal Stem Cells and Radiation Injury.

    Science.gov (United States)

    Kiang, Juliann G

    2016-08-01

    Recent understanding of the cellular and molecular signaling activations in adult mesenchymal stem cells (MSCs) has provided new insights into their potential clinical applications, particularly for tissue repair and regeneration. This review focuses on these advances, specifically in the context of self-renewal for tissue repair and recovery after radiation injury. Thus far, MSCs have been characterized extensively and shown to be useful in mitigation and therapy for acute radiation syndrome and cognitive dysfunction. Use of MSCs for treating radiation injury alone or in combination with additional trauma is foreseeable. PMID:27356065

  14. Mesenchymal Stem Cells as a Potent Cell Source for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Elham Zomorodian

    2012-01-01

    Full Text Available While small bone defects heal spontaneously, large bone defects need surgical intervention for bone transplantation. Autologous bone grafts are the best and safest strategy for bone repair. An alternative method is to use allogenic bone graft. Both methods have limitations, particularly when bone defects are of a critical size. In these cases, bone constructs created by tissue engineering technologies are of utmost importance. Cells are one main component in the manufacture of bone construct. A few cell types, including embryonic stem cells (ESCs, adult osteoblast, and adult stem cells, can be used for this purpose. Mesenchymal stem cells (MSCs, as adult stem cells, possess characteristics that make them good candidate for bone repair. This paper discusses different aspects of MSCs that render them an appropriate cell type for clinical use to promote bone regeneration.

  15. Busulfan,cyclophosphamide and etoposide as conditioning for autologous stem cell transplantation in multiple myeloma

    Institute of Scientific and Technical Information of China (English)

    张春阳

    2013-01-01

    Objective To evaluate the efficacy and safety of dose-reduced intravenous busulfan,cyclophosphamide and etoposide(BCV)as conditioning for autologous stem cell transplantation(ASCT)in multiple myeloma(MM)

  16. Modeling sarcomagenesis using multipotent mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Rene Rodriguez; Ruth Rubio; Pablo Menendez

    2012-01-01

    Because of their unique properties,multipotent mesenchymal stem cells (MSCs) represent one of the most promising adult stem cells being used worldwide in a wide array of clinical applications.Overall,compelling evidence supports the long-term safety of ex vivo expanded human MSCs,which do not seem to transform spontaneously.However,experimental data reveal a link between MSCs and cancer,and MSCs have been reported to inhibit or promote tumor growth depending on yet undefined conditions.Interestingly,solid evidence based on transgenic mice and genetic intervention of MSCs has placed these cells as the most likely cell of origin for certain sarcomas.This research area is being increasingly explored to develop accurate MSC-based models of sarcomagenesis,which will be undoubtedly valuable in providing a better understanding about the etiology and pathogenesis of mesenchymal cancer,eventually leading to the development of more specific therapies directed against the sarcoma-initiating cell.Unfortunately,still little is known about the mechanisms underlying MSC transformation and further studies are required to develop bona fide sarcoma models based on human MSCs.Here,we comprehensively review the existing MSC-based models of sarcoma and discuss the most common mechanisms leading to tumoral transformation of MSCs and sarcomagenesis.

  17. Viability of mesenchymal stem cells during electrospinning

    Directory of Open Access Journals (Sweden)

    G. Zanatta

    2012-02-01

    Full Text Available Tissue engineering is a technique by which a live tissue can be re-constructed and one of its main goals is to associate cells with biomaterials. Electrospinning is a technique that facilitates the production of nanofibers and is commonly used to develop fibrous scaffolds to be used in tissue engineering. In the present study, a different approach for cell incorporation into fibrous scaffolds was tested. Mesenchymal stem cells were extracted from the wall of the umbilical cord and mononuclear cells from umbilical cord blood. Cells were re-suspended in a 10% polyvinyl alcohol solution and subjected to electrospinning for 30 min under a voltage of 21 kV. Cell viability was assessed before and after the procedure by exclusion of dead cells using trypan blue staining. Fiber diameter was observed by scanning electron microscopy and the presence of cells within the scaffolds was analyzed by confocal laser scanning microscopy. After electrospinning, the viability of mesenchymal stem cells was reduced from 88 to 19.6% and the viability of mononuclear cells from 99 to 8.38%. The loss of viability was possibly due to the high viscosity of the polymer solution, which reduced the access to nutrients associated with electric and mechanical stress during electrospinning. These results suggest that the incorporation of cells during fiber formation by electrospinning is a viable process that needs more investigation in order to find ways to protect cells from damage.

  18. Mesenchymal stem cells: cell biology and potential use in therapy

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Kristiansen, Malthe; Abdallah, Basem M

    2004-01-01

    Mesenchymal stem cells are clonogenic, non-haematopoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages e.g. osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages e.g. neuronal-like cells. Several methods...... are currently available for isolation of the mesenchymal stem cells based on their physical and immunological characteristics. Because of the ease of their isolation and their extensive differentiation potential, mesenchymal stem cells are among the first stem cell types to be introduced in the clinic. Recent...... studies have demonstrated that the life span of mesenchymal stem cells in vitro can be extended by increasing the levels of telomerase expression in the cells and thus allowing culture of large number of cells needed for therapy. In addition, it has been shown that it is possible to culture the cells...

  19. Myeloablative Chemotherapy with Autologous Stem Cell Transplant for Desmoplastic Small Round Cell Tumor

    OpenAIRE

    Forlenza, Christopher J.; Kushner, Brian H.; Nancy Kernan; Farid Boulad; Heather Magnan; Leonard Wexler; Wolden, Suzanne L.; LaQuaglia, Michael P.; Shakeel Modak

    2015-01-01

    Desmoplastic small round cell tumor (DSRCT), a rare, aggressive neoplasm, has a poor prognosis. In this prospective study, we evaluated the role of myeloablative chemotherapy, followed by autologous stem cell transplant in improving survival in DSRCT. After high-dose induction chemotherapy and surgery, 19 patients with chemoresponsive DSRCT underwent autologous stem cell transplant. Myeloablative chemotherapy consisted of carboplatin (400–700 mg/m2/day for 3 days) + thiotepa (300 mg/m2/day fo...

  20. Current state and future directions of autologous hematopoietic stem cell transplantation in systemic lupus erythematosus

    OpenAIRE

    Illei, Gabor G.; Cervera, Ricard; Burt, Richard K.; Doria, Andrea; Hiepe, Falk; Jayne, David; Pavletic, Steven; Martin, Thierry; Marmont, Alberto; Saccardi, Riccardo; Voskuyl, Alexandre E; Farge, Dominique

    2011-01-01

    Autologous hematopoietic stem cell transplantation (AHSCT) has been proposed as a treatment modality which may arrest the autoimmune disease process and lead to sustained treatment-free remissions. Since the first consensus statement in 1997, approximately 200 autologous bone marrow or hematopoietic stem cell transplantations have been reported world-wide for SLE. The current state of AHSCT in SLE was reviewed at a recent meeting of the Autoimmune Working Party of the European Group for Blood...

  1. Isolation and characterization of equine amnion mesenchymal stem cells

    OpenAIRE

    Coli, Alessandra; Nocchi, Francesca; Lamanna, Roberta; Iorio, Mariacarla; Lapi, Simone; Urciuoli, Patrizia; Scatena, Fabrizio; Giannessi, Elisabetta; Stornelli, Maria Rita; Passeri, Simona

    2011-01-01

    The amnion is a particular tissue whose cells show features of multipotent stem cells proposed for use in cellular therapy and regenerative medicine. From equine amnion collected after the foal birth we have isolated MSCs (mesenchymal stem cells), namely EAMSCs (equine amnion mesenchymal stem cells), from the mesoblastic layer. The cells were grown in α-MEM (α-modified minimum essential medium) and the effect of EGF (epidermal growth factor) supplementation was evaluated. To assess the growth...

  2. [Immunoregulatory role of mesenchymal stem cells in bone reparation processes].

    Science.gov (United States)

    Zubov, D O

    2008-01-01

    Bone marrow contains mesenchymal stem cells (MSC) including osteoblast progenitor cells. When culturedunder conditions promoting an osteoblastic phenotype,MSC proliferate to form colonies that produce alkaline phosphatase and, subsequently, a mature osteoblastic phenotype. Transplantation of cultured autologous MSC to patients with non-healing bone fractures gives a good result leading to complete bone fracture consolidation. The aim of the study is to determine a quantitative production of IL-1beta, IL-2, IL-4, IL-6, IL-8 and TNF-alpha by cultured uncommitted and committed osteogenic MSC. The results showed that the cytokine profile consisting of IL-1beta, IL-2, IL-4, IL-6, IL-8 and TNF-alpha is secreted by cultured MSC. The secretion of IL-1beta and IL-2 by cultured MSC together with hyper production of IL-6 (up to 276.5 pg/ml, pactivators of bone resorption, inflammation and some immunological reactions in the process of altered osteoreparation. PMID:18756772

  3. Mesenchymal stem cells (MSCs) as skeletal therapeutics - an update.

    Science.gov (United States)

    Saeed, Hamid; Ahsan, Muhammad; Saleem, Zikria; Iqtedar, Mehwish; Islam, Muhammad; Danish, Zeeshan; Khan, Asif Manzoor

    2016-01-01

    Mesenchymal stem cells hold the promise to treat not only several congenital and acquired bone degenerative diseases but also to repair and regenerate morbid bone tissues. Utilizing MSCs, several lines of evidences advocate promising clinical outcomes in skeletal diseases and skeletal tissue repair/regeneration. In this context, both, autologous and allogeneic cell transfer options have been utilized. Studies suggest that MSCs are transplanted either alone by mixing with autogenous plasma/serum or by loading onto repair/induction supportive resorb-able scaffolds. Thus, this review is aimed at highlighting a wide range of pertinent clinical therapeutic options of MSCs in the treatment of skeletal diseases and skeletal tissue regeneration. Additionally, in skeletal disease and regenerative sections, only the early and more recent preclinical evidences are discussed followed by all the pertinent clinical studies. Moreover, germane post transplant therapeutic mechanisms afforded by MSCs have also been conversed. Nonetheless, assertive use of MSCs in the clinic for skeletal disorders and repair is far from a mature therapeutic option, therefore, posed challenges and future directions are also discussed. Importantly, for uniformity at all instances, term MSCs is used throughout the review. PMID:27084089

  4. Mesenchymal and induced pluripotent stem cells: general insights and clinical perspectives

    Directory of Open Access Journals (Sweden)

    Zomer HD

    2015-09-01

    Full Text Available Helena D Zomer,1 Atanásio S Vidane,1 Natalia N Gonçalves,1 Carlos E Ambrósio2 1Department of Surgery, Faculty of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, SP, Brazil; 2Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil Abstract: Mesenchymal stem cells have awakened a great deal of interest in regenerative medicine due to their plasticity, and immunomodulatory and anti-inflammatory properties. They are high-yield and can be acquired through noninvasive methods from adult tissues. Moreover, they are nontumorigenic and are the most widely studied. On the other hand, induced pluripotent stem (iPS cells can be derived directly from adult cells through gene reprogramming. The new iPS technology avoids the embryo destruction or manipulation to generate pluripotent cells, therefore, are exempt from ethical implication surrounding embryonic stem cell use. The pre-differentiation of iPS cells ensures the safety of future approaches. Both mesenchymal stem cells and iPS cells can be used for autologous cell transplantations without the risk of immune rejection and represent a great opportunity for future alternative therapies. In this review we discussed the therapeutic perspectives using mesenchymal and iPS cells. Keywords: cell transplantation, cell therapy, iPS, MSC

  5. SECOND AUTOLOGOUS STEM CELL TRANSPLANTATION FOR RELAPSED LYMPHOMA AFTER A PRIOR AUTOLOGOUS TRANSPLANT

    Science.gov (United States)

    Smith, Sonali M.; van Besien, Koen; Carreras, Jeanette; Bashey, Asad; Cairo, Mitchell S.; Freytes, Cesar O.; Gale, Robert Peter; Hale, Gregory A.; Hayes-Lattin, Brandon; Holmberg, Leona A.; Keating, Armand; Maziarz, Richard T.; McCarthy, Philip L.; Navarro, Willis H.; Pavlovsky, Santiago; Schouten, Harry C.; Seftel, Matthew; Wiernik, Peter H.; Vose, Julie M.; Lazarus, Hillard M.; Hari, Parameswaran

    2012-01-01

    We determined treatment-related mortality (TRM), progression free survival (PFS), and overall survival (OS) after a second autologous HCT (HCT2) for patients with lymphoma relapse after a prior HCT (HCT1). Outcomes for patients with either Hodgkin lymphoma (HL, n=21) or non-Hodgkin lymphoma (NHL, n=19) receiving HCT2 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) were analyzed. The median age at HCT2 was 38 years (range, 16–61) and 22 (58%) patients had a Karnofsky performance score less than 90. HCT2 was performed >1 year after HCT1 in 82%. The probability of TRM at day 100 was 15% (95% CI, 3–22%). The 1, 3 and 5 yr probabilities of PFS were 50% (95% CI, 34–66%), 36% (95% CI, 21–52%) and 30% (95% CI, 16–46%), respectively. Corresponding probabilities of survival were 65% (95% CI, 50–79%), 36% (95% CI, 22–52%) and 30% (95% CI, 17–46%), respectively. At a median follow up of 72 months (range, 12–124 months) after HCT2, 29 patients (73%) have died, 18 (62%) secondary to relapsed lymphoma. The outcomes of patients with HL and NHL were similar. In summary, this series represents the largest reported group of patients with relapsed lymphomas undergoing SCT2 following failed SCT1, and with long-term follow-up. Our series suggests that SCT2 is feasible in patients relapsing after prior HCT1, with a lower TRM than that reported for allogeneic transplant in this setting. HCT2 should be considered for patients with relapsed HL or NHL after HCT1 without alternative allogeneic stem cell transplant options. PMID:18640574

  6. Mesenchymal Stem Cells: Angels or Demons?

    Directory of Open Access Journals (Sweden)

    Rebecca S. Y. Wong

    2011-01-01

    Full Text Available Mesenchymal stem cells (MSCs have been used in cell-based therapy in various disease conditions such as graft-versus-host and heart diseases, osteogenesis imperfecta, and spinal cord injuries, and the results have been encouraging. However, as MSC therapy gains popularity among practitioners and researchers, there have been reports on the adverse effects of MSCs especially in the context of tumour modulation and malignant transformation. These cells have been found to enhance tumour growth and metastasis in some studies and have been related to anticancer-drug resistance in other instances. In addition, various studies have also reported spontaneous malignant transformation of MSCs. The mechanism of the modulatory behaviour and the tumorigenic potential of MSCs, warrant urgent exploration, and the use of MSCs in patients with cancer awaits further evaluation. However, if MSCs truly play a role in tumour modulation, they can also be potential targets of cancer treatment.

  7. Mesenchymal Stem Cells: Angels or Demons?

    Science.gov (United States)

    Wong, Rebecca S. Y.

    2011-01-01

    Mesenchymal stem cells (MSCs) have been used in cell-based therapy in various disease conditions such as graft-versus-host and heart diseases, osteogenesis imperfecta, and spinal cord injuries, and the results have been encouraging. However, as MSC therapy gains popularity among practitioners and researchers, there have been reports on the adverse effects of MSCs especially in the context of tumour modulation and malignant transformation. These cells have been found to enhance tumour growth and metastasis in some studies and have been related to anticancer-drug resistance in other instances. In addition, various studies have also reported spontaneous malignant transformation of MSCs. The mechanism of the modulatory behaviour and the tumorigenic potential of MSCs, warrant urgent exploration, and the use of MSCs in patients with cancer awaits further evaluation. However, if MSCs truly play a role in tumour modulation, they can also be potential targets of cancer treatment. PMID:21822372

  8. Application of Nanoscaffolds in Mesenchymal Stem Cell-Based Therapy

    OpenAIRE

    Ghoraishizadeh, Saman; Ghorishizadeh, Afsoon; Ghoraishizadeh, Peyman; Daneshvar, Nasibeh; Boroojerdi, Mohadese Hashem

    2014-01-01

    Regenerative medicine is an alternative solution for organ transplantation. Stem cells and nanoscaffolds are two essential components in regenerative medicine. Mesenchymal stem cells (MSCs) are considered as primary adult stem cells with high proliferation capacity, wide differentiation potential, and immunosuppression properties which make them unique for regenerative medicine and cell therapy. Scaffolds are engineered nanofibers that provide suitable microenvironment for cell signalling whi...

  9. Characterization of neural stemness status through the neurogenesis process for bone marrow mesenchymal stem cells.

    Science.gov (United States)

    Mohammad, Maeda H; Al-Shammari, Ahmed M; Al-Juboory, Ahmad Adnan; Yaseen, Nahi Y

    2016-01-01

    The in vitro isolation, identification, differentiation, and neurogenesis characterization of the sources of mesenchymal stem cells (MSCs) were investigated to produce two types of cells in culture: neural cells and neural stem cells (NSCs). These types of stem cells were used as successful sources for the further treatment of central nervous system defects and injuries. The mouse bone marrow MSCs were used as the source of the stem cells in this study. β-Mercaptoethanol (BME) was used as the main inducer of the neurogenesis pathway to induce neural cells and to identify NSCs. Three types of neural markers were used: nestin as the immaturation stage marker, neurofilament light chain as the early neural marker, and microtubule-associated protein 2 as the maturation marker through different time intervals in the neurogenesis process starting from the MSCs, (as undifferentiated cells), NSCs, production stages, and toward neuron cells (as differentiated cells). The results of different exposure times to BME of the neural markers analysis done by immunocytochemistry and real time-polymerase chain reaction helped us to identify the exact timing for the neural stemness state. The results showed that the best exposure time that may be used for the production of NSCs was 6 hours. The best maintenance media for NSCs were also identified. Furthermore, we optimized exposure to BME with different times and concentrations, which could be an interesting way to modulate specific neuronal differentiation and obtain autologous neuronal phenotypes. This study was able to characterize NSCs in culture under differentiation for neurogenesis in the pathway of the neural differentiation process by studying the expressed neural genes and the ability to maintain these NSCs in culture for further differentiation in thousands of functional neurons for the treatment of brain and spinal cord injuries and defects. PMID:27143939

  10. Disseminated Fusarium infection in autologous stem cell transplant recipient

    OpenAIRE

    Vivian Iida Avelino-Silva; Jessica Fernandes Ramos; Fabio Eudes Leal; Leonardo Testagrossa; Yana Sarkis Novis

    2015-01-01

    Disseminated infection by Fusariumis a rare, frequently lethal condition in severely immunocompromised patients, including bone marrow transplant recipients. However, autologous bone marrow transplant recipients are not expected to be at high risk to develop fusariosis. We report a rare case of lethal disseminated Fusariuminfection in an autologous bone marrow transplant recipient during pre-engraftment phase.

  11. Comparison of different culture conditions for human mesenchymal stromal cells for clinical stem cell therapy

    DEFF Research Database (Denmark)

    Haack-Sorensen, M.; Friis, T.; Bindslev, L.;

    2008-01-01

    used for MSC cultivation in animal studies simulating clinical stem cell therapy. MATERIAL AND METHODS: Human mononuclear cells (MNCs) were isolated from BM aspirates by density gradient centrifugation and cultivated in a GMP-accepted medium (EMEA medium) or in one of four other media. RESULTS: FACS...... compliant medium for MSC cultivation, expansion and differentiation. The expanded and differentiated MSCs can be used in autologous mesenchymal stromal cell therapy in patients with ischaemic heart disease Udgivelsesdato: 2008......OBJECTIVE: Mesenchymal stromal cells (MSCs) from adult bone marrow (BM) are considered potential candidates for therapeutic neovascularization in cardiovascular disease. When implementing results from animal trials in clinical treatment, it is essential to isolate and expand the MSCs under...

  12. Labeling and Imaging Mesenchymal Stem Cells with Quantum Dots

    Science.gov (United States)

    Mesenchymal stem cells (MSCs) are multipotent cells with the potential to differentiate into bone, cartilage, adipose and muscle cells. Adult derived MSCs are being actively investigated because of their potential to be utilized for therapeutic cell-based transplantation. Methods...

  13. Glucocorticoids induce autophagy in rat bone marrow mesenchymal stem cells

    DEFF Research Database (Denmark)

    Wang, L.; Fan, J.; Lin, Y. S.;

    2015-01-01

    and their responses to diverse stimuli, however, the role of autophagy in glucocorticoidinduced damage to bone marrow mesenchymal stem cells (BMSCs) remains unclear. The current study confirmed that glucocorticoid administration impaired the proliferation of BMSCs. Transmission electron microscopy...

  14. Cryopreservation of Adipose-Derived Mesenchymal Stem Cells

    OpenAIRE

    Miyagi-Shiohira, Chika; Kurima, Kiyoto; Kobayashi, Naoya; Saitoh, Issei; Watanabe, Masami; Noguchi, Yasufumi; Matsushita,Masayuki; Noguchi,Hirofumi

    2015-01-01

    Mesenchymal stem cells (MSCs) have the potential to differentiate into cells of mesodermal origin such as osteoblasts, adipocytes, myocytes, and chondrocytes. They possess an immunosuppressive effect, which makes them a viable cell population for the cell-based therapy of treatment-resistant immune diseases. Adipose-derived mesenchymal stem cells (ASCs) have been demonstrated to have the ability to acquire the properties of subcutaneous adipose tissue particularly easily, and cryopreservation...

  15. Mesenchymal stem cell therapy for heart disease.

    Science.gov (United States)

    Gnecchi, Massimiliano; Danieli, Patrizia; Cervio, Elisabetta

    2012-08-19

    Mesenchymal stem cells (MSC) are adult stem cells with capacity for self-renewal and multi-lineage differentiation. Initially described in the bone marrow, MSC are also present in other organs and tissues. From a therapeutic perspective, because of their easy preparation and immunologic privilege, MSC are emerging as an extremely promising therapeutic agent for tissue regeneration and repair. Studies in animal models of myocardial infarction have demonstrated the ability of transplanted MSC to engraft and differentiate into cardiomyocytes and vascular cells. Most importantly, engrafted MSC secrete a wide array of soluble factors that mediate beneficial paracrine effects and may greatly contribute to cardiac repair. Together, these properties can be harnessed to both prevent and reverse remodeling in the ischemically injured ventricle. In proof-of-concept and phase I clinical trials, MSC therapy improved left ventricular function, induced reverse remodeling, and decreased scar size. In this review we will focus on the current understanding of MSC biology and MSC mechanism of action in cardiac repair. PMID:22521741

  16. Mesenchymal stem cells: characteristics and clinical applications.

    Directory of Open Access Journals (Sweden)

    Sylwia Bobis

    2007-01-01

    Full Text Available Mesenchymal stem cells (MSCs are bone marrow populating cells, different from hematopoietic stem cells, which possess an extensive proliferative potential and ability to differentiate into various cell types, including: osteocytes, adipocytes, chondrocytes, myocytes, cardiomyocytes and neurons. MSCs play a key role in the maintenance of bone marrow homeostasis and regulate the maturation of both hematopoietic and non-hematopoietic cells. The cells are characterized by the expression of numerous surface antigens, but none of them appears to be exclusively expressed on MSCs. Apart from bone marrow, MSCs are located in other tissues, like: adipose tissue, peripheral blood, cord blood, liver and fetal tissues. MSCs have been shown to be powerful tools in gene therapies, and can be effectively transduced with viral vectors containing a therapeutic gene, as well as with cDNA for specific proteins, expression of which is desired in a patient. Due to such characteristics, the number of clinical trials based on the use of MSCs increase. These cells have been successfully employed in graft versus host disease (GvHD treatment, heart regeneration after infarct, cartilage and bone repair, skin wounds healing, neuronal regeneration and many others. Of special importance is their use in the treatment of osteogenesis imperfecta (OI, which appeared to be the only reasonable therapeutic strategy. MSCs seem to represent a future powerful tool in regenerative medicine, therefore they are particularly important in medical research.

  17. Hepatitis B-related events in autologous hematopoietic stem cell transplantation recipients

    Institute of Scientific and Technical Information of China (English)

    zcan; eneli; Zübeyde; Nur; zkurt; Kadir; Acar; Seyyal; Rota; Sahika; Zeynep; Aki; Zeynep; Arzu; Yegin; Münci; Yagci; Seren; zenirler; Gülsan; Türkz; Sucak

    2010-01-01

    AIM: To investigate the frequency of occult hepatitis B, the clinical course of hepatitis B virus (HBV) reactivation and reverse seroconversion and associated risk factors in autologous hematopoietic stem cell transplantation (HSCT) recipients. METHODS: This study was conducted in 90 patients undergoing autologous HSCT. Occult HBV infection was investigated by HBV-DNA analysis prior to transplantation, while HBV serology and liver function tests were screened prior to and serially after transplantation. HBV...

  18. Mesenchymal Stem Cell-Mediated Functional Tooth Regeneration in Swine

    OpenAIRE

    Wataru Sonoyama; Yi Liu; Dianji Fang; Takayoshi Yamaza; Byoung-Moo Seo; Chunmei Zhang; He Liu; Stan Gronthos; Cun-Yu Wang; Songlin Wang; Songtao Shi

    2006-01-01

    Mesenchymal stem cell-mediated tissue regeneration is a promising approach for regenerative medicine for a wide range of applications. Here we report a new population of stem cells isolated from the root apical papilla of human teeth (SCAP, stem cells from apical papilla). Using a minipig model, we transplanted both human SCAP and periodontal ligament stem cells (PDLSCs) to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. This wo...

  19. Mesenchymal stem cells: From stem cells to sarcomas.

    Science.gov (United States)

    Lye, Kwan Liang; Nordin, Norshariza; Vidyadaran, Sharmili; Thilakavathy, Karuppiah

    2016-06-01

    Mesenchymal stem cells (MSCs) have garnered vast interests in clinical settings, especially in regenerative medicine due to their unique properties-they are reliably isolated and expanded from various tissue sources; they are able to differentiate into mesodermal tissues such as bones, cartilages, adipose tissues, and muscles; and they have unique immunosuppressive properties. However, there are some concerns pertaining to the role of MSCs in the human body. On one hand, they are crucial component in the regeneration and repair of the human body. On the contrary, they are shown to transform into sarcomas. Although the exact mechanisms are still unknown, many new leads have pointed to the belief that MSCs do play a role in sarcomagenesis. This review focuses on the current updates and findings of the role of MSCs in their transformation process into sarcomas. PMID:26992453

  20. Umbilical cord mesenchymal stem cells: adjuvants for human cell transplantation.

    Science.gov (United States)

    Friedman, Robb; Betancur, Monica; Boissel, Laurent; Tuncer, Hande; Cetrulo, Curtis; Klingemann, Hans

    2007-12-01

    The Wharton's jelly of the umbilical cord is rich in mesenchymal stem cells (UC-MSCs) that fulfill the criteria for MSCs. Here we describe a novel, simple method of obtaining and cryopreserving UC-MSCs by extracting the Wharton's jelly from a small piece of cord, followed by mincing the tissue and cryopreserving it in autologous cord plasma to prevent exposure to allogeneic or animal serum. This direct freezing of cord microparticles without previous culture expansion allows the processing and freezing of umbilical cord blood (UCB) and UC-MSCs from the same individual on the same day on arrival in the laboratory. UC-MSCs produce significant concentrations of hematopoietic growth factors in culture and augment hematopoietic colony formation when co-cultured with UCB mononuclear cells. Mice undergoing transplantation with limited numbers of human UCB cells or CD34(+) selected cells demonstrated augmented engraftment when UC-MSCs were co-transplanted. We also explored whether UC-MSCs could be further manipulated by transfection with plasmid-based vectors. Electroporation was used to introduce cDNA and mRNA constructs for GFP into the UC-MSCs. Transfection efficiency was 31% for cDNA and 90% for mRNA. These data show that UC-MSCs represent a reliable, easily accessible, noncontroversial source of MSCs. They can be prepared and cryopreserved under good manufacturing practices (GMP) conditions and are able to enhance human hematopoietic engraftment in SCID mice. Considering their cytokine production and their ability to be easily transfected with plasmid-based vectors, these cells should have broad applicability in human cell-based therapies. PMID:18022578

  1. Fatal CMV-Infection after Autologous Stem Cell Transplantation in Refractory Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    László Váróczy

    2012-01-01

    Full Text Available High-dose chemotherapy followed by autologous stem cell transplantation can be a rescue for patients with severe refractory systemic lupus erythematosus (SLE. However, the procedure might have fatal complications including infections and bleeding. We report on a young female patient with SLE whose disease started in her early childhood. After many years, severe renal, neurological, and bone marrow involvement developed that did not respond to conventional therapy. She was selected for autologous stem cell transplantation. A successful peripheral stem cell apheresis was performed in March 2006. The nonselected graft was reinfused in August 2006 after a conditioning chemotherapy containing high-dose cyclophosphamide and antithymocyte globulin. Engraftment was detected within 11 days. On the 38th posttransplant day, severe cytomegalovirus (CMV infection developed that included pneumonitis, hepatitis, and pancytopenia. The patient died in a week due to multiorgan failure. With her case, we want to call the attention to this rare, but lethal complication of the autologous transplantation.

  2. Mesenchymal stem cell implantation in atrophic nonunion of the long bones

    Science.gov (United States)

    Phedy, P.; Kholinne, E.; Djaja, Y. P.; Kusnadi, Y.; Merlina, M.; Yulisa, N. D.

    2016-01-01

    Objectives To explore the therapeutic potential of combining bone marrow-derived mesenchymal stem cells (BM-MSCs) and hydroxyapatite (HA) granules to treat nonunion of the long bone. Methods Ten patients with an atrophic nonunion of a long bone fracture were selectively divided into two groups. Five subjects in the treatment group were treated with the combination of 15 million autologous BM-MSCs, 5g/cm3 (HA) granules and internal fixation. Control subjects were treated with iliac crest autograft, 5g/cm3 HA granules and internal fixation. The outcomes measured were post-operative pain (visual analogue scale), level of functionality (LEFS and DASH), and radiograph assessment. Results Post-operative pain evaluation showed no significant differences between the two groups. The treatment group demonstrated faster initial radiographic and functional improvements. Statistically significant differences in functional scores were present during the first (p = 0.002), second (p = 0.005) and third (p = 0.01) month. Both groups achieved similar outcomes by the end of one-year follow-up. No immunologic or neoplastic side effects were reported. Conclusions All cases of nonunion of a long bone presented in this study were successfully treated using autologous BM-MSCs. The combination of autologous BM-MSCs and HA granules is a safe method for treating nonunion. Patients treated with BM-MSCs had faster initial radiographic and functional improvements. By the end of 12 months, both groups had similar outcomes. Cite this article: H.D. Ismail, P. Phedy, E. Kholinne, Y. P. Djaja, Y. Kusnadi, M. Merlina, N. D. Yulisa. Mesenchymal stem cell implantation in atrophic nonunion of the long bones: A translational study. Bone Joint Res 2016;5:287–293. DOI: 10.1302/2046-3758.57.2000587. PMID:27412657

  3. Mesenchymal stem cell therapy and lung diseases.

    Science.gov (United States)

    Akram, Khondoker M; Samad, Sohel; Spiteri, Monica; Forsyth, Nicholas R

    2013-01-01

    Mesenchymal stem cells (MSCs), a distinct population of adult stem cells, have amassed significant interest from both medical and scientific communities. An inherent multipotent differentiation potential offers a cell therapy option for various diseases, including those of the musculoskeletal, neuronal, cardiovascular and pulmonary systems. MSCs also secrete an array of paracrine factors implicated in the mitigation of pathological conditions through anti-inflammatory, anti-apoptotic and immunomodulatory mechanisms. The safety and efficacy of MSCs in human application have been confirmed through small- and large-scale clinical trials. However, achieving the optimal clinical benefit from MSC-mediated regenerative therapy approaches is entirely dependent upon adequate understanding of their healing/regeneration mechanisms and selection of appropriate clinical conditions. MSC-mediated acute alveolar injury repair. A cartoon depiction of an injured alveolus with associated inflammation and AEC apoptosis. Proposed routes of MSC delivery into injured alveoli could be by either intratracheal or intravenous routes, for instance. Following delivery a proposed mechanism of MSC action is to inhibit/reduce alveolar inflammation by abrogation of IL-1_-depenedent Tlymphocyte proliferation and suppression of TNF-_ secretion via macrophage activation following on from stimulation by MSC-secreted IL-1 receptor antagonist (IL-1RN). The inflammatory environment also stimulates MSC to secrete prostaglandin-E2 (PGE2) which can stimulate activated macrophages to secrete the anti-inflammatory cytokine IL-10. Inhibition of AEC apoptosis following injury can also be promoted via MSC stimulated up-regulation of the anti-apoptotic Bcl-2 gene. MSC-secreted KGF can stimulate AECII proliferation and migration propagating alveolar epithelial restitution. Alveolar structural engraftment of MSC is a rare event. PMID:22772131

  4. Viscoelastic behaviour of human mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Leong Kam W

    2008-07-01

    Full Text Available Abstract Background In this study, we have investigated the viscoelastic behaviour of individual human adult bone marrow-derived mesenchymal stem cells (hMSCs and the role of F-actin filaments in maintaining these properties, using micropipette aspiration technique together with a standard linear viscoelastic solid model. Results Under a room temperature of 20°C, the instantaneous and equilibrium Young's modulus, E0 and E∞, were found to be 886 ± 289 Pa and 372 ± 125 Pa, respectively, while the apparent viscosity, μ, was 2710 ± 1630 Pa·s. hMSCs treated with cytochalasin D up to 20 μM at 20°C registered significant drop of up to 84% in stiffness and increase of up to 255% in viscosity. At the physiological temperature of 37°C, E0 and E∞ have decreased by 42–66% whereas μ has increased by 95%, compared to the control. Majority of the hMSCs behave as viscoelastic solid with a rapid initial increase in aspiration length and it gradually levels out with time. Three other types of non-typical viscoelastic behavior of hMSCs were also seen. Conclusion hMSCs behave as viscoelastic solid. Its viscoelstic behaviour are dependent on the structural integrity of the F-actin filaments and temperature.

  5. Mesenchymal stem cells and inflammatory lung diseases.

    Science.gov (United States)

    Iyer, S S; Co, C; Rojas, M

    2009-03-01

    Mesenchymal stem cells (MSCs) are emerging as a therapeutic modality in various inflammatory disease states. A number of ongoing randomized Phase I/II clinical trials are evaluating the effects of allogeneic MSC infusion in patients with multiple sclerosis, graft-versus-host disease, Crohn's disease, and severe chronic myocardial ischemia. MSCs are also being considered as a potential therapy in patients with inflammatory lung diseases. Several studies, including our own, have demonstrated compelling benefits from the administration of MSCs in animal models of lung injury. These studies are leading to growing interest in the therapeutic use of MSCs in inflammatory lung diseases. In this Review, we describe how the immunoregulatory effects of MSCs can confer substantial protection in the setting of lung diseases such as acute lung injury, chronic obstructive pulmonary disease, asthma, and pulmonary hypertension. We also address potential pitfalls related to the therapeutic use of MSCs in fibrotic lung diseases such as idiopathic pulmonary fibrosis. In addition, we identify emerging areas for MSC- based therapies in modulating oxidative stress and in attenuating inflammation in alcohol-related acute lung injury. PMID:19352305

  6. Mesenchymal stem cells: from experiment to clinic

    Directory of Open Access Journals (Sweden)

    Otto William R

    2011-09-01

    Full Text Available Abstract There is currently much interest in adult mesenchymal stem cells (MSCs and their ability to differentiate into other cell types, and to partake in the anatomy and physiology of remote organs. It is now clear these cells may be purified from several organs in the body besides bone marrow. MSCs take part in wound healing by contributing to myofibroblast and possibly fibroblast populations, and may be involved in epithelial tissue regeneration in certain organs, although this remains more controversial. In this review, we examine the ability of MSCs to modulate liver, kidney, heart and intestinal repair, and we update their opposing qualities of being less immunogenic and therefore tolerated in a transplant situation, yet being able to contribute to xenograft models of human tumour formation in other contexts. However, such observations have not been replicated in the clinic. Recent studies showing the clinical safety of MSC in several pathologies are discussed. The possible opposing powers of MSC need careful understanding and control if their clinical potential is to be realised with long-term safety for patients.

  7. Research progresses in treating diabetic foot with autologous stem cell transplantation

    International Nuclear Information System (INIS)

    Because the distal arteries of lower extremities become narrowed or even occluded in diabetic foot, the clinical therapeutic results for diabetic foot have been unsatisfactory so far. Autologous stem cell transplantation that has emerged in recent years is a new, safe and effective therapy for diabetic foot, which achieves its excellent clinical success in restoring the blood supply of ischemic limb by way of therapeutic angiogenesis. Now autologous stem cell transplantation has become one of the hot points in medical research both at home and abroad, moreover, it has brought a new hope of cure to the patients with diabetic foot. (authors)

  8. Autologous Bone Marrow Stem Cell Infusion (AMBI therapy for Chronic Liver Diseases

    Directory of Open Access Journals (Sweden)

    Rajkumar JS

    2007-01-01

    Full Text Available Liver Cirrhosis is the end stage of chronic liver disease which may happen due to alcoholism, viral infections due to Hepatitis B, Hepatitis C viruses and is difficult to treat. Liver transplantation is the only available definitive treatment which is marred by lack of donors, post operative complications such as rejection and high cost. Autologous bone marrow stem cells have shown a lot of promise in earlier reported animal studies and clinical trials. We have in this study administered in 22 patients with chronic liver disease, autologous bone marrow stem cell whose results are presented herewith.

  9. A Comparison of Culture Characteristics between Human Amniotic Mesenchymal Stem Cells and Dental Stem Cells

    OpenAIRE

    Yusoff, Nurul Hidayat; Alshehadat, Saaid Ayesh; Azlina, Ahmad; Kannan, Thirumulu Ponnuraj; Hamid, Suzina Sheikh Abdul

    2015-01-01

    In the past decade, the field of stem cell biology is of major interest among researchers due to its broad therapeutic potential. Stem cells are a class of undifferentiated cells that are able to differentiate into specialised cell types. Stem cells can be classified into two main types: adult stem cells (adult tissues) and embryonic stem cells (embryos formed during the blastocyst phase of embryological development). This review will discuss two types of adult mesenchymal stem cells, dental ...

  10. 经冠状动脉自体骨髓间充质干细胞移植治疗急性心肌梗死:3个月疗效随访%Intracoronary transplantation of autologous bone marrow mesenchymal stem cells in the treatment of acute myocardial infarction: A 3-month follow-up on the therapeutic effect

    Institute of Scientific and Technical Information of China (English)

    林松; 吴承权; 何晓红; 段宝祥; 陈绍良; 叶飞; 方五旺; 马玉玲; 单守杰; 周陵; 张俊杰; 王峰

    2006-01-01

    ,(44±18)%,P<0.05);代谢缺损面积治疗后较治疗前明显减少((33±17)%,(43±21)%,P<0.05);治疗前共有199个节段血流灌注及糖代谢缺损匹配,判定为坏死心肌,治疗后79个节段血流灌注代谢明显改善,仍有120个节段血流灌注、糖代谢无明显改善(P<0.05).⑥超声心动图结果:患者术后射血分数值术后显著大于术前[(53±8)%,(42±7)%,P<0.05].结论:经冠状动脉途径植入人骨髓间充质干细胞治疗心肌梗死,方法简单易行,治疗后梗死面积明显减少,坏死区域心肌血流灌注、代谢改善,术前判定为无存活心肌节段术后明显减少,患者心功能得到改善.%BACKGROUND: The area of myocardial infarction is the determinative factor of acute myocardial infarction prognosis. Amelioration of blood transportation and replacement therapy can reduce infarction area. Bone marrow mesenchymal stem cells can differentiate into cardiovascular tissue and are easy to obtain. After cultured and expanded in vitro, they can become the ideal cells for cardiovascular replacement therapy.OBJECTIVE: To evaluate the therapeutic effect of intracoronary transplantation of bone marrow mesenchymal stem cells in the treatment of myocardial infarction. DESIGN: Self-control observation taking the patients as subjects.SETTING: Department of Cardiology, Department of Nuclear Medicine,Echocardiogram Room, Nanjing First Hospital Affiliated to Nanjing Medical University.PARTICIPANTS: Totally 20 patients with acute myocardial infarction who received the therapy of bone marrow mesenchymal stem cells transplantation in the Department of Cardiology, Nanjing First Hospital Affiliated to Nanjing Medical University during March 2003 to March 2004 were recurited. Informed consents were obtained from the patients, and the complete postoperative follow up was over 3 months. The patients include 15 male and 5 female, and they were aged (64±10) years.METHODS: All the patients underwent

  11. Secretome of Olfactory Mucosa Mesenchymal Stem Cell, a Multiple Potential Stem Cell.

    Science.gov (United States)

    Ge, Lite; Jiang, Miao; Duan, Da; Wang, Zijun; Qi, Linyu; Teng, Xiaohua; Zhao, Zhenyu; Wang, Lei; Zhuo, Yi; Chen, Ping; He, Xijing; Lu, Ming

    2016-01-01

    Nasal olfactory mucosa mesenchymal stem cells (OM-MSCs) have the ability to promote regeneration in the nervous system in vivo. Moreover, with view to the potential for clinical application, OM-MSCs have the advantage of being easily accessible from patients and transplantable in an autologous manner, thus eliminating immune rejection and contentious ethical issues. So far, most studies have been focused on the role of OM-MSCs in central nervous system replacement. However, the secreted proteomics of OM-MSCs have not been reported yet. Here, proteins secreted by OM-MSCs cultured in serum-free conditions were separated on SDS-PAGE and identified by LC-MS/MS. As a result, a total of 274 secreted proteins were identified. These molecules are known to be important in neurotrophy, angiogenesis, cell growth, differentiation, and apoptosis, and inflammation which were highly correlated with the repair of central nervous system. The proteomic profiling of the OM-MSCs secretome might provide new insights into their nature in the neural recovery. However, proteomic analysis for clinical biomarkers of OM-MSCs needs to be further studied. PMID:26949398

  12. The Use Of Laser Irradiation To Stimulate Adipose Derived Stem Cell Proliferation And Differentiation For Use In Autologous Grafts

    Science.gov (United States)

    Abrahamse, Heidi

    2009-09-01

    Stem cells are characterized by the qualities of self-renewal, long term viability, and the ability to differentiate into various cell types. Historically, stem cells have been isolated from the inner cell mass of blastocysts and harvesting these cells resulted in the death of the embryo leading to religious, political and ethical issues. The identification and subsequent isolation of adult stem cells from bone marrow stroma have been welcomed as an alternate source for stem cells. The clinical use of Mesenchymal Stem Cells (MSCs) presented problems such as limited cell number, pain and morbidity upon isolation. Adipose tissue is derived from the mesenchyme, is easily isolated, a reliable source of stem cells and able to differentiate into different cell types including smooth muscle. Over the past few years, the identification and characterization of stem cells has led the potential use of these cells as a promising alternative to cell replacement therapy. Smooth muscle is a major component of human tissues and is essential for the normal functioning of many different organs. Low intensity laser irradiation has been shown to increase viability, protein expression and migration of stem cells in vitro, and to stimulate proliferation of various types of stem cells. In addition, the use of laser irradiation to stimulate differentiation in the absence of growth factors has also been demonstrated in normal human neural progenitor cells (NHNPCs) in vitro where NHNPCs are not only capable of being sustained by light in the absence of growth factors, but that they are also able to differentiate normally as assessed by neurite formation. Our work has focused on the ability of laser irradiation to proliferate adipose derived stem cells (ADSCs), maintain ADSC character and increase the rate and maintenance of differentiation of ADSCs into smooth muscle and skin fibroblast cells. Current studies are also investigating the effect of different irradiation wavelengths and

  13. New perspectives in human stem cell therapeutic research

    OpenAIRE

    Trounson Alan

    2009-01-01

    Abstract Human stem cells are in evaluation in clinical stem cell trials, primarily as autologous bone marrow studies, autologous and allogenic mesenchymal stem cell trials, and some allogenic neural stem cell transplantation projects. Safety and efficacy are being addressed for a number of disease state applications. There is considerable data supporting safety of bone marrow and mesenchymal stem cell transplants but the efficacy data are variable and of mixed benefit. Mechanisms of action o...

  14. Micro-fracture enhanced by autologous bone marrow mesenchymal stem cells extracellular matrix scaffold to treat articular cartilage defects in the knee of pigs%微骨折与自体骨髓间充质干细胞外基质支架修复猪膝关节软骨缺损

    Institute of Scientific and Technical Information of China (English)

    李祥全; 唐成; 宋科荣; 金成哲

    2014-01-01

    BACKGROUND:Micro-fracture surgery method is simple, easy to operate, which is an effective way to treat articular cartilage defects, but there are stil some problems such as regenerated fibrocartilage and regenerated cartilage degradation. Scholars have focused on the use of various methods to improve the micro-fracture effect on repairing cartilage defects. OBJECTIVE:To explore the effects of micro-fracture enhanced by autologous bone marrow mesenchymal stem cells extracellular matrix (aBMSC-dECM) scaffold for treating cartilage defects in minipig models. METHODS:Bone marrow was extracted from the minipigs and bone marrow mesenchymal stem cells were obtained. aBMSC-dECM membranes were col ected. Cross-linking and freeze-drying technology were used to make the three-dimensional porous aBMSC-dECM scaffold. Ful thickness cartilage defects, 2 mm in depth and 6 mm in diameter, were created on the femoral condyles and trochlea grooves of the two knees of the minipigs. The right knees were treated with micro-fracture as control and the left were treated with micro-fracture enhanced by aBMSC-dECM scaffold. Six months later, histological examination and Wakitani score were used to evaluate the cartilage regeneration, and glycosaminoglycans and DNA contents in the regenerative tissue were determined. RESULTS AND CONCLUSION:After 6 months, the tissue treated by micro-fracture enhanced by aBMSC-dECM scaffold got better surface and integrated with the surrounding cartilage. Safranin O and fast green staining and Masson staining showed that the regenerated cartilage of the left knee, with abundant matrix and dense bone trabeculae, was better than that of the right. Wakitani score of the left knee was higher than that of the right. Glycosaminoglycans content of the left knee was much more than that of the right, while the DNA content was lower in the left knee than the right knee. Better results were observed in the left knee undergoing micro-fracture enhanced by a

  15. Therapeutic Potential of Mesenchymal Stem Cells in Regenerative Medicine

    OpenAIRE

    Patel, Devang M.; Jainy Shah; Srivastava, Anand S.

    2013-01-01

    Mesenchymal stem cells (MSCs) are stromal cells that have the ability to self-renew and also exhibit multilineage differentiation into both mesenchymal and nonmesenchymal lineages. The intrinsic properties of these cells make them an attractive candidate for clinical applications. MSCs are of keen interest because they can be isolated from a small aspirate of bone marrow or adipose tissues and can be easily expanded in vitro. Moreover, their ability to modulate immune responses makes them an ...

  16. Mesenchymal stem cell-mediated functional tooth regeneration in swine.

    Directory of Open Access Journals (Sweden)

    Wataru Sonoyama

    Full Text Available Mesenchymal stem cell-mediated tissue regeneration is a promising approach for regenerative medicine for a wide range of applications. Here we report a new population of stem cells isolated from the root apical papilla of human teeth (SCAP, stem cells from apical papilla. Using a minipig model, we transplanted both human SCAP and periodontal ligament stem cells (PDLSCs to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. This work integrates a stem cell-mediated tissue regeneration strategy, engineered materials for structure, and current dental crown technologies. This hybridized tissue engineering approach led to recovery of tooth strength and appearance.

  17. Tumourigenicity and radiation resistance of mesenchymal stem cells

    DEFF Research Database (Denmark)

    D'Andrea, Filippo Peder; Horsman, Michael Robert; Kassem, Moustapha;

    2012-01-01

    Background. Cancer stem cells are believed to be more radiation resistant than differentiated tumour cells of the same origin. It is not known, however, whether normal nontransformed adult stem cells share the same radioresistance as their cancerous counterpart. Material and methods....... Nontumourigenic (TERT4) and tumourigenic (TRET20) cell lines, from an immortalised mesenchymal stem cell line, were grown in culture prior to irradiation and gene expression analysis. Radiation resistance was measured using a clonogenic assay. Differences in gene expression between the two cell lines, both under...... intercellular matrix. These results also indicate that cancer stem cells are more radiation resistant than stem cells of the same origin....

  18. Tandem autologous/reduced-intensity conditioning allogeneic stem-cell transplantation versus autologous transplantation in myeloma: long-term follow-up

    NARCIS (Netherlands)

    Bjorkstrand, B.; Iacobelli, S.; Hegenbart, U.; Gruber, A.; Greinix, H.; Volin, L.; Narni, F.; Musto, P.; Beksac, M.; Bosi, A.; Milone, G.; Corradini, P.; Goldschmidt, H.; Witte, T.J.M. de; Morris, C.; Niederwieser, D.; Gahrton, G.

    2011-01-01

    PURPOSE: Results of allogeneic stem-cell transplantation (allo) in myeloma are controversial. In this trial autologous stem-cell transplantation (auto) followed by reduced-intensity conditioning matched sibling donor allo (auto-allo) was compared with auto only in previously untreated multiple myelo

  19. File list: ALL.Oth.20.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Oth.20.AllAg.Mesenchymal_stem_cells hg19 All antigens Others Mesenchymal stem c...ttp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Oth.20.AllAg.Mesenchymal_stem_cells.bed ...

  20. File list: Unc.Oth.50.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.50.AllAg.Mesenchymal_stem_cells hg19 Unclassified Others Mesenchymal stem c...ells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Oth.50.AllAg.Mesenchymal_stem_cells.bed ...

  1. File list: Unc.Oth.50.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.50.AllAg.Mesenchymal_stem_cells mm9 Unclassified Others Mesenchymal stem ce...lls http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.50.AllAg.Mesenchymal_stem_cells.bed ...

  2. File list: ALL.Oth.05.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Oth.05.AllAg.Mesenchymal_stem_cells mm9 All antigens Others Mesenchymal stem ce...X228662,SRX228660,SRX228665,SRX228678,SRX228661 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Oth.05.AllAg.Mesenchymal_stem_cells.bed ...

  3. File list: Unc.Oth.05.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.05.AllAg.Mesenchymal_stem_cells mm9 Unclassified Others Mesenchymal stem ce...lls http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.05.AllAg.Mesenchymal_stem_cells.bed ...

  4. File list: Oth.Oth.50.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Oth.50.AllAg.Mesenchymal_stem_cells hg19 TFs and others Others Mesenchymal stem...X1027439,SRX1027441,SRX1027449,SRX1027452,SRX1027451,SRX1027440 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Oth.50.AllAg.Mesenchymal_stem_cells.bed ...

  5. File list: Pol.Oth.20.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Oth.20.AllAg.Mesenchymal_stem_cells hg19 RNA polymerase Others Mesenchymal stem... cells SRX1027436,SRX1027435,SRX1027434,SRX1027433 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Oth.20.AllAg.Mesenchymal_stem_cells.bed ...

  6. File list: Unc.Oth.05.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.05.AllAg.Mesenchymal_stem_cells hg19 Unclassified Others Mesenchymal stem c...ells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Oth.05.AllAg.Mesenchymal_stem_cells.bed ...

  7. File list: Oth.Oth.10.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Oth.10.AllAg.Mesenchymal_stem_cells mm9 TFs and others Others Mesenchymal stem ...cells SRX228677,SRX228676,SRX228679,SRX228678 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Oth.10.AllAg.Mesenchymal_stem_cells.bed ...

  8. File list: His.Oth.50.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.50.AllAg.Mesenchymal_stem_cells hg19 Histone Others Mesenchymal stem cells ...76722,SRX376723,SRX1027442 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Oth.50.AllAg.Mesenchymal_stem_cells.bed ...

  9. File list: Oth.Oth.50.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Oth.50.AllAg.Mesenchymal_stem_cells mm9 TFs and others Others Mesenchymal stem ...cells SRX228677,SRX228679,SRX228676,SRX228678 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Oth.50.AllAg.Mesenchymal_stem_cells.bed ...

  10. File list: ALL.Oth.50.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Oth.50.AllAg.Mesenchymal_stem_cells hg19 All antigens Others Mesenchymal stem c...ttp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Oth.50.AllAg.Mesenchymal_stem_cells.bed ...

  11. File list: His.Oth.05.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.05.AllAg.Mesenchymal_stem_cells mm9 Histone Others Mesenchymal stem cells S...,SRX318103,SRX228666,SRX228665 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Oth.05.AllAg.Mesenchymal_stem_cells.bed ...

  12. File list: His.Oth.20.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.20.AllAg.Mesenchymal_stem_cells hg19 Histone Others Mesenchymal stem cells ...027442,SRX376722,SRX376723 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Oth.20.AllAg.Mesenchymal_stem_cells.bed ...

  13. File list: DNS.Oth.10.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Oth.10.AllAg.Mesenchymal_stem_cells mm9 DNase-seq Others Mesenchymal stem cells... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Oth.10.AllAg.Mesenchymal_stem_cells.bed ...

  14. File list: Pol.Oth.50.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Oth.50.AllAg.Mesenchymal_stem_cells hg19 RNA polymerase Others Mesenchymal stem... cells SRX1027436,SRX1027435,SRX1027434,SRX1027433 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Oth.50.AllAg.Mesenchymal_stem_cells.bed ...

  15. File list: Unc.Oth.10.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.10.AllAg.Mesenchymal_stem_cells hg19 Unclassified Others Mesenchymal stem c...ells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Oth.10.AllAg.Mesenchymal_stem_cells.bed ...

  16. File list: His.Oth.50.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.50.AllAg.Mesenchymal_stem_cells mm9 Histone Others Mesenchymal stem cells S...,SRX228669,SRX228666,SRX228664 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Oth.50.AllAg.Mesenchymal_stem_cells.bed ...

  17. File list: ALL.Oth.10.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Oth.10.AllAg.Mesenchymal_stem_cells hg19 All antigens Others Mesenchymal stem c...ttp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Oth.10.AllAg.Mesenchymal_stem_cells.bed ...

  18. File list: Unc.Oth.10.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.10.AllAg.Mesenchymal_stem_cells mm9 Unclassified Others Mesenchymal stem ce...lls http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.10.AllAg.Mesenchymal_stem_cells.bed ...

  19. Physiological problems in patients undergoing autologous and allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Sevgisun Kapucu

    2014-01-01

    Full Text Available Objective: Stem cell transplantation is usually performed in an effort to extend the patient′s life span and to improve their quality of life. This study was conducted to determine the postoperative physiological effects experienced by patients who had undergone autologous and allogeneic stem cell transplantation. Methods: The research is a descriptive study conducted with a sample of 60 patients at Stem Cell Transplantation Units in Ankara. Percentile calculation and chi-square tests were used to evaluate the data. Results: When a comparison was made between patients who had undergone allogeneic Hematopoietic stem cell transplantation (HSCT and those who had undergone autologous HSCT, results indicated that problems occurred more often for the allogeneic HSCT patients. The problems included: Digestion (94.3%, dermatological (76.7%, cardiac and respiratory (66.7%, neurological (66.7%, eye (56.7%, infections (26.7% and Graft Versus Host Disease (5 patients. Furthermore, the problems with pain (50%, numbness and tingling (40%, and speech disorders (3 patients were observed more often in autologous BMT patients. Conclusion: Autologous and allogeneic patients experienced most of physical problems due to they receive high doses of chemotherapy. Therefore, it is recommended that an interdisciplinary support team approach should be usedtohelp reduce and manage the problems that may arise during patient care.

  20. Up-Front Autologous Stem-Cell Transplantation in Peripheral T-Cell Lymphoma

    DEFF Research Database (Denmark)

    d'Amore, Francesco; Relander, Thomas; Lauritzsen, Grete F; Jantunen, Esa; Hagberg, Hans; Anderson, Harald; Holte, Harald; Osterborg, Anders; Merup, Mats; Brown, Peter De Nully; Kuittinen, Outi; Erlanson, Martin; Ostenstad, Bjørn; Fagerli, Unn-Merete; Gadeberg, Ole Vestergaard; Sundström, Christer; Delabie, Jan; Ralfkiaer, Elisabeth; Vornanen, Martine; Toldbod, Helle

    2012-01-01

    Systemic peripheral T-cell lymphomas (PTCLs) respond poorly to conventional therapy. To evaluate the efficacy of a dose-dense approach consolidated by up-front high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) in PTCL, the Nordic Lymphoma Group (NLG) conducted a large...

  1. Induced autologous stem cell transplantation for treatment of rabbit renal interstitial fibrosis.

    Directory of Open Access Journals (Sweden)

    Guang-Ping Ruan

    Full Text Available INTRODUCTION: Renal interstitial fibrosis (RIF is a significant cause of end-stage renal failure. The goal of this study was to characterize the distribution of transplanted induced autologous stem cells in a rabbit model of renal interstitial fibrosis and evaluate its therapeutic efficacy for treatment of renal interstitial fibrosis. METHODS: A rabbit model of renal interstitial fibrosis was established. Autologous fibroblasts were cultured, induced and labeled with green fluorescent protein (GFP. These labeled stem cells were transplanted into the renal artery of model animals at 8 weeks. RESULTS: Eight weeks following transplantation of induced autologous stem cells, significant reductions (P < 0.05 were observed in serum creatinine (SCr (14.8 ± 1.9 mmol/L to 10.1 ± 2.1 mmol/L and blood urea nitrogen (BUN (119 ± 22 µmol/L to 97 ± 13 µmol/L, indicating improvement in renal function. CONCLUSIONS: We successfully established a rabbit model of renal interstitial fibrosis and demonstrated that transplantation of induced autologous stem cells can repair kidney damage within 8 weeks. The repair occurred by both inhibition of further development of renal interstitial fibrosis and partial reversal of pre-existing renal interstitial fibrosis. These beneficial effects lead to the development of normal tissue structure and improved renal function.

  2. Nanoscale Mechanical Stimulation of Human Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    H Nikukar

    2014-05-01

    We observed significant responses after 1 and 2-week stimulations in cell number, cell shapes and phenotypical markers. Microarray was performed for all groups. Cell count showed normal cell growth with stimulation. However, cell surface area, cell perimeter, and arboration after 1-week stimulation showed significant increases. Immunofluorescent studies have showed significant increase in osteocalcin production after stimulation. Conclusions: Nanoscale mechanical vibration showed significant changes in human mesenchymal stem cell behaviours. Cell morphology changed to become more polygonal and increased expression of the osteoblast markers were noted. These findings with gene regulation changes suggesting nanoscale mechanostimulation has stimulated osteoblastogenesis.  Keywords:  Mesenchymal, Nanoscale, Stem Cells.

  3. Human mesenchymal stem cells: from basic biology to clinical applications

    DEFF Research Database (Denmark)

    Abdallah, B M; Kassem, M

    2008-01-01

    Mesenchymal stem cells (MSC) are a group of clonogenic cells present among the bone marrow stroma and capable of multilineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. Due to their ease of isolation and their differentiation potential, MSC are being...... introduced into clinical medicine in variety of applications and through different ways of administration. Here, we discuss approaches for isolation, characterization and directing differentiation of human mesenchymal stem cells (hMSC). An update of the current clinical use of the cells is also provided....

  4. Loss of quiescence and impaired function of CD34+/CD38low cells one year following autologous stem cell transplantation

    OpenAIRE

    Woolthuis, Carolien M.; Brouwers-Vos, Annet Z.; Huls, Gerwin; de Wolf, Joost Th. M.; Schuringa, Jan Jacob; Vellenga, Edo

    2013-01-01

    Patients who have undergone autologous stem cell transplantation are subsequently more susceptible to chemotherapy-induced bone marrow toxicity. In the present study, bone marrow primitive progenitor cells were examined one year after autologous stem cell transplantation and compared with normal bone marrow and mobilized peripheral blood stem cells. Post-transplantation bone marrow contained a significantly lower percentage of quiescent cells in the CD34+/CD38low fraction compared to normal b...

  5. Autologous Bone Marrow Stem Cells combined with Allograft Cancellous Bone in Treatment of Nonunion

    Directory of Open Access Journals (Sweden)

    Le Thua Trung Hau

    2015-12-01

    Full Text Available Autologous cancellous bone graft is currently used as a gold standard method for treatment of bone nonunion. However, there is a limit to the amount of autologous cancellous bone that can be harvested and the donor site morbidity presents a major disadvantage to autologous bone grafting. Embedding viable cells within biological scaffolds appears to be extremely promising. The purpose of this study was to assess the outcome of autologous bone marrow stem cells combined with a cancellous bone allograft as compared to an autologous bone graft in the treatment of bone nonunion. Bone marrow aspiration concentrate (BMAC was previously produced from bone marrow aspirate via a density gradient centrifugation. Autologous cancellous bone was harvested in 9 patients and applied to the nonunion site. In 18 patients of the clinical trial group after the debridement, the bone gaps were filled with a composite of BMAC and allograft cancellous bone chips (BMAC-ACB. Bone consolidation was obtained in 88.9 %, and the mean interval between the cell transplantation and union was 4.6 +/- 1.5 months in the autograft group. Bone union rate was 94.4 % in group of composite BMAC-ACB implantation. The time to union in BMAC-ACB grafting group was 3.3 +/- 0.90 months, and led to faster healing when compared to the autograft. A mean concentration of autologous progenitor cells was found to be 2.43 +/- 1.03 (x106 CD34+ cells/ml, and a mean viability of CD34+ cells was 97.97 +/- 1.47 (%. This study shows that the implantation of BMAC has presented the efficacy for treatment of nonunion and may contribute an available alternative to autologous cancellous bone graft. But large clinical application of BM-MSCs requires a more appropriate and profound scientific investigations. [Biomed Res Ther 2015; 2(12.000: 409-417

  6. Isolation and culture of umbilical vein mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    D.T. Covas

    2003-09-01

    Full Text Available Bone marrow contains a population of stem cells that can support hematopoiesis and can differentiate into different cell lines including adipocytes, osteocytes, chondrocytes, myocytes, astrocytes, and tenocytes. These cells have been denoted mesenchymal stem cells. In the present study we isolated a cell population derived from the endothelium and subendothelium of the umbilical cord vein which possesses morphological, immunophenotypical and cell differentiation characteristics similar to those of mesenchymal stem cells isolated from bone marrow. The cells were isolated from three umbilical cords after treatment of the umbilical vein lumen with collagenase. The cell population isolated consisted of adherent cells with fibroblastoid morphology which, when properly stimulated, gave origin to adipocytes and osteocytes in culture. Immunophenotypically, this cell population was found to be positive for the CD29, CD13, CD44, CD49e, CD54, CD90 and HLA-class 1 markers and negative for CD45, CD14, glycophorin A, HLA-DR, CD51/61, CD106, and CD49d. The characteristics described are the same as those presented by bone marrow mesenchymal stem cells. Taken together, these findings indicate that the umbilical cord obtained from term deliveries is an important source of mesenchymal stem cells that could be used in cell therapy protocols.

  7. Adult human nasal mesenchymal-like stem cells restore cochlear spiral ganglion neurons after experimental lesion.

    Science.gov (United States)

    Bas, Esperanza; Van De Water, Thomas R; Lumbreras, Vicente; Rajguru, Suhrud; Goss, Garrett; Hare, Joshua M; Goldstein, Bradley J

    2014-03-01

    A loss of sensory hair cells or spiral ganglion neurons from the inner ear causes deafness, affecting millions of people. Currently, there is no effective therapy to repair the inner ear sensory structures in humans. Cochlear implantation can restore input, but only if auditory neurons remain intact. Efforts to develop stem cell-based treatments for deafness have demonstrated progress, most notably utilizing embryonic-derived cells. In an effort to bypass limitations of embryonic or induced pluripotent stem cells that may impede the translation to clinical applications, we sought to utilize an alternative cell source. Here, we show that adult human mesenchymal-like stem cells (MSCs) obtained from nasal tissue can repair spiral ganglion loss in experimentally lesioned cochlear cultures from neonatal rats. Stem cells engraft into gentamicin-lesioned organotypic cultures and orchestrate the restoration of the spiral ganglion neuronal population, involving both direct neuronal differentiation and secondary effects on endogenous cells. As a physiologic assay, nasal MSC-derived cells engrafted into lesioned spiral ganglia demonstrate responses to infrared laser stimulus that are consistent with those typical of excitable cells. The addition of a pharmacologic activator of the canonical Wnt/β-catenin pathway concurrent with stem cell treatment promoted robust neuronal differentiation. The availability of an effective adult autologous cell source for inner ear tissue repair should contribute to efforts to translate cell-based strategies to the clinic. PMID:24172073

  8. Derivation of multipotent mesenchymal precursors from human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    2005-06-01

    Full Text Available BACKGROUND: Human embryonic stem cells provide access to the earliest stages of human development and may serve as a source of specialized cells for regenerative medicine. Thus, it becomes crucial to develop protocols for the directed differentiation of embryonic stem cells into tissue-restricted precursors. METHODS AND FINDINGS: Here, we present culture conditions for the derivation of unlimited numbers of pure mesenchymal precursors from human embryonic stem cells and demonstrate multilineage differentiation into fat, cartilage, bone, and skeletal muscle cells. CONCLUSION: Our findings will help to elucidate the mechanism of mesoderm specification during embryonic stem cell differentiation and provide a platform to efficiently generate specialized human mesenchymal cell types for future clinical applications.

  9. Autologous tissue patch rich in stem cells created in the subcutaneous tissue

    Institute of Scientific and Technical Information of China (English)

    Ignacio; Garcia-Gomez; Krishnamurthy; P; Gudehithlu; Jose; A; L; Arruda; Ashok; K; Singh

    2015-01-01

    AIM:To investigate whether we could create natural autologous tissue patches in the subcutaneous space for organ repair. METHODS: We implanted the following three types of inert foreign bodies in the subcutaneous tissue of rats to produce autologous tissue patches of different geometries:(1) a large-sized polyvinyl tube(L = 25 mm,internal diameter = 7 mm) sealed at both ends by heat application for obtaining a large flat piece of tissue patch for organ repair;(2) a fine polyvinyl tubing(L = 25 mm,internal diameter = 3 mm) for creating cylindrically shaped grafts for vascular or nerve repair; and(3) a slurry of polydextran particle gel for inducing a bladder-like tissue. Implantation of inert materials was carried out by making a small incision on one or either side of the thoracic-lumbar region of rats. Subcutaneous pockets were created by blunt dissection around the incision into which the inert bodies were inserted(1 or 2 per rat). The incisions were closed with silk sutures,and the animals were allowed to recover. In case of the polydextran gel slurry 5 m L of the slurry was injected in the subcutaneous space using an 18 gauge needle. After implanting the foreign bodies a newly regenerated encapsulating tissue developed around the foreign bodies. The tissues were harvested after 4-42 d of implantation and studied by gross examination,histology,and histochemistry for organization,vascularity,and presence of mesenchymal stem cells(MSCs)(CD271+CD34+ cells). RESULTS: Implanting a large cylindrically shaped polyvinyl tube resulted in a large flat sheet of tissue that could be tailored to a specific size and shape for use as a tissue patch for repairing large organs. Implanting a smaller sized polyvinyl tube yielded a cylindrical tissue that could be useful for repairing nerves and blood vessels. This type of patch could be obtained in different lengths by varying the length of the implanted tube. Implanting a suspension of inert polydextran suspension gave rise to a

  10. High dose therapy with autologous stem cell support in malignant disorders

    International Nuclear Information System (INIS)

    New biomedical knowledge may improve the diagnostic procedures and treatment provided by the Health Services, but at additional cost. In a social democratic health care system, the hospital budgets have no room for expensive, new procedures or treatments, unless these are funded through extra allocation from the central authorities. High dose therapy with autologous stem cell support in malignant disorders is an example of a new and promising, but rather expensive treatment, but its role in cancer therapy has yet to be established. The indications for testing high dose therapy with autologous stem cell support in various malignancies are discussed, with emphasis on the principles for deciding which categories of disease should have priority. The authors suggest some malignant disorder for which high dose therapy with stem cell support should be explored versus conventional treatment in randomized prospective trials. 8 refs., 1 tab

  11. Impairment of mesenchymal stem cells derived from oral leukoplakia

    OpenAIRE

    Zhang, Zhihui; Song, Jiangyuan; Han, Ying; Mu, Dongdong; Su, Sha; Ji, Xiaoli; Liu, Hongwei

    2015-01-01

    Oral leukoplakia is one of the common precancerous lesions in oral mucosa. To compare the biological characteristics and regenerative capacities of mesenchymal stem cells (MSCs) from oral leukoplakia (epithelial hyperplasia and dysplasia) and normal oral mucosa, MSCs were isolated by enzyme digestion. Then these cells were identified by the expression of MSC related markers, STRO-1, CD105 and CD90, with the absent for the hematopoietic stem cell marker CD34 by flow cytometric detection. The s...

  12. Specific differentiation of mesenchymal stem cells by small molecules

    OpenAIRE

    Song, Heesang; Chang, Woochul; Song, Byeong-Wook; Hwang, Ki-Chul

    2011-01-01

    Mesenchymal stem cells (MSCs) are multipotent, self-renewing cells harboring multi-lineage differentiation potential and immunosuppressive properties that make them an attractive candidate for biological cell-based regenerative medicine. In addition to its undoubted clinical interest, controlling the fate and behaviors of MSCs is a crucial prerequisite for their therapeutic applications in regenerative medicine. Stem cell differentiation and modulation of functional activities are generally c...

  13. Immunomodulation by Mesenchymal Stem Cells in Veterinary Species

    OpenAIRE

    Carrade, Danielle D.; Borjesson, Dori L.

    2013-01-01

    Mesenchymal stem cells (MSC) are adult-derived multipotent stem cells that have been derived from almost every tissue. They are classically defined as spindle-shaped, plastic-adherent cells capable of adipogenic, chondrogenic, and osteogenic differentiation. This capacity for trilineage differentiation has been the foundation for research into the use of MSC to regenerate damaged tissues. Recent studies have shown that MSC interact with cells of the immune system and modulate their function. ...

  14. Isolation and culture of umbilical vein mesenchymal stem cells

    OpenAIRE

    D.T. Covas; J.L.C. Siufi; A.R.L. Silva; M. D. Orellana

    2003-01-01

    Bone marrow contains a population of stem cells that can support hematopoiesis and can differentiate into different cell lines including adipocytes, osteocytes, chondrocytes, myocytes, astrocytes, and tenocytes. These cells have been denoted mesenchymal stem cells. In the present study we isolated a cell population derived from the endothelium and subendothelium of the umbilical cord vein which possesses morphological, immunophenotypical and cell differentiation characteristics similar to tho...

  15. Collagen scaffold remodeling by human mesenchymal stem cells

    OpenAIRE

    Han, SJ; Chan, BP

    2011-01-01

    Type I collagen has been widely used as scaffold for tissue engineering because of its excellent biocompatibility and negligible immunogenicity. We previously have developed a collagen microencapsulation technology entrapping many cells including human mesenchymal stem cells (hMSCs) in microspheres made of nanofibrous collagen meshwork. Nevertheless, little is understood about how stem cells interact with and remodel the collagen meshwork. This study aims to investigate collagen remodeling by...

  16. Mesenchymal stem cells for the treatment of tendon disorders

    Czech Academy of Sciences Publication Activity Database

    Machová-Urdzíková, Lucia; Lesný, Petr; Syková, Eva; Jendelová, Pavla

    2013-01-01

    Roč. 6, 8A (2013), s. 14-23. ISSN 1937-6871 R&D Projects: GA ČR GAP304/10/0326 Institutional support: RVO:68378041 Keywords : Tendinophaty * Mesenchymal Stem Cells * Tendon Rupture Subject RIV: FP - Other Medical Disciplines

  17. Proteomic techniques for characterisation of mesenchymal stem cell secretome.

    Czech Academy of Sciences Publication Activity Database

    Kupcová Skalníková, Helena

    2013-01-01

    Roč. 95, č. 12 (2013), s. 2196-2211. ISSN 0300-9084 R&D Projects: GA MŠk ED2.1.00/03.0124; GA TA ČR TA01011466 Institutional support: RVO:67985904 Keywords : mesenchymal stem cells * secretome * exosome * conditioned medium * proteomics Subject RIV: CE - Biochemistry Impact factor: 3.123, year: 2013

  18. Paracrine Molecules of Mesenchymal Stem Cells for Hematopoietic Stem Cell Niche

    OpenAIRE

    Tian Li; Yaojiong Wu

    2011-01-01

    Hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are both adult stem cells residing in the bone marrow. MSCs interact with HSCs, they stimulate and enhance the proliferation of HSCs by secreting regulatory molecules and cytokines, providing a specialized microenvironment for controlling the process of hematopoiesis. In this paper we discuss how MSCs contribute to HSC niche, maintain the stemness and proliferation of HSCs, and support HSC transplantation.

  19. Neurogenic differentiation from adipose-derived stem cells and application for autologous transplantation in spinal cord injury.

    Science.gov (United States)

    Zhao, Yong; Jiang, Hui; Liu, Xin-wei; Chen, Jian-Ting; Xiang, Liang-Bi; Zhou, Da-Peng

    2015-09-01

    Mesenchymal stem cells derived from adipose tissue have the capacity to differentiate into endodermal, mesoderm and ectodermal cell lineages in vitro, which are an ideal engraft in tissue-engineered repair. In this study, mouse adipose-derived stem cells (ADSCs) were isolated from subcutaneous fat. The markers of ADSCs, CD13, CD29, CD44, CD71, CD73, CD90, CD105, CD166, Nestin, GFAP and MAP-2 were detected by immunofluorescence assays. The ADSCs were cultured in cocktail factors (including ATRA, GGF-2, bFGF, PDGF and forskolin) for neurogenic differentiation. The neurogenic cells markers, Nestin, GFAP and MAP-2 were analyzed using immunofluorescence and real-time PCR after dramatic changes in morphology. Neurogenic cells from ADSCs were autologous transplanted into the mouse of spinal cord injury for observation neurogenic cells colonization in spinal cord. The result demonstrated that the mouse ADSCs were positive for the CD13, CD29, CD44, CD71, CD73, CD90, CD105 and CD166 but negative for neurogenic cell markers, MAP-2, GFAP and Nestin. After neurogenic differentiation, the neurogenic cells were positive for neurogenic cell special markers, gene expression level showed a time-lapse increase, and the cells were successful colonized into spinal cord. In conclusion, our research shows that a population of neuronal cells can be specifically generated from ADSCs and that induced cells may allow for participation in tissue-repair. PMID:25330756

  20. Age-related molecular genetic changes of murine bone marrow mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Webster Keith A

    2010-04-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSC are pluripotent cells, present in the bone marrow and other tissues that can differentiate into cells of all germ layers and may be involved in tissue maintenance and repair in adult organisms. Because of their plasticity and accessibility these cells are also prime candidates for regenerative medicine. The contribution of stem cell aging to organismal aging is under debate and one theory is that reparative processes deteriorate as a consequence of stem cell aging and/or decrease in number. Age has been linked with changes in osteogenic and adipogenic potential of MSCs. Results Here we report on changes in global gene expression of cultured MSCs isolated from the bone marrow of mice at ages 2, 8, and 26-months. Microarray analyses revealed significant changes in the expression of more than 8000 genes with stage-specific changes of multiple differentiation, cell cycle and growth factor genes. Key markers of adipogenesis including lipoprotein lipase, FABP4, and Itm2a displayed age-dependent declines. Expression of the master cell cycle regulators p53 and p21 and growth factors HGF and VEGF also declined significantly at 26 months. These changes were evident despite multiple cell divisions in vitro after bone marrow isolation. Conclusions The results suggest that MSCs are subject to molecular genetic changes during aging that are conserved during passage in culture. These changes may affect the physiological functions and the potential of autologous MSCs for stem cell therapy.

  1. Glial origin of mesenchymal stem cells in a tooth model system

    NARCIS (Netherlands)

    Kaukua, Nina; Shahidi, Maryam Khatibi; Konstantinidou, Chrysoula; Dyachuk, Vyacheslav; Kaucka, Marketa; Furlan, Alessandro; An, Zhengwen; Wang, Longlong; Hultman, Isabell; Ahrlund-Richter, Lars; Blom, Hans; Brismar, Hjalmar; Lopes, Natalia Assaife; Pachnis, Vassilis; Suter, Ueli; Clevers, Hans; Thesleff, Irma; Sharpe, Paul; Ernfors, Patrik; Fried, Kaj; Adameyko, Igor

    2014-01-01

    Mesenchymal stem cells occupy niches in stromal tissues where they provide sources of cells for specialized mesenchymal derivatives during growth and repair. The origins of mesenchymal stem cells have been the subject of considerable discussion, and current consensus holds that perivascular cells fo

  2. Characterization of mesenchymal stem cells derived from equine adipose tissue

    OpenAIRE

    Carvalho, A.M.; A.L.M. Yamada; M.A. Golim; L.E.C. Álvarez; L.L. Jorge; M.L. Conceição; E. Deffune; C.A. Hussni; A.L.G. Alves

    2013-01-01

    Stem cell therapy has shown promising results in tendinitis and osteoarthritis in equine medicine. The purpose of this work was to characterize the adipose-derived mesenchymal stem cells (AdMSCs) in horses through (1) the assessment of the capacity of progenitor cells to perform adipogenic, osteogenic and chondrogenic differentiation; and (2) flow cytometry analysis using the stemness related markers: CD44, CD90, CD105 and MHC Class II. Five mixed-breed horses, aged 2-4 years-old were used to...

  3. GATA2 regulates differentiation of bone marrow-derived mesenchymal stem cells

    OpenAIRE

    Kamata, Mayumi; Okitsu, Yoko; Fujiwara, Tohru; Kanehira, Masahiko; Nakajima, Shinji; Takahashi, Taro; Inoue, Ai; Fukuhara, Noriko; Onishi, Yasushi; Ishizawa, Kenichi; Shimizu, Ritsuko; Yamamoto, Masayuki; Harigae, Hideo

    2014-01-01

    The bone marrow microenvironment comprises multiple cell niches derived from bone marrow mesenchymal stem cells. However, the molecular mechanism of bone marrow mesenchymal stem cell differentiation is poorly understood. The transcription factor GATA2 is indispensable for hematopoietic stem cell function as well as other hematopoietic lineages, suggesting that it may maintain bone marrow mesenchymal stem cells in an immature state and also contribute to their differentiation. To explore this ...

  4. UPDATE ON THE ROLE OF AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA

    Directory of Open Access Journals (Sweden)

    Patrizia Tosi

    2012-11-01

    Full Text Available Autologous stem cell transplantation is considered the standard of care for multiple myeloma patients aged < 65 years with no relevant comorbidities. The addition of drugs acting both on bone marrow microenvironment and on neoplastic plasma cells has significantly increased the proportion of patients achieving a complete remission after induction therapy, and these results are mantained after high-dose melphalan, leading to a prolonged disease control. Studies are being carried out in order to evaluate whether short term consolidation or long-term maintenance therapy can result into disease eradication at the molecular level thus increasing also patients survival. The efficacy of these new drugs has raised the issue of deferring the transplant after achivng a second response upon relapse. Another controversial point is the optimal treatment strategy for high-risk patients, that do not benefit from autologous stem cell transplantation and for whom the efficacy of new drugs is still matter of debate.

  5. Noncultured Autologous Adipose-Derived Stem Cells Therapy for Chronic Radiation Injury

    Directory of Open Access Journals (Sweden)

    Sadanori Akita

    2010-01-01

    Full Text Available Increasing concern on chronic radiation injuries should be treated properly for life-saving improvement of wound management and quality of life. Recently, regenerative surgical modalities should be attempted with the use of noncultured autologous adipose-derived stem cells (ADSCs with temporal artificial dermis impregnated and sprayed with local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Autologous adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and tested for Patients who were uneventfully healed with minimal donor-site morbidity, which lasts more than 1.5 years.

  6. [Monomorphic post-transplant T-lymphoproliferative disorder after autologous stem cell transplantation for multiple myeloma].

    Science.gov (United States)

    Ishikawa, Tetsuya; Shimizu, Hiroaki; Takei, Toshifumi; Koya, Hiroko; Iriuchishima, Hirono; Hosiho, Takumi; Hirato, Junko; Kojima, Masaru; Handa, Hiroshi; Nojima, Yoshihisa; Murakami, Hirokazu

    2016-01-01

    We report a rare case of T cell type monomorphic post-transplant lymphoproliferative disorders (PTLD) after autologous stem cell transplantation. A 53-year-old man with multiple myeloma received autologous stem cell transplantation and achieved a very good partial response. Nine months later, he developed a high fever and consciousness disturbance, and had multiple swollen lymph nodes and a high titer of Epstein-Barr (EB) virus DNA in his peripheral blood. Neither CT nor MRI of the brain revealed any abnormalities. Cerebrospinal fluid contained no malignant cells, but the EB virus DNA titer was high. Lymph node biopsy revealed T cell type monomorphic PTLD. Soon after high-dose treatment with methotrexate and cytosine arabinoside, the high fever and consciousness disturbance subsided, and the lymph node swelling and EB virus DNA disappeared. Given the efficacy of chemotherapy in this case, we concluded that the consciousness disturbance had been induced by central nervous system involvement of monomorphic PTLD. PMID:26861102

  7. Optimizing autologous cell grafts to improve stem cell gene therapy.

    Science.gov (United States)

    Psatha, Nikoletta; Karponi, Garyfalia; Yannaki, Evangelia

    2016-07-01

    Over the past decade, stem cell gene therapy has achieved unprecedented curative outcomes for several genetic disorders. Despite the unequivocal success, clinical gene therapy still faces challenges. Genetically engineered hematopoietic stem cells are particularly vulnerable to attenuation of their repopulating capacity once exposed to culture conditions, ultimately leading to low engraftment levels posttransplant. This becomes of particular importance when transduction rates are low or/and competitive transplant conditions are generated by reduced-intensity conditioning in the absence of a selective advantage of the transduced over the unmodified cells. These limitations could partially be overcome by introducing megadoses of genetically modified CD34(+) cells into conditioned patients or by transplanting hematopoietic stem cells hematopoietic stem cells with high engrafting and repopulating potential. On the basis of the lessons gained from cord blood transplantation, we summarize the most promising approaches to date of increasing either the numbers of hematopoietic stem cells for transplantation or/and their engraftability, as a platform toward the optimization of engineered stem cell grafts. PMID:27106799

  8. Autologous peripheral blood stem cell transplantation in children and adolescents with non-Hodgkin lymphoma

    OpenAIRE

    Gui, Wei; Su, Liping; He, Jianxia; WANG, LIEYANG; Guan, Tao

    2015-01-01

    The aim of this study was to evaluate the effect and safety of autologous peripheral blood stem cell transplantation (APBSCT) in children and adolescents with non-Hodgkin lymphoma (NHL). Ten patients with NHL were analyzed retrospectively. In all the patients, lymph node enlargement was most frequently detected. Patients with a mediastinal mass presented with a cough, palpitation and shortness of breath. Extranodal patients presented with abdominal pain, inability to walk and vaginal bleeding...

  9. Stomatitis-Related Pain in Women with Breast Cancer Undergoing Autologous Hematopoietic Stem Cell Transplant

    OpenAIRE

    Fall-Dickson, Jane M.; Mock, Victoria; Berk, Ronald A.; Grimm, Patricia M.; Davidson, Nancy; Gaston-Johansson, Fannie

    2008-01-01

    The purpose of this cross-sectional, correlational study was to describe stomatitis-related pain in women with breast cancer undergoing autologous hematopoietic stem cell transplant. Hypotheses tested were that significant, positive relationships would exist between oral pain and stomatitis, state anxiety, depression, and alteration in swallowing. Stomatitis, sensory dimension of oral pain, and state anxiety were hypothesized to most accurately predict oral pain overall intensity. Thirty-two ...

  10. Autologous Stem Cell Transplant Study in Lymphoma Patients: Statistical Analysis of Multi-State Models

    Czech Academy of Sciences Publication Activity Database

    Furstová, J.; Valenta, Zdeněk

    ISCB, 2012. s. 67-68. ISBN 978-82-8045-026-5. [Annual Conference of the International Society for Clinical Biostatistics /33./. 19.08.2012-23.08.2012, Bergen] Grant ostatní: ESF CZ.1.07/2.4.00/174.0117 Institutional support: RVO:67985807 Keywords : multi-state model * disability model * illness-death model * Markov model * autologous stem cell transplant Subject RIV: BB - Applied Statistics, Operational Research

  11. Autologous Stem Cell Transplantation in Patients with Acute Myeloid Leukemia: a Single-Centre Experience

    Directory of Open Access Journals (Sweden)

    Kakucs Enikő

    2013-04-01

    Full Text Available Introduction: Autologous haemopoietic stem cell transplantation (SCT is an important treatment modality for patients with acute myeloid leukemia with low and intermediate risk disease. It has served advantages over allogenic transplantation, because it does not need a matched donor, there is no graft versus host disease, there are less complications and a faster immune reconstitution than in the allo-setting. The disadvantage is the lack of the graft versus leukaemia effect.

  12. Autologous bone marrow stem cells--properties and advantages.

    Science.gov (United States)

    Rice, Claire M; Scolding, Neil J

    2008-02-15

    The properties of self-renewal and multi-lineage differentiation make stem cells attractive candidates for use in cellular reparative therapy, particularly in neurological diseases where there is a paucity of treatment options. However, clinical trials using foetal material in Parkinson's disease have been disappointing and highlighted problems associated with the use of embryonic stem cells, including ethical issues and practical concerns regarding teratoma formation. Understandably, this has led investigators to explore alternative sources of stem cells for transplantation. The expression of neuroectodermal markers by cells of bone marrow origin focused attention on these adult stem cells. Although early enthusiasm has been tempered by dispute regarding the validity of reports of in vitro (trans)differentiation, the demonstration of functional benefit in animal models of neurological disease is encouraging. Here we will review some of the required properties of stem cells for use in transplantation therapy with specific reference to the development of bone marrow-derived cells as a source of cells for repair in demyelination. PMID:17669432

  13. A Rat Model of Autologous Oral Mucosal Epithelial Transplantation for Corneal Limbal Stem Cell Failure

    Institute of Scientific and Technical Information of China (English)

    Weihua Li; Qiaoli Li; Wencong Wang; Kaijing Li; Shiqi Ling; Yuanzhe Yang; Lingyi Liang

    2014-01-01

    Purpose:.To establish an animal model of autologous oral mucosa grafting for limbal stem cell deficiency. Methods:.The study was carried from August to October 2012. Fourteen SD rats were randomly and evenly allocated to study group A and control group B. Limbal stem cell defi-ciency was established by alkali burn in the right eye of each rat in both groups. Rats in group A received autologous oral mucosa strip transplantation following the chemical burn. Rats in group B did not receive surgery after the chemical burn. Topical antibiotics and dexamethasone were used in all rats. Corneal clarity,.corneal fluorescein staining,.oral mucosal graft survival, and complications at postoperative days 1,3,7, 14 were observed. Results:.The oral mucosa strip graft was detached in one rat in group A. Reepithelialization was observed starting from the graft position and was completed within 14 days in the re-maining 6 eyes in group A. However, persistent corneal ep-ithelium defect was observed in all eyes in group B, among which corneal melting and perforation was observed in 2 eyes and corneal opacification with neovascularization was ob-served in the remaining 5 eyes. Conclusion:.Autologous oral mucosa strip grafting for limbal stem cell deficiency can be achieved by a rat model following chemical burn. The fate of the transplanted oral mucosal ep-ithelial cells warrants further study. (Eye Science 2014; 29:1-5).

  14. Comparison of Gene Expression in Human Embryonic Stem Cells, hESC-Derived Mesenchymal Stem Cells and Human Mesenchymal Stem Cells

    OpenAIRE

    Romain Barbet; Isabelle Peiffer; Antoinette Hatzfeld; Pierre Charbord; Hatzfeld, Jacques A.

    2011-01-01

    We present a strategy to identify developmental/differentiation and plasma membrane marker genes of the most primitive human Mesenchymal Stem Cells (hMSCs). Using sensitive and quantitative TaqMan Low Density Arrays (TLDA) methodology, we compared the expression of 381 genes in human Embryonic Stem Cells (hESCs), hESC-derived MSCs ...

  15. Human mesenchymal stem cells are susceptible to lysis by CD8(+) T cells and NK cells.

    Science.gov (United States)

    Crop, Meindert J; Korevaar, Sander S; de Kuiper, Ronella; IJzermans, Jan N M; van Besouw, Nicole M; Baan, Carla C; Weimar, Willem; Hoogduijn, Martin J

    2011-01-01

    There is growing interest in the use of mesenchymal stem cells (MSCs) to improve the outcome of organ transplantation. The immunogenicity of MSCs is, however, unclear and is important for the efficacy of MSC therapy and for potential sensitization against donor antigens. We investigated the susceptibility of autologous and allogeneic MSCs for lysis by CD8(+) T-lymphocytes and NK cells in a kidney transplant setting. MSCs were derived from adipose tissue of human kidney donors and were CD90(+), CD105(+), CD166(+), and HLA class I(+). They showed differentiation ability and immunosuppressive capacity. Lysis of MSCs by peripheral blood mononuclear cells (PBMCs), FACS-sorted CD8(+) T cells, and NK cells was measured by europium release assay. Allogeneic MSCs were susceptible for lysis by cytotoxic CD8(+) T cells and NK cells, while autologous MSCs were lysed by NK cells only. NK cell-mediated lysis was inversely correlated with the expression of HLA class I on MSCs. Lysis of autologous MSCs was not dependent on culturing of MSCs in FBS, and MSCs in suspension as well as adherent to plastic were lysed by NK cells. Pretransplant recipient PBMCs did not lyse donor MSCs, but PBMCs isolated 3, 6, and 12 months after transplantation showed increasing lysing ability. After 12 months, CD8(+) T-cell-mediated lysis of donor MSCs persisted, indicating there was no evidence for desensitization against donor MSCs. Lysis of MSCs is important to take into account when MSCs are considered for clinical application. Our results suggest that the HLA background of MSCs and timing of MSC administration are important for the efficacy of MSC therapy. PMID:21396164

  16. Umbilical cord-derived stem cells (MODULATISTTM show strong immunomodulation capacity compared to adipose tissue-derived or bone marrow-derived mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Phuc Van Pham

    2016-06-01

    Full Text Available Introduction: Mesenchymal stem cells (MSCs show great promise in regenerative medicine. Clinical applications of MSCs have recently increased significantly, especially for immune diseases. Autologous transplantation is considered a safe therapy. However, its main disadvantages are poor stability and quality of MSCs from patient to patient, and labor-intensive and time-consuming culture procedures. Therefore, allogeneic MSC transplantation has recently emerged as a potential replacement for autologous transplantation. and ldquo;Off the shelf and rdquo; MSC products, or so-called and ldquo;stem cell drugs and rdquo;, have rapidly developed; these products have already been approved in various countries, including Canada, Korea and Japan. This study aims to evaluate a new stem cell product or and ldquo;drug and rdquo;, termed ModulatistTM, derived from umbilical cord mesenchymal stem cells (UCMSCs, which have strong immunomodulatory properties, compared to bone marrow-derived MSCs (BMMSCs or adipose tissue-derived stem cells (ADSCs. Methods: ModulatistTM was produced from MSCs derived from whole umbilical cord (UC tissue (which includes Wharton's jelly and UC, according to GMP compliant procedures. Bone marrow- and adipose tissue-derived MSCs were isolated and proliferated in standard conditions, according to GMP compliant procedures. Immunomodulation mediated by MSCs was assessed by allogenic T cell suppression and cytokine release; role of prostaglandin E2 in the immunomodulation was also evaluated. Results: The results showed that ModulatistTM exhibited stronger immunomodulation than BMMSC and ADSC in vitro. ModulatistTM strongly suppressed allogeneic T cells proliferation and decreased cytokine production, compared to BMMSCs and ADSCs. Conclusion: ModulatistTM is a strong immunomodulator and promising MSC product. It may be useful to modulate or treat autoimmune diseases. [Biomed Res Ther 2016; 3(6.000: 687-696

  17. The Role of Wharton’s Jelly Mesenchymal Stem Cells in Skin Reconstruction

    OpenAIRE

    Rostamzadeh; Anjomshoa; Kurd; Chai; Jahangiri; Nilforoushzadeh; Zare

    2015-01-01

    Context Stem cell therapy, especially in the segment of mesenchymal stem cells (MSCs), is one of the most promising areas of regenerative medicine. Evidence Acquisition According to research conducted by various researchers, Wharton’s Jelly mesenchymal stem cells (WJMSCs) have several advantages compared to others sources, in regenerative medicine: WJMSCs are more primary cells; WJMSCs can be easily isolated and without invasive p...

  18. Umbilical cord mesenchymal stem cell transplantation ameliorates burn-induced acute kidney injury in rats.

    Science.gov (United States)

    Lu, Gang; Huang, Sha; Chen, Yongbin; Ma, Kui

    2013-09-01

    Excessive systemic inflammation following burns could lead to acute kidney injury (AKI). Mesenchymal stromal cells (MSCs) suppress immune cell responses and have beneficial effects in various inflammatory-related immune disorders. However, autologous MSCs are not vital enough for the treatment because of the severely burned patients' deleterious condition. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) could be a suitable substitute cell candidate but no data are available on the therapeutic effectiveness of UC-MSCs transplantation for burn injury and its consequences. In this study, UC-MSCs or ulinastatin was administered intravenously in the rats with burn trauma, and the therapeutic effects of UC-MSCs on the survival of severe burn-induced AKI rats and functional protection of kidney were analyzed. Results showed that UC-MSCs promoted the survival and prevented commitment to apoptosis of resident kidney cells and reduced organ microscopic damage in kidneys after thermal trauma. Thus, our study demonstrates that intravenously delivered UC-MSCs protected the host from death caused by kidney injury subsequent to severe burn, identifying UC-MSCs transplantation may be an attractive candidate for cell-based treatments for burns and induced organ damage. PMID:24043673

  19. Autologous peripheral hematopoietic stem-cell transplantation in a patient with refractory pemphigus

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The aim of this study is to explore the effectiveness of autologous peripheral hematopoietic stem-cell transplantation in the treatment of refractory pemphigus.A 35-year-old male patient presented with a 4-year history of recurrent bullae on his trunk and extremities.The diagnosis of pemphigus was made on the basis of the clinical,histologic and immunofluorescence findings.The patient had shown resistance to conventional therapy with glucocorticoid and immunosuppressive agents.Two months before admission,he complained of hip joint pain.X-ray and CT scan revealed aseptic necrosis of the femoral head.Stem-cell mobilization was achieved by treatment with cyclophosphamide,granulocyte colony-stimulating factor (G-CSF)and rituximab.Peripheral blood stem cells were collected via leukapheresis and cryopreserved for later use.Immunoablation was accomplished by using cyclophosphamide(200 mg/kg;divided into 50 mg/kg on days-5,-4,-3,and-2),antithymocyte globulin(ATG;10 mg/kg;divided into 2.5 mg/kg on days-6,-5,-4,and-3),and rituximab (1200 mg/d;divided into 600 mg/d on days 0 and 7).Autologous peripheral hematopoietic stem cell transplantation was followed by reconstitution of the immune system which was monitored by flow cytometry.The glucocorticoid was withdrawn immediately after transplantation.The pemphigus titer turned negative 6 weeks after transplantation and remained negative.The patient was in complete drug-free remission with no evidence of residual clinical or serological activity of pemphigus during 1 year of followup.The patient's response suggests that autologous peripheral hematopoietic stem cell transplantation may be a potential "cure" for refractory pemphigus.However,further studies are needed to evaluate the risk-benefit ratio of this approach in patients with pemphigus showing resistance to conventional therapy.

  20. Mesenchymal stem cells as vectors for lung cancer therapy

    OpenAIRE

    Kolluri, K. K.; Laurent, G. J.; Janes, S.M.

    2013-01-01

    Despite recent advances in treatment, lung cancer accounts for one third of all cancer-related deaths, underlining the need of development of new therapies. Mesenchymal stem cells (MSCs) possess the ability to specifically home into tumours and their metastases. This property of MSCs could be exploited for the delivery of various anti-tumour agents directly into tumours. However, MSCs are not simple delivery vehicles but cells with active physiological process. This review outlines various ag...

  1. Human bone marrow-derived mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Lopez M

    2007-01-01

    Full Text Available Mesenchymal stem cells (MSCs have elicited a great clinical interest, particularly in the areas of regenerative medicine and induction of tolerance in allogeneic transplantation. Previous reports demonstrated the feasibility of transplanting MSCs, which generates new prospects in cellular therapy. Recently, injection of MSCs induced remission of steroid-resistant acute graft-versus-host disease (GVHD. This review summarizes the knowledge and possible future clinical uses of MSCs.

  2. Induction of mesenchymal stem cell chondrogenesis by polyacrylate substrates

    OpenAIRE

    Glennon-Alty, Laurence; Williams, Rachel; Dixon, Simon; Murray, Patricia

    2013-01-01

    Mesenchymal stem cells (MSCs) can generate chondrocytes in vitro, but typically need to be cultured as aggregates in the presence of transforming growth factor beta (TGF-β), which makes scale-up difficult. Here we investigated if polyacrylate substrates modelled on the functional group composition and distribution of the Arg-Gly-Asp (RGD) integrin-binding site could induce MSCs to undergo chondrogenesis in the absence of exogenous TGF-β. Within a few days of culture on the biomimetic polyacry...

  3. Recruitment of Mesenchymal Stem Cells Into Prostate Tumors Promotes Metastasis

    OpenAIRE

    Jung, Younghun; Kim, Jin Koo; SHIOZAWA, YUSUKE; Wang, Jingcheng; Mishra, Anjali; Joseph, Jeena; Berry, Janice E.; McGee, Samantha; Lee, Eunsohl; Sun, Hongli; Wang, Jianhua; Jin, Taocong; Zhang, Honglai; Dai, Jinlu; Paul H Krebsbach

    2013-01-01

    Tumors recruit mesenchymal stem cells (MSCs) to facilitate healing, which induces their conversion into cancer-associated fibroblasts that facilitate metastasis. However, this process is poorly understood on the molecular level. Here we show that the CXCR6 ligand CXCL16 facilitates MSC or Very Small Embryonic-Like (VSEL) cells recruitment into prostate tumors. CXCR6 signaling stimulates the conversion of MSCs into cancer-associated fibroblasts, which secrete stromal-derived factor-1, also kno...

  4. Mesenchymal stem cell-derived exosomes facilitate nasopharyngeal carcinoma progression

    OpenAIRE

    Shi, Si; Zhang, Qicheng; Xia, Yunfei; You, Bo; Shan, Ying; Bao, Lili; Li, Li; You, Yiwen; Gu, Zhifeng

    2016-01-01

    Mesenchymal stem cells (MSCs), which are capable of differentiating into multiple cell types, are reported to exert multiple effects on tumor development. However, the relationship between MSCs and nasopharyngeal carcinoma (NPC) cells remains unclear. Exosomes are small membrane vesicles that can be released by several cell types, including MSCs. Exosomes, which can carry membrane and cytoplasmic constituents, have been described as participants in a novel mechanism of cell-to-cell communicat...

  5. Symptomatic knee osteoarthritis treatment using autologous adipose derived stem cells and platelet-rich plasma: a clinical study

    Directory of Open Access Journals (Sweden)

    Phuc Van Pham

    2014-01-01

    Full Text Available Osteoarthritis is one of the most common diseases, and it affects 12% of the population around the world. Although the disease is chronic, it significantly reduces the patient's quality of life. At present, stem cell therapy is considered to be an efficient approach for treating this condition. Mesenchymal stem cells (MSCs show the most potential for stem cell therapy of osteoarthritis. In fact, MSCs can differentiate into certain mesodermal tissues such as cartilage and bone. Therefore, in the present study, we applied adipose tissue-derived MSCs to osteoarthritis treatment. This study aimed to evaluate the clinical efficiency of autologous adipose tissue-derived MSC transplantation in patients with confirmed osteoarthritis at grade II and III. Adipose tissue was isolated from the belly, and used for extraction of the stromal vascular fraction (SVF. The SVF was mixed with activated platelet- rich plasma before injection. The clinical efficiencies were evaluated by the pain score (VAS, Lysholm score, and MRI findings. We performed the procedure in 21 cases from 2012 to 2013. All 21 patients showed improved joint function after 8.5 months. The pain score decreased from 7.6+/-0.5 before injection to 3.5+/-0.7 at 3 months and 1.5+/-0.5 at 6 months after injection. The Lysholm score increased from 61+/-11 before injection to 82+/-8.1 after injection. Significant improvements were noted in MRI findings, with increased thickness of the cartilage layer. Moreover, there were no side-effects or complications related to microorganism infection, graft rejection, or tumorigenesis. These results provide a new opportunity for osteoarthritis treatment. Level of evidence: IV. [Biomed Res Ther 2014; 1(1.000: 02-08

  6. Mesenchymal stem cells in diabetes treatment: progress and perspectives

    Directory of Open Access Journals (Sweden)

    Yu CHENG

    2016-08-01

    Full Text Available Diabetes is a chronic metabolic disorder caused by relative or absolute insulin deficient or reduced sensitivity of target cells to insulin. Mesenchymal stem cells (MSCs are adult stem cells with multiple differentiation potential, self-renewable and immunoregulatory properties. Accumulating evidences from clinic or animal experiments recent years showed that MSCs infusion could ameliorate hyperglycemia in diabetes. The research progress of MSCs in diabetes treatment is summarized and a corresponding perspective is herewith proposed in present paper. DOI: 10.11855/j.issn.0577-7402.2016.07.16

  7. Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury

    OpenAIRE

    Anbari, Fatemeh; Khalili, Mohammad Ali; Bahrami, Ahmad Reza; Khoradmehr, Arezoo; Sadeghian, Fatemeh; Fesahat, Farzaneh; Nabi, Ali

    2014-01-01

    To investigate the supplement of lost nerve cells in rats with traumatic brain injury by intravenous administration of allogenic bone marrow mesenchymal stem cells, this study established a Wistar rat model of traumatic brain injury by weight drop impact acceleration method and administered 3 × 106 rat bone marrow mesenchymal stem cells via the lateral tail vein. At 14 days after cell transplantation, bone marrow mesenchymal stem cells differentiated into neurons and astrocytes in injured rat...

  8. Chitosan-collagen porous scaffold and bone marrow mesenchymal stem cell transplantation for ischemic stroke

    OpenAIRE

    Feng Yan; Wei Yue; Yue-lin Zhang; Guo-chao Mao; Ke Gao; Zhen-xing Zuo; Ya-jing Zhang; Hui Lu

    2015-01-01

    In this study, we successfully constructed a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffold in vitro, transplanted either the composite or bone marrow mesenchymal stem cells alone into the ischemic area in animal models, and compared their effects. At 14 days after co-transplantation of bone marrow mesenchymal stem cells and the hitosan-collagen scaffold, neurological function recovered noticeably. Vascular endothelial growth factor expression and nestin-labe...

  9. Myeloablative Chemotherapy with Autologous Stem Cell Transplant for Desmoplastic Small Round Cell Tumor

    Directory of Open Access Journals (Sweden)

    Christopher J. Forlenza

    2015-01-01

    Full Text Available Desmoplastic small round cell tumor (DSRCT, a rare, aggressive neoplasm, has a poor prognosis. In this prospective study, we evaluated the role of myeloablative chemotherapy, followed by autologous stem cell transplant in improving survival in DSRCT. After high-dose induction chemotherapy and surgery, 19 patients with chemoresponsive DSRCT underwent autologous stem cell transplant. Myeloablative chemotherapy consisted of carboplatin (400–700 mg/m2/day for 3 days + thiotepa (300 mg/m2/day for 3 days ± topotecan (2 mg/m2/day for 5 days. All patients were engrafted and there was no treatment-related mortality. Seventeen patients received radiotherapy to sites of prior or residual disease at a median of 12 weeks after transplant. Five-year event-free and overall survival were 11 ± 7% and 16 ± 8%, respectively. Two patients survive disease-free 16 and 19 years after transplant (both in complete remission before transplant. 14 patients had progression and died of disease at a median of 18 months following autologous transplant. These data do not justify the use of myeloablative chemotherapy with carboplatin plus thiotepa in patients with DSRCT. Alternative therapies should be considered for this aggressive neoplasm.

  10. Defining Molecular Phenotypes of Mesenchymal and hematopoietic Stem Cells derived from Peripheral blood of Acute Lymphocytic Leukemia patients for regenerative stem cell therapy

    Science.gov (United States)

    Potdar, PD; Subedi, RP

    2011-01-01

    Acute Lymphocytic Leukemia (ALL) is a clonal myeloid disorder affecting all age groups, characterized by accumulation of immature blast cells in bone marrow and in peripheral blood. Autologous Bone Marrow Transplantation is a present treatment for cure of ALL patients, which is very expensive, invasive process and may have possibility of transplantation of malignant stem cells to patients. In the present study, we hypothesized to isolate large number of normal Mesenchymal & Hematopoietic stem cells from peripheral blood of ALL patients, which will be further characterized for their normal phenotypes by using specific molecular stem cell markers. This is the first study, which defines the existing phenotypes of isolated MSCs and HSCs from peripheral blood of ALL patients. We have established three cell lines in which two were Mesenchymal stem cells designated as MSCALL and MSCnsALL and one was suspension cell line designated as HSCALL. The HSCALL cell line was developed from the lymphocyte like cells secreted by MSCALL cells. Our study also showed that MSCALL from peripheral blood of ALL patient secreted hematopoietic stem cells in vitro culture. We have characterized all three-cell lines by 14 specific stem cell molecular markers. It was found that both MSC cell lines expressed CD105, CD13, and CD73 with mixed expression of CD34 and CD45 at early passage whereas, HSCALL cell line expressed prominent feature of hematopoietic stem cells such as CD34 and CD45 with mild expression of CD105 and CD13. All three-cell lines expressed LIF, OCT4, NANOG, SOX2, IL6, and DAPK. These cells mildly expressed COX2 and did not express BCR-ABL. Overall it was shown that isolated MSCs and HSCs can be use as a model system to study the mechanism of leukemia at stem cell level and their use in stem cell regeneration therapy for Acute Lymphocytic Leukemia. PMID:24693170

  11. Defining Molecular Phenotypes of Mesenchymal and hematopoietic Stem Cells derived from Peripheral blood of Acute Lymphocytic Leukemia patients for regenerative stem cell therapy

    Directory of Open Access Journals (Sweden)

    Pravin D. Potdar

    2011-01-01

    Full Text Available Acute Lymphocytic Leukemia (ALL is a clonal myeloid disorder affecting all age groups, characterized by accumulation of immature blast cells in bone marrow and in peripheral blood. Autologous Bone Marrow Transplantation is a present treatment for cure of ALL patients, which is very expensive, invasive process and may have possibility of transplantation of malignant stem cells to patients. In the present study, we hypothesized to isolate large number of normal Mesenchymal & Hematopoietic stem cells from peripheral blood of ALL patients, which will be further characterized for their normal phenotypes by using specific molecular stem cell markers. This is the first study, which defines the existing phenotypes of isolated MSCs and HSCs from peripheral blood of ALL patients. We have established three cell lines in which two were Mesenchymal stem cells designated as MSCALL and MSCnsALL and one was suspension cell line designated as HSCALL. The HSCALL cell line was developed from the lymphocyte like cells secreted by MSCALL cells. Our study also showed that MSCALL from peripheral blood of ALL patient secreted hematopoietic stem cells in vitro culture. We have characterized all three-cell lines by 14 specific stem cell molecular markers. It was found that both MSC cell lines expressed CD105, CD13, and CD73 with mixed expression of CD34 and CD45 at early passage whereas, HSCALL cell line expressed prominent feature of hematopoietic stem cells such as CD34 and CD45 with mild expression of CD105 and CD13. All three-cell lines expressed LIF, OCT4, NANOG, SOX2, IL6, and DAPK. These cells mildly expressed COX2 and did not express BCR-ABL. Overall it was shown that isolated MSCs and HSCs can be use as a model system to study the mechanism of leukemia at stem cell level and their use in stem cell regeneration therapy for Acute Lymphocytic Leukemia.

  12. Mesenchymal markers on human adipose stem/progenitor cells

    Science.gov (United States)

    Zimmerlin, Ludovic; Donnenberg, Vera S.; Rubin, J. Peter; Donnenberg, Albert D.

    2014-01-01

    The stromal-vascular fraction (SVF) of adipose tissue is a rich source of multipotent stem cells. We and others have described 3 major populations of stem/progenitor cells in this fraction, all closely associated with small blood vessels: endothelial progenitor cells (EPC, CD45−/CD31+/CD34+), pericytes (CD45−/CD31−/CD146+) and supra-adventitial adipose stromal cells (SA-ASC, CD45−/CD31−/CD146−/CD34+). EPC are luminal, pericytes are adventitial and SA-ASC surround the vessel like a sheath. The multipotency of the pericytes and SA-ASC compartments is strikingly similar to that of CD45−/CD34−/CD73+/CD105+/CD90+ bone marrow-derived mesenchymal stem cells (BM-MSC). Here we determine the extent to which this mesenchymal expression pattern is expressed on the 3 adipose stem/progenitor populations. Eight independent adipose tissue samples were analyzed in a single tube (CD105-FITC/CD73-PE/CD146-PETXR/CD14-PECY5/CD33-PECY5/CD235A-PECY5/CD31-PECY7/CD90-APC/CD34-A700/CD45-APCCY7/DAPI). Adipose EPC were highly proliferative with 14.3±2.8% (mean ± SEM) having >2N DNA. About half (53.1±7.6%) coexpressed CD73 and CD105, and 71.9±7.4% expressed CD90. Pericytes were less proliferative (8.2±3.4% >2N DNA) with a smaller proportion (29.6±6.9% CD73+/CD105+, 60.5±10.2% CD90+) expressing mesenchymal associated markers. However, the CD34+ subset of CD146+ pericytes, were both highly proliferative (15.1±3.6% with >2N DNA) and of uniform mesenchymal phenotype (93.3±3.7% CD73+/CD105+, 97.8±0.7% CD90+), suggesting transit amplifying progenitor cells. SA-ASC were the least proliferative (3.7 ± 0.8%>2N DNA) but were also highly mesenchymal in phenotype (94.4±3.2% CD73+/CD105+, 95.5±1.2% CD90+). These data imply a progenitor/progeny relationship between pericytes and SA-ASC, the most mesenchymal of SVF cells. Despite phenotypic and functional similarities to BM-MSC, SA-ASC are distinguished by CD34 expression. PMID:23184564

  13. Bone marrow mesenchymal stem cell transplantation combined with core decompression and bone grafting in the repair of osteonecrosis of femoral head

    Institute of Scientific and Technical Information of China (English)

    Zhang Yang; Wang Nan; Yang Li-feng; Ma Ji; Li Zhi

    2015-01-01

    BACKGROUND: Core decompression alone for osteonecrosis of femoral head easily causes fovea of femoral head and colapse of inner microstructure. Therefore, autologous bone is needed for filing and supporting. Moreover, bone marrow stem cel transplantation can decrease the incidence of femoral head colapse. OBJECTIVE:To discuss the clinical effects of core decompression and bone grafting combined with autotransplantation of bone marrow mesenchymal stem cels for osteonecrosis of femoral head. METHODS: A total of 33 patients were treated by core decompression and bone grafting combined with autotransplantation of bone marrow mesenchymal stem cels in the Fourth Department of Bone Surgery, Central Hospital Affiliated to Shenyang Medical Colege in China from December 2012 to May 2013. RESULTS AND CONCLUSION:After the treatment by core decompression and bone grafting combined with autotransplantation of bone marrow mesenchymal stem cels, Harris hip function score increased and pain disappeared in patients with osteonecrosis of femoral head. They could do various labors. Radiographs or CT examination displayed normal femoral head in 30 hips, accounting for 79%. Pain significantly reduced. Normal or slight limp walking was found in 15 hips, accounting for 40%. There were 35 hips in patients, whose walking distance was extended, accounting for 92%. 24 hips dysfunction was improved markedly, accounting for 63%. Al results suggested that core decompression and bone grafting combined with autotransplantation of bone marrow mesenchymal stem cels improved the local blood supply of femoral head, and played a positive role in promoting the necrotic bone absorption and bone repairing.

  14. Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies

    Science.gov (United States)

    Li, Guihong; Yu, Fengbo; Lei, Ting; Gao, Haijun; Li, Peiwen; Sun, Yuxue; Huang, Haiyan; Mu, Qingchun

    2016-01-01

    Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research.

  15. Our Experience with Autologous Bone Marrow Stem Cell Application in Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Mukund K

    2009-01-01

    Full Text Available Background - Use of autologous bone marrow stem cell is a newly evolving treatment modality for end stage cardiac failure as reported in the literature. We report our experience with two patients with dilated cardiomyopathy who underwent this treatment after failure of maximal conventional therapy. Methods - A 29 year old Male patient with history of orthopnea and PND, with a diagnosis of dilated cardiomyopathy and echocardiographic evidence of severe LV dysfunction was referred for further treatment. His echo on admission showed EF of 17% and no other abnormal findings except elevated bilirubin levels. He was in NYHA functional class IV. He received intracoronary injection of autologous bone marrow stem cells in January 2009. 254X106 cells were injected with a CD34+ of 0.20%. His clinical condition stabilized and he was discharged home. He received a second injection of 22X106 in vitro expanded stem cells with a CD34+ of 0.72% in Aug 2009. He is now in NYHA class II-III with EF 24%. A 31year old Male patient with history of increasing shortness of breath, severe over the past 3-4 days was admitted for evaluation and treatment. His echo on admission showed EF of 20% and was in NYHA functional class IV. Coronary angiogram was normal and he was stabilized on maximal anti failure measures. He received intracoronary autologous bone marrow stem cell injection of 56X106 with a CD34+ of 0.53% in August 2009. His clinical condition stabilized over the next 10 days and he was discharged home. Conclusions - In our experience of two cases of dilated cardiomyopathy, safety of intracoronary injection of autologous bone marrow stem cells both isolated and in vitro expanded has been proven in both the cases with efficacy proven in one of the cases. Long term follow-up of these two cases and inclusion of more number of similar cases where all available conventional therapies have not resulted in significant improvement for such studies are planned.

  16. Mesenchymal Stem Cells and Induced Pluripotent Stem Cells as Therapies for Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Juan Xiao

    2015-04-01

    Full Text Available Multiple sclerosis (MS is a chronic, autoimmune, inflammatory demyelinating disorder of the central nervous system that leads to permanent neurological deficits. Current MS treatment regimens are insufficient to treat the irreversible neurological disabilities. Tremendous progress in the experimental and clinical applications of cell-based therapies has recognized stem cells as potential candidates for regenerative therapy for many neurodegenerative disorders including MS. Mesenchymal stem cells (MSC and induced pluripotent stem cell (iPSCs derived precursor cells can modulate the autoimmune response in the central nervous system (CNS and promote endogenous remyelination and repair process in animal models. This review highlights studies involving the immunomodulatory and regenerative effects of mesenchymal stem cells and iPSCs derived cells in animal models, and their translation into immunomodulatory and neuroregenerative treatment strategies for MS.

  17. Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: a case series

    Directory of Open Access Journals (Sweden)

    Pak Jaewoo

    2011-07-01

    Full Text Available Abstract Introduction This is a series of clinical case reports demonstrating that a combination of percutaneously injected autologous adipose-tissue-derived stem cells, hyaluronic acid, platelet rich plasma and calcium chloride may be able to regenerate bones in human osteonecrosis, and with addition of a very low dose of dexamethasone, cartilage in human knee osteoarthritis. Case reports Stem cells were obtained from adipose tissue of abdominal origin by digesting lipoaspirate tissue with collagenase. These stem cells, along with hyaluronic acid, platelet rich plasma and calcium chloride, were injected into the right hip of a 29-year-old Korean woman and a 47-year-old Korean man. They both had a history of right hip osteonecrosis of the femoral head. For cartilage regeneration, a 70-year-old Korean woman and a 79-year-old Korean woman, both with a long history of knee pain due to osteoarthritis, were injected with stem cells along with hyaluronic acid, platelet rich plasma, calcium chloride and a nanogram dose of dexamethasone. Pre-treatment and post-treatment MRI scans, physical therapy, and pain score data were then analyzed. Conclusions The MRI data for all the patients in this series showed significant positive changes. Probable bone formation was clear in the patients with osteonecrosis, and cartilage regeneration in the patients with osteoarthritis. Along with MRI evidence, the measured physical therapy outcomes, subjective pain, and functional status all improved. Autologous mesenchymal stem cell injection, in conjunction with hyaluronic acid, platelet rich plasma and calcium chloride, is a promising minimally invasive therapy for osteonecrosis of femoral head and, with low-dose dexamethasone, for osteoarthritis of human knees.

  18. The Impact of Epigenetics on Mesenchymal Stem Cell Biology.

    Science.gov (United States)

    Ozkul, Yusuf; Galderisi, Umberto

    2016-11-01

    Changes in epigenetic marks are known to be important regulatory factors in stem cell fate determination and differentiation. In the past years, the investigation of the epigenetic regulation of stem cell biology has largely focused on embryonic stem cells (ESCs). Contrarily, less is known about the epigenetic control of gene expression during differentiation of adult stem cells (AdSCs). Among AdSCs, mesenchymal stem cells (MSCs) are the most investigated stem cell population because of their enormous potential for therapeutic applications in regenerative medicine and tissue engineering. In this review, we analyze the main studies addressing the epigenetic changes in MSC landscape during in vitro cultivation and replicative senescence, as well as follow osteocyte, chondrocyte, and adipocyte differentiation. In these studies, histone acetylation, DNA methylation, and miRNA expression are among the most investigated phenomena. We describe also epigenetic changes that are associated with in vitro MSC trans-differentiation. Although at the at initial stage, the epigenetics of MSCs promise to have profound implications for stem cell basic and applied research. J. Cell. Physiol. 231: 2393-2401, 2016. © 2016 Wiley Periodicals, Inc. PMID:26960183

  19. Transdifferentiation of Human Hair Follicle Mesenchymal Stem Cells into Red Blood Cells by OCT4

    Directory of Open Access Journals (Sweden)

    Zhijing Liu

    2015-01-01

    Full Text Available Shortage of red blood cells (RBCs, erythrocytes can have potentially life-threatening consequences for rare or unusual blood type patients with massive blood loss resulting from various conditions. Erythrocytes have been derived from human pluripotent stem cells (PSCs, but the risk of potential tumorigenicity cannot be ignored, and a majority of these cells produced from PSCs express embryonic ε- and fetal γ-globins with little or no adult β-globin and remain nucleated. Here we report a method to generate erythrocytes from human hair follicle mesenchymal stem cells (hHFMSCs by enforcing OCT4 gene expression and cytokine stimulation. Cells generated from hHFMSCs expressed mainly the adult β-globin chain with minimum level of the fetal γ-globin chain. Furthermore, these cells also underwent multiple maturation events and formed enucleated erythrocytes with a biconcave disc shape. Gene expression analyses showed that OCT4 regulated the expression of genes associated with both pluripotency and erythroid development during hHFMSC transdifferentiation toward erythroid cells. These findings show that mature erythrocytes can be generated from adult somatic cells, which may serve as an alternative source of RBCs for potential autologous transfusion.

  20. Autologous bone marrow stem cell intralesional transplantation repairing bisphosphonate related osteonecrosis of the jaw

    Directory of Open Access Journals (Sweden)

    Cella Luigi

    2011-08-01

    Full Text Available Abstract Purpose Bisphosphonate - related osteonecrosis of the JAW (BRONJ is a well known side effect of bisphosphonate therapies in oncologic and non oncologic patients. Since to date no definitive consensus has been reached on the treatment of BRONJ, novel strategies for the prevention, risk reduction and treatment need to be developed. We report a 75 year old woman with stage 3 BRONJ secondary to alendronate and pamidronate treatment of osteoporosis. The patient was unresponsive to recommended treatment of the disease, and her BRONJ was worsening. Since bone marrow stem cells are know as being multipotent and exhibit the potential for differentiation into different cells/tissue lineages, including cartilage, bone and other tissue, we performed autologous bone marrow stem cell transplantation into the BRONJ lesion of the patient. Methods Under local anesthesia a volume of 75 ml of bone marrow were harvested from the posterior superior iliac crest by aspiration into heparinized siringes. The cell suspension was concentrated, using Ficoll - Hypaque® centrifugation procedures, in a final volume of 6 ml. Before the injection of stem cells into the osteonecrosis, the patient underwent surgical toilet, local anesthesia was done and spongostan was applied as a carrier of stem cells suspension in the bone cavity, then 4 ml of stem cells suspension and 1 ml of patient's activated platelet-rich plasma were injected in the lesion of BRONJ. Results A week later the residual spongostan was removed and two weeks later resolution of symptoms was obtained. Then the lesion improved with progressive superficialization of the mucosal layer and CT scan, performed 15 months later, shows improvement also of bone via concentric ossification: so complete healing of BRONJ (stage 0 was obtained in our patient, and 30 months later the patient is well and without signs of BRONJ. Conclusion To our knowledge this is the first case of BRONJ successfully treated with

  1. ¬Mesenchymal Stem Cell Fate: Applying Biomaterials for Control of Stem Cell Behaviour

    OpenAIRE

    Hilary Jane Anderson; Matthew John Dalby; Jugal eSahoo; Rein eUljin

    2016-01-01

    Mesenchymal Stem Cell Fate: Applying Biomaterials for Control of Stem Cell BehaviourHilary J Anderson1, Jugal Kishore Sahoo2, Rein V Ulijn2,3, Matthew J Dalby1*1 Centre for Cell Engineering, University of Glasgow, Glasgow, UK.2 Technology and Innovation centre, Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow, UK. 3 Advanced Science Research Centre (ASRC) and Hunter College, City University of New York, NY 10031, NY, USA. Correspondence:*Hilary Andersonh.anderson...

  2. Pretreatment of Cardiac Stem Cells With Exosomes Derived From Mesenchymal Stem Cells Enhances Myocardial Repair

    OpenAIRE

    Zhang, Zhiwei; Yang, Junjie; Yan, Weiya; Li, Yangxin; Shen, Zhenya; Asahara, Takayuki

    2016-01-01

    Background Exosomes derived from mesenchymal stem cells (MSCs) were proved to boost cell proliferation and angiogenic potency. We explored whether cardiac stem cells (CSCs) preconditioned with MSC exosomes could survive and function better in a myocardial infarction model. Methods and Results DiI‐labeled exosomes were internalized with CSCs. They stimulated proliferation, migration, and angiotube formation of CSCs in a dose‐dependent manner. In a rat myocardial infarction model, MSC exosome–p...

  3. Mesenchymal stem cell subpopulations: phenotype, property and therapeutic potential.

    Science.gov (United States)

    Mo, Miaohua; Wang, Shan; Zhou, Ying; Li, Hong; Wu, Yaojiong

    2016-09-01

    Mesenchymal stem cells (MSC) are capable of differentiating into cells of multiple cell lineages and have potent paracrine effects. Due to their easy preparation and low immunogenicity, MSC have emerged as an extremely promising therapeutic agent in regenerative medicine for diverse diseases. However, MSC are heterogeneous with respect to phenotype and function in current isolation and cultivation regimes, which often lead to incomparable experimental results. In addition, there may be specific stem cell subpopulations with definite differentiation capacity toward certain lineages in addition to stem cells with multi-differentiation potential. Recent studies have identified several subsets of MSC which exhibit distinct features and biological activities, and enhanced therapeutic potentials for certain diseases. In this review, we give an overview of these subsets for their phenotypic, biological and functional properties. PMID:27141940

  4. Mesenchymal Stem Cells: Application for Immunomodulation and Tissue Repair

    DEFF Research Database (Denmark)

    Horwood, Nicole J.; Dazzi, Francesco; Zaher, Walid; Kassem, Moustapha

    Mesenchymal stem cells (MSC) are stem cell populations present among the bone marrow stroma and a number of other tissues that are capable of multi-lineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. MSC provide supportive stroma for growth and...... differentiation of hematopoietic stem cells (HSC) and hematopoiesis. These cells have been described as important immunoregulators due to their ability to suppress T cells proliferation. MSC can also directly contribute to tissue repair by migrating to sites of injury and providing a source of cells for...... differentiation and/or providing bystander support for resident stromal cells. This chapter discusses the cellular and molecular properties of MSC, the mechanisms by which they can modulate immune responses and the clinical applications of MSC in disorders such as graft-versus-host disease and aplastic anaemia...

  5. Mesenchymal stem cells: biological characteristics and potential clinical applications

    DEFF Research Database (Denmark)

    Kassem, Moustapha

    2004-01-01

    Mesenchymal stem cells (MSC) are clonogenic, non-hematpoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages, for example, osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages, for example, neuronal...... among the first stem cell types to be introduced in the clinic. Several studies have demonstrated the possible use of MSC in systemic transplantation for systemic diseases, local implantation for local tissue defects, as a vehicle for genes in gene therapy protocols or to generate transplantable tissues......-like cells. Several methods are currently available for isolation of the MSC based on their physical and physico-chemical characteristics, for example, adherence to plastics or other extracellular matrix components. Because of the ease of their isolation and their extensive differentiation potential, MSC are...

  6. The beneficial effects of intracoronary autologous bone marrow stem cell transfer as an adjunct to percutaneous coronary intervention in patients with acute myocardial infarction.

    Science.gov (United States)

    Wang, Xiang; Xi, Wei-Chun; Wang, Fang

    2014-11-01

    The efficacy of post-percutaneous coronary intervention (PCI) intracoronary injection with bone marrow mesenchymal stem cells (BMSCs) in patients with acute myocardial infarction (AMI) remains controversial. Here, 58 patients with AMI undergoing PCI were randomly divided into two groups: BMSC and control groups. Autologous BSMCs were then generated in vitro from the BMSC patients. After transplantation, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimensions (LVDd), and infarct size (IS) were evaluated in both groups. LVEF, LVDd, and IS improved after BMSC transplantation but the changes were not significantly different from those in the controls. The number of adverse events and rehospitalization rates after 1 month were significantly higher in the control group than in the BMSC group. BMSC transplantation thus benefits patients by decreasing the number of adverse events and reducing the rehospitalization rate in the early stages following PCI. PMID:24975729

  7. The role of mesenchymal stem cells and serotonin in the development of experimental pancreatitis.

    Science.gov (United States)

    Lazebnic, L B; Lychkova, A E; Knyazev, O V

    2013-08-01

    Pancreatitis was modeled before and after preliminary transplantation of stem cells and serotonin. It was demonstrated that transplantation of mesenchymal stem cells and activation of serotoninergic system prevent the development of pancreatitis. PMID:24143388

  8. File list: Oth.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 TFs and others Cardiovascular Umbi.../assembled/Oth.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  9. File list: Pol.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 RNA polymerase Cardiovascular Umbi.../assembled/Pol.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  10. File list: His.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 Histone Cardiovascular Umbi.../hg19/assembled/His.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  11. File list: NoD.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 No description Cardiovascular Umbi.../assembled/NoD.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  12. File list: Unc.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 Unclassified Cardiovascular Umbi...ssembled/Unc.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  13. File list: NoD.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 No description Cardiovascular Umbi.../assembled/NoD.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  14. File list: Pol.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 RNA polymerase Cardiovascular Umbi.../assembled/Pol.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  15. File list: Unc.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 Unclassified Cardiovascular Umbi...ssembled/Unc.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  16. File list: NoD.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 No description Cardiovascular Umbi.../assembled/NoD.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  17. File list: Pol.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 RNA polymerase Cardiovascular Umbi.../assembled/Pol.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  18. File list: Oth.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 TFs and others Cardiovascular Umbi.../assembled/Oth.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  19. File list: His.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 Histone Cardiovascular Umbi.../hg19/assembled/His.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  20. File list: His.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 Histone Cardiovascular Umbi.../hg19/assembled/His.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  1. File list: Oth.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 TFs and others Cardiovascular Umbi.../assembled/Oth.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  2. File list: Unc.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 Unclassified Cardiovascular Umbi...ssembled/Unc.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  3. File list: Unc.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 Unclassified Cardiovascular Umbi...ssembled/Unc.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  4. File list: Pol.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 RNA polymerase Cardiovascular Umbi.../assembled/Pol.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  5. File list: NoD.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 No description Cardiovascular Umbi.../assembled/NoD.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  6. File list: Oth.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 TFs and others Cardiovascular Umbi.../assembled/Oth.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  7. Recruitment of Mesenchymal Stem Cells Into Prostate Tumors Promotes Metastasis

    Science.gov (United States)

    Jung, Younghun; Kim, Jin Koo; Shiozawa, Yusuke; Wang, Jingcheng; Mishra, Anjali; Joseph, Jeena; Berry, Janice E.; McGee, Samantha; Lee, Eunsohl; Sun, Hongli; Wang, Jianhua; Jin, Taocong; Zhang, Honglai; Dai, Jinlu; Krebsbach, Paul H.; Keller, Evan T.; Pienta, Kenneth J.; Taichman, Russell S.

    2013-01-01

    Tumors recruit mesenchymal stem cells (MSCs) to facilitate healing, which induces their conversion into cancer-associated fibroblasts that facilitate metastasis. However, this process is poorly understood on the molecular level. Here we show that the CXCR6 ligand CXCL16 facilitates MSC or Very Small Embryonic-Like (VSEL) cells recruitment into prostate tumors. CXCR6 signaling stimulates the conversion of MSCs into cancer-associated fibroblasts, which secrete stromal-derived factor-1, also known as CXCL12. CXCL12 expressed by cancer-associated fibroblasts then binds to CXCR4 on tumor cells and induces an epithelial to mesenchymal transition, which ultimately promotes metastasis to secondary tumor sites. Our results provide the molecular basis for MSC recruitment into tumors and how this process leads to tumor metastasis. PMID:23653207

  8. [Outcomes of using autologous peripheral-blood stem cells in patients with chronic lower arterial insufficiency].

    Science.gov (United States)

    Maksimov, A V; Kiiasov, A P; Plotnikov, M V; Maianskaia, S D; Shamsutdinova, I I; Gazizov, I M; Mavlikeev, M O

    2011-01-01

    Presented herein are the outcomes of using autologous peripheral blood stem cells (SCs) in patients with stage II В lower limb chronic obliterating diseases (according to A.V. Pokrovsky's classification). Autologous SCs had previously been stimulated by means of the recombinant granulocytic colony stimulating factor (G-CSF) for five days. On day six, we performed mobilization of the peripheral blood stem cells on the MSC+ unit by means of leukopheresis followed by intramuscular administration of half of the obtained dose into the affected extremity. The mean number of the transplanted mononuclears amounted to 6.73 ± 2.2 x 10(9) cells, with the number of CD34+ cells averaging 2.94 ± 2.312 x 10(7). Assessing the therapeutic outcomes at 3 and 6 months of follow-up showed a statistically significant increase in the ankle-brachial pressure index (ABPI) [being at baseline 0.59 ± 0.04, at 3 months - 0.66 ± 0.04 (P=0.001), and after 6 months - 0.73 ± .08 (P=0.035)], accompanied and followed by improved measures of the treadmill test, with the pain-free walking distance at baseline equalling 102.2 ± 11.55 m, after 3 months - 129 ± 11.13 m (P<0.001), and after 6 months - 140 ± 13.11 m=0.021 vs baseline). The findings of the immunohistochemical study confirmed the development of neoangiogenesis in the skeletal muscle and a 25 percent increase in the capillary-network density following administration of autologous stem cells into the muscle. The method of transplanting peripheral-blood autologous stem cells for treatment of patients presenting with distal forms of chronic obliterating insufficiency of the lower limbs proved safe and efficient. The findings obtained during this study made it possible to recommend extending the indications for its application at the expense of patients with critical ischaemia. PMID:21983456

  9. File list: NoD.Oth.10.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Oth.10.AllAg.Mesenchymal_stem_cells hg19 No description Others Mesenchymal stem...RX302073,ERX302070,ERX302072,ERX302074 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Oth.10.AllAg.Mesenchymal_stem_cells.bed ...

  10. File list: InP.Oth.05.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Oth.05.AllAg.Mesenchymal_stem_cells mm9 Input control Others Mesenchymal stem c...ells SRX318104,SRX318102,SRX228663,SRX228662,SRX228660,SRX228661 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Oth.05.AllAg.Mesenchymal_stem_cells.bed ...

  11. File list: NoD.Oth.20.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Oth.20.AllAg.Mesenchymal_stem_cells hg19 No description Others Mesenchymal stem...RX302072,ERX302066,ERX302075,ERX302074 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Oth.20.AllAg.Mesenchymal_stem_cells.bed ...

  12. File list: DNS.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 DNase-seq Cardiovascular Umbi...lical cord-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  13. File list: DNS.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 DNase-seq Cardiovascular Umbi...lical cord-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  14. File list: DNS.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 DNase-seq Cardiovascular Umbi...lical cord-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  15. Mesenchymal stem cell therapy for acute radiation syndrome.

    Science.gov (United States)

    Fukumoto, Risaku

    2016-01-01

    Acute radiation syndrome affects military personnel and civilians following the uncontrolled dispersal of radiation, such as that caused by detonation of nuclear devices and inappropriate medical treatments. Therefore, there is a growing need for medical interventions that facilitate the improved recovery of victims and patients. One promising approach may be cell therapy, which, when appropriately implemented, may facilitate recovery from whole body injuries. This editorial highlights the current knowledge regarding the use of mesenchymal stem cells for the treatment of acute radiation syndrome, the benefits and limitations of which are under investigation. Establishing successful therapies for acute radiation syndrome may require using such a therapeutic approach in addition to conventional approaches. PMID:27182446

  16. Human bone-marrow-derived mesenchymal stem cells

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Abdallah, Basem M

    2008-01-01

    Mesenchymal stem cells (MSC) are a group of cells present in bone-marrow stroma and the stroma of various organs with the capacity for mesoderm-like cell differentiation into, for example, osteoblasts, adipocytes, and chondrocytes. MSC are being introduced in the clinic for the treatment...... of a variety of clinical conditions. The aim of this review is to provide an update regarding the biology of MSC, their identification and culture, and mechanisms controlling their proliferation and differentiation. We also review the current status of their clinical use. Areas in which research is needed...

  17. Infusion of Autologous Retrodifferentiated Stem Cells into Patients with Beta-Thalassemia

    Directory of Open Access Journals (Sweden)

    Ilham Saleh Abuljadayel

    2006-01-01

    Full Text Available Beta-thalassemia is a genetic, red blood cell disorder affecting the beta-globin chain of the adult hemoglobin gene. This results in excess accumulation of unpaired alpha-chain gene products leading to reduced red blood cell life span and the development of severe anemia. Current treatment of this disease involves regular blood transfusion and adjunct chelation therapy to lower blood transfusion–induced iron overload. Fetal hemoglobin switching agents have been proposed to treat genetic blood disorders, such as sickle cell anemia and beta-thalassemia, in an effort to compensate for the dysfunctional form of the beta-globin chain in adult hemoglobin. The rationale behind this approach is to pair the excess normal alpha-globin chain with the alternative fetal gamma-chain to promote red blood cell survival and ameliorate the anemia. Reprogramming of differentiation in intact, mature, adult white blood cells in response to inclusion of monoclonal antibody CR3/43 has been described. This form of retrograde development has been termed “retrodifferentiation”, with the ability to re-express a variety of stem cell markers in a heterogeneous population of white blood cells. This form of reprogramming, or reontogeny, to a more pluripotent stem cell state ought to recapitulate early hematopoiesis and facilitate expression of a fetal and/or adult program of hemoglobin synthesis or regeneration on infusion and subsequent redifferentiation. Herein, the outcome of infusion of autologous retrodifferentiated stem cells (RSC into 21 patients with beta-thalassemia is described. Over 6 months, Infusion of 3-h autologous RSC subjected to hematopoietic-conducive conditions into patients with beta-thalassemia reduced mean blood transfusion requirement, increased mean fetal hemoglobin synthesis, and significantly lowered mean serum ferritin. This was always accompanied by an increase in mean corpuscular volume (MCV, mean corpuscular hemoglobin (MCH, and mean

  18. Chitosan-collagen porous scaffold and bone marrow mesenchymal stem cell transplantation for ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    Feng Yan; Wei Yue; Yue-lin Zhang; Guo-chao Mao; Ke Gao; Zhen-xing Zuo; Ya-jing Zhang; Hui Lu

    2015-01-01

    In this study, we successfully constructed a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffoldin vitro, transplanted either the composite or bone marrow mesenchymal stem cells alone into the ischemic area in animal models, and compared their effects. At 14 days after co-transplantation of bone marrow mesenchymal stem cells and the hi-tosan-collagen scaffold, neurological function recovered noticeably. Vascular endothelial growth factor expression and nestin-labeled neural precursor cells were detected in the ischemic area, surrounding tissue, hippocampal dentate gyrus and subventricular zone. Simultaneously, a high level of expression of glial ifbrillary acidic protein and a low level of expression of neuron-spe-ciifc enolase were visible in BrdU-labeled bone marrow mesenchymal stem cells. These ifndings suggest that transplantation of a composite of bone marrow mesenchymal stem cells and a chi-tosan-collagen scaffold has a neuroprotective effect following ischemic stroke.

  19. Chitosan-collagen porous scaffold and bone marrow mesenchymal stem cell transplantation for ischemic stroke

    Directory of Open Access Journals (Sweden)

    Feng Yan

    2015-01-01

    Full Text Available In this study, we successfully constructed a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffold in vitro, transplanted either the composite or bone marrow mesenchymal stem cells alone into the ischemic area in animal models, and compared their effects. At 14 days after co-transplantation of bone marrow mesenchymal stem cells and the hitosan-collagen scaffold, neurological function recovered noticeably. Vascular endothelial growth factor expression and nestin-labeled neural precursor cells were detected in the ischemic area, surrounding tissue, hippocampal dentate gyrus and subventricular zone. Simultaneously, a high level of expression of glial fibrillary acidic protein and a low level of expression of neuron-specific enolase were visible in BrdU-labeled bone marrow mesenchymal stem cells. These findings suggest that transplantation of a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffold has a neuroprotective effect following ischemic stroke.

  20. Immunoregulatory effects of bone marrow-derived mesenchymal stem cells in the nasal polyp microenvironment.

    Science.gov (United States)

    Pezato, Rogério; de Almeida, Danilo Cândido; Bezerra, Thiago Freire; Silva, Fernando de Sá; Perez-Novo, Claudina; Gregório, Luís Carlos; Voegels, Richard Louis; Câmara, Niels Olsen; Bachert, Claus

    2014-01-01

    Nasal polyposis is a severe, chronic inflammatory condition of the paranasal sinuses and is frequently associated with asthma and aspirin sensitivity. Mesenchymal stem cells exhibit a potent immunosuppressive effect in several inflammatory conditions, and their role in nasal polyposis remains little explored. Hence, we investigated whether bone marrow-derived mesenchymal stem cells could modulate cell phenotype in the nasal polyp milieu. After coculture with mesenchymal stem cells, the frequency of these inflammatory cells was found to decrease. Furthermore, mesenchymal stem cells promoted strong inhibition of CD4+ and CD8+ T cell proliferation, increased the frequency of CD4+CD25+Foxp3 T cells, and changed the global cytokine profile from an inflammatory to an anti-inflammatory response. We believe that mesenchymal stem cells may be a very useful adjunct for investigation of the inflammatory process in nasal polyposis, contributing to better understanding of the inflammatory course of this condition. PMID:24707116

  1. Immunoregulatory Effects of Bone Marrow-Derived Mesenchymal Stem Cells in the Nasal Polyp Microenvironment

    Directory of Open Access Journals (Sweden)

    Rogério Pezato

    2014-01-01

    Full Text Available Nasal polyposis is a severe, chronic inflammatory condition of the paranasal sinuses and is frequently associated with asthma and aspirin sensitivity. Mesenchymal stem cells exhibit a potent immunosuppressive effect in several inflammatory conditions, and their role in nasal polyposis remains little explored. Hence, we investigated whether bone marrow-derived mesenchymal stem cells could modulate cell phenotype in the nasal polyp milieu. After coculture with mesenchymal stem cells, the frequency of these inflammatory cells was found to decrease. Furthermore, mesenchymal stem cells promoted strong inhibition of CD4+ and CD8+ T cell proliferation, increased the frequency of CD4+CD25+Foxp3 T cells, and changed the global cytokine profile from an inflammatory to an anti-inflammatory response. We believe that mesenchymal stem cells may be a very useful adjunct for investigation of the inflammatory process in nasal polyposis, contributing to better understanding of the inflammatory course of this condition.

  2. Chondrogenic potential of human bone marrow mesenchymal stem cells and adipose-derived mesenchymal stem cells

    Czech Academy of Sciences Publication Activity Database

    Danisovic, L.; Lesný, Petr; Jendelová, Pavla; Teyssler, P.; Havlas, V.; Fujeriková, G.; Syková, Eva

    2006-01-01

    Roč. 8, Supplement 1 (2006), s. 191-191. ISSN 1465-3249. [ ISCT 2006. 04.05.2006-07.05.2006, Berlin] R&D Projects: GA MŠk(CZ) 1M0021620803; GA MZd(CZ) NR8121 Institutional research plan: CEZ:AV0Z50390512 Keywords : Mesenchymal Subject RIV: FH - Neurology

  3. UPDATE ON THE ROLE OF AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA

    Directory of Open Access Journals (Sweden)

    Patrizia Tosi

    2012-01-01

    Full Text Available

    Autologous stem cell transplantation is considered the standard of care for multiple myeloma patients aged < 65 years with no relevant comorbidities. The addition of drugs acting both on bone marrow microenvironment and on neoplastic plasma cells has significantly increased the proportion of patients achieving a complete remission after induction therapy, and these results are mantained after high-dose melphalan, leading to a prolonged disease control. Studies are being carried out in order to evaluate whether short term consolidation or long-term maintenance therapy can result into disease eradication at the molecular level thus increasing also patients survival. The efficacy of these new drugs has raised the issue of deferring the transplant after achivng a second response upon relapse. Another controversial point is the optimal treatment strategy for high-risk patients, that do not benefit from autologous stem cell transplantation and for whom the efficacy of new drugs is still matter of debate.

  4. The role of autologous haemopoietic stem cell transplantation in the treatment of autoimmune disorders.

    Science.gov (United States)

    Rebeiro, P; Moore, J

    2016-01-01

    Autologous haemopoietic stem cell transplantation (HSCT) has been used for over 30 years for malignant haematological diseases, such as myeloma and lymphoma, with considerable success. More recently this procedure has been adopted as a form of high dose immunosuppression in selected patients with autoimmune diseases that are resistant to conventional therapies. Animal models have previously outlined the rationale and validity of HSCT in patients with these non-malignant, but in many cases, life-threatening conditions. Recent data have that deletion of putative autoreactive immune clones with reconstitution of a thymic driven, tolerant immune system occurs in HSCT for auto-immune patients. Two randomised control trials have confirmed that HSCT is superior to monthly cyclophosphamide in systemic sclerosis with a highly significant disease free and overall survival benefit demonstrated in the Autologous Stem cell Transplantation International Scleroderma trial. Over 2000 patients worldwide with autoimmune conditions have been treated with HSCT - the commonest indications being multiple sclerosis (MS) and systemic sclerosis. Encouraging relapse free survival of 70-80% at 4 years, in heavily pre-treated MS patients, has been demonstrated in Phase II trials. A Phase III trial in MS patients who have failed interferon is currently accruing patients. Future challenges include improvements in safety of HSCT, particularly in cardiac assessment of systemic sclerosis patients, cost-benefit analyses of HSCT compared to standard therapy and establishment of centres of excellence to continue to enhance the safety and benefit of this exciting new therapy. PMID:26524106

  5. Autologous Stem Cell Injection for Spinal Cord Injury - A Clinical Study from India.

    Directory of Open Access Journals (Sweden)

    Ravikumar R

    2007-01-01

    Full Text Available We studied 100 patients with Spinal Cord injury (SCI after Autologous Stem cell Injection in the Spinal fluid with a Follow up of 6 months post Stem cell injection. There were 69 males and 31 females; age ranging from 8 years to 55 years.? Time after Spinal Injury ranged from 11 years - 3 months (Average: 4.5 years. The Level of Injury ranged from Upper Thoracic (T1-T7 - 34 pts, Lower thoracic (T7-T12 -45 pts, Lumbar -12, Cervical-9 pts. All patients had an MRI Scan, urodynamic study and SSEP (somatosensory Evoked Potential tests before and 3 months after Stem cell Injection.80% of patients had Grade 0 power in the Lower limbs and rest had grade 1-2 power before stem cell injections. 70% of cases had complete lack of Bladder control and 95% had reduced detrusor function.We Extracted CD34 and CD 133 marked Stem cells from 100 ml of Bone marrow Aspirate using Ficoll Gradient method with Cell counting done using flowcytometry.15 ml of the Stem cell concentrate was injected into the Lumbar spinal fluid in aseptic conditions. The CD 34/CD45 counts ranged from 120-400 million cells in the total volume.6 months after Injection, 8 patients had more than 2 grades of Motor power improvement, 3 are able to walk with support. 1 patient with T12/L1 injury was able to walk without support. 12 had sensory tactile and Pain perception improvement and 8 had objective improvement in bladder control and Bladder Muscle contractility. A total of 18 patients had reported or observed improvement in Neurological status. 85% of patients who had motor Improvement had Lesions below T8. MRI, SSEP and Urodynamic Study data are gathered at regular intervals. Conclusion: This study shows that Quantitative and qualitative Improvement in the Neurological status of paralyzed patients after Spinal cord injury is possible after autologous bone marrow Stem cell Injections in select patients. There was no report of Allodynia indicating the safety of the procedure. Further studies to

  6. Interaction between Mesenchymal Stem Cells and B-Cells

    Science.gov (United States)

    Fan, Linxiao; Hu, Chenxia; Chen, Jiajia; Cen, Panpan; Wang, Jie; Li, Lanjuan

    2016-01-01

    Mesenchymal stem cells (MSCs) are multipotent; non-hematopoietic stem cells. Because of their immunoregulatory abilities; MSCs are widely used for different clinical applications. Compared with that of other immune cells; the investigation of how MSCs specifically regulate B-cells has been superficial and insufficient. In addition; the few experimental studies on this regulation are often contradictory. In this review; we summarize the various interactions between different types or states of MSCs and B-cells; address how different types of MSCs and B-cells affect this interaction and examine how other immune cells influence the regulation of B-cells by MSCs. Finally; we hypothesize why there are conflicting results on the interaction between MSCs and B-cells in the literature. PMID:27164080

  7. Therapeutic Implications of Mesenchymal Stem Cells in Liver Injury

    Directory of Open Access Journals (Sweden)

    Maria Ausiliatrice Puglisi

    2011-01-01

    Full Text Available Mesenchymal stem cells (MSCs, represent an attractive tool for the establishment of a successful stem-cell-based therapy of liver diseases. A number of different mechanisms contribute to the therapeutic effects exerted by MSCs, since these cells can differentiate into functional hepatic cells and can also produce a series of growth factors and cytokines able to suppress inflammatory responses, reduce hepatocyte apoptosis, regress liver fibrosis, and enhance hepatocyte functionality. To date, the infusion of MSCs or MSC-conditioned medium has shown encouraging results in the treatment of fulminant hepatic failure and in end-stage liver disease in experimental settings. However, some issues under debate hamper the use of MSCs in clinical trials. This paper summarizes the biological relevance of MSCs and the potential benefits and risks that can result from translating the MSC research to the treatment of liver diseases.

  8. Transplantation of mesenchymal stem cells improves type 1 diabetes mellitus.

    Science.gov (United States)

    Li, Lisha; Li, Furong; Gao, Feng; Yang, Yali; Liu, Yuanyuan; Guo, Pingping; Li, Yulin

    2016-05-01

    Bone-marrow-derived stem cells can regenerate pancreatic tissue in a model of type 1 diabetes mellitus. Mesenchymal stem cells (MSCs) form the main part of bone marrow. We show that the intrapancreatic transplantation of MSCs elevates serum insulin and C-peptide, while decreasing blood glucose. MSCs engrafted into the damaged rat pancreas become distributed into the blood vessels, acini, ducts, and islets. Renascent islets, islet-like clusters, and a small number of MSCs expressing insulin protein have been observed in the pancreas of diabetic rats. Intrapancreatic transplantation of MSCs triggers a series of molecular and cellular events, including differentiation towards the pancreas directly and the provision of a niche to start endogenous pancreatic regeneration, which ameliorates hypoinsulinemia and hyperglycemia caused by streptozotocin. These data establish the many roles of MSCs in the restoration of the function of an injured organ. PMID:26650464

  9. Mesenchymal stem cells: a new trend for cell therapy

    Institute of Scientific and Technical Information of China (English)

    Xin WEI; Xue YANG; Zhi-peng HAN; Fang-fang QU; Li SHAO; Yu-fang SHI

    2013-01-01

    Mesenchymal stem cells (MSCs),the major stem cells for cell therapy,have been used in the clinic for approximately 10 years.From animal models to clinical trials,MSCs have afforded promise in the treatment of numerous diseases,mainly tissue injury and immune disorders.In this review,we summarize the recent opinions on methods,timing and cell sources for MSC administration in clinical applications,and provide an overview of mechanisms that are significant in MSC-mediated therapies.Although MSCs for cell therapy have been shown to be safe and effective,there are still challenges that need to be tackled before their wide application in the clinic.

  10. Treatment of chronic hepatic cirrhosis with autologous bone marrow stem cells transplantation in rabbits

    International Nuclear Information System (INIS)

    Objective: To evaluate the feasibility of treatment for rabbit model with hepatic cirrhosis by transplantation of autologous bone marrow-derived stem cells via the hepatic artery and evaluate the effect of hepatocyte growth-promoting factors (pHGF) in the treatment of stem cells transplantation to liver cirrhosis. To provide empirical study foundation for future clinical application. Methods: Chronic hepatic cirrhosis models of rabbits were developed by subcutaneous injection with 50% CCl4 0.2 ml/kg. Twenty-five model rabbits were randomly divided into three experimental groups, stem cells transplant group (10), stem cells transplant + pHGF group (10) and control group (5). Autologous bone marrow was harvested from fibia of each rabbit, and stem cells were disassociated using density gradient centrifugation and transplanted into liver via the hepatic artery under fluoroscopic guidance. In the stem cells transplant + pHGF group, the hepatocyte growth-promoting factor was given via intravenous injection with 2 mg/kg every other day for 20 days. Liver function tests were monitored at 4, 8,12 weeks intervals and histopathologic examinations were performed at 12 weeks following transplantation. The data were analyzed using analysis of variance Results: Following transplantation of stern cells, the liver function of rabbits improved gradually. Twelve weeks after transplantation, the activity of ALT and AST decreased from (73.0±10.6) U/L and (152.4± 22.8) U/L to (48.0±1.0) U/L and (86.7±2.1) U/L respectively; and the level of ALB and PTA increased from (27.5±1.8) g/L and 28.3% to (33.2±0.5) g/L and 44.1% respectively. The changes did not have statistically significant difference when compared to the control group (P>0.05). However, in the stem cellstransplant + pHGF group, the activity of ALT and AST decreased to (43.3±0.6) U/L and (78.7±4.0) U/L respectively and the level of ALB and PTA increased to (35.7±0.4) g/L and 50.5% respectively. The difference was

  11. Human mesenchymal stem cells - current trends and future prospective.

    Science.gov (United States)

    Ullah, Imran; Subbarao, Raghavendra Baregundi; Rho, Gyu Jin

    2015-01-01

    Stem cells are cells specialized cell, capable of renewing themselves through cell division and can differentiate into multi-lineage cells. These cells are categorized as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and adult stem cells. Mesenchymal stem cells (MSCs) are adult stem cells which can be isolated from human and animal sources. Human MSCs (hMSCs) are the non-haematopoietic, multipotent stem cells with the capacity to differentiate into mesodermal lineage such as osteocytes, adipocytes and chondrocytes as well ectodermal (neurocytes) and endodermal lineages (hepatocytes). MSCs express cell surface markers like cluster of differentiation (CD)29, CD44, CD73, CD90, CD105 and lack the expression of CD14, CD34, CD45 and HLA (human leucocyte antigen)-DR. hMSCs for the first time were reported in the bone marrow and till now they have been isolated from various tissues, including adipose tissue, amniotic fluid, endometrium, dental tissues, umbilical cord and Wharton's jelly which harbours potential MSCs. hMSCs have been cultured long-term in specific media without any severe abnormalities. Furthermore, MSCs have immunomodulatory features, secrete cytokines and immune-receptors which regulate the microenvironment in the host tissue. Multilineage potential, immunomodulation and secretion of anti-inflammatory molecules makes MSCs an effective tool in the treatment of chronic diseases. In the present review, we have highlighted recent research findings in the area of hMSCs sources, expression of cell surface markers, long-term in vitro culturing, in vitro differentiation potential, immunomodulatory features, its homing capacity, banking and cryopreservation, its application in the treatment of chronic diseases and its use in clinical trials. PMID:25797907

  12. Implications of mesenchymal stem cells in regenerative medicine.

    Science.gov (United States)

    Kariminekoo, Saber; Movassaghpour, Aliakbar; Rahimzadeh, Amirbahman; Talebi, Mehdi; Shamsasenjan, Karim; Akbarzadeh, Abolfazl

    2016-05-01

    Mesenchymal stem cells (MSCs) are a population of multipotent progenitors which reside in bone marrow, fat, and some other tissues and can be isolated from various adult and fetal tissues. Self-renewal potential and multipotency are MSC's hallmarks. They have the capacity of proliferation and differentiation into a variety of cell lineages like osteoblasts, condrocytes, adipocytes, fibroblasts, cardiomyocytes. MSCs can be identified by expression of some surface molecules like CD73, CD90, CD105, and lack of hematopoietic specific markers including CD34, CD45, and HLA-DR. They are hopeful tools for regenerative medicine for repairing injured tissues. Many studies have focused on two significant features of MSC therapy: (I) systemically administered MSCs home to sites of ischemia or injury, and (II) MSCs can modulate T-cell-mediated immunological responses. MSCs express chemokine receptors and ligands involved in cells migration and homing process. MSCs induce immunomedulatory effects on the innate (dendritic cells, monocyte, natural killer cells, and neutrophils) and the adaptive immune system cells (T helper-1, cytotoxic T lymphocyte, and B lymphocyte) by secreting soluble factors like TGF-β, IL-10, IDO, PGE-2, sHLA-G5, or by cell-cell interaction. In this review, we discuss the main applications of mesenchymal stem in Regenerative Medicine and known mechanisms of homing and Immunomodulation of MSCs. PMID:26757594

  13. Mesenchymal stem cell and osteoarthritis: a literature review

    Directory of Open Access Journals (Sweden)

    Zhaleh Shariati Sarabi

    2016-04-01

    Full Text Available The most common disease in the aged population is osteoarthritis (OA that is resulting in progressive dysfunction following isolated cartilage injuries, subchondral bone remodeling, tissue loss, marginal osteophytes, and loss of joint space. Mesenchymal stem cells (MSCs are multipotent stem cells; they are able to produce many or all joint tissues. Bone marrow and adipose tissue are rich sources of mesenchymal cells that are useful for the reconstruction of injured tissues such as bone, cartilage, or cardiac muscle. Recently, some studies have been performed on the use of the direct intra-articular injection of mononuclear cells (MNCs and MSCs as potential therapeutic targets in OA. In this review, the history of MSCs in the treatment of OA are explained. Injection of Bone Marrow Aspirates Concentrate (BMAC has significantly improved both joint pain and function in radiologic findings; some studies suggested that the injection would be even more effective in early to moderate phases of OA. Injection of MSCs in combination with growth factors may be better solution for the treatment.

  14. Induction of mesenchymal stem cell chondrogenesis by polyacrylate substrates.

    Science.gov (United States)

    Glennon-Alty, Laurence; Williams, Rachel; Dixon, Simon; Murray, Patricia

    2013-04-01

    Mesenchymal stem cells (MSCs) can generate chondrocytes in vitro, but typically need to be cultured as aggregates in the presence of transforming growth factor beta (TGF-β), which makes scale-up difficult. Here we investigated if polyacrylate substrates modelled on the functional group composition and distribution of the Arg-Gly-Asp (RGD) integrin-binding site could induce MSCs to undergo chondrogenesis in the absence of exogenous TGF-β. Within a few days of culture on the biomimetic polyacrylates, both mouse and human MSCs, and a mesenchymal-like mouse-kidney-derived stem cell line, began to form multi-layered aggregates and started to express the chondrocyte-specific markers, Sox9, collagen II and aggrecan. Moreover, collagen II tended to be expressed in the centre of the aggregates, similarly to developing limb buds in vivo. Surface analysis of the substrates indicated that those with the highest surface amine content were most effective at promoting MSC chondrogenesis. These results highlight the importance of surface group functionality and the distribution of those groups in the design of substrates to induce MSC chondrogenesis. PMID:23237986

  15. Heterogeneity in proliferative potential of ovine mesenchymal stem cell colonies.

    Science.gov (United States)

    Rhodes, N P; Srivastava, J K; Smith, R F; Longinotti, C

    2004-04-01

    Bone marrow biopsies were taken from the iliac crest of 28 individual sheep from three different breeds, ranging in age from 4 months to 8 years and mesenchymal stem cells (MSCs) isolated using selection due to plastic adherence. Cells were cultured in medium that had been selected for its effect on observed MSC proliferation, until populations of greater than 50 million had been obtained from each biopsy. The identity of the isolated cell populations as progenitors of the mesenchymal lineage was verified by deriving both osteoblastic and chondrocytic phenotypes when cultured in osteogenic and chondrogenic medium supplements, respectively. The rate of cell proliferation for each marrow biopsy was measured at each passage and the number of initial stem cells in each sample estimated. There was no statistically significant correlation between the age of the sheep and MSC proliferative potential, or age and estimated initial MSC number. There was no apparent significant difference between proliferation rate and sheep breed and colonies established from frozen cells grew at similar rates to pre-frozen cells. Counter intuitively, there appeared to be a negatively correlated trend between proliferation rate and MSC concentration in the samples. It is concluded that no initial descriptive statistics of the marrow biopsies can assist in estimating the proliferative potential, and therefore the timing of future surgeries, of MSCs sampled for the purposes of tissue engineering. PMID:15332606

  16. Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy

    Institute of Scientific and Technical Information of China (English)

    Justin; D; Glenn; Katharine; A; Whartenby

    2014-01-01

    Mesenchymal stem cells(MSCs) are a pleiotropic population of cells that are self-renewing and capable of differentiating into canonical cells of the mesenchyme, including adipocytes, chondrocytes, and osteocytes. They employ multi-faceted approaches to maintain bone marrow niche homeostasis and promote wound healing during injury. Biomedical research has long sought to exploit their pleiotropic properties as a basis for cell therapy for a variety of diseases and to facilitate hematopoietic stem cell establishment and stromal reconstruction in bone marrow transplantation. Early results demonstrated their usage as safe, and there was little host response to these cells. The discovery of their immunosuppressive functions ushered in a new interest in MSCs as a promising therapeutic tool to suppress inflammation and down-regulate pathogenic immune responses in graft-versus-host and autoimmune diseases such as multiple sclerosis, autoimmune diabetes, and rheumatoid arthritis. MSCs produce a large number of soluble and membrane-bound factors, some of which inhibit immune responses. However, the full range of MSC-mediated immune-modulation remains incompletely understood, as emerging reports also reveal that MSCs can adopt an immunogenic phenotype, stimulate immune cells, and yield seemingly contradictory results in experimental animal models of inflammatory disease. The present review describes the large body of literature that has been accumulated on the fascinating biology of MSCs and their complex effects on immune responses.

  17. Cryopreservation of Adipose-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Miyagi-Shiohira, Chika; Kurima, Kiyoto; Kobayashi, Naoya; Saitoh, Issei; Watanabe, Masami; Noguchi, Yasufumi; Matsushita, Masayuki; Noguchi, Hirofumi

    2015-12-17

    Mesenchymal stem cells (MSCs) have the potential to differentiate into cells of mesodermal origin such as osteoblasts, adipocytes, myocytes, and chondrocytes. They possess an immunosuppressive effect, which makes them a viable cell population for the cell-based therapy of treatment-resistant immune diseases. Adipose-derived mesenchymal stem cells (ASCs) have been demonstrated to have the ability to acquire the properties of subcutaneous adipose tissue particularly easily, and cryopreservation is currently performed as a routine method for preserving ASCs to safely acquire large numbers of cells. However, many studies have reported that cellular activity after freezing and thawing may be affected by the solutions used for cryopreservation. Dimethyl sulfoxide (DMSO) is commonly used as a cryopreservation medium as it diffuses into the cell through the plasma membrane and protects the cells from the damage caused by freezing. As substitutes for DMSO or animal-derived serum, cell banker series, polyvinylpyrrolidone (PVP), sericin and maltose, and methyl cellulose (MC) have been investigated for their clinical applications. It is critical to develop a reliable cell cryopreservation protocol for regenerative medicine using MSCs. PMID:26858903

  18. Cell therapy of congenital corneal diseases with umbilical mesenchymal stem cells: lumican null mice.

    Directory of Open Access Journals (Sweden)

    Hongshan Liu

    Full Text Available BACKGROUND: Keratoplasty is the most effective treatment for corneal blindness, but suboptimal medical conditions and lack of qualified medical personnel and donated cornea often prevent the performance of corneal transplantation in developing countries. Our study aims to develop alternative treatment regimens for congenital corneal diseases of genetic mutation. METHODOLOGY/PRINCIPAL FINDINGS: Human mesenchymal stem cells isolated from neonatal umbilical cords were transplanted to treat thin and cloudy corneas of lumican null mice. Transplantation of umbilical mesenchymal stem cells significantly improved corneal transparency and increased stromal thickness of lumican null mice, but human umbilical hematopoietic stem cells failed to do the same. Further studies revealed that collagen lamellae were re-organized in corneal stroma of lumican null mice after mesenchymal stem cell transplantation. Transplanted umbilical mesenchymal stem cells survived in the mouse corneal stroma for more than 3 months with little or no graft rejection. In addition, these cells assumed a keratocyte phenotype, e.g., dendritic morphology, quiescence, expression of keratocyte unique keratan sulfated keratocan and lumican, and CD34. Moreover, umbilical mesenchymal stem cell transplantation improved host keratocyte functions, which was verified by enhanced expression of keratocan and aldehyde dehydrogenase class 3A1 in lumican null mice. CONCLUSIONS/SIGNIFICANCE: Umbilical mesenchymal stem cell transplantation is a promising treatment for congenital corneal diseases involving keratocyte dysfunction. Unlike donated corneas, umbilical mesenchymal stem cells are easily isolated, expanded, stored, and can be quickly recovered from liquid nitrogen when a patient is in urgent need.

  19. Articular cartilage-derived cells hold a strong osteogenic differentiation potential in comparison to mesenchymal stem cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Salamon, Achim, E-mail: achim.salamon@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Jonitz-Heincke, Anika, E-mail: anika.jonitz@med.uni-rostock.de [Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Center, Doberaner Straße 142, D-18057 Rostock (Germany); Adam, Stefanie, E-mail: stefanie.adam@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Rychly, Joachim, E-mail: joachim.rychly@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Müller-Hilke, Brigitte, E-mail: brigitte.mueller-hilke@med.uni-rostock.de [Institute of Immunology, Rostock University Medical Center, Schillingallee 68, D-18057 Rostock (Germany); Bader, Rainer, E-mail: rainer.bader@med.uni-rostock.de [Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Center, Doberaner Straße 142, D-18057 Rostock (Germany); Lochner, Katrin, E-mail: katrin.lochner@med.uni-rostock.de [Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Center, Doberaner Straße 142, D-18057 Rostock (Germany); Peters, Kirsten, E-mail: kirsten.peters@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany)

    2013-11-01

    Cartilaginous matrix-degenerative diseases like osteoarthritis (OA) are characterized by gradual cartilage erosion, and also by increased presence of cells with mesenchymal stem cell (MSC) character within the affected tissues. Moreover, primary chondrocytes long since are known to de-differentiate in vitro and to be chondrogenically re-differentiable. Since both findings appear to conflict with each other, we quantitatively assessed the mesenchymal differentiation potential of OA patient cartilage-derived cells (CDC) towards the osteogenic and adipogenic lineage in vitro and compared it to that of MSC isolated from adipose tissue (adMSC) of healthy donors. We analyzed expression of MSC markers CD29, CD44, CD105, and CD166, and, following osteogenic and adipogenic induction in vitro, quantified their expression of osteogenic and adipogenic differentiation markers. Furthermore, CDC phenotype and proliferation were monitored. We found that CDC exhibit an MSC CD marker expression pattern similar to adMSC and a similar increase in proliferation rate during osteogenic differentiation. In contrast, the marked reduction of proliferation observed during adipogenic differentiation of adMSC was absent in CDC. Quantification of differentiation markers revealed a strong osteogenic differentiation potential for CDC, however almost no capacity for adipogenic differentiation. Since in the pathogenesis of OA, cartilage degeneration coincides with high bone turnover rates, the high osteogenic differentiation potential of OA patient-derived CDC may affect clinical therapeutic regimens aiming at autologous cartilage regeneration in these patients. - Highlights: • We analyze the mesenchymal differentiation capacity of cartilage-derived cells (CDC). • CDC express mesenchymal stem cell (MSC) markers CD29, CD44, CD105, and CD166. • CDC and MSC proliferation is reduced in adipogenesis and increased in osteogenesis. • Adipogenic differentiation is virtually absent in CDC, but

  20. Articular cartilage-derived cells hold a strong osteogenic differentiation potential in comparison to mesenchymal stem cells in vitro

    International Nuclear Information System (INIS)

    Cartilaginous matrix-degenerative diseases like osteoarthritis (OA) are characterized by gradual cartilage erosion, and also by increased presence of cells with mesenchymal stem cell (MSC) character within the affected tissues. Moreover, primary chondrocytes long since are known to de-differentiate in vitro and to be chondrogenically re-differentiable. Since both findings appear to conflict with each other, we quantitatively assessed the mesenchymal differentiation potential of OA patient cartilage-derived cells (CDC) towards the osteogenic and adipogenic lineage in vitro and compared it to that of MSC isolated from adipose tissue (adMSC) of healthy donors. We analyzed expression of MSC markers CD29, CD44, CD105, and CD166, and, following osteogenic and adipogenic induction in vitro, quantified their expression of osteogenic and adipogenic differentiation markers. Furthermore, CDC phenotype and proliferation were monitored. We found that CDC exhibit an MSC CD marker expression pattern similar to adMSC and a similar increase in proliferation rate during osteogenic differentiation. In contrast, the marked reduction of proliferation observed during adipogenic differentiation of adMSC was absent in CDC. Quantification of differentiation markers revealed a strong osteogenic differentiation potential for CDC, however almost no capacity for adipogenic differentiation. Since in the pathogenesis of OA, cartilage degeneration coincides with high bone turnover rates, the high osteogenic differentiation potential of OA patient-derived CDC may affect clinical therapeutic regimens aiming at autologous cartilage regeneration in these patients. - Highlights: • We analyze the mesenchymal differentiation capacity of cartilage-derived cells (CDC). • CDC express mesenchymal stem cell (MSC) markers CD29, CD44, CD105, and CD166. • CDC and MSC proliferation is reduced in adipogenesis and increased in osteogenesis. • Adipogenic differentiation is virtually absent in CDC, but

  1. Challenging complications of treatment – human herpes virus 6 encephalitis and pneumonitis in a patient undergoing autologous stem cell transplantation for relapsed Hodgkin's disease: a case report

    Directory of Open Access Journals (Sweden)

    Pauls Sandra

    2009-07-01

    Full Text Available Abstract Background Reactivation of human herpesvirus 6 (HHV-6 occurs frequently in patients after allogeneic stem cell transplantation and is associated with bone-marrow suppression, enteritis, pneumonitis, pericarditis and also encephalitis. After autologous stem cell transplantation or intensive polychemotherapy HHV-6 reactivation is rarely reported. Case report This case demonstrates a severe symptomatic HHV-6 infection with encephalitis and pneumonitis after autologous stem cell transplantation of a patient with relapsed Hodgkin's disease. Conclusion Careful diagnostic work up in patients with severe complications after autologous stem cell transplantation is mandatory to identify uncommon infections.

  2. Adipose-Derived Mesenchymal Stem Cell Protects Kidneys against Ischemia-Reperfusion Injury through Suppressing Oxidative Stress and Inflammatory Reaction

    Directory of Open Access Journals (Sweden)

    Chua Sarah

    2011-05-01

    Full Text Available Abstract Background Reactive oxygen species are important mediators exerting toxic effects on various organs during ischemia-reperfusion (IR injury. We hypothesized that adipose-derived mesenchymal stem cells (ADMSCs protect the kidney against oxidative stress and inflammatory stimuli in rat during renal IR injury. Methods Adult male Sprague-Dawley (SD rats (n = 24 were equally randomized into group 1 (sham control, group 2 (IR plus culture medium only, and group 3 (IR plus immediate intra-renal administration of 1.0 × 106 autologous ADMSCs, followed by intravenous ADMSCs at 6 h and 24 h after IR. The duration of ischemia was 1 h, followed by 72 hours of reperfusion before the animals were sacrificed. Results Serum creatinine and blood urea nitrogen levels and the degree of histological abnormalities were markedly lower in group 3 than in group 2 (all p Conclusion ADMSC therapy minimized kidney damage after IR injury through suppressing oxidative stress and inflammatory response.

  3. Early combined treatment with sildenafil and adipose-derived mesenchymal stem cells preserves heart function in rat dilated cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Fu Morgan

    2010-09-01

    Full Text Available Abstract Background We investigated whether early combined autologous adipose-derived mesenchymal stem cell (ADMSC and sildenafil therapy offers an additive benefit in preserving heart function in rat dilated cardiomyopathy (DCM. Methods Adult Lewis rats (n = 8 per group were divided into group 1 (normal control, group 2 (saline-treated DCM rats, group 3 [2.0 × 106 ADMSC implanted into left ventricular (LV myocardium of DCM rats], group 4 (DCM rats with sildenafil 30 mg/kg/day, orally, and group 5 (DCM rats with combined ADMSC-sildenafil. Treatment was started 1 week after DCM induction and the rats were sacrificed on day 90. Results The results showed that mitochondrial protein expressions of connexin43 and cytochrome-C were lowest in group 2, and lower in groups 3 and 4 than in group 5 (p Conclusion Early combined ADMSC/sildenafil is superior to either treatment alone in preserving LV function.

  4. Differentiation of human gingival mesenchymal stem cells into neuronal lineages in 3D bioconjugated injectable protein hydrogel construct for the management of neuronal disorder.

    Science.gov (United States)

    Rao, Suresh Ranga; Subbarayan, Rajasekaran; Dinesh, Murugan Girija; Arumugam, Gnanamani; Raja, Selvaraj Thirupathi Kumara

    2016-01-01

    The success of regeneration attempt is based on an ideal combination of stem cells, scaffolding and growth factors. Tissue constructs help to maintain stem cells in a required area for a desired time. There is a need for easily obtainable cells, potentially autologous stem cells and a biologically acceptable scaffold for use in humans in different difficult situations. This study aims to address these issues utilizing a unique combination of stem cells from gingiva and a hydrogel scaffold, based on a natural product for regenerative application. Human gingival mesenchymal stem cells (HGMSCs) were, with due induction, differentiated to neuronal lineages to overcome the problems associated with birth tissue-related stem cells. The differentiation potential of neuronal lineages was confirmed with suitable specific markers. The properties of mesenchymal stem cells in encapsulated form were observed to be similar to free cells. The encapsulated cells (3D) were then subjected to differentiation into neuronal lineages with suitable inducers, and the morphology and gene expression of transient cells were analyzed. HGMSCs was differentiated into neuronal lineages as both free and encapsulated forms without any significant differences. The presence of Nissl bodies and the neurite outgrowth confirm the differentiation. The advantages of this new combination appear to make it a promising tissue construct for translational application. PMID:26869025

  5. Differentiation of human gingival mesenchymal stem cells into neuronal lineages in 3D bioconjugated injectable protein hydrogel construct for the management of neuronal disorder

    Science.gov (United States)

    Rao, Suresh Ranga; Subbarayan, Rajasekaran; Dinesh, Murugan Girija; Arumugam, Gnanamani; Raja, Selvaraj Thirupathi Kumara

    2016-01-01

    The success of regeneration attempt is based on an ideal combination of stem cells, scaffolding and growth factors. Tissue constructs help to maintain stem cells in a required area for a desired time. There is a need for easily obtainable cells, potentially autologous stem cells and a biologically acceptable scaffold for use in humans in different difficult situations. This study aims to address these issues utilizing a unique combination of stem cells from gingiva and a hydrogel scaffold, based on a natural product for regenerative application. Human gingival mesenchymal stem cells (HGMSCs) were, with due induction, differentiated to neuronal lineages to overcome the problems associated with birth tissue-related stem cells. The differentiation potential of neuronal lineages was confirmed with suitable specific markers. The properties of mesenchymal stem cells in encapsulated form were observed to be similar to free cells. The encapsulated cells (3D) were then subjected to differentiation into neuronal lineages with suitable inducers, and the morphology and gene expression of transient cells were analyzed. HGMSCs was differentiated into neuronal lineages as both free and encapsulated forms without any significant differences. The presence of Nissl bodies and the neurite outgrowth confirm the differentiation. The advantages of this new combination appear to make it a promising tissue construct for translational application. PMID:26869025

  6. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Ya-jing Zhou; Jian-min Liu; Shu-ming Wei; Yun-hao Zhang; Zhen-hua Qu; Shu-bo Chen

    2015-01-01

    Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administrationvia the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve ifbers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and lfuorogold-labeled nerve ifbers were increased and hindlimb motor function of spinal cord-injured rats was mark-edly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.

  7. Clinical application of mesenchymal stem cells for aseptic bone necrosis

    Directory of Open Access Journals (Sweden)

    Tomoki Aoyama

    2008-11-01

    Full Text Available Since 2007, we had started clinical trial using mesenchymal stem cell (MSCs for the treatment of aseptic bone necrosis as a first clinical trial permitted by Japanese Health, Labour and Welfare Ministry.Aseptic bone necrosis of the femoral head commonly occurs in patients with two to four decades, causing severe musculoskeletal disability. Although its diagnosis is easy with X-ray and MRI, there has been no gold standard invented for treatment of this disease. MSCs represent a stem cell population in adult tissues that can be isolated and expanded in culture, and differentiate into cells with different nature. Combination with β-tri-calcium phosphate and vascularized bone graft, we succeeded to treat bone necrosis of the femoral head.Regenerative medicine using stem cells is hopeful and shed a light on intractable disease. To become widespread, Basic, Translational, Application, and Developmental study is needed.? From an experience of cell therapy using MSCs, we started to research induced pluripotent stem cell (iPS for clinical application.

  8. Protocols for in vitro Differentiation of Human Mesenchymal Stem Cells into Osteogenic, Chondrogenic and Adipogenic Lineages.

    Science.gov (United States)

    Ciuffreda, Maria Chiara; Malpasso, Giuseppe; Musarò, Paola; Turco, Valentina; Gnecchi, Massimiliano

    2016-01-01

    Mesenchymal stem cells (MSC) possess high plasticity and the potential to differentiate into several different cell types; this characteristic has implications for cell therapy and reparative biotechnologies. MSC have been originally isolated from the bone marrow (BM-MSC), but they have been found also in other tissues such as adipose tissue, cord blood, synovium, skeletal muscle, and lung. MSC are able to differentiate in vitro and in vivo into several cell types such as bone, osteocytes, chondrocytes, adipocytes, and skeletal myocytes, just to name a few.During the last two decades, an increasing number of studies have proven the therapeutic potential of MSC for the treatment of neurodegenerative diseases, spinal cord and brain injuries, cardiovascular diseases, diabetes mellitus, and diseases of the skeleton. Their immuno-privileged profile allows both autologous and allogeneic use. For all these reasons, the scientific appeal of MSC is constantly on the rise.The identity of MSC is currently based on three main criteria: plastic-adherence capacity, defined epitope profile, and capacity to differentiate in vitro into osteocytes, chondrocytes, and adipocytes. Here, we describe standard protocols for the differentiation of BM-MSC into the osteogenic, chondrogenic, and adipogenic lineages. PMID:27236670

  9. Chondrocytes, Mesenchymal Stem Cells, and Their Combination in Articular Cartilage Regenerative Medicine.

    Science.gov (United States)

    Nazempour, A; Van Wie, B J

    2016-05-01

    Articular cartilage (AC) is a highly organized connective tissue lining, covering the ends of bones within articulating joints. Its highly ordered structure is essential for stable motion and provides a frictionless surface easing load transfer. AC is vulnerable to lesions and, because it is aneural and avascular, it has limited self-repair potential which often leads to osteoarthritis. To date, no fully successful treatment for osteoarthritis has been reported. Thus, the development of innovative therapeutic approaches is desperately needed. Autologous chondrocyte implantation, the only cell-based surgical intervention approved in the United States for treating cartilage defects, has limitations because of de-differentiation of articular chondrocytes (AChs) upon in vitro expansion. De-differentiation can be abated if initial populations of AChs are co-cultured with mesenchymal stem cells (MSCs), which not only undergo chondrogenesis themselves but also support chondrocyte vitality. In this review we summarize studies utilizing AChs, non-AChs, and MSCs and compare associated outcomes. Moreover, a comprehensive set of recent human studies using chondrocytes to direct MSC differentiation, MSCs to support chondrocyte re-differentiation and proliferation in co-culture environments, and exploratory animal intra- and inter-species studies are systematically reviewed and discussed in an innovative manner allowing side-by-side comparisons of protocols and outcomes. Finally, a comprehensive set of recommendations are made for future studies. PMID:26987846

  10. Mesenchymal Stem/Stromal Cells from Discarded Neonatal Sternal Tissue: In Vitro Characterization and Angiogenic Properties

    Directory of Open Access Journals (Sweden)

    Shuyun Wang

    2016-01-01

    Full Text Available Autologous and nonautologous bone marrow mesenchymal stem/stromal cells (MSCs are being evaluated as proangiogenic agents for ischemic and vascular disease in adults but not in children. A significant number of newborns and infants with critical congenital heart disease who undergo cardiac surgery already have or are at risk of developing conditions related to inadequate tissue perfusion. During neonatal cardiac surgery, a small amount of sternal tissue is usually discarded. Here we demonstrate that MSCs can be isolated from human neonatal sternal tissue using a nonenzymatic explant culture method. Neonatal sternal bone MSCs (sbMSCs were clonogenic, had a surface marker expression profile that was characteristic of bone marrow MSCs, were multipotent, and expressed pluripotency-related genes at low levels. Neonatal sbMSCs also demonstrated in vitro proangiogenic properties. Sternal bone MSCs cooperated with human umbilical vein endothelial cells (HUVECs to form 3D networks and tubes in vitro. Conditioned media from sbMSCs cultured in hypoxia also promoted HUVEC survival and migration. Given the neonatal source, ease of isolation, and proangiogenic properties, sbMSCs may have relevance to therapeutic applications.

  11. Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats

    Directory of Open Access Journals (Sweden)

    J.C. Zhang

    2014-10-01

    Full Text Available Administration or expression of growth factors, as well as implantation of autologous bone marrow cells, promote in vivo angiogenesis. This study investigated the angiogenic potential of combining both approaches through the allogenic transplantation of bone marrow-derived mesenchymal stem cells (MSCs expressing human basic fibroblast growth factor (hbFGF. After establishing a hind limb ischemia model in Sprague Dawley rats, the animals were randomly divided into four treatment groups: MSCs expressing green fluorescent protein (GFP-MSC, MSCs expressing hbFGF (hbFGF-MSC, MSC controls, and phosphate-buffered saline (PBS controls. After 2 weeks, MSC survival and differentiation, hbFGF and vascular endothelial growth factor (VEGF expression, and microvessel density of ischemic muscles were determined. Stable hbFGF expression was observed in the hbFGF-MSC group after 2 weeks. More hbFGF-MSCs than GFP-MSCs survived and differentiated into vascular endothelial cells (P<0.001; however, their differentiation rates were similar. Moreover, allogenic transplantation of hbFGF-MSCs increased VEGF expression (P=0.008 and microvessel density (P<0.001. Transplantation of hbFGF-expressing MSCs promoted angiogenesis in an in vivo hind limb ischemia model by increasing the survival of transplanted cells that subsequently differentiated into vascular endothelial cells. This study showed the therapeutic potential of combining cell-based therapy with gene therapy to treat ischemic disease.

  12. Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, J.C. [Department of Vascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou (China); Zheng, G.F. [Department of Vascular Surgery, The People' s Hospital of Ganzhou, Ganzhou (China); Wu, L.; Ou Yang, L.Y.; Li, W.X. [Department of Vascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou (China)

    2014-08-08

    Administration or expression of growth factors, as well as implantation of autologous bone marrow cells, promote in vivo angiogenesis. This study investigated the angiogenic potential of combining both approaches through the allogenic transplantation of bone marrow-derived mesenchymal stem cells (MSCs) expressing human basic fibroblast growth factor (hbFGF). After establishing a hind limb ischemia model in Sprague Dawley rats, the animals were randomly divided into four treatment groups: MSCs expressing green fluorescent protein (GFP-MSC), MSCs expressing hbFGF (hbFGF-MSC), MSC controls, and phosphate-buffered saline (PBS) controls. After 2 weeks, MSC survival and differentiation, hbFGF and vascular endothelial growth factor (VEGF) expression, and microvessel density of ischemic muscles were determined. Stable hbFGF expression was observed in the hbFGF-MSC group after 2 weeks. More hbFGF-MSCs than GFP-MSCs survived and differentiated into vascular endothelial cells (P<0.001); however, their differentiation rates were similar. Moreover, allogenic transplantation of hbFGF-MSCs increased VEGF expression (P=0.008) and microvessel density (P<0.001). Transplantation of hbFGF-expressing MSCs promoted angiogenesis in an in vivo hind limb ischemia model by increasing the survival of transplanted cells that subsequently differentiated into vascular endothelial cells. This study showed the therapeutic potential of combining cell-based therapy with gene therapy to treat ischemic disease.

  13. Mesenchymal stem cells as a potent cell source for articular cartilage regeneration

    Institute of Scientific and Technical Information of China (English)

    Mohamadreza; Baghaban; Eslaminejad; Elham; Malakooty; Poor

    2014-01-01

    Since articular cartilage possesses only a weak capac-ity for repair, its regeneration potential is considered one of the most important challenges for orthopedic surgeons. The treatment options, such as marrow stimulation techniques, fail to induce a repair tissue with the same functional and mechanical properties of native hyaline cartilage. Osteochondral transplantation is considered an effective treatment option but is as-sociated with some disadvantages, including donor-site morbidity, tissue supply limitation, unsuitable mechani-cal properties and thickness of the obtained tissue. Although autologous chondrocyte implantation results in reasonable repair, it requires a two-step surgical pro-cedure. Moreover, chondrocytes expanded in culture gradually undergo dedifferentiation, so lose morpho-logical features and specialized functions. In the search for alternative cells, scientists have found mesenchymal stem cells(MSCs) to be an appropriate cellular mate-rial for articular cartilage repair. These cells were origi-nally isolated from bone marrow samples and further investigations have revealed the presence of the cells in many other tissues. Furthermore, chondrogenic dif-ferentiation is an inherent property of MSCs noticedat the time of the cell discovery. MSCs are known to exhibit homing potential to the damaged site at which they differentiate into the tissue cells or secrete a wide spectrum of bioactive factors with regenerative proper-ties. Moreover, these cells possess a considerable im-munomodulatory potential that make them the general donor for therapeutic applications. All of these topics will be discussed in this review.

  14. Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats

    International Nuclear Information System (INIS)

    Administration or expression of growth factors, as well as implantation of autologous bone marrow cells, promote in vivo angiogenesis. This study investigated the angiogenic potential of combining both approaches through the allogenic transplantation of bone marrow-derived mesenchymal stem cells (MSCs) expressing human basic fibroblast growth factor (hbFGF). After establishing a hind limb ischemia model in Sprague Dawley rats, the animals were randomly divided into four treatment groups: MSCs expressing green fluorescent protein (GFP-MSC), MSCs expressing hbFGF (hbFGF-MSC), MSC controls, and phosphate-buffered saline (PBS) controls. After 2 weeks, MSC survival and differentiation, hbFGF and vascular endothelial growth factor (VEGF) expression, and microvessel density of ischemic muscles were determined. Stable hbFGF expression was observed in the hbFGF-MSC group after 2 weeks. More hbFGF-MSCs than GFP-MSCs survived and differentiated into vascular endothelial cells (P<0.001); however, their differentiation rates were similar. Moreover, allogenic transplantation of hbFGF-MSCs increased VEGF expression (P=0.008) and microvessel density (P<0.001). Transplantation of hbFGF-expressing MSCs promoted angiogenesis in an in vivo hind limb ischemia model by increasing the survival of transplanted cells that subsequently differentiated into vascular endothelial cells. This study showed the therapeutic potential of combining cell-based therapy with gene therapy to treat ischemic disease

  15. In vitro cell motility as a potential mesenchymal stem cell marker for multipotency.

    Science.gov (United States)

    Bertolo, Alessandro; Gemperli, Armin; Gruber, Marco; Gantenbein, Benjamin; Baur, Martin; Pötzel, Tobias; Stoyanov, Jivko

    2015-01-01

    Mesenchymal stem cells (MSCs) are expected to have a fundamental role in future cell-based therapies because of their high proliferative ability, multilineage potential, and immunomodulatory properties. Autologous transplantations have the "elephant in the room" problem of wide donor variability, reflected by variability in MSC quality and characteristics, leading to uncertain outcomes in the use of these cells. We propose life imaging as a tool to characterize populations of human MSCs. Bone marrow MSCs from various donors and in vitro passages were evaluated for their in vitro motility, and the distances were correlated to the adipogenic, chondrogenic, and osteogenic differentiation potentials and the levels of senescence and cell size. Using life-image measuring of track lengths of 70 cells per population for a period of 24 hours, we observed that slow-moving cells had the higher proportion of senescent cells compared with fast ones. Larger cells moved less than smaller ones, and spindle-shaped cells had an average speed. Both fast cells and slow cells were characterized by a low differentiation potential, and average-moving cells were more effective in undergoing all three lineage differentiations. Furthermore, heterogeneity in single cell motility within a population correlated with the average-moving cells, and fast- and slow-moving cells tended toward homogeneity (i.e., a monotonous moving pattern). In conclusion, in vitro cell motility might be a useful tool to quickly characterize and distinguish the MSC population's differentiation potential before additional use. PMID:25473086

  16. Short intensive sequential therapy followed by autologous stem cell transplantation in adult Burkitt, Burkitt-like and lymphoblastic lymphoma

    NARCIS (Netherlands)

    G. van Imhoff (Gustaaf); B. van der Holt (Bronno); M.A. MacKenzie (Marius); G.J. Ossenkoppele (Gert); P.W. Wijermans (Pierre); M.H.H. Kramer (Mark); M.B. van 't Veer (Mars); H. Schouten (Harry); M. van Marwijk Kooy (Marinus); M.H.J. van Oers (Marinus); J. Raemaekers; P. Sonneveld (Pieter); L.A.M.H. Meulendijks (L. A M H); P.M. Kluin; H.C. Kluin-Nelemans (H.); L.F. Verdonck (Leo)

    2005-01-01

    textabstractThe feasibility and efficacy of up-front high-dose sequential chemotherapy followed by autologous stem cell transplantation (ASCT) in previously untreated adults (median age 33 years; range 15-64) with Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL) or lymphoblastic lymphoma (LyLy), b

  17. Short intensive sequential therapy followed by autologous stem cell transplantation in adult Burkitt, Burkitt-like and lymphoblastic lymphoma

    NARCIS (Netherlands)

    van Imhoff, GW; van der Holt, B; MacKenzie, MA; Ossenkoppele, GJ; Wijermans, PW; Kramer, MHH; van't Veer, MB; Schouten, HC; Kooy, MV; van Oers, MHJ; Raemaekers, JMM; Sonneveld, P; Meulendijks, LAMH; Kluin, PM; Kluin-Nelemans, HC; Verdonck, LF

    2005-01-01

    The feasibility and efficacy of up- front high- dose sequential chemotherapy followed by autologous stem cell transplantation ( ASCT) in previously untreated adults ( median age 33 years; range 15 - 64) with Burkitt lymphoma ( BL), Burkitt- like lymphoma ( BLL) or lymphoblastic lymphoma ( LyLy), bot

  18. Pre-emptive treatment with rituximab of molecular relapse after autologous stem cell transplantation in mantle cell lymphoma

    DEFF Research Database (Denmark)

    Andersen, Niels S; Pedersen, Lone B; Laurell, Anna;

    2009-01-01

    PURPOSE: Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell...

  19. Treatment of massive gastrointestinal bleeding occurred during autologous stem cell transplantation with recombinant activated factor VII and octreotide

    Directory of Open Access Journals (Sweden)

    Erman Atas

    2015-01-01

    Full Text Available After hematopoietic stem cell transplantation (HSCT, patients may suffer from bleeding. One of the bleeding type is gastrointestinal (GI which has serious morbidity and mortality in children with limited treatment options. Herein, we presented a child with upper GI bleeding post autologous HSCT controlled successfully by using recombinant activated factor VII (rFVIIa and octreotide infusion.

  20. Preimmunization of donor lymphocytes enhances antitumor immunity of autologous hematopoietic stem cell transplantation

    International Nuclear Information System (INIS)

    Lymphopenia-induced homeostatic proliferation (HP) of T cells following autologous hematopoietic stem cell transplantation (HSCT) skews the T-cell repertoire by engaging tumor-associated antigens (TAAs), leading to an induction of antitumor immunity. Here, as the tumor-reactive lymphocytes preferentially proliferate during the condition of HP, we examined whether the priming of a donor lymphocytes to TAAs could enhance HP-induced antitumor immunity in autologous HSCT recipients. First, to examine whether the tumor-bearing condition of donor influences the antitumor effect of HSCT, the lymphocytes isolated from CT26 tumor-bearing mice were infused into lethally irradiated mice. The growth of tumors was substantially suppressed in the mice that received HSCT from a tumor-bearing donor compared with a naïve donor, suggesting that a fraction of donor lymphocytes from tumor-bearing mice are primed in response to TAAs and remain responsive upon transplantation. We previously reported that type I interferon (IFN) maturates the dendritic cells and promotes the priming of T cells. We then investigated whether the further priming of donor cells by IFN-α can strengthen the antitumor effect of HSCT. The intratumoral IFN-α gene transfer significantly increased the number of IFN-γ-positive lymphocytes in response to CT26 cells but not the syngeneic lymphocytes in donor mice. The infusion of primed donor lymphocytes markedly suppressed the tumor growth in recipient mice, and cured 64% of the treated mice. Autologous HSCT with the infusion of primed donor lymphocytes is a promising strategy to induce an effective antitumor immunity for solid cancers

  1. Mesenchymal stem cell therapy for osteoarthritis: current perspectives

    Directory of Open Access Journals (Sweden)

    Wyles CC

    2015-08-01

    Full Text Available Cody C Wyles,1 Matthew T Houdek,2 Atta Behfar,3 Rafael J Sierra,21Mayo Medical School, 2Department of Orthopedic Surgery, 3Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USAAbstract: Osteoarthritis (OA is a painful chronic condition with a significant impact on quality of life. The societal burden imposed by OA is increasing in parallel with the aging population; however, no therapies have demonstrated efficacy in preventing the progression of this degenerative joint disease. Current mainstays of therapy include activity modification, conservative pain management strategies, weight loss, and if necessary, replacement of the affected joint. Mesenchymal stem cells (MSCs are a multipotent endogenous population of progenitors capable of differentiation to musculoskeletal tissues. MSCs have a well-documented immunomodulatory role, managing the inflammatory response primarily through paracrine signaling. Given these properties, MSCs have been proposed as a potential regenerative cell therapy source for patients with OA. Research efforts are focused on determining the ideal source for derivation, as MSCs are native to several tissues. Furthermore, optimizing the mode of delivery remains a challenge both for appropriate localization of MSCs and for directed guidance toward stemming the local inflammatory process and initiating a regenerative response. Scaffolds and matrices with growth factor adjuvants may prove critical in this effort. The purpose of this review is to summarize the current state of MSC-based therapeutics for OA and discuss potential barriers that must be overcome for successful implementation of cell-based therapy as a routine treatment strategy in orthopedics.Keywords: mesenchymal stem cell, osteoarthritis, treatment, regenerative medicine, cell therapy

  2. Myogenic differentiation of mesenchymal stem cells for muscle regeneration in urinary tract

    Institute of Scientific and Technical Information of China (English)

    YANG Bin; ZHENG Jun-hua; ZHANG Yuan-yuan

    2013-01-01

    Objective This article was to review the current status of adult mesenchymal stem cells transplantation for muscle regeneration in urinary tract and propose the future prospect in this field.Data sources The data used in this review were mainly obtained from articles listed in Medline and PubMed (2000-2013).The search terms were "mesenchymal stem cells","bladder","stress urinary incontinence" and "tissue engineering".Study selection Articles regarding the adult mesenchymal stem cells for tissue engineering of bladder and stress urinary incontinence were selected and reviewed.Results Adult mesenchymal stem cells had been identified and well characterized in human bone marrow,adipose tissue,skeletal muscle and urine,and demonstrated the capability of differentiating into smooth muscle cells and skeletal muscle cells under myogenic differentiation conditions in vitro.Multiple preclinical and clinical studies indicated that adult mesenchymal stem cells could restore and maintain the structure and function of urinary muscle tissues after transplanted,and potentially improve the quality of life in patients.Conclusions Smooth or skeletal myogenic differentiation of mesenchymal stem cells with regenerative medicine technology may provide a novel approach for muscle regeneration and tissue repair in urinary tract.The long-term effect and safety of mesenchymal stem cell transplantation should be further evaluated before this approach becomes widely used in patients.

  3. Freeze-Dried Rat Bone Marrow Mesenchymal Stem Cell Paracrine Factors: A Simplified Novel Material for Skin Wound Therapy

    Science.gov (United States)

    Peng, Yan; Xuan, Min; Zou, Jiping; Liu, Hongwei; Zhuo, Ziyuan; Wan, Yu

    2015-01-01

    The mesenchymal stem cell (MSC) supernatant is well known as a rich source of autologous cytokines and universally used for tissue regeneration in current clinical medicine. However, the limitation of conditioned medium used in open-wound repair compels the need to find a more sophisticated way to take advantage of the trophic factors of MSCs. We have now fabricated a three-dimensional membrane from freeze-dried bone marrow mesenchymal stem cells-conditioned medium (FBMSC-CM) using a simple freeze-dried protocol. Scanning electron microscopy images showed the microstructure of the FBMSC-CM membrane (FBMSC-CMM) resembling a mesh containing growth factors. ELISA was used to test the paracrine factors retained in the FBMSC-CMM, and the results indicated that FBMSC-CMM withheld over 80% of the paracrine factors. Live/dead assays were adopted to test the toxicity of the FBMSC-CMM on cultured rat dermal fibroblasts, and the results confirmed its biological safety with low toxicity. Moreover, the FBMSC-CMM could significantly accelerate wound healing and enhance the neovascularization as well as epithelialization through strengthening the trophic factors in the wound bed as determined by immunohistochemical staining. Thus, the ability to maintain paracrine factors and enhance the effectiveness of these growth factors in the wound as well as the simple procedure and economical materials required for production qualifies the FBMSC-CMM to be a candidate biomaterial for open-wound regeneration. PMID:25343727

  4. Analysis of the feasibility of early hospital discharge after autologous hematopoietic stem cell transplantation and the implications to nursing care

    OpenAIRE

    Alessandra Barban; Fabio Luiz Coracin; Priscila Tavares Musqueira; Andrea Barban; Lilian Piron Ruiz; Milton Artur Ruiz; Rosaura Saboya; Frederico Luiz Dulley

    2014-01-01

    INTRODUCTION: Autologous hematopoietic stem cell transplantation is a conduct used to treat some hematologic diseases and to consolidate the treatment of others. In the field of nursing, the few published scientific studies on nursing care and early hospital discharge of transplant patients are deficient. Knowledge about the diseases treated using hematopoietic stem cell transplantation, providing guidance to patients and caregivers and patient monitoring are important nursing activities in ...

  5. Instant stem cell therapy: Characterization and concentration of human mesenchymal stem cells in vitro

    OpenAIRE

    Kasten, P; I Beyen; Egermann, M.; AJ Suda; AA Moghaddam; Zimmermann, G; R Luginbühl

    2008-01-01

    In regenerative medicine, there is an approach to avoid expansion of the mesenchymal stem cell (MSC) before implantation. The aim of this study was to compare methods for instant MSC therapy by use of a portable, automatic and closed system centrifuge that allows for the concentration of MSCs. The main outcome measures were the amount of MSCs per millilitre of bone marrow (BM), clusters of differentiation (CD), proliferation and differentiation capacities of the MSC. A volume reduction protoc...

  6. [Bone and Stem Cells. The mechanism of osteogenic differentiation from mesenchymal stem cell].

    Science.gov (United States)

    Ohata, Yasuhisa; Ozono, Keiichi

    2014-04-01

    Osteoblasts and osteocytes originate from pluripotent mesenchymal stem cells. Mesenchymal stem cells commit to osteogenic lineage and differentiate into mature osteoblasts and osteocytes through osteoprogenitor cells and preosteoblasts in response to multiple stimuli. The osteoblast commitment, differentiation, and functions are governed by several transcription factors. Among these transcription factors, runt-related transcription factor 2 (Runx2) is a crucial factor in osteoblast differentiation and controls bone formation. Differentiation toward these osteogenic lineage is controlled by a multitude of cytokines including WNTs, bone morphogenetic protein (BMP) , transforming growth factor-β (TGF-β) , hedgehog, parathyroid hormone (PTH) /parathyroid hormone related protein (PTHrP) , insulin-like growth factor-1 (IGF-1) , fibroblast growth factor (FGF) , and Notch. Although regulation of Runx2 activity is a point of convergence of many of the signal transduction routes, there is also a high degree of cross-talk between these pathways. Thus, the combined action of the signal transduction pathways induced by some cytokines determines the commitment and differentiation of mesenchymal stem cells toward the osteogenic lineage. PMID:24681495

  7. Therapeutic Use of Stem Cell Transplantation for Cell Replacement or Cytoprotective Effect of Microvesicle Released from Mesenchymal Stem Cell

    OpenAIRE

    Choi, Moonhwan; Ban, Taehyun; Rhim, TaiYoun

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is the most common and severe type of idiopathic interstitial pneumonias (IIP), and which is currently no method was developed to restore normal structure and function. There are several reports on therapeutic effects of adult stem cell transplantations in animal models of pulmonary fibrosis. However, little is known about how mesenchymal stem cell (MSC) can repair the IPF. In this study, we try to provide the evidence to show that transplanted mesenchymal ...

  8. Engraftment Syndrome after Autologous Stem Cell Transplantation: An Update Unifying the Definition and Management Approach.

    Science.gov (United States)

    Cornell, Robert Frank; Hari, Parameswaran; Drobyski, William R

    2015-12-01

    Engraftment syndrome (ES) encompasses a continuum of periengraftment complications after autologous hematopoietic stem cell transplantation. ES may include noninfectious fever, skin rash, diarrhea, hepatic dysfunction, renal dysfunction, transient encephalopathy, and capillary leak features, such as noncardiogenic pulmonary infiltrates, hypoxia, and weight gain with no alternative etiologic basis other than engraftment. Given its pleiotropic clinical presentation, the transplant field has struggled to clearly define ES and related syndromes. Here, we present a comprehensive review of ES in all documented disease settings. Furthermore, we discuss the proposed risk factors, etiology, and clinical relevance of ES. Finally, our current approach to ES is included along with a proposed treatment algorithm for the management of this complication. PMID:26327628

  9. Localized extramedullary relapse after autologous hematopoietic stem cell transplantation in multiple myeloma

    International Nuclear Information System (INIS)

    Extramedullary plasmacytomas are rare manifestation of plasma cell malignancies. After hematopoietic stem cell transplantation HSCT, presentation of localized plasmacytoma with extramedullary growth is very unusual. We report a case of a 56-year-old woman with Dune-Salmon stage IIIA immunoglobulin A-kappa multiple myeloma, which presented 120 days after autologous HSCT with extramedullary plasmacytoma arising from a lymph node in supraclavicular region. The patient had no pretransplant-history related with extramedullary disease. There was no increase of plasma cells in bone marrow or monoclonal protein in urine or serum. Aspiration smears of lymph node revealed a population of plasmacytoid cells at various stages of maturation. The patient was successfully treated with local radiotherapy and has remained progression-free for more than 20 months. (author)

  10. Autologous peripheral blood stem cell transplantation in malignancies involving bone marrow.

    Science.gov (United States)

    Sica, S; Leone, G; Teofili, L; Pierelli, L; Menichella, G; Di Mario, A; Paoloni, A; Iovino, M S; Bizzi, B

    1991-03-01

    Six patients suffering from refractory malignancies (3 NHL, 1 MM, 1 AML, 1 neuroblastoma) received high dose of chemotherapy and autologous peripheral blood stem cell transplantation (APBSCT). The recruitment of PBSC was performed using conventional salvatage schedules of therapy. The patients received a median of 8.69 MNC/kg bw and 20.87 CFU-GM x 10(4)/kg bw. Prompt engraftment occurred in all patients and the median number of days to achieve WBC greater than 1 x 10(9)/l was 16.5 (range 7-26), PMN greater than 0.5 x 10(9)/l was 21.5 (range 6-37) and PLTs greater than 50 x 10(9)/l was 17.5 (range 4-31). Four patients achieved a complete remission. One patient (neuroblastoma) died of progressive disease after a partial response. One patient died in relapse because of drug related toxicity. PMID:1677914

  11. Mesenchymal Stem Cells for Cardiac Regeneration: Translation to Bedside Reality

    Directory of Open Access Journals (Sweden)

    Mohammad T. Elnakish

    2012-01-01

    Full Text Available Cardiovascular disease (CVD is the leading cause of death worldwide. According to the World Health Organization (WHO, an estimate of 17.3 million people died from CVDs in 2008 and by 2030, the number of deaths is estimated to reach almost 23.6 million. Despite the development of a variety of treatment options, heart failure management has failed to inhibit myocardial scar formation and replace the lost cardiomyocyte mass with new functional contractile cells. This shortage is complicated by the limited ability of the heart for self-regeneration. Accordingly, novel management approaches have been introduced into the field of cardiovascular research, leading to the evolution of gene- and cell-based therapies. Stem cell-based therapy (aka, cardiomyoplasty is a rapidly growing alternative for regenerating the damaged myocardium and attenuating ischemic heart disease. However, the optimal cell type to achieve this goal has not been established yet, even after a decade of cardiovascular stem cell research. Mesenchymal stem cells (MSCs in particular have been extensively investigated as a potential therapeutic approach for cardiac regeneration, due to their distinctive characteristics. In this paper, we focus on the therapeutic applications of MSCs and their transition from the experimental benchside to the clinical bedside.

  12. Characterization of mesenchymal stem cells derived from equine adipose tissue

    Directory of Open Access Journals (Sweden)

    A.M. Carvalho

    2013-08-01

    Full Text Available Stem cell therapy has shown promising results in tendinitis and osteoarthritis in equine medicine. The purpose of this work was to characterize the adipose-derived mesenchymal stem cells (AdMSCs in horses through (1 the assessment of the capacity of progenitor cells to perform adipogenic, osteogenic and chondrogenic differentiation; and (2 flow cytometry analysis using the stemness related markers: CD44, CD90, CD105 and MHC Class II. Five mixed-breed horses, aged 2-4 years-old were used to collect adipose tissue from the base of the tail. After isolation and culture of AdMSCs, immunophenotypic characterization was performed through flow cytometry. There was a high expression of CD44, CD90 and CD105, and no expression of MHC Class II markers. The tri-lineage differentiation was confirmed by specific staining: adipogenic (Oil Red O, osteogenic (Alizarin Red, and chondrogenic (Alcian Blue. The equine AdMSCs are a promising type of adult progenitor cell for tissue engineering in veterinary medicine.

  13. Guidance of mesenchymal stem cells on fibronectin structured hydrogel films.

    Directory of Open Access Journals (Sweden)

    Annika Kasten

    Full Text Available Designing of implant surfaces using a suitable ligand for cell adhesion to stimulate specific biological responses of stem cells will boost the application of regenerative implants. For example, materials that facilitate rapid and guided migration of stem cells would promote tissue regeneration. When seeded on fibronectin (FN that was homogeneously immmobilized to NCO-sP(EO-stat-PO, which otherwise prevents protein binding and cell adhesion, human mesenchymal stem cells (MSC revealed a faster migration, increased spreading and a more rapid organization of different cellular components for cell adhesion on fibronectin than on a glass surface. To further explore, how a structural organization of FN controls the behavior of MSC, adhesive lines of FN with varying width between 10 µm and 80 µm and spacings between 5 µm and 20 µm that did not allow cell adhesion were generated. In dependance on both line width and gaps, cells formed adjacent cell contacts, were individually organized in lines, or bridged the lines. With decreasing sizes of FN lines, speed and directionality of cell migration increased, which correlated with organization of the actin cytoskeleton, size and shape of the nuclei as well as of focal adhesions. Together, defined FN lines and gaps enabled a fine tuning of the structural organization of cellular components and migration. Microstructured adhesive substrates can mimic the extracellular matrix in vivo and stimulate cellular mechanisms which play a role in tissue regeneration.

  14. Epstein-Barr Virus–Associated Posttransplantation Lymphoproliferative Disorder after High-Dose Immunosuppressive Therapy and Autologous CD34-Selected Hematopoietic Stem Cell Transplantation for Severe Autoimmune Diseases

    OpenAIRE

    Nash, Richard A.; Dansey, Roger; Storek, Jan; Georges, George E.; Bowen, James D.; Holmberg, Leona A.; Kraft, George H.; Maureen D Mayes; McDonagh, Kevin T; Chen, Chien-Shing; DiPersio, John; LeMaistre, C. Fred; Pavletic, Steven; Sullivan, Keith M.; Sunderhaus, Julie

    2003-01-01

    High-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation (HSCT) is currently being evaluated for the control of severe autoimmune diseases. The addition of antithymocyte globulin (ATG) to high-dose chemoradiotherapy in the high-dose immunosuppressive therapy regimen and CD34 selection of the autologous graft may induce a higher degree of immunosuppression compared with conventional autologous HSCT for malignant diseases. Patients may be at higher risk...

  15. Symptomatic knee osteoarthritis treatment using autologous adipose derived stem cells and platelet-rich plasma: a clinical study

    OpenAIRE

    Phuc Van Pham; Khanh Hong-Thien Bui; Triet Dinh Duong; Nhan Thanh Nguyen; Thanh Duc Nguyen; Vien Tuong Le; Viet Thanh Mai; Nhan Lu-Chinh Phan; Dung Minh Le and Ngoc Kim Ngoc

    2014-01-01

    Osteoarthritis is one of the most common diseases, and it affects 12% of the population around the world. Although the disease is chronic, it significantly reduces the patient's quality of life. At present, stem cell therapy is considered to be an efficient approach for treating this condition. Mesenchymal stem cells (MSCs) show the most potential for stem cell therapy of osteoarthritis. In fact, MSCs can differentiate into certain mesodermal tissues such as cartilage and bone. Therefore, in ...

  16. Bone reconstruction of large defects using bone marrow derived autologous stem cells.

    Science.gov (United States)

    Lucarelli, Enrico; Donati, Davide; Cenacchi, Annarita; Fornasari, Pier Maria

    2004-04-01

    Bone is a tissue that has the ability to heal itself when fractured. Occasionally, a critical defect can be formed when part of the bone is lost or excised, in this case the bone fails to heal and requires bone reconstruction to prevent a non-union defect. Autogenous cancellous bone is the current gold standard treatment in bone loss. Because the amount of autogenous cancellous bone that can be harvested is limited, the expanding need for bone reconstruction is paired by the growth of interest in the discipline of tissue engineering. Labs worldwide are working to provide the right carrier and the right set of cells that, once retransplanted, will ensure bone repair. Several investigators have focused their attention on a subset of autologous non-hematopoietic stem/progenitor cells contained in the adult bone marrow stroma, referred to as stromal stem cells (SSC), as the appropriate cells to be transplanted. The use of autologous cells is facilitated by less stringent ethical and regulatory issues and does not require the patient to be immunologically suppressed. In pre-clinical and clinical protocols of critical defects in which SSC are employed, two approaches are mainly used: in the first, SSC are derived from bone marrow and directly introduced at the lesion site, in the second, SSC are derived from several sites and are expanded ex vivo before being implanted. Both approaches, equally correct in principle, will have to demonstrate, with definitive evidence of their efficacy, their capability of solving a critical clinical problem such as non-union. In this report we outline the difficulties of working with SSC. PMID:15062758

  17. Application of reticulated platelets to transfusion management during autologous stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Parco S

    2012-01-01

    Full Text Available Sergio Parco, Fulvia VascottoInstitute for Maternal and Child Health – IRCCS Burlo Garofolo, Trieste, ItalyBackground: The immature (or reticulated platelet fraction (IPF is rich in nucleic acids, especially RNA, and can be used as a predictive factor for platelet recovery in platelet immunomediated consumption or in postchemotherapy myelosuppression. Our aim was to determine if transfusions with IPF-rich solutions, during autologous peripheral blood stem cell transplantation, reduce the occurrence of bleeding and hemorrhagic complications.Patients and methods: Transfusions were administered to 40 children, affected with hematological pathologies, who underwent autologous peripheral hematopoietic progenitor cell transplantation. There were two groups of 20 patients, one group treated with IPF-poor and the other with IPF-rich solutions. In the two groups, the conditioning regimen was the same for the same pathology (hematological pathologies: 14 acute lymphoblastic leukemia; twelve acute myelocytic leukemia; four non-Hodgkin's lymphoma; two Hodgkin's lymphoma; eight solid tumors. A new automated analyzer was used to quantify the IPF: the XE2100 (Sysmex, Kobe, Japan blood cell counter with upgraded software.Results: The 20 patients who received solutions with a high percentage of IPF (3%–9% of total number of infused platelets required fewer transfusions than the 20 patients who received transfusions with a low percentage of IPF (0%–1% of total number of infused platelets: 83 versus 129 (mean of number of transfusions 4.15 versus 6.45 and a significant difference was found between the two groups by using the Mann–Whitney test (P < 0.001. The prophylactic transfusions decreased from three to two per week. There was only one case of massive hemorrhage.Conclusion: The use of IPF solutions reduces the number of transfusions and bleedings after peripheral blood stem cell transplantation in pediatric patients.Keywords: children, reticulated

  18. Mesenchymal stem cells protect from hypoxia-induced alveolar epithelial-mesenchymal transition.

    Science.gov (United States)

    Uzunhan, Yurdagül; Bernard, Olivier; Marchant, Dominique; Dard, Nicolas; Vanneaux, Valérie; Larghero, Jérôme; Gille, Thomas; Clerici, Christine; Valeyre, Dominique; Nunes, Hilario; Boncoeur, Emilie; Planès, Carole

    2016-03-01

    Administration of bone marrow-derived human mesenchymal stem cells (hMSC) reduces lung inflammation, fibrosis, and mortality in animal models of lung injury, by a mechanism not completely understood. We investigated whether hMSC would prevent epithelial-mesenchymal transition (EMT) induced by hypoxia in primary rat alveolar epithelial cell (AEC). In AEC cultured on semipermeable filters, prolonged hypoxic exposure (1.5% O2 for up to 12 days) induced phenotypic changes consistent with EMT, i.e., a change in cell morphology, a decrease in transepithelial resistance (Rte) and in the expression of epithelial markers [zonula occludens-1 (ZO-1), E-cadherin, AQP-5, TTF-1], together with an increase in mesenchymal markers [vimentin, α-smooth muscle actin (α-SMA)]. Expression of transcription factors driving EMT such as SNAIL1, ZEB1, and TWIST1 increased after 2, 24, and 48 h of hypoxia, respectively. Hypoxia also induced TGF-β1 mRNA expression and the secretion of active TGF-β1 in apical medium, and the expression of connective tissue growth factor (CTGF), two inducers of EMT. Coculture of AEC with hMSC partially prevented the decrease in Rte and in ZO-1, E-cadherin, and TTF-1 expression, and the increase in vimentin expression induced by hypoxia. It also abolished the increase in TGF-β1 expression and in TGF-β1-induced genes ZEB1, TWIST1, and CTGF. Finally, incubation with human recombinant KGF at a concentration similar to what was measured in hMSC-conditioned media restored the expression of TTF-1 and prevented the increase in TWIST1, TGF-β1, and CTGF in hypoxic AEC. Our results indicate that hMSC prevent hypoxia-induced alveolar EMT through the paracrine modulation of EMT signaling pathways and suggest that this effect is partly mediated by KGF. PMID:26702148

  19. Circulating mesenchymal stem cells and their clinical implications

    Directory of Open Access Journals (Sweden)

    Liangliang Xu

    2014-01-01

    Full Text Available Circulating mesenchymal stem cells (MSCs is a new cell source for tissue regeneration and tissue engineering. The characteristics of circulating MSCs are similar to those of bone marrow-derived MSCs (BM-MSCs, but they exist at a very low level in healthy individuals. It has been demonstrated that MSCs are able to migrate to the sites of injury and that they have some distinct genetic profiles compared to BM-MSCs. The current review summaries the basic knowledge of circulating MSCs and their potential clinical applications, such as mobilizing the BM-MSCs into circulation for therapy. The application of MSCs to cure a broad spectrum of diseases is promising, such as spinal cord injury, cardiovascular repair, bone and cartilage repair. The current review also discusses the issues of using of allogeneic MSCs for clinical therapy.

  20. Mesenchymal stem cells as a therapeutic tool to treat sepsis

    Institute of Scientific and Technical Information of China (English)

    Eleuterio Lombardo; Tom van der Poll; Olga DelaRosa; Wilfried Dalemans

    2015-01-01

    Sepsis is a clinical syndrome caused by a deregulatedhost response to an infection. Sepsis is the mostfrequent cause of death in hospitalized patients.Although knowledge of the pathogenesis of sepsishas increased substantially during the last decades,attempts to design effective and specific therapiestargeting components of the derailed host responsehave failed. Therefore, there is a dramatic need fornew and mechanistically alternative therapies to treatthis syndrome. Based on their immunomodulatoryproperties, adult mesenchymal stem or stromal cells(MSCs) can be a novel therapeutic tool to treat sepsis.Indeed, MSCs reduce mortality in experimental modelsof sepsis by modulating the deregulated inflammatoryresponse against bacteria through the regulation ofmultiple inflammatory networks, the reprogrammingof macrophages and neutrophils towards a more antiinflammatoryphenotype and the release of antimicrobialpeptides. This report will review the currentknowledge on the effects of MSC treatment in preclinicalexperimental small animal models of sepsis.

  1. Mesenchymal stem cells reduce the irradiation induced lung injury

    International Nuclear Information System (INIS)

    Objective: To evaluate the role of mesenchymal stem cells (MSCs) derived from mouse bone and embryo dorsal aorta (DA) area in the treatment of irradiation induced lung injury of mouse model. Methods: The mice were divided into four groups as normal control group, irradiation group,bone MSCs treatment group and DA MSCs treatment group. Immunohistochemical Analysis of lung tissue was observed after 9 months of treatment. Results: Fibrosis and alveolar infiltration were scored in each group. The score for fibrosis and alveolar is 0. 17 in normal control group, 2 in irradiation group, 1 in bone MSCs treat group and 1.38 in DA MSCs treat group. Conclusion: The extent of irradiation Induced Lung Injury could be reduced thorough the treatment of MSCs derived from mouse bone and embryos dorsal aorta ( DA ) area. (authors)

  2. Mesenchymal Stem Cells as Immunomodulators in a Vascularized Composite Allotransplantation

    Directory of Open Access Journals (Sweden)

    Yur-Ren Kuo

    2012-01-01

    Full Text Available Vascularized composite allotransplantations (VCAs are not routinely performed for tissue reconstruction because of the potentially harmful adverse effects associated with lifelong administration of immunosuppressive agents. Researchers have been eagerly seeking alternative methods that circumvent the long-term use of immunosuppressants. Mesenchymal stem cells (MSCs show promise as an immunomodulatory therapeutic agent and are currently being tested in preclinical and clinical settings as therapies for autoimmune disorders or transplant rejection. The mechanisms by which MSCs modulate the immune response are still under thorough investigation, but these most likely involve expression of local factors influencing T-cell regulation, modulation of cytokine expression (e.g., IL-10, TGF-β, TNF-, INF-γ, etc., and interactions with dendritic or antigen presenting cells. In this paper, we summarize the current understanding of immunomodulation achieved by MSC therapies and introduce a possible outline for future clinical applications in VCA.

  3. Immunomodulatory functions of mesenchymal stem cells and possible mechanisms.

    Science.gov (United States)

    Wang, Qing; Ding, Gang; Xu, Xin

    2016-09-01

    In addition to their well-studied self-renewal capabilities and multipotent differentiation properties, mesenchymal stem cells (MSCs) have been reported to possess profound immunomodulatory functions both in vitro and in vivo. More and more studies have shown that MSCs are capable of interacting closely with almost all subsets of immune cells, such as T cells, B cells, dendritic cells, natural killer cells, macrophages, and neutrophils etc. The immunomodulatory property of MSCs may shed light on the treatment of a variety of autoimmune and inflammation-related diseases. In this article, we will review the studies on the immunomodulatory and anti-inflammatory functions of MSCs and the mechanisms responsible for the interaction between immune cells and MSCs, which could improve the development of promising approaches for cell-mediated immune therapies. PMID:26932157

  4. Dual origin of mesenchymal stem cells contributing to organ growth and repair

    OpenAIRE

    Feng, Jifan; Andrea MANTESSO; Bari, Cosimo; Nishiyama, Akiko; Sharpe, Paul T.

    2011-01-01

    In many adult tissues, mesenchymal stem cells (MSCs) are closely associated with perivascular niches and coexpress many markers in common with pericytes. The ability of pericytes to act as MSCs, however, remains controversial. By using genetic lineage tracing, we show that some pericytes differentiate into specialized tooth mesenchyme-derived cells—odontoblasts—during tooth growth and in response to damage in vivo. As the pericyte-derived mesenchymal cell contribution to odontoblast different...

  5. Transformation of human mesenchymal stem cells in radiation carcinogenesis: long-term effect of ionizing radiation

    DEFF Research Database (Denmark)

    Christensen, Rikke; Alsner, Jan; Sørensen, Flemming Brandt;

    2008-01-01

    Increasing evidence on cancer stem cells suggest that stem cells are susceptive to carcinogenesis and consequently can be the origin of many cancers. We have recently established a telomerase-transduced human mesenchymal stem cell line and subsequently irradiated this in order to achieve malignant...

  6. Patterns of amino acid metabolism by proliferating human mesenchymal stem cells

    NARCIS (Netherlands)

    Higuera, G.A.; Schop, D.; Spitters, T.W.; Dijkhuizen, R.; Bracke, M.; Bruijn, J.D.; Martens, D.E.; Karperien, M.; Boxtel, van A.J.B.; Blitterswijk, van C.A.

    2012-01-01

    The nutritional requirements of stem cells have not been determined; in particular, the amino acid metabolism of stem cells is largely unknown. In this study, we investigated the amino acid metabolism of human mesenchymal stem cells (hMSCs), with focus on two questions: Which amino acids are consume

  7. Mesenchymal stem cells are highly resistant to sulfur mustard.

    Science.gov (United States)

    Schmidt, Annette; Scherer, Michael; Thiermann, Horst; Steinritz, Dirk

    2013-12-01

    The effect of sulfur mustard (SM) to the direct injured tissues of the skin, eyes and airways is well investigated. Little is known about the effect of SM to mesenchymal stem cells (MSC). However, this is an interesting aspect. Comparing the clinical picture of SM it is known today that MSC play an important role e.g. in chronic impaired wound healing. Therefore we wanted to get an understanding about how SM affects MSC and if these findings might become useful to get a better understanding of the effect of sulfur mustard gas with respect to skin wounds. We used mesenchymal stem cells, isolated from femoral heads from healthy donors and treated them with a wide range of SM to ascertain the dose-response-curve. With the determined inhibitory concentrations IC1 (1μM), IC5 (10μM), IC10 (20μM) and IC25 (40μM) we did further investigations. We analyzed the migratory ability and the differentiation capacity under influence of SM. Already very low concentrations of SM demonstrated a strong effect to the migratory activity whereas the differentiation capacity seemed not to be affected. Putting these findings together it seems to be likely that a link between MSC and the impaired wound healing after SM exposure might exist. Same as in patients with chronic impaired wound healing MSC had shown a reduced migratory activity. The fact that MSC are able to tolerate very high concentrations of SM and still do not lose their differentiation capacity may reveal new ways of treating wounds caused by sulfur mustard. PMID:23933411

  8. EXERCISE in pediatric autologous stem cell transplant patients: a randomized controlled trial protocol

    Directory of Open Access Journals (Sweden)

    Chamorro-Viña Carolina

    2012-09-01

    Full Text Available Abstract Background Hematopoietic stem cell transplantation is an intensive therapy used to improve survivorship and cure various oncologic diseases. However, this therapy is associated with high mortality rates and numerous negative side-effects. The recovery of the immune system is a special concern and plays a key role in the success of this treatment. In healthy populations it is known that exercise plays an important role in immune system regulation, but little is known about the role of exercise in the hematological and immunological recovery of children undergoing hematopoietic stem cell transplant. The primary objective of this randomized-controlled trial (RCT is to study the effect of an exercise program (in- and outpatient on immune cell recovery in patients undergoing an autologous stem cell transplantation. The secondary objective is to determine if an exercise intervention diminishes the usual deterioration in quality of life, physical fitness, and the acquisition of a sedentary lifestyle. Methods This RCT has received approval from The Conjoint Health Research Ethics Board (CHREB of the University of Calgary (Ethics ID # E-24476. Twenty-four participants treated for a malignancy with autologous stem cell transplant (5 to 18 years in the Alberta Children’s Hospital will be randomly assigned to an exercise or control group. The exercise group will participate in a two-phase exercise intervention (in- and outpatient from hospitalization until 10 weeks after discharge. The exercise program includes strength, flexibility and aerobic exercise. During the inpatient phase this program will be performed 5 times/week and will be supervised. The outpatient phase will combine a supervised session with two home-based exercise sessions with the use of the Wii device. The control group will follow the standard protocol without any specific exercise program. A range of outcomes, including quantitative and functional recovery of immune system

  9. Mesenchymal stem cells from rats with chronic kidney disease exhibit premature senescence and loss of regenerative potential.

    Directory of Open Access Journals (Sweden)

    Barbara Mara Klinkhammer

    Full Text Available Mesenchymal stem cell (MSC transplantation has the potential for organ repair. Nevertheless, some factors might lessen the regenerative potential of MSCs, e.g. donor age or systemic disease. It is thus important to carefully assess the patient's suitability for autologous MSC transplantation. Here we investigated the effects of chronic kidney disease (CKD on MSC function. We isolated bone marrow MSCs from remnant kidney rats (RK with CKD (CKD-RK-MSC and found signs of premature senescence: spontaneous adipogenesis, reduced proliferation capacity, active senescence-associated-β-galactosidase, accumulation of actin and a modulated secretion profile. The functionality of CKD-RK-MSCs in vivo was tested in rats with acute anti-Thy1.1-nephritis, where healthy MSCs have been shown to be beneficial. Rats received healthy MSCs, CKD-RK-MSC or medium by injection into the left renal artery. Kidneys receiving healthy MSCs exhibited accelerated healing of glomerular lesions, whereas CKD-RK-MSC or medium exerted no benefit. The negative influence of advanced CKD/uremia on MSCs was confirmed in a second model of CKD, adenine nephropathy (AD. MSCs from rats with adenine nephropathy (CKD-AD-MSC also exhibited cellular modifications and functional deficits in vivo. We conclude that CKD leads to a sustained loss of in vitro and in vivo functionality in MSCs, possibly due to premature cellular senescence. Considering autologous MSC therapy in human renal disease, studies identifying uremia-associated mechanisms that account for altered MSC function are urgently needed.

  10. Evaluation of intrarenal mesenchymal stem cell injection for treatment of chronic kidney disease in cats: a pilot study.

    Science.gov (United States)

    Quimby, Jessica M; Webb, Tracy L; Gibbons, Debra S; Dow, Steven W

    2011-06-01

    The feasibility of autologous intrarenal mesenchymal stem cell (MSC) therapy in cats with chronic kidney disease (CKD) was investigated. Six cats (two healthy, four with CKD) received a single unilateral intrarenal injection of autologous bone marrow-derived or adipose tissue-derived MSC (bmMSC or aMSC) via ultrasound guidance. Minimum database and glomerular filtration rate (GFR) via nuclear scintigraphy were determined pre-injection, at 7 days and at 30 days post-injection. Intrarenal injection did not induce immediate or long-term adverse effects. Two cats with CKD that received aMSC experienced modest improvement in GFR and a mild decrease in serum creatinine concentration. Despite the possible benefits of intrarenal MSC injections for CKD cats, the number of sedations and interventions required to implement this approach would likely preclude widespread clinical application. We concluded that MSC could be transferred safely by ultrasound-guided intrarenal injection in cats, but that alternative sources and routes of MSC therapy should be investigated. PMID:21334237

  11. Chondrogenic potential of human adult mesenchymal stem cells is independent of age or osteoarthritis etiology

    NARCIS (Netherlands)

    Scharstuhl, A.; Schewe, B.; Benz, K.; Gaissmaier, C.; Bühring, H.J.; Stoop, R.

    2007-01-01

    Osteoarthritis (OA) is a multifactorial disease strongly correlated with history of joint trauma, joint dysplasia, and advanced age. Mesenchymal stem cells (MSCs) are promising cells for biological cartilage regeneration. Conflicting data have been published concerning the availability of MSCs from

  12. Citalopram increases the differentiation efifcacy of bone marrow mesenchymal stem cells into neuronal-like cells

    Institute of Scientific and Technical Information of China (English)

    Javad Verdi; Seyed Abdolreza Mortazavi-Tabatabaei; Shiva Sharif; Hadi Verdi; Alireza Shoae-Hassani

    2014-01-01

    Several studies have demonstrated that selective serotonin reuptake inhibitor antidepressants can promote neuronal cell proliferation and enhance neuroplasticity both in vitro and in vivo. It is hypothesized that citalopram, a selective serotonin reuptake inhibitor, can promote the neuronal differentiation of adult bone marrow mesenchymal stem cells. Citalopram strongly enhanced neuronal characteristics of the cells derived from bone marrow mesenchymal stem cells. The rate of cell death was decreased in citalopram-treated bone marrow mesenchymal stem cells than in control cells in neurobasal medium. In addition, the cumulative population doubling level of the citalopram-treated cells was signiifcantly increased compared to that of control cells. Also BrdU incorporation was elevated in citalopram-treated cells. These ifndings suggest that citalopram can improve the neuronal-like cell differentiation of bone marrow mesenchymal stem cells by increasing cell proliferation and survival while maintaining their neuronal characteristics.

  13. Imaging gene expression in human mesenchymal stem cells: from small to large animals

    DEFF Research Database (Denmark)

    Willmann, Jürgen K; Paulmurugan, Ramasamy; Rodriguez-Porcel, Martin;

    2009-01-01

    To evaluate the feasibility of reporter gene imaging in implanted human mesenchymal stem cells (MSCs) in porcine myocardium by using clinical positron emission tomography (PET)-computed tomography (CT) scanning....

  14. Study on phenotypic and cytogenetic characteristics of bone marrow mesenchymal stem cells in myelodysplastic syndromes

    Institute of Scientific and Technical Information of China (English)

    宋陆茜

    2013-01-01

    Objective To investigate phenotype,cell differentiation and cytogenetic properties of bone marrow(BM) mesenchymal stem cells(MSC)separated from the myelodysplastic syndrome(MDS) patients,and to analyze cytogenetic

  15. The paracrine effect of mesenchymal human stem cells restored hearing in β-tubulin induced autoimmune sensorineural hearing loss.

    Science.gov (United States)

    Yoo, T J; Du, Xiaoping; Zhou, Bin

    2015-12-01

    The aim of this study was to examine the activities of hASCs (Human Adipose tissue Derived Stem Cells) on experimental autoimmune hearing loss (EAHL) and how human stem cells regenerated mouse cochlea cells. We have restored hearing in 19 years old white female with autoimmune hearing loss with autologous adipose tissue derived stem cells and we wish to understand the mechanism of restoration of hearing in animal model. BALB/c mice underwent to develop EAHL; mice with EAHL were given hASCs intraperitoneally once a week for 6 consecutive weeks. ABR were examined over time. The helper type 1 autoreactive responses and T-reg cells were examined. H&E staining or immunostaining with APC conjugated anti-HLA-ABC antibody were conducted. The organ of Corti, stria vascularis, spira ligament and spiral ganglion in stem cell group are normal. In control group, without receiving stem cells, the organ of Corti is replaced by a single layer of cells, atrophy of stria vascularis. Systemic infusion of hASCs significantly improved hearing function and protected hair cells in established EAHL. The hASCs decreased the proliferation of antigen specific Th1/Th17 cells and induced the production of anti-inflammatory cytokine interleukin10 in splenocytes. They also induced the generation of antigen specific CD4(+)CD25(+)Foxp3(+)T-reg cells. The experiment showed the restoration is due to the paracrine activities of human stem cells, since there are newly regenerated mice spiral ganglion cells, not human mesenchymal stem cells derived tissue given by intraperitoneally. PMID:26235980

  16. Mesenchymal stem cell therapy in lung disorders: pathogenesis of lung diseases and mechanism of action of mesenchymal stem cell.

    Science.gov (United States)

    Inamdar, Ajinkya C; Inamdar, Arati A

    2013-10-01

    Lung disorders such as asthma, acute respiratory distress syndrome (ARDS), chronic obstructive lung disease (COPD), and interstitial lung disease (ILD) show a few common threads of pathogenic mechanisms: inflammation, aberrant immune activity, infection, and fibrosis. Currently no modes of effective treatment are available for ILD or emphysema. Being anti-inflammatory, immunomodulatory, and regenerative in nature, the administration of mesenchymal stem cells (MSCs) has shown the capacity to control immune dysfunction and inflammation in the lung. The intravenous infusion of MSCs, the common mode of delivery, is followed by their entrapment in lung vasculature before MSCs reach to other organ systems thus indicating the feasible and promising approach of MSCs therapy for lung diseases. In this review, we discuss the mechanistic basis for MSCs therapy for asthma, ARDS, COPD, and ILD. PMID:23992090

  17. Chondroitinase ABC plus bone marrow mesenchymal stem cells for repair of spinal cord injury☆

    OpenAIRE

    Zhang, Chun; He, Xijing; Li, Haopeng; Wang, Guoyu

    2013-01-01

    As chondroitinase ABC can improve the hostile microenvironment and cell transplantation is proven to be effective after spinal cord injury, we hypothesized that their combination would be a more effective treatment option. At 5 days after T8 spinal cord crush injury, rats were injected with bone marrow mesenchymal stem cell suspension or chondroitinase ABC 1 mm from the edge of spinal cord damage zone. Chondroitinase ABC was first injected, and bone marrow mesenchymal stem cell suspension was...

  18. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    OpenAIRE

    Ya-jing Zhou; Jian-min Liu; Shu-ming Wei; Yun-hao Zhang; Zhen-hua Qu; Shu-bo Chen

    2015-01-01

    Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-l...

  19. Mesenchymal Stem Cells Isolated from Adipose and Other Tissues: Basic Biological Properties and Clinical Applications

    OpenAIRE

    Hakan Orbay; Morikuni Tobita; Hiroshi Mizuno

    2012-01-01

    Mesenchymal stem cells (MSCs) are adult stem cells that were initially isolated from bone marrow. However, subsequent research has shown that other adult tissues also contain MSCs. MSCs originate from mesenchyme, which is embryonic tissue derived from the mesoderm. These cells actively proliferate, giving rise to new cells in some tissues, but remain quiescent in others. MSCs are capable of differentiating into multiple cell types including adipocytes, chondrocytes, osteocytes, and cardiomyoc...

  20. Interaction of bone marrow-derived mesenchymal stem cells on neuroblastoma cells

    OpenAIRE

    Kwong, Rebecca Sze-Wai.

    2012-01-01

    Background Mesenchymal stem cells (MSC) were first discovered in the 1970s by scientist A.J. Friedenstein and his colleagues. Friedenstein isolated the first mesenchymal stem cells and was credited for discovering its multilineage differentiation potential. To this day, an extensive amount of research has been conducted on the use of these cells in the treatment of degenerative diseases and various autoimmune disorders. Its migratory ability and immunosuppressive characteristics make MSCs...

  1. Mesenchymal stem cells preconditioned with trimetazidine promote neovascularization of hearts under hypoxia/reoxygenation injury

    OpenAIRE

    Hu, Xiaowu; Yang, Junjie; Wang, Ying; Zhang, You; Ii, Masaaki; Shen, Zhenya; Hui, Jie

    2015-01-01

    Background: Cell-based angiogenesis is a promising treatment for ischemic diseases; however, survival of implanted cells is impaired by the ischemic microenvironment. In this study, mesenchymal stem cells (MSCs) for cell transplantation were preconditioned with trimetazidine (TMZ). We hypothesized that TMZ enhances the survival rate of MSCs under hypoxic stimuli through up-regulation of HIF1-α. Methods and results: Bone marrow-derived rat mesenchymal stem cells were preconditioned with 10 μM ...

  2. Neuroprotection and immunomodulation by xenografted human mesenchymal stem cells following spinal cord ventral root avulsion

    OpenAIRE

    Ribeiro, Thiago B.; Duarte, Adriana S. S.; Longhini, Ana Leda F.; Fernando Pradella; Farias, Alessandro S.; Angela C. M. Luzo; Oliveira, Alexandre L. R.; Sara Teresinha Olalla Saad

    2015-01-01

    The present study investigates the effects of xenotransplantation of Adipose Tissue Mesenchymal Stem Cells (AT-MSCs) in animals after ventral root avulsion. AT-MSC has similar characteristics to bone marrow mesenchymal stem cells (BM-MSCs), such as immunomodulatory properties and expression of neurotrophic factors. In this study, Lewis rats were submitted to surgery for unilateral avulsion of the lumbar ventral roots and received 5 × 105 AT-MSCs via the lateral funiculus. Two weeks after cell...

  3. Isolation, culturing and characterization of rat adipose tissue-derived mesenchymal stem cells: a simple technique

    OpenAIRE

    NİYAZ, Mehmet; Özer Aylin GÜRPINAR; GÜNAYDIN, Serdar; Onur, Mehmet Ali

    2012-01-01

    In this study, our aim was to develop a new simple technique for isolation of mesenchymal stem cells from adipose tissue. For this purpose, mesenchymal stem cells were isolated from rat adipose tissue by using the primary explant culture technique. When the cells became confluent, they were passaged 4 times by using the standard trypsinization method with trypsin/EDTA solution. Cells at second passage were characterized by using immunofluorescence staining against CD13 and CD29 markers. The r...

  4. Citalopram increases the differentiation efficacy of bone marrow mesenchymal stem cells into neuronal-like cells

    OpenAIRE

    Verdi, Javad; Mortazavi-Tabatabaei, Seyed AbdolReza; Sharif, Shiva; Verdi, Hadi; Shoae-Hassani, Alireza

    2014-01-01

    Several studies have demonstrated that selective serotonin reuptake inhibitor antidepressants can promote neuronal cell proliferation and enhance neuroplasticity both in vitro and in vivo. It is hypothesized that citalopram, a selective serotonin reuptake inhibitor, can promote the neuronal differentiation of adult bone marrow mesenchymal stem cells. Citalopram strongly enhanced neuronal characteristics of the cells derived from bone marrow mesenchymal stem cells. The rate of cell death was d...

  5. Application of mesenchymal stem cells in bone regenerative procedures in oral implantology. A literature review

    OpenAIRE

    Viña, José A.; El-Alami, Marya; Gambini, Juan; Borrás Blasco, Consuelo; Viña, Jose; Peñarrocha, María A.

    2014-01-01

    Objective: The aim of this work was to review de literature about the role of mesenchymal stem cells in bone regenerative procedures in oral implantology, specifically, in the time require to promote bone regeneration. Study Design: A bibliographic search was carried out in PUBMED with a combination of different key words. Animal and human studies that assessed histomorphometrically the influence of mesenchymal stem cells on bone regeneration procedures in oral implantology surgeries were ...

  6. Plerixafor for autologous stem-cell mobilization and transplantation for patients in Ontario

    Science.gov (United States)

    Kouroukis, C.T.; Varela, N.P.; Bredeson, C.; Kuruvilla, J.; Xenocostas, A.

    2016-01-01

    Background High-dose chemotherapy with autologous stem-cell transplantation (asct) is an accepted part of standard therapy for patients with hematologic malignancies. Usually, stem-cell mobilization uses granulocyte colony–stimulating factor (g-csf); however, some patients are not able to be mobilized with chemotherapy and g-csf, and such patients could be at higher risk of failing mobilization. Plerixafor is a novel mobilization agent that is absorbed quickly after subcutaneous injection and, at the recommended dose of 0.24 mg/kg, provides a sustained increase in circulating CD34+ cells for 10–18 hours. The main purpose of the present report was to evaluate the most current evidence on the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct for patients in Ontario so as to make recommendations for clinical practice and to assist Cancer Care Ontario in decision-making with respect to this intervention. Methods The medline and embase databases were systematically searched for evidence from January 1996 to March 2015, and the best available evidence was used to draft recommendations relevant to the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct. Final approval of this practice guideline report was obtained from both the Stem Cell Transplant Steering Committee and the Report Approval Panel of the Program in Evidence-Based Care. Recommendations These recommendations apply to adult patients considered for asct: ■ Adding plerixafor to g-csf is an option for initial mobilization in patients with non-Hodgkin lymphoma or multiple myeloma who are eligible for asct when chemotherapy cannot be used and only g-csf mobilization is available.■ For patients with a low peripheral blood CD34+ cell count (for example, <10/μL) at the time of anticipated stem-cell harvesting, or with an inadequate first-day apheresis collection, it is recommended that plerixafor be added to the

  7. Eccentric exercise facilitates mesenchymal stem cell appearance in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    M Carmen Valero

    Full Text Available Eccentric, or lengthening, contractions result in injury and subsequently stimulate the activation and proliferation of satellite stem cells which are important for skeletal muscle regeneration. The discovery of alternative myogenic progenitors in skeletal muscle raises the question as to whether stem cells other than satellite cells accumulate in muscle in response to exercise and contribute to post-exercise repair and/or growth. In this study, stem cell antigen-1 (Sca-1 positive, non-hematopoetic (CD45⁻ cells were evaluated in wild type (WT and α7 integrin transgenic (α7Tg mouse muscle, which is resistant to injury yet liable to strain, 24 hr following a single bout of eccentric exercise. Sca-1⁺CD45⁻ stem cells were increased 2-fold in WT muscle post-exercise. The α7 integrin regulated the presence of Sca-1⁺ cells, with expansion occurring in α7Tg muscle and minimal cells present in muscle lacking the α7 integrin. Sca-1⁺CD45⁻ cells isolated from α7Tg muscle following exercise were characterized as mesenchymal-like stem cells (mMSCs, predominantly pericytes. In vitro multiaxial strain upregulated mMSC stem cells markers in the presence of laminin, but not gelatin, identifying a potential mechanistic basis for the accumulation of these cells in muscle following exercise. Transplantation of DiI-labeled mMSCs into WT muscle increased Pax7⁺ cells and facilitated formation of eMHC⁺DiI⁻ fibers. This study provides the first demonstration that mMSCs rapidly appear in skeletal muscle in an α7 integrin dependent manner post-exercise, revealing an early event that may be necessary for effective repair and/or growth following exercise. The results from this study also support a role for the α7 integrin and/or mMSCs in molecular- and cellular-based therapeutic strategies that can effectively combat disuse muscle atrophy.

  8. Eccentric exercise facilitates mesenchymal stem cell appearance in skeletal muscle.

    Science.gov (United States)

    Valero, M Carmen; Huntsman, Heather D; Liu, Jianming; Zou, Kai; Boppart, Marni D

    2012-01-01

    Eccentric, or lengthening, contractions result in injury and subsequently stimulate the activation and proliferation of satellite stem cells which are important for skeletal muscle regeneration. The discovery of alternative myogenic progenitors in skeletal muscle raises the question as to whether stem cells other than satellite cells accumulate in muscle in response to exercise and contribute to post-exercise repair and/or growth. In this study, stem cell antigen-1 (Sca-1) positive, non-hematopoetic (CD45⁻) cells were evaluated in wild type (WT) and α7 integrin transgenic (α7Tg) mouse muscle, which is resistant to injury yet liable to strain, 24 hr following a single bout of eccentric exercise. Sca-1⁺CD45⁻ stem cells were increased 2-fold in WT muscle post-exercise. The α7 integrin regulated the presence of Sca-1⁺ cells, with expansion occurring in α7Tg muscle and minimal cells present in muscle lacking the α7 integrin. Sca-1⁺CD45⁻ cells isolated from α7Tg muscle following exercise were characterized as mesenchymal-like stem cells (mMSCs), predominantly pericytes. In vitro multiaxial strain upregulated mMSC stem cells markers in the presence of laminin, but not gelatin, identifying a potential mechanistic basis for the accumulation of these cells in muscle following exercise. Transplantation of DiI-labeled mMSCs into WT muscle increased Pax7⁺ cells and facilitated formation of eMHC⁺DiI⁻ fibers. This study provides the first demonstration that mMSCs rapidly appear in skeletal muscle in an α7 integrin dependent manner post-exercise, revealing an early event that may be necessary for effective repair and/or growth following exercise. The results from this study also support a role for the α7 integrin and/or mMSCs in molecular- and cellular-based therapeutic strategies that can effectively combat disuse muscle atrophy. PMID:22253772

  9. Proteomic Applications in the Study of Human Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Jesús Mateos

    2014-02-01

    Full Text Available Mesenchymal stem cells (MSCs are undifferentiated cells with an unlimited capacity for self-renewal and able to differentiate towards specific lineages under appropriate conditions. MSCs are, a priori, a good target for cell therapy and clinical trials as an alternative to embryonic stem cells, avoiding ethical problems and the chance for malignant transformation in the host. However, regarding MSCs, several biological implications must be solved before their application in cell therapy, such as safe ex vivo expansion and manipulation to obtain an extensive cell quantity amplification number for use in the host without risk accumulation of genetic and epigenetic abnormalities. Cell surface markers for direct characterization of MSCs remain unknown, and the precise molecular mechanisms whereby growth factors stimulate their differentiation are still missing. In the last decade, quantitative proteomics has emerged as a promising set of techniques to address these questions, the answers to which will determine whether MSCs retain their potential for use in cell therapy. Proteomics provides tools to globally analyze cellular activity at the protein level. This proteomic profiling allows the elucidation of connections between broad cellular pathways and molecules that were previously impossible to determine using only traditional biochemical analysis. However; thus far, the results obtained must be orthogonally validated with other approaches. This review will focus on how these techniques have been applied in the evaluation of MSCs for their future applications in safe therapies.

  10. The sensitivity of human mesenchymal stem cells to ionizing radiation

    International Nuclear Information System (INIS)

    Purpose: Recent studies have shown that mesenchymal stem cells (MSCs) obtained from bone marrow transplantation patients originate from the host. This clinical observation suggests that MSCs in their niches could be resistant to irradiation. However, the biologic responses of bone marrow MSCs to irradiation have rarely been described in the literature. Methods and Materials: In this study, human bone marrow-derived, clonally expanded MSCs were used to investigate their sensitivity to irradiation in vitro, and the cellular mechanisms that may facilitate resistance to irradiation. The human lung cancer cell line A549 and the breast cancer cell line HCC1937 were used as controls for radiosensitivity; the former line has been shown to be radioresistant and the latter radiosensitive. We then examined their in vitro biologic changes and sensitivities to radiation therapy. Results: Our results suggest that MSCs are characterized as resistant to irradiation. Several cellular mechanisms were demonstrated that may facilitate resistance to irradiation: ATM protein phosphorylation, activation of cell-cycle checkpoints, double-strand break repair by homologous recombination and nonhomologous end joining (NHEJ), and the antioxidant capacity for scavenging reactive oxygen species. Conclusions: As demonstrated, MSCs possess a better antioxidant reactive oxygen species-scavenging capacity and active double-strand break repair to facilitate their radioresistance. These findings provide a better understanding of radiation-induced biologic responses in MSCs and may lead to the development of better strategies for stem cell treatment and cancer therapy

  11. Clinical Applications of Mesenchymal Stem Cells in Chronic Diseases

    Directory of Open Access Journals (Sweden)

    Andrea Farini

    2014-01-01

    Full Text Available Extraordinary progress in understanding several key features of stem cells has been made in the last ten years, including definition of the niche, and identification of signals regulating mobilization and homing as well as partial understanding of the mechanisms controlling self-renewal, commitment, and differentiation. This progress produced invaluable tools for the development of rational cell therapy protocols that have yielded positive results in preclinical models of genetic and acquired diseases and, in several cases, have entered clinical experimentation with positive outcome. Adult mesenchymal stem cells (MSCs are nonhematopoietic cells with multilineage potential to differentiate into various tissues of mesodermal origin. They can be isolated from bone marrow and other tissues and have the capacity to extensively proliferate in vitro. Moreover, MSCs have also been shown to produce anti-inflammatory molecules which can modulate humoral and cellular immune responses. Considering their regenerative potential and immunoregulatory effect, MSC therapy is a promising tool in the treatment of degenerative, inflammatory, and autoimmune diseases. It is obvious that much work remains to be done to increase our knowledge of the mechanisms regulating development, homeostasis, and tissue repair and thus to provide new tools to implement the efficacy of cell therapy trials.

  12. Mesenchymal stem cell therapy for cirrhosis: Present and future perspectives.

    Science.gov (United States)

    Eom, Young Woo; Kim, Gaeun; Baik, Soon Koo

    2015-09-28

    Cirrhosis occurs as a result of various chronic liver injuries, which may be caused by viral infections, alcohol abuse and the administration of drugs and chemicals. Recently, bone marrow cells (BMCs), hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) have been used for developing treatments for cirrhosis. Clinical trials have investigated the therapeutic potential of BMCs, HSCs and MSCs for the treatment of cirrhosis based on their potential to differentiate into hepatocytes. Although the therapeutic mechanisms of BMC, HSC and MSC treatments are still not fully characterized, the evidence thus far has indicated that the potential therapeutic mechanisms of MSCs are clearer than those of BMCs or HSCs with respect to liver regenerative medicine. MSCs suppress inflammatory responses, reduce hepatocyte apoptosis, increase hepatocyte regeneration, reverse liver fibrosis and enhance liver functionality. This paper summarizes the clinical studies that have used BMCs, HSCs and MSCs in patients with liver failure or cirrhosis. We also present the potential therapeutic mechanisms of BMCs, HSCs and MSCs for the improvement of liver function. PMID:26420953

  13. Genetic Engineering of Mesenchymal Stem Cells for Regenerative Medicine.

    Science.gov (United States)

    Nowakowski, Adam; Walczak, Piotr; Janowski, Miroslaw; Lukomska, Barbara

    2015-10-01

    Mesenchymal stem cells (MSCs), which can be obtained from various organs and easily propagated in vitro, are one of the most extensively used types of stem cells and have been shown to be efficacious in a broad set of diseases. The unique and highly desirable properties of MSCs include high migratory capacities toward injured areas, immunomodulatory features, and the natural ability to differentiate into connective tissue phenotypes. These phenotypes include bone and cartilage, and these properties predispose MSCs to be therapeutically useful. In addition, MSCs elicit their therapeutic effects by paracrine actions, in which the metabolism of target tissues is modulated. Genetic engineering methods can greatly amplify these properties and broaden the therapeutic capabilities of MSCs, including transdifferentiation toward diverse cell lineages. However, cell engineering can also affect safety and increase the cost of therapy based on MSCs; thus, the advantages and disadvantages of these procedures should be discussed. In this review, the latest applications of genetic engineering methods for MSCs with regenerative medicine purposes are presented. PMID:26140302

  14. Suitability of human mesenchymal stem cells for gene therapy depends on the expansion medium

    International Nuclear Information System (INIS)

    Great hope is set in the use of mesenchymal stem cells for gene therapy and regenerative medicine. Since the frequency of this subpopulation of stem cells in bone marrow is low, mesenchymal stem cells are expanded ex vivo and manipulated prior to experimental or clinical use. Different methods for isolation and expansion are available, but the particular effect on the stem cell character is unclear. While the isolation of mesenchymal stem cells by density centrifugation followed by selection of the plastic adherent fraction is frequently used, the composition of expansion media differs. Thus, in the present study we cultured mesenchymal stem cells isolated from five healthy young volunteers in three widely used expansion media and performed a detailed analysis of the effect on morphology, proliferation, clonogenicity, passaging, differentiation and senescence. By this way we clearly show that the type of expansion medium used determines the stem cell character and time of senescence which is critical for future gene therapeutic and regenerative approaches using mesenchymal stem cells

  15. Autologous bone marrow stem cell transplantation for the treatment of type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    WANG Li; ZHAO Shi; MAO Hong; ZHOU Ling; WANG Zhong-jing; WANG Hong-xiang

    2011-01-01

    Background Autologous peripheral stem cell transplantation was first reported in 2007 to treat type 1 diabetes mellitus (DM) and achieved encouraging effect,but whether similar outcome can be achieved in type 2 DM is not well demonstrated.The objective of this study was to determine the effect of combination of autologous bone marrow stem cell transplantation (BMT) and hyperbaric oxygen treatment on type 2 DM.Methods The study involved 31 patients with type 2 DM (aged 33 to 62 years) from January 2009 to January 2011 in the Central Hospital of Wuhan,China.Clinical variables (body mass index,duration of DM,insulin requirement,oral hypoglycemic drugs,time free from insulin,time free from oral drugs) and laboratory variables (hemoglobin A1c (HbA1c)),mononuclear cells infused,and C-peptide in four time points) were assessed.Purified bone marrow stem cells were infused into major pancreatic arteries.Follow-up was performed at the 30,90,180,360,540 and 720 days (mean 321 days) after BMT.Results Mean HbA1c values showed a significant reduction during follow-up in all patients after BMT.It decreased by more than 1.5% (from 8.7% to 7.1%) as quickly as at 30 days after BMT.Afterwards mean HbA1c fluctuated between plus or minus 0.5% until 24 months rather than declined continuously.At 90 days after the combined therapy C-peptide increased significantly compared with baseline (P <0.0001).But in other time points C-peptide was similar with baseline data (P>0.3).All patients had insulin and/or oral hypoglycemic drugs reduced to different levels.The dose of insulin of 7 patients (7/26,27%) reduced for a period of time after BMT.Conclusions Combined therapy of intrapancreatic BMT and hyperbaric oxygen treatment can improve glucose control and reduce the dose of insulin and/or oral hypoglycemic drugs in type 2 DM patients,but it only improve pancreatic β-cell function transiently.Further randomized controlled clinical trials involved more patients will be required to

  16. Use of FK506 and bone marrow mesenchymal stem cells for rat hind limb allografts

    Institute of Scientific and Technical Information of China (English)

    Youxin Song; Zhujun Wang; Zhixue Wang; Hong Zhang; Xiaohui Li; Bin Chen

    2012-01-01

    Dark Agouti rat donor hind limbs were orthotopically transplanted into Lewis rat recipients to verify the effects of bone marrow mesenchymal stem cells on neural regeneration and functional recovery of allotransplanted limbs in the microenvironment of immunotolerance. bone marrow mesenchymal stem cells were intramuscularly (gluteus maximus) injected with FK506 (tacrolimus) daily, and were transplanted to the injured nerves. Results indicated that the allograft group not receiving therapy showed severe rejection, with transplanted limbs detaching at 10 days after transplantation with complete necrosis. The number of myelinated axons and Schwann cells in the FK506 and FK506 + bone marrow mesenchymal stem cells groups were significantly increased. We observed a lesser degree of gastrocnemius muscle degeneration, and increased polymorphic fibers along with other pathological changes in the FK506 + bone marrow mesenchymal stem cells group. The FK506 + bone marrow mesenchymal stem cells group showed significantly better recovery than the autograft and FK506 groups. The results demonstrated that FK506 improved the immune microenvironment. FK506 combined with bone marrow mesenchymal stem cells significantly promoted sciatic nerve regeneration, and improved sensory recovery and motor function in hind limb allotransplant.

  17. Long-term multilineage engraftment of autologous genome-edited hematopoietic stem cells in nonhuman primates.

    Science.gov (United States)

    Peterson, Christopher W; Wang, Jianbin; Norman, Krystin K; Norgaard, Zachary K; Humbert, Olivier; Tse, Collette K; Yan, Jenny J; Trimble, Richard G; Shivak, David A; Rebar, Edward J; Gregory, Philip D; Holmes, Michael C; Kiem, Hans-Peter

    2016-05-19

    Genome editing in hematopoietic stem and progenitor cells (HSPCs) is a promising novel technology for the treatment of many human diseases. Here, we evaluated whether the disruption of the C-C chemokine receptor 5 (CCR5) locus in pigtailed macaque HSPCs by zinc finger nucleases (ZFNs) was feasible. We show that macaque-specific CCR5 ZFNs efficiently induce CCR5 disruption at levels of up to 64% ex vivo, 40% in vivo early posttransplant, and 3% to 5% in long-term repopulating cells over 6 months following HSPC transplant. These genome-edited HSPCs support multilineage engraftment and generate progeny capable of trafficking to secondary tissues including the gut. Using deep sequencing technology, we show that these ZFNs are highly specific for the CCR5 locus in primary cells. Further, we have adapted our clonal tracking methodology to follow individual CCR5 mutant cells over time in vivo, reinforcing that CCR5 gene-edited HSPCs are capable of long-term engraftment. Together, these data demonstrate that genome-edited HSPCs engraft, and contribute to multilineage repopulation after autologous transplantation in a clinically relevant large animal model, an important step toward the development of stem cell-based genome-editing therapies for HIV and potentially other diseases as well. PMID:26980728

  18. Italian consensus conference for the outpatient autologous stem cell transplantation management in multiple myeloma.

    Science.gov (United States)

    Martino, M; Lemoli, R M; Girmenia, C; Castagna, L; Bruno, B; Cavallo, F; Offidani, M; Scortechini, I; Montanari, M; Milone, G; Postacchini, L; Olivieri, A

    2016-08-01

    Multiple myeloma (MM) is the leading indication for autologous stem cell transplantation (ASCT) worldwide. The safety and efficacy of reducing hospital stay for MM patients undergoing ASCT have been widely explored, and different outpatient models have been proposed. However, there is no agreement on the criteria for selecting patients eligible for this strategy as well as the standards for their clinical management. On the basis of this rationale, the Italian Group for Stem Cell Transplantation (GITMO) endorsed a project to develop guidelines for the management of outpatient ASCT in MM, using evidence-based knowledge and consensus-formation techniques. An expert panel convened to discuss the currently available data on the practice of outpatient ASCT management and formulated recommendations according to the supporting evidence. Evidence gaps were filled with consensus-based statements. Three main topics were addressed: (1) the identification of criteria for selecting MM patients eligible for outpatient ASCT management; (2) the definition of standard procedures for performing outpatient ASCT (model, supportive care and monitoring during the aplastic phase); (3) the definition of the standard criteria and procedures for re-hospitalization during the aplastic phase at home. Herein, we report the summary and the results of the discussion and the consensus. PMID:27042841

  19. Clinical outcomes after autologous haematopoietic stem cell transplantation in patients with progressive multiple sclerosis

    Institute of Scientific and Technical Information of China (English)

    XU Juan; JI Bing-xin; SU Li; DONG Hui-qing; SUN Xue-jing; LIU Cong-yan

    2006-01-01

    Background Multiple sclerosis (MS) is a continuously disabling disease and it is unresponsive to high dose steroid and immunomodulation with disease progression. The autologous haematopoietic stem cell transplantation (ASCT) has been introduced in the treatment of refractory forms of multiple sclerosis. In this study, the clinical outcomes followed by ASCT were evaluated for patients with progressive MS.Methods Twenty-two patients with secondary progressive MS were treated with ASCT. Peripheral blood stem cells were obtained by leukapheresis after mobilization with granulocyte colony stimulating factor. Etoposide,melphalan, carmustin and cytosine arabinoside were administered as conditioning regimen. Outcomes were evaluated by the expanded disability status scale and progression free survival. No maintenance treatment was administered during a median follow-up of 39 months (range, 6 to 59 months).Results No death occurred following the treatment. The overall confirmed progression free survival rate was77% up to 59 months after transplantation which was significantly higher compared with pre-transplantation (P=0.000). Thirteen patients (59%) had remarkable improvement in neurological manifestations, four (18%)stabilized their disability status and five (23%) showed clinical recurrence of active symptoms.Conclusions ASCT as a therapy is safe and available. It can improve or stabilize neurological manifestations in most patients with progressive MS following failure of conventional therapy.

  20. [High dosage therapy and autologous peripheral stem cell transplantation in breast carcinoma].

    Science.gov (United States)

    Kier, P; Ruckser, R; Buxhofer, V; Habertheuer, K H; Zelenka, P; Tatzreiter, G; Hübl, G; Kittl, E; Hauser, A; Sebesta, C; Hinterberger, W

    2000-01-01

    42 breast cancer patients were treated by high-dose chemotherapy (HDC) and autologous peripheral stem-cell transplantation (ASTx) in the Donauspital between 1992 and 1999. 24 patients had stage II/III breast cancer with high risk for relapse. The other 18 patients underwent HDC and ASTx in chemosensitive stage IV. After previous conventional chemotherapy peripheral stem-cells were harvested by one cycle of mobilisation chemotherapy (epirubicin/taxol, FEC 120 or cyclophosphamide) followed by cytokine stimulation. 16 patients were treated by a tandem transplantation (conditioning protocol for 1st ASTx was melphalan 200 mg/m2 and for 2nd transplant it was CTC: cyclophosphamide 6 g/m2; thiotepa 500 mg/m2; carboplatin 800 mg/m2). The other 26 patients received one HDC with CTC as conditioning protocol. The HDC was well tolerated by all patients, there was no transplant-related mortality. The median survival and the progression-free survival (PFS) after HDC and ASTx in stage IV breast cancer patients were 28 and 11 months, respectively. The median survival and PFS were not yet reached in stage II/III patients after 55 months. The actuarial survival and PFS in that patient group were 70% after 55 months. Our data confirm the low risk and good efficacy of HDC and ASTx in breast cancer patients. Nevertheless randomised studies are necessary to evaluate the importance of HDC compared to intensified conventional protocols without ASTx. PMID:11261276

  1. [High dosage chemotherapy with autologous stem cell transplantation in multiple myeloma].

    Science.gov (United States)

    Ruckser, R; Kier, P; Buxhofer, V; Kittl, E; Tatzreiter, G; Vedovelli, H; Zelenka, P; Hübl, G; Hinterberger, W

    2000-01-01

    Between 1992 and 1999 15 patients (pts.) suffering from multiple myeloma (MM) were treated with high-dose chemotherapy and consecutive autologous stem-cell transplantation (ASTx). 10/15 pts underwent two courses of ASTx (tandem- or double ASTx). So 25 ASTx were performed in these 15 pts. in total. All pts. were under 60 a. of age. 13/15 pts. received 6 cycles of chemotherapy on an average according to the VAD-protocol (Vincristin, Adriamycin, Dexamethason). Mobilisation of peripheral hematopoietic stem cells was performed with high-dose cyclophosphamide and hematopoietic growth-factors (CSFs). The conditioning protocol consisted of high-dose melphalan (200-225 mg/m2) in 24/25 ASTx. In one single case total body irradiation (TBI) plus melphalan 140 mg/m2 was used. 2/15 pts. died within 30 days from ASTx; one patient from interstitial pneumonia after TBI, and the other, who was in a very advanced stage of his disease with multiple pretreatment courses before ASTx. The overall survival (OS) was in the mean 68 months, the progression-free survival (PFS) after ASTx 21 m respectively. In pts. with MM high-dose melphalan (up to 225 mg/m2) without TBI plus ASTx is a safe and effective procedure when performed in the early course of the disease. PMID:11261278

  2. Total Marrow Irradiation as Part of Autologous Stem Cell Transplantation for Asian Patients with Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Shih-Chiang Lin

    2013-01-01

    Full Text Available To compare the outcomes of melphalan 200 mg/m2 (HDM200 and 8 Gy total marrow irradiation (TMI delivered by helical tomotherapy plus melphalan 140 mg/m2 (HDM140 + TMI 8 Gy in newly diagnosed symptomatic multiple myeloma (MM Asian patients. Between 2007 and 2010, nine consecutive myeloma patients who were scheduled to undergo autologous stem cell transplantation (ASCT were studied. The patients received three cycles of vincristine-adriamycin-dexamethasone (VAD regimen as induction chemotherapy, and if they had a partial response, peripheral blood stem cells were collected by dexamethasone-etoposide-cyclophosphamide-cisplatin (DECP. In arm A, six patients received the HDM200. In arm B, three patients received HDM140 + TMI 8 Gy. In arm B, the neutropenic duration was slightly longer than in arm A (P=0.048. However, hematologic recovery (except for neutrophils, transfusion requirement, median duration of hospitalization, and the dose of G-CSF were similar in both arms. The median duration of overall survival and event-free survival was similar in the two arms (P=0.387. As a conditioning regiment, HDM140 + TMI 8 Gy provide another chance for MM Asian patients who were not feasible for HDM200.

  3. Autologous fat injection to face and neck: from soft tissue augmentation to regenerative medicine

    OpenAIRE

    MAZZOLA, R.F.; Cantarella, G; Torretta, S.; Sbarbati, A.; Lazzari, L; Pignataro, L

    2011-01-01

    SUMMARY Minimally-invasive autologous fat injection of the head and neck region can be considered a valid alternative to major invasive surgical procedures both for aesthetic and functional purposes. The favourable outcomes of autologous fat injection in otolaryngological practice are due to the filling of soft tissue and, mainly, to the potential regenerative effect of adipose-derived mesenchymal stem cells. Herewith, some important biological preliminary remarks are described underlying the...

  4. Clinical Trials With Mesenchymal Stem Cells: An Update.

    Science.gov (United States)

    Squillaro, Tiziana; Peluso, Gianfranco; Galderisi, Umberto

    2016-01-01

    In the last year, the promising features of mesenchymal stem cells (MSCs), including their regenerative properties and ability to differentiate into diverse cell lineages, have generated great interest among researchers whose work has offered intriguing perspectives on cell-based therapies for various diseases. Currently the most commonly used adult stem cells in regenerative medicine, MSCs, can be isolated from several tissues, exhibit a strong capacity for replication in vitro, and can differentiate into osteoblasts, chondrocytes, and adipocytes. However, heterogeneous procedures for isolating and cultivating MSCs among laboratories have prompted the International Society for Cellular Therapy (ISCT) to issue criteria for identifying unique populations of these cells. Consequently, the isolation of MSCs according to ISCT criteria has produced heterogeneous, nonclonal cultures of stromal cells containing stem cells with different multipotent properties, committed progenitors, and differentiated cells. Though the nature and functions of MSCs remain unclear, nonclonal stromal cultures obtained from bone marrow and other tissues currently serve as sources of putative MSCs for therapeutic purposes, and several findings underscore their effectiveness in treating different diseases. To date, 493 MSC-based clinical trials, either complete or ongoing, appear in the database of the US National Institutes of Health. In the present article, we provide a comprehensive review of MSC-based clinical trials conducted worldwide that scrutinizes biological properties of MSCs, elucidates recent clinical findings and clinical trial phases of investigation, highlights therapeutic effects of MSCs, and identifies principal criticisms of the use of these cells. In particular, we analyze clinical trials using MSCs for representative diseases, including hematological disease, graft-versus-host disease, organ transplantation, diabetes, inflammatory diseases, and diseases in the liver, kidney

  5. Antibody responses to vaccination and immune function in patients with haematological malignancies - studies in patients with chronic lymphocytic leukaemia autologous stem cell recipients

    OpenAIRE

    Velden, A.M.T. van der

    2007-01-01

    This thesis concerns the antibody responses to vaccination and immune function of patients with several forms of haematological diseases. Antibody responses in patients with chronic lymphocytic leukaemia (CLL) and in autologous stem cell transplant recipients were studied. In the autologous stem cell transplantation (aSCT) group, immune reconstitution after aSCT was analysed in detail during 15 months following transplantation. The first part of the thesis concerns patients with chronic lymph...

  6. Adipose Tissue-Derived Mesenchymal Stem Cells as a New Host Cell in Latent Leishmaniasis

    OpenAIRE

    Allahverdiyev, Adil M; Bagirova, Melahat; Elcicek, Serhat; Koc, Rabia Cakir; Baydar, Serap Yesilkir; Findikli, Necati; Oztel, Olga N.

    2011-01-01

    Some protozoan infections such as Toxoplasma, Cryptosporidium, and Plasmodium can be transmitted through stem cell transplantations. To our knowledge, so far, there is no study about transmission of Leishmania parasites in stem cell transplantation and interactions between parasites and stem cells in vitro. Therefore, the aim of this study was to investigate the interaction between different species of Leishmania parasites and adipose tissue-derived mesenchymal stem cells (ADMSCs). ADMSCs hav...

  7. Phenotypic Plasticity and Epithelial-Mesenchymal Transitions in Cancer - and Normal Stem Cells?

    OpenAIRE

    Scheel, Christina; Weinberg, Robert A.

    2011-01-01

    Cancer stem cells (CSCs) are similar to normal stem cells in their ability to self-renew and to generate large populations of more differentiated descendants. In contrast to the hierarchical organization that is presumed to be the prevalent mode of normal tissue homeostasis, phenotypic plasticity allows cancer cells to dynamically enter into and exit from stem-cell states. The Epithelial-Mesenchymal Transition (EMT) has been closely associated with the acquisition of both invasive and stem-ce...

  8. Abrogation of Age-Induced MicroRNA-195 Rejuvenates the Senescent Mesenchymal Stem Cells by Reactivating Telomerase.

    Science.gov (United States)

    Okada, Motoi; Kim, Ha Won; Matsu-ura, Kaoru; Wang, Yi-Gang; Xu, Meifeng; Ashraf, Muhammad

    2016-01-01

    Previously, we reported that a novel subpopulation of young mesenchymal stem cells (YMSCs) existed in old bone marrow, which possessed high antiaging properties as well as excellent efficacy for cardiac repair. MicroRNAs (miRNAs) have emerged as key regulators in post-transcriptional gene expression programs, and however, it is unknown whether miRNAs directly control stem cell senescence. Here we present the first evidence that miR-195 overexpressed in old MSCs (OMSCs) induces stem cell senescence deteriorating their regenerative ability by directly deactivating telomerase reverse transcriptase (Tert), and abrogation of miR-195 can reverse stem cell aging. MiRNAs profiling analysis in YMSCs and OMSCs by microarray showed that miR-140, miR-146a/b, and miR-195 were significantly upregulated in OMSCs, which led us to hypothesize that these are age-induced miRNAs involved in stem cell senescence. Of these miRNAs, we found miR-195 directly targeted 3'-untranslated region of Tert gene by computational target prediction analysis and luciferase assay, and knockdown of miR-195 significantly increased Tert expression in OMSCs. Strikingly, miR-195 inhibition significantly induced telomere relengthening in OMSCs along with reduced expression of senescence-associated β-galactosidase. Moreover, silencing miR-195 in OMSCs by transfection of miR-195 inhibitor significantly restored antiaging factors expression including Tert and Sirt1 as well as phosphorylation of Akt and FOXO1. Notably, abrogation of miR-195 markedly restored proliferative abilities in OMSCs. Transplantation of OMSCs with knocked out miR-195 reduced infarction size and improved LV function. In conclusion, rejuvenation of aged stem cells by miR-195 inhibition would be a promising autologous therapeutic strategy for cardiac repair in the elderly patients. PMID:26390028

  9. Function of mesenchymal stem cells following loading of gold nanotracers

    Directory of Open Access Journals (Sweden)

    et al

    2011-02-01

    Full Text Available Laura M Ricles1, Seung Yun Nam1,2, Konstantin Sokolov3,1, Stanislav Y Emelianov1,3, Laura J Suggs11Department of Biomedical Engineering, 2Department of Electrical and Computer Engineering, The University of Texas at Austin, Austin, TX, USA; 3Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USABackground: Stem cells can differentiate into multiple cell types, and therefore can be used for cellular therapies, including tissue repair. However, the participation of stem cells in tissue repair and neovascularization is not well understood. Therefore, implementing a noninvasive, long-term imaging technique to track stem cells in vivo is needed to obtain a better understanding of the wound healing response. Generally, we are interested in developing an imaging approach to track mesenchymal stem cells (MSCs in vivo after delivery via a polyethylene glycol modified fibrin matrix (PEGylated fibrin matrix using MSCs loaded with gold nanoparticles as nanotracers. The objective of the current study was to assess the effects of loading MSCs with gold nanoparticles on cellular function.Methods: In this study, we utilized various gold nanoparticle formulations by varying size and surface coatings and assessed the efficiency of cell labeling using darkfield microscopy. We hypothesized that loading cells with gold nanotracers would not significantly alter cell function due to the inert and biocompatible characteristics of gold. The effect of nanoparticle loading on cell viability and cytotoxicity was analyzed using a LIVE/DEAD stain and an MTT assay. The ability of MSCs to differentiate into adipocytes and osteocytes after nanoparticle loading was also examined. In addition, nanoparticle loading and retention over time was assessed using inductively coupled plasma mass spectrometry (ICP-MS.Conclusion: Our results demonstrate that loading MSCs with gold nanotracers does not alter cell function and, based on the ICP

  10. Immortalized mesenchymal stem cells: an alternative to primary mesenchymal stem cells in neuronal differentiation and neuroregeneration associated studies

    Directory of Open Access Journals (Sweden)

    Gong Min

    2011-11-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs can be induced to differentiate into neuronal cells under appropriate cellular conditions and transplanted in brain injury and neurodegenerative diseases animal models for neuroregeneration studies. In contrast to the embryonic stem cells (ESCs, MSCs are easily subject to aging and senescence because of their finite ability of self-renewal. MSCs senescence seriously affected theirs application prospects as a promising tool for cell-based regenerative medicine and tissue engineering. In the present study, we established a reversible immortalized mesenchymal stem cells (IMSCs line by using SSR#69 retrovirus expressing simian virus 40 large T (SV40T antigen as an alternative to primary MSCs. Methods The retroviral vector SSR#69 expressing simian virus 40 large T (SV40T antigen was used to construct IMSCs. IMSCs were identified by flow cytometry to detect cell surface makers. To investigate proliferation and differentiation potential of IMSCs, cell growth curve determination and mesodermal trilineage differentiation tests were performed. Neuronal differentiation characteristics of IMSCs were detected in vitro. Before IMSCs transplantation, we excluded its tumorigenicity in nude mice firstly. The Morris water maze tests and shuttle box tests were performed five weeks after HIBD models received cells transplantation therapy. Results In this study, reversible IMSCs were constructed successfully and had the similar morphology and cell surface makers as primary MSCs. IMSCs possessed better ability of proliferation and anti-senescence compared with primary MSCs, while maintained multilineage differentiation capacity. Neural-like cells derived from IMSCs had similar expressions of neural-specific genes, protein expression patterns and resting membrane potential (RMP compared with their counterparts derived from primary MSCs. There was no bump formation in nude mice subcutaneously injected with IMSCs. IMSCs

  11. Case of relapsed AIDS-related plasmablastic lymphoma treated with autologous stem cell transplantation and highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Hiroki Goto

    2011-03-01

    Full Text Available Plasmablastic lymphoma is a rare and aggressive malignancy strongly associated with HIV infection. The refractory/relapsed disease rate is high, and the survival rate is characteristically poor. There are no satisfactory salvage regimens for relapsed cases. We successfully performed autologous stem cell transplantation using a regimen consisting of MCNU (ranimustine, etoposide, cytarabine, and melphalan in a Japanese patient with relapsed AIDS-related plasmablastic lymphoma of the oral cavity. Highly active antiretroviral therapy continued during the therapy. Therapy-related toxicity was tolerable, and a total of 40 Gy of irradiation was administered after autologous stem cell transplantation. The patient has remained in complete remission for 16 months since transplantation.

  12. Bone marrow mesenchymal stem cells repair spinal cord ischemia/reperfusion injury by promoting axonal growth and anti-autophagy

    OpenAIRE

    Yin, Fei; Meng, Chunyang; Lu, Rifeng; Li, Lei; Zhang, Ying; Chen, Hao; Qin, Yonggang; Guo, Li

    2014-01-01

    Bone marrow mesenchymal stem cells can differentiate into neurons and astrocytes after transplantation in the spinal cord of rats with ischemia/reperfusion injury. Although bone marrow mesenchymal stem cells are known to protect against spinal cord ischemia/reperfusion injury through anti-apoptotic effects, the precise mechanisms remain unclear. In the present study, bone marrow mesenchymal stem cells were cultured and proliferated, then transplanted into rats with ischemia/reperfusion injury...

  13. Transplantation of neurotrophin-3-transfected bone marrow mesenchymal stem cells for the repair of spinal cord injury

    OpenAIRE

    Dong, Yuzhen; Yang, Libin; Yang, Lin; Zhao, Hongxing; Zhang, Chao; Wu, Dapeng

    2014-01-01

    Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesenchymal stem cells in vivo remains a problem. Neurotrophin-3 promotes motor neuron survival and it is hypothesized that its transfection can enhance the therapeutic effect. We show that in vitro transfection of neurotrophin-3 gene increases the number of bone marrow mesenchymal stem cells in the region of spinal ...

  14. High-Dose Chemotherapy Followed by Autologous Stem Cell Transplantation for Metastatic Rhabdomyosarcoma—A Systematic Review

    OpenAIRE

    Frank Peinemann; Nicolaus Kröger; Carmen Bartel; Ulrich Grouven; Max Pittler; Rudolf Erttmann; Michael Kulig

    2011-01-01

    INTRODUCTION: Patients with metastatic rhabdomyosarcoma (RMS) have a poor prognosis. The aim of this systematic review is to investigate whether high-dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation (HSCT) in patients with metastatic RMS has additional benefit or harm compared to standard chemotherapy. METHODS: Systematic literature searches were performed in MEDLINE, EMBASE, and The Cochrane Library. All databases were searched from inception to Februar...

  15. Substantial variation in post-engraftment infection prophylaxis and revaccination practice in autologous stem cell transplant patients.

    Science.gov (United States)

    Lim, H Y; Grigg, A

    2016-03-01

    There is a paucity of evidence supporting the necessity or duration of Pneumocystis jirovecii and antiviral prophylaxis as well as revaccination following autologous stem cell transplant (ASCT). A survey aimed at evaluating these policies was distributed to 34 ASCT centres across Australasia. The 26 survey respondents demonstrated significant heterogeneity in their infection prophylaxis and revaccination strategy post-transplant despite the availability of consensual guidelines. PMID:26968596

  16. High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation for adult histiocytic disorders with central nervous system involvement

    OpenAIRE

    Gaspar, Nathalie; Van Den Neste, Eric; Boudou, Pascaline; Haroche, Julien; Wechsler, Bertrand; Hoang-Xuan, Khe; Amoura, Zahir; Guillevin, Remy; Savatovski, Julien; Azar, Nabih; Piette, Jean-Charles; Leblond, Veronique

    2006-01-01

    We postulated that high-dose chemotherapy (HDC) followed by peripheral autologous hematopoietic stem cell transplantation might help to control refractory central nervous system (CNS) histiocytic disorders. Six patients with histiocytic CNS involvement were treated in this way. Two patients achieved non-active disease status, although one relapsed at 84 months. Two patients had regressive disease, one of whom progressed at 21 months. One patient had progressive disease at 14 months. One patie...

  17. Challenges and outcomes of a randomized study of early nutrition support during autologous stem-cell transplantation

    OpenAIRE

    Kiss, N.; Seymour, J.F.; Prince, H M; Dutu, G.

    2014-01-01

    Patients undergoing myeloablative conditioning regimens and autologous stem-cell transplantation (asct) are at high risk of malnutrition. This randomized study aimed to determine if early nutrition support (commenced when oral intake is less than 80% of estimated requirements) compared with usual care (commenced when oral intake is less than 50% of estimated requirements) reduces weight loss in well-nourished patients undergoing high-nutritional-risk conditioning chemotherapy and asct.

  18. Clostridium difficile infection after adult autologous stem cell transplantation: A multicenter study of epidemiology and risk factors

    OpenAIRE

    Alonso, Carolyn D.; Dufresne, Simon F.; Hanna, David B.; Labbé, Annie-Claude; Treadway, Suzanne B.; Neofytos, Dionissios; Bélanger, Sylvie; Huff, Carol Ann; Laverdière, Michel; Marr, Kieren A.

    2013-01-01

    We sought to describe the epidemiology of Clostridium difficile infection (CDI) among adult recipients of autologous hematopoietic stem cell transplantation (auto HSCT) within the first year after HSCT in centers with variable epidemiology of hyper-toxigenic strains. A multicenter, retrospective nested case-control study was conducted among 873 auto HSCT recipients at Johns Hopkins Hospital (JHH, Baltimore, MD) and Hôpital Maisonneuve-Rosemont (HMR, Montreal, Canada) between 1/2003-12/2008. D...

  19. Células-tronco mesenquimais Mesenchymal stem cell

    Directory of Open Access Journals (Sweden)

    Betânia Souza Monteiro

    2010-02-01

    Full Text Available Dentre todas as células-tronco estudadas até o presente momento, as mesenquimais (MSC destacam-se por sua elevada plasticidade, podendo originar tecidos mesodermais e não mesodermais. Além disso, possuem características imunomoduladoras e imunossupressoras que ampliam as possibilidades de utilização terapêutica. As MSC secretam uma grande variedade de citocinas pró e anti-inflamatórias e fatores de crescimento e, por meio dessas moléculas bioativas, proporcionam a modulação da resposta inflamatória, o restabelecimento do suprimento vascular e a reparação adequada do tecido, contribuindo para a homeostasia tissular e imunológica sob condições fisiológicas. Também podem induzir as demais células presentes no nicho tecidual a secretarem outros fatores solúveis que estimulam a diferenciação dessas células indiferenciadas, favorecendo o processo de reparação. A terapia celular com MSC é uma alternativa terapêutica promissora, porém a compreensão da biologia dessas células ainda é uma ciência em formação. Este artigo tem por objetivo realizar uma breve revisão sobre as células mesenquimais indiferenciadas.Of all the stem cells studied so far, the mesenchymal stem cells (MSC stand out for their high plasticity and capacity of generating mesodermal and non-mesodermal tissues. In addition, immunomodulatory and immunosuppressive features that expand possibilities for therapeutic use are present in these cells. A variety of pro and anti-inflammatory cytokines and growth factors are secrete for MSC and provide a modulation of inflammatory response, re-establishment of vascular supply and adequate repair of the tissue, contributing to tissue homeostasis under physiologic conditions. Therefore, they can induce secretion of soluble factors that stimulate their differentiation by other cells present at the niche's tissue, promoting the repair process. Cell therapy using MSC is a promises therapeutic alternative, but

  20. Stemness Evaluation of Mesenchymal Stem Cells from Placentas According to Developmental Stage: Comparison to Those from Adult Bone Marrow

    OpenAIRE

    Sung, Hwa Jung; Hong, Soon Cheol; Yoo, Ji Hyun; Oh, Jee Hyun; Shin, Hye Jin; Choi, In Young; Ahn, Ki Hoon; Kim, Sun Haeng; Park, Yong; Kim, Byung Soo

    2010-01-01

    This study was done to evaluate the stemness of human mesenchymal stem cells (hMSCs) derived from placenta according to the development stage and to compare the results to those from adult bone marrow (BM). Based on the source of hMSCs, three groups were defined: group I included term placentas, group II included first-trimester placentas, and group III included adult BM samples. The stemness was evaluated by the proliferation capacity, immunophenotypic expression, mesoderm differentiation, e...

  1. Mesenchymal Stem Cells Retain Their Defining Stem Cell Characteristics After Exposure to Ionizing Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Nicolay, Nils H., E-mail: n.nicolay@dkfz.de [Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg (Germany); Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg (Germany); Sommer, Eva; Lopez, Ramon; Wirkner, Ute [Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg (Germany); Trinh, Thuy [Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg (Germany); Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg (Germany); Sisombath, Sonevisay [Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg (Germany); Debus, Jürgen [Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg (Germany); Ho, Anthony D.; Saffrich, Rainer [Department of Hematology and Oncology, Heidelberg University Hospital, Heidelberg (Germany); Huber, Peter E. [Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg (Germany); Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg (Germany)

    2013-12-01

    Purpose: Mesenchymal stem cells (MSCs) have the ability to migrate to lesion sites and undergo differentiation into functional tissues. Although this function may be important for tissue regeneration after radiation therapy, the influence of ionizing radiation (IR) on cellular survival and the functional aspects of differentiation and stem cell characteristics of MSCs have remained largely unknown. Methods and Materials: Radiation sensitivity of human primary MSCs from healthy volunteers and primary human fibroblast cells was examined, and cellular morphology, cell cycle effects, apoptosis, and differentiation potential after exposure to IR were assessed. Stem cell gene expression patterns after exposure to IR were studied using gene arrays. Results: MSCs were not more radiosensitive than human primary fibroblasts, whereas there were considerable differences regarding radiation sensitivity within individual MSCs. Cellular morphology, cytoskeletal architecture, and cell motility were not markedly altered by IR. Even after high radiation doses up to 10 Gy, MSCs maintained their differentiation potential. Compared to primary fibroblast cells, MSCs did not show an increase in irradiation-induced apoptosis. Gene expression analyses revealed an upregulation of various genes involved in DNA damage response and DNA repair, but expression of established MSC surface markers appeared only marginally influenced by IR. Conclusions: These data suggest that human MSCs are not more radiosensitive than differentiated primary fibroblasts. In addition, upon photon irradiation, MSCs were able to retain their defining stem cell characteristics both on a functional level and regarding stem cell marker expression.

  2. Mesenchymal Stem Cells Retain Their Defining Stem Cell Characteristics After Exposure to Ionizing Radiation

    International Nuclear Information System (INIS)

    Purpose: Mesenchymal stem cells (MSCs) have the ability to migrate to lesion sites and undergo differentiation into functional tissues. Although this function may be important for tissue regeneration after radiation therapy, the influence of ionizing radiation (IR) on cellular survival and the functional aspects of differentiation and stem cell characteristics of MSCs have remained largely unknown. Methods and Materials: Radiation sensitivity of human primary MSCs from healthy volunteers and primary human fibroblast cells was examined, and cellular morphology, cell cycle effects, apoptosis, and differentiation potential after exposure to IR were assessed. Stem cell gene expression patterns after exposure to IR were studied using gene arrays. Results: MSCs were not more radiosensitive than human primary fibroblasts, whereas there were considerable differences regarding radiation sensitivity within individual MSCs. Cellular morphology, cytoskeletal architecture, and cell motility were not markedly altered by IR. Even after high radiation doses up to 10 Gy, MSCs maintained their differentiation potential. Compared to primary fibroblast cells, MSCs did not show an increase in irradiation-induced apoptosis. Gene expression analyses revealed an upregulation of various genes involved in DNA damage response and DNA repair, but expression of established MSC surface markers appeared only marginally influenced by IR. Conclusions: These data suggest that human MSCs are not more radiosensitive than differentiated primary fibroblasts. In addition, upon photon irradiation, MSCs were able to retain their defining stem cell characteristics both on a functional level and regarding stem cell marker expression

  3. A gold nanoparticle pentapeptide: gene fusion to induce therapeutic gene expression in mesenchymal stem cells.

    Science.gov (United States)

    Muroski, Megan E; Morgan, Thomas J; Levenson, Cathy W; Strouse, Geoffrey F

    2014-10-22

    Mesenchymal stem cells (MSC) have been identified as having great potential as autologous cell therapeutics to treat traumatic brain injury and spinal injury as well as neuronal and cardiac ischemic events. All future clinical applications of MSC cell therapies must allow the MSC to be harvested, transfected, and induced to express a desired protein or selection of proteins to have medical benefit. For the full potential of MSC cell therapy to be realized, it is desirable to systematically alter the protein expression of therapeutically beneficial biomolecules in harvested MSC cells with high fidelity in a single transfection event. We have developed a delivery platform on the basis of the use of a solid gold nanoparticle that has been surface modified to produce a fusion containing a zwitterionic, pentapeptide designed from Bax inhibiting peptide (Ku70) to enhance cellular uptake and a linearized expression vector to induce enhanced expression of brain-derived neurotrophic factor (BDNF) in rat-derived MSCs. Ku70 is observed to effect >80% transfection following a single treatment of femur bone marrow isolated rat MSCs with efficiencies for the delivery of a 6.6 kbp gene on either a Au nanoparticle (NP) or CdSe/ZnS quantum dot (QD). Gene expression is observed within 4 d by optical measurements, and secretion is observed within 10 d by Western Blot analysis. The combination of being able to selectively engineer the NP, to colocalize biological agents, and to enhance the stability of those agents has provided the strong impetus to utilize this novel class of materials to engineer primary MSCs. PMID:25198921

  4. Secreted trophic factors of mesenchymal stem cells support neurovascular and musculoskeletal therapies.

    Science.gov (United States)

    Hofer, Heidi R; Tuan, Rocky S

    2016-01-01

    Adult mesenchymal stem cells (MSCs) represent a subject of intense experimental and biomedical interest. Recently, trophic activities of MSCs have become the topic of a number of revealing studies that span both basic and clinical fields. In this review, we focus on recent investigations that have elucidated trophic mechanisms and shed light on MSC clinical efficacy relevant to musculoskeletal applications. Innate differences due to MSC sourcing may play a role in the clinical utility of isolated MSCs. Pain management, osteochondral, nerve, or blood vessel support by MSCs derived from both autologous and allogeneic sources have been examined. Recent mechanistic insights into the trophic activities of these cells point to ultimate regulation by nitric oxide, nuclear factor-kB, and indoleamine, among other signaling pathways. Classic growth factors and cytokines-such as VEGF, CNTF, GDNF, TGF-β, interleukins (IL-1β, IL-6, and IL-8), and C-C ligands (CCL-2, CCL-5, and CCL-23)-serve as paracrine control molecules secreted or packaged into extracellular vesicles, or exosomes, by MSCs. Recent studies have also implicated signaling by microRNAs contained in MSC-derived exosomes. The response of target cells is further regulated by their microenvironment, involving the extracellular matrix, which may be modified by MSC-produced matrix metalloproteinases (MMPs) and tissue inhibitor of MMPs. Trophic activities of MSCs, either resident or introduced exogenously, are thus intricately controlled, and may be further fine-tuned via implant material modifications. MSCs are actively being investigated for the repair and regeneration of both osteochondral and other musculoskeletal tissues, such as tendon/ligament and meniscus. Future rational and effective MSC-based musculoskeletal therapies will benefit from better mechanistic understanding of MSC trophic activities, for example using analytical "-omics" profiling approaches. PMID:27612948

  5. visual bone marrow mesenchymal stem cell transplantation in the repair of spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Rui-ping Zhang; Cheng Xu; Yin Liu; Jian-ding Li; Jun Xie

    2015-01-01

    An important factor in improving functional recovery from spinal cord injury using stem cells is maximizing the number of transplanted cells at the lesion site. Here, we established a contusion model of spinal cord injury by dropping a weight onto the spinal cord at T7–8. Superparamagnet-ic iron oxide-labeled bone marrow mesenchymal stem cells were transplanted into the injured spinal cordvia the subarachnoid space. An outer magnetic ifeld was used to successfully guide the labeled cells to the lesion site. Prussian blue staining showed that more bone marrow mesen-chymal stem cells reached the lesion site in these rats than in those without magnetic guidance or superparamagnetic iron oxide labeling, and immunolfuorescence revealed a greater number of complete axons at the lesion site. Moreover, the Basso, Beattie and Bresnahan (BBB) locomotor rating scale scores were the highest in rats with superparamagnetic labeling and magnetic guid-ance. Our data conifrm that superparamagnetic iron oxide nanoparticles effectively label bone marrow mesenchymal stem cells and impart sufficient magnetism to respond to the external magnetic ifeld guides. More importantly, superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells can be dynamically and non-invasively trackedin vivo using magnetic resonance imaging. Superparamagnetic iron oxide labeling of bone marrow mesenchymal stem cells coupled with magnetic guidance offers a promising avenue for the clinical treatment of spinal cord injury.

  6. 12 hours after cerebral ischemia is the optimal time for bone marrow mesenchymal stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Seyed Mojtaba Hosseini; Mohammad Farahmandnia; Zahra Razi; Somayeh Delavarifar; Benafsheh Shakibajahromi

    2015-01-01

    Cell therapy using stem cell transplantation against cerebral ischemia has been reported. However, it remains controversial regarding the optimal time for cell transplantation and the transplantation route. Rat models of cerebral ischemia were established by occlusion of the middle cerebral artery. At 1, 12 hours, 1, 3, 5 and 7 days after cerebral ischemia, bone marrow mesenchymal stem cells were injected via the tail vein. At 28 days after cerebral ischemia, rat neurological function was evaluated using a 6-point grading scale and the pathological change of ischemic cerebral tissue was observed by hematoxylin-eosin staining. Under the lfuorescence microscope, the migration of bone marrow mesenchymal stem cells was examined by PKH labeling. Caspase-3 activity was measured using spectrophotometry. The optimal neurological function recovery, lowest degree of ischemic cerebral damage, greatest number of bone marrow mesenchymal stem cells migrating to peri-ischemic area, and lowest caspase-3 activity in the ischemic cerebral tissue were observed in rats that underwent bone marrow mesenchymal stem cell transplantation at 12 hours after cerebral ischemia. These ifndings suggest that 12 hours after cerebral ischemia is the optimal time for tail vein injection of bone marrow mesenchymal stem cell transplantation against cerebral ischemia, and the strongest neuroprotective effect of this cell therapy appears at this time.

  7. Factors affecting directional migration of bone marrow mesenchymal stem cells to the injured spinal cord

    Institute of Scientific and Technical Information of China (English)

    Peng Xia; Su Pan; Jieping Cheng; Maoguang Yang; Zhiping Qi; Tingting Hou; Xiaoyu Yang

    2014-01-01

    Microtubule-associated protein 1B plays an important role in axon guidance and neuronal migration. In the present study, we sought to discover the mechanisms underlying microtu-bule-associated protein 1B mediation of axon guidance and neuronal migration. We exposed bone marrow mesenchymal stem cells to okadaic acid or N-acetyl-D-erythro-sphingosine (an inhibitor and stimulator, respectively, of protein phosphatase 2A) for 24 hours. The expression of the phosphorylated form of type I microtubule-associated protein 1B in the cells was greater after exposure to okadaic acid and lower after N-acetyl-D-erythro-sphingosine. We then injected the bone marrow mesenchymal stem cells through the ear vein into rabbit models of spinal cord contusion. The migration of bone marrow mesenchymal stem cells towards the injured spinal cord was poorer in cells exposed to okadaic acid-and N-acetyl-D-erythro-sphingosine than in non-treated bone marrow mesenchymal stem cells. Finally, we blocked phosphatidylinosi-tol 3-kinase (PI3K) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways in rabbit bone marrow mesenchymal stem cells using the inhibitors LY294002 and U0126, respectively. LY294002 resulted in an elevated expression of phosphorylated type I microtubule-associated protein 1B, whereas U0126 caused a reduction in expression. The present data indicate that PI3K and ERK1/2 in bone marrow mesenchymal stem cells modulate the phosphorylation of micro-tubule-associated protein 1B via a cross-signaling network, and affect the migratory efifciency of bone marrow mesenchymal stem cells towards injured spinal cord.

  8. Markers of stemness in equine mesenchymal stem cells: a plea for uniformity.

    Science.gov (United States)

    De Schauwer, Catharina; Meyer, Evelyne; Van de Walle, Gerlinde R; Van Soom, Ann

    2011-05-01

    Mesenchymal stromal cells (MSC) are a very promising subpopulation of adult stem cells for cell-based regenerative therapies in veterinary medicine. Despite major progress in the knowledge on adult stem cells during recent years, a proper identification of MSC remains a challenge. In human medicine, the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy (ISCT) recently proposed three criteria to define MSC. Firstly, cells must be plastic-adherent when maintained under standard culture conditions. Secondly, MSC must express CD73, CD90 and CD105, and lack expression of CD34, CD45, CD14 or CD11b, CD79α or CD19 and MHC class II antigens. Thirdly, MSC must be able to differentiate into osteoblasts, adipocytes and chondroblasts in vitro. Successful isolation and differentiation of equine MSC from different sources such as bone marrow, fat tissue, umbilical cord blood, Wharton's Jelly or peripheral blood has been widely reported. However, their unequivocal immunophenotyping is hampered by the lack of a single specific marker and the limited availability of monoclonal anti-horse antibodies, which are two major factors complicating successful research on equine MSC. Detection of gene expression on mRNA level is hereby a valuable alternative, although the need still exists to test several antibody clones in search for cross-reactivity. To date, commercial antibodies recognizing equine epitopes are only available for CD13, CD44 and MHC-II. Moreover, as the expression of certain adult stem cell markers may differ between species, it is mandatory to define a set of CD markers which can be uniformly applied for the identification of equine MSC. PMID:21196039

  9. Radiation response of mesenchymal stem cells derived from bone marrow and human pluripotent stem cells

    International Nuclear Information System (INIS)

    Mesenchymal stem cells (MSCs) isolated from human pluripotent stem cells are comparable with bone marrow-derived MSCs in their function and immunophenotype. The purpose of this exploratory study was comparative evaluation of the radiation responses of mesenchymal stem cells derived from bone marrow- (BMMSCs) and from human embryonic stem cells (hESMSCs). BMMSCs and hESMSCs were irradiated at 0 Gy (control) to 16 Gy using a linear accelerator commonly used for cancer treatment. Cells were harvested immediately after irradiation, and at 1 and 5 days after irradiation. Cell cycle analysis, colony forming ability (CFU-F), differentiation ability, and expression of osteogenic-specific runt-related transcription factor 2 (RUNX2), adipogenic peroxisome proliferator-activated receptor gamma (PPARγ), oxidative stress-specific dismutase-1 (SOD1) and Glutathione peroxidase (GPX1) were analyzed. Irradiation arrested cell cycle progression in BMMSCs and hESMSCs. Colony formation ability of irradiated MSCs decreased in a dose-dependent manner. Irradiated hESMSCs showed higher adipogenic differentiation compared with BMMSCs, together with an increase in the adipogenic PPARγ expression. PPARγ expression was upregulated as early as 4 h after irradiation, along with the expression of SOD1. More than 70% downregulation was found in Wnt3A, Wnt4, Wnt7A, Wnt10A and Wnt11 in BMMSCs, but not in hESMSCs. hESMSCs are highly proliferative but radiosensitive compared with BMMSCs. Increased PPARγ expression relative to RUNX2 and downregulation of Wnt ligands in irradiated MSCs suggest Wnt mediated the fate determination of irradiated MSCs. (author)

  10. Tissue distribution and engraftment of human mesenchymal stem cells immortalized by human telomerase reverse transcriptase gene

    DEFF Research Database (Denmark)

    Bentzon, J.F.; Stenderup, K.; Hansen, F.D.;

    2005-01-01

    Engraftment of mesenchymal stem cells (MSC) in peripheral tissues for replenishing of local stem cell function has been proposed as a therapeutic approach to degenerative diseases. We have previously reported the development of an immortalized human telomerase reverse transcriptase transduced MSC...

  11. IFNγ and B7-H1 in the immunology of mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Mesenchymal stem cells (MSCs) are found in multiple organs in the fetus,cord blood and adult tissues [1]. However, in adults, the bone marrow is the major source of these stem cells. MSCs surround the blood vessels of bone marrow and are also in contact with the trabeculae [2].

  12. Human Mesenchymal Stem Cell Morphology and Migration on Microtextured Titanium

    Science.gov (United States)

    Banik, Brittany L.; Riley, Thomas R.; Platt, Christina J.; Brown, Justin L.

    2016-01-01

    The implant used in spinal fusion procedures is an essential component to achieving successful arthrodesis. At the cellular level, the implant impacts healing and fusion through a series of steps: first, mesenchymal stem cells (MSCs) need to adhere and proliferate to cover the implant; second, the MSCs must differentiate into osteoblasts; third, the osteoid matrix produced by the osteoblasts needs to generate new bone tissue, thoroughly integrating the implant with the vertebrate above and below. Previous research has demonstrated that microtextured titanium is advantageous over smooth titanium and PEEK implants for both promoting osteogenic differentiation and integrating with host bone tissue; however, no investigation to date has examined the early morphology and migration of MSCs on these surfaces. This study details cell spreading and morphology changes over 24 h, rate and directionality of migration 6–18 h post-seeding, differentiation markers at 10 days, and the long-term morphology of MSCs at 7 days, on microtextured, acid-etched titanium (endoskeleton), smooth titanium, and smooth PEEK surfaces. The results demonstrate that in all metrics, the two titanium surfaces outperformed the PEEK surface. Furthermore, the rough acid-etched titanium surface presented the most favorable overall results, demonstrating the random migration needed to efficiently cover a surface in addition to morphologies consistent with osteoblasts and preosteoblasts.

  13. PPAR-γ Signaling Crosstalk in Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Ichiro Takada

    2010-01-01

    Full Text Available Peroxisome proliferator-activated receptor-gamma (PPAR-γ is a member of the nuclear receptor (NR superfamily of ligand-activated transcriptional factors. Among other functions, PPAR-γ acts as a key regulator of the adipogenesis. Since several cytokines (IL-1, TNF-α, TGF-β had been known to inhibit adipocyte differentiation in mesenchymal stem cells (MSCs, we examined the effect of these cytokines on the transactivation function of PPAR-γ. We found that the TNF-α/IL-1-activated TAK1/TAB1/NIK (NFκB-inducible kinase signaling cascade inhibited both the adipogenesis and Tro-induced transactivation by PPAR-γ by blocking the receptor binding to the cognate DNA response elements. Furthermore, it has been shown that the noncanonical Wnts are expressed in MSCs and that Wnt-5a was capable to inhibit transactivation by PPAR-γ. Treatment with Wnt5a-activated NLK (nemo-like kinase induced physical association of the endogenous NLK and H3K9 histone methyltransferase (SETDB1 protein complexes with PPAR-γ. This resulted in histoneH3K9 tri-methylation at PPAR-γ target gene promoters. Overall, our data show that cytokines and noncanonical Wnts play a crucial role in modulation of PPAR-γ regulatory function in its target cells and tissues.

  14. Oxidative stress induces senescence in human mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Brandl, Anita [Department of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany); Meyer, Matthias; Bechmann, Volker [Department of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany); Nerlich, Michael [Department of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany); Angele, Peter, E-mail: Peter.Angele@klinik.uni-regensburg.de [Department of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany)

    2011-07-01

    Mesenchymal stem cells (MSCs) contribute to tissue repair in vivo and form an attractive cell source for tissue engineering. Their regenerative potential is impaired by cellular senescence. The effects of oxidative stress on MSCs are still unknown. Our studies were to investigate into the proliferation potential, cytological features and the telomere linked stress response system of MSCs, subject to acute or prolonged oxidant challenge with hydrogen peroxide. Telomere length was measured using the telomere restriction fragment assay, gene expression was determined by rtPCR. Sub-lethal doses of oxidative stress reduced proliferation rates and induced senescent-morphological features and senescence-associated {beta}-galactosidase positivity. Prolonged low dose treatment with hydrogen peroxide had no effects on cell proliferation or morphology. Sub-lethal and prolonged low doses of oxidative stress considerably accelerated telomere attrition. Following acute oxidant insult p21 was up-regulated prior to returning to initial levels. TRF1 was significantly reduced, TRF2 showed a slight up-regulation. SIRT1 and XRCC5 were up-regulated after oxidant insult and expression levels increased in aging cells. Compared to fibroblasts and chondrocytes, MSCs showed an increased tolerance to oxidative stress regarding proliferation, telomere biology and gene expression with an impaired stress tolerance in aged cells.

  15. Mesenchymal Stem Cells Respond to Hypoxia by Increasing Diacylglycerols.

    Science.gov (United States)

    Lakatos, Kinga; Kalomoiris, Stefanos; Merkely, Béla; Nolta, Jan A; Fierro, Fernando A

    2016-02-01

    Mesenchymal stem cells (MSC) are currently being tested clinically for a plethora of conditions, with most approaches relying on the secretion of paracrine signals by MSC to modulate the immune system, promote wound healing, and induce angiogenesis. Hypoxia has been shown to affect MSC proliferation, differentiation, survival and secretory profile. Here, we investigate changes in the lipid composition of human bone marrow-derived MSC after exposure to hypoxia. Using mass spectrometry, we compared the lipid profiles of MSC derived from five different donors, cultured for two days in either normoxia (control) or hypoxia (1% oxygen). Hypoxia induced a significant increase of total triglycerides, fatty acids and diacylglycerols (DG). Remarkably, reduction of DG levels using the phosphatidylcholine-specific phospholipase C inhibitor D609 inhibited the secretion of VEGF and Angiopoietin-2, but increased the secretion of interleukin-8, without affecting significantly their respective mRNA levels. Functionally, incubation of MSC in hypoxia with D609 inhibited the potential of the cells to promote migration of human endothelial cells in a wound/scratch assay. Hence, we show that hypoxia induces in MSC an increase of DG that may affect the angiogenic potential of these cells. PMID:26212931

  16. Cell Fate and Differentiation of Bone Marrow Mesenchymal Stem Cells

    Science.gov (United States)

    Jimi, Eijiro

    2016-01-01

    Osteoblasts and bone marrow adipocytes originate from bone marrow mesenchymal stem cells (BMMSCs) and there appears to be a reciprocal relationship between adipogenesis and osteoblastogenesis. Alterations in the balance between adipogenesis and osteoblastogenesis in BMMSCs wherein adipogenesis is increased relative to osteoblastogenesis are associated with decreased bone quality and quantity. Several proteins have been reported to regulate this reciprocal relationship but the exact nature of the signals regulating the balance between osteoblast and adipocyte formation within the bone marrow space remains to be determined. In this review, we focus on the role of Transducin-Like Enhancer of Split 3 (TLE3), which was recently reported to regulate the balance between osteoblast and adipocyte formation from BMMSCs. We also discuss evidence implicating canonical Wnt signalling, which plays important roles in both adipogenesis and osteoblastogenesis, in regulating TLE3 expression. Currently, there is demand for new effective therapies that target the stimulation of osteoblast differentiation to enhance bone formation. We speculate that reducing TLE3 expression or activity in BMMSCs could be a useful approach towards increasing osteoblast numbers and reducing adipogenesis in the bone marrow environment. PMID:27298623

  17. mTOR and the differentiation of mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Xinxin Xiang; Jing Zhao; Geyang Xu; Yin Li; Weizhen Zhang

    2011-01-01

    The mammalian target of rapamycin (mTOR), an evolutionarily conserved serine-threonine protein kinase,belongs to the phosphoinositide 3-kinase (PI3K)-related kinase family, which contains a lipid kinase-like domain within their C-terminal region. Recent studies have revealed that mTOR as a critical intracellular molecule can sense the extracellular energy status and regulate the cell growth and proliferation in a variety of cells and tissues. This review summarizes our current understanding about the effects of mTOR on cell differentiation and tissue development, with an emphasis on the lineage determination of mesenchymal stem cells, mTOR can promote adipogenesis in white adipocytes, brown adipocytes, and muscle satellite cells, while rapamycin inhibits the adipogenic function of mTOR. mTOR signaling may function to affect osteoblast proliferation and differentiation, however, rapamycin has been reported to either inhibit or promote osteogenesis. Although the precise mechanism remains unclear, mTOR is indispensable for myogenesis. Depending on the cell type, rapamycin has been reported to inhibit, promote, or have no effect on myogenesis.

  18. The Role of Mesenchymal Stem Cell in Cancer Development

    Directory of Open Access Journals (Sweden)

    Hiroshi eYagi

    2013-11-01

    Full Text Available The role of mesenchymal stem cells (MSCs in cancer development is still controversial. MSCs may promote tumor progression through immune modulation, but other tumor suppressive effects of MSCs have also been described. The discrepancy between these results may arise from issues related to different tissue sources, individual donor variability, and injection timing of MSCs. The expression of critical receptors such as Toll-like receptor (TLR is variable at each time point of treatment, which may also determine the effects of MSCs on tumor progression. However, factors released from malignant cells, as well as surrounding tissues and the vasculature, are still regarded as a black box. Thus, it is still difficult to clarify the specific role of MSCs in cancer development. Whether MSCs support or suppress tumor progression is currently unclear, but it is clear that systemically administered MSCs can be recruited and migrate toward tumors. These findings are important because they can be used as a basis for initiating studies to explore the incorporation of engineered MSCs as novel anti-tumor carriers, for the development of tumor-targeted therapies.

  19. Oxidative stress induces senescence in human mesenchymal stem cells

    International Nuclear Information System (INIS)

    Mesenchymal stem cells (MSCs) contribute to tissue repair in vivo and form an attractive cell source for tissue engineering. Their regenerative potential is impaired by cellular senescence. The effects of oxidative stress on MSCs are still unknown. Our studies were to investigate into the proliferation potential, cytological features and the telomere linked stress response system of MSCs, subject to acute or prolonged oxidant challenge with hydrogen peroxide. Telomere length was measured using the telomere restriction fragment assay, gene expression was determined by rtPCR. Sub-lethal doses of oxidative stress reduced proliferation rates and induced senescent-morphological features and senescence-associated β-galactosidase positivity. Prolonged low dose treatment with hydrogen peroxide had no effects on cell proliferation or morphology. Sub-lethal and prolonged low doses of oxidative stress considerably accelerated telomere attrition. Following acute oxidant insult p21 was up-regulated prior to returning to initial levels. TRF1 was significantly reduced, TRF2 showed a slight up-regulation. SIRT1 and XRCC5 were up-regulated after oxidant insult and expression levels increased in aging cells. Compared to fibroblasts and chondrocytes, MSCs showed an increased tolerance to oxidative stress regarding proliferation, telomere biology and gene expression with an impaired stress tolerance in aged cells.

  20. Immunomodulatory effect of Mesenchymal Stem Cells on B cells

    Directory of Open Access Journals (Sweden)

    Marcella eFranquesa

    2012-07-01

    Full Text Available The research on T cell immunosuppression therapies has attracted most of the attention in clinical transplantation. However, B cells and humoral immune responses are increasingly acknowledged as crucial mediators of chronic allograft rejection. Indeed, humoral immune responses can lead to renal allograft rejection even in patients whose cell-mediated immune responses are well controlled. On the other hand, newly studied B cell subsets with regulatory effects have been linked to tolerance achievement in transplantation. Better understanding of the regulatory and effector B cell responses may therefore lead to new therapeutic approaches.Mesenchymal Stem Cells (MSC are arising as a potent therapeutic tool in transplantation due to their regenerative and immunomodulatory properties. The research on MSCs has mainly focused on their effects on T cells and although data regarding the modulatory effects of MSCs on alloantigen-specific humoral response in humans is scarce, it has been demonstrated that MSCs significantly affect B cell functioning. In the present review we will analyze and discuss the results in this field.

  1. Mesenchymal stem cell-based therapy in kidney transplantation.

    Science.gov (United States)

    Chen, Cheng; Hou, Jianquan

    2016-01-01

    Kidney transplantation is the best treatment for end-stage renal disease, but its implementation is limited by organ shortage and immune rejection. Side effects of current immunosuppressive drugs, such as nephrotoxicity, opportunistic infection, and tumorigenic potential, influence long-term graft outcomes. In recent years, continued research and subsequent discoveries concerning the properties and potential utilization of mesenchymal stem cells (MSCs) have aroused considerable interest and expectations. Biological characteristics of MSCs, including multi-lineage differentiation, homing potential, paracrine effect and immunomodulation, have opened new horizons for applications in kidney transplantation. However, many studies have shown that the biological activity of MSCs depends on internal inflammatory conditions, and the safety and efficacy of the clinical application of MSCs remain controversial. This review summarizes the findings of a large number of studies and aims to provide an objective viewpoint based on a comprehensive analysis of the presently established benefits and obstacles of implementing MSC-based therapy in kidney transplantation, and to promote its clinical translation. PMID:26852923

  2. Mechanisms of mesenchymal stem/stromal cell function.

    Science.gov (United States)

    Spees, Jeffrey L; Lee, Ryang Hwa; Gregory, Carl A

    2016-01-01

    The past decade has seen an explosion of research directed toward better understanding of the mechanisms of mesenchymal stem/stromal cell (MSC) function during rescue and repair of injured organs and tissues. In addition to delineating cell-cell signaling and molecular controls for MSC differentiation, the field has made particular progress in defining several other mechanisms through which administered MSCs can promote tissue rescue/repair. These include: 1) paracrine activity that involves secretion of proteins/peptides and hormones; 2) transfer of mitochondria by way of tunneling nanotubes or microvesicles; and 3) transfer of exosomes or microvesicles containing RNA and other molecules. Improved understanding of MSC function holds great promise for the application of cell therapy and also for the development of powerful cell-derived therapeutics for regenerative medicine. Focusing on these three mechanisms, we discuss MSC-mediated effects on immune cell responses, cell survival, and fibrosis and review recent progress with MSC-based or MSC-derived therapeutics. PMID:27581859

  3. Mesenchymal Stem Cell (MSC) Aggregate Formation in vivo

    Science.gov (United States)

    Bartosh, Thomas J.; Ylostalo, Joni H.

    2016-01-01

    Human mesenchymal stem/progenitor cells (MSCs) isolated from various adult tissues show remarkable therapeutic potential and are being employed in clinical trials for the treatment of numerous diseases (Prockop et al., 2010). While routes of cell administration vary, profound beneficial effects of MSCs in animal models have been observed following intraperitoneal injections of the cells (Roddy et al., 2011). Similar to MSC spheres formed in culture under conditions where attachment to plastic is not permitted (Bartosh et al., 2010), MSCs injected into the peritoneum of mice spontaneously aggregate into 3D sphere-like structures (Bartosh et al., 2013). During the process of sphere assembly and compaction, MSCs upregulate expression of numerous therapeutic anti-inflammatory and immune modulatory factors. Here we describe the method we previously used for the generation of human bone marrow-derived MSC aggregates/spheres in vivo (Bartosh et al., 2013). By tagging the MSCs with green fluorescent protein (GFP), the aggregates formed can be easily visualized, collected and analyzed for changes in cellular properties and interactions with host immune cells.

  4. Generation of Insulin-Producing Human Mesenchymal Stem Cells Using Recombinant Adeno-Associated Virus

    OpenAIRE

    Kim, Jeong Hwan; Park, Si-Nae; Suh, Hwal

    2007-01-01

    The purpose of current experiment is the generation of insulin-producing human mesenchymal stem cells as therapeutic source for the cure of type 1 diabetes. Type 1 diabetes is generally caused by insulin deficiency accompanied by the destruction of islet β-cells. In various trials for the treatment of type 1 diabetes, cell-based gene therapy using stem cells is considered as one of the most useful candidate for the treatment. In this experiment, human mesenchymal stem cells were transduced wi...

  5. Phase 1 Trial of Autologous Bone Marrow Stem Cell Transplantation in Patients with Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Zurab Kakabadze

    2016-01-01

    Full Text Available Introduction. A total of 18 patients, with complete motor deficits and paraplegia caused by thoracic and lumbar spine trauma without muscle atrophy or psychiatric problems, were included into this study. Materials and Methods. The bone marrow was aspirated from the anterior iliac crest under local anesthesia and the mononuclear fraction was isolated by density gradient method. At least 750 million mononuclear-enriched cells, suspended in 2 mL of saline, were infused intrathecally. Results and Discussion. The study reports demonstrated improvement of motor and sensory functions of various degrees observed in 9 of the 18 (50% cases after bone marrow stem cell transplantation. Measured by the American Spinal Injury Association (ASIA scale, 7 (78% out of the 9 patients observed an improvement by one grade, while two cases (22% saw an improvement by two grades. However, there were no cases in which the condition was improved by three grades. Conclusions. Analysis of subsequent treatment results indicated that the transplantation of mononuclear-enriched autologous BMSCs is a feasible and safe technique. However, successful application of the BMSCs in the clinical practice is associated with the necessity of executing more detailed examinations to evaluate the effect of BMSCs on the patients with spinal cord injury.

  6. Phase 1 Trial of Autologous Bone Marrow Stem Cell Transplantation in Patients with Spinal Cord Injury.

    Science.gov (United States)

    Kakabadze, Zurab; Kipshidze, Nickolas; Mardaleishvili, Konstantine; Chutkerashvili, Gocha; Chelishvili, Irakli; Harders, Albrecht; Loladze, George; Shatirishvili, Gocha; Kipshidze, Nodar; Chakhunashvili, David; Chutkerashvili, Konstantine

    2016-01-01

    Introduction. A total of 18 patients, with complete motor deficits and paraplegia caused by thoracic and lumbar spine trauma without muscle atrophy or psychiatric problems, were included into this study. Materials and Methods. The bone marrow was aspirated from the anterior iliac crest under local anesthesia and the mononuclear fraction was isolated by density gradient method. At least 750 million mononuclear-enriched cells, suspended in 2 mL of saline, were infused intrathecally. Results and Discussion. The study reports demonstrated improvement of motor and sensory functions of various degrees observed in 9 of the 18 (50%) cases after bone marrow stem cell transplantation. Measured by the American Spinal Injury Association (ASIA) scale, 7 (78%) out of the 9 patients observed an improvement by one grade, while two cases (22%) saw an improvement by two grades. However, there were no cases in which the condition was improved by three grades. Conclusions. Analysis of subsequent treatment results indicated that the transplantation of mononuclear-enriched autologous BMSCs is a feasible and safe technique. However, successful application of the BMSCs in the clinical practice is associated with the necessity of executing more detailed examinations to evaluate the effect of BMSCs on the patients with spinal cord injury. PMID:27433165

  7. Fractionated stem cell infusions for patients with plasma cell myeloma undergoing autologous hematopoietic cell transplantation.

    Science.gov (United States)

    Landau, Heather; Wood, Kevin; Chung, David J; Koehne, Guenther; Lendvai, Nikoletta; Hassoun, Hani; Lesokhin, Alexander; Hoover, Elizabeth; Zheng, Junting; Devlin, Sean M; Giralt, Sergio

    2016-08-01

    We conducted a phase II trial investigating the impact of fractionated hematopoietic cell infusions on engraftment kinetics and symptom burden in patients with plasma cell myeloma (PCM) undergoing autologous hematopoietic cell transplant (AHCT). We hypothesized that multiple hematopoietic cell infusions would reduce duration of neutropenia and enhance immune recovery resulting in a better tolerated procedure. Twenty-six patients received high-dose melphalan followed by multiple cell infusions (Days 0, +2, +4, +6) and were compared to PCM patients (N = 77) who received high-dose melphalan and a single infusion (Day 0) (concurrent control group). The primary endpoint was number of days with ANC Inventory. Median duration of neutropenia was similar in study (4 days, range 3-5) and control patients (4 days, range 3-9) (p = 0.654). There was no significant difference in the number of red cell or platelet transfusions, days of fever, diarrhea, antibiotics, number of documented infections, or length of admission. Symptom burden surveys showed that AHCT was well-tolerated in both study and control patients. We conclude that fractionated stem cell infusions following high-dose melphalan do not enhance engraftment kinetics or significantly alter patients' clinical course following AHCT in PCM. PMID:26758672

  8. Proliferation and Differentiation of Autologic and Allogenic Stem Cells in Supralethally X-Irradiated Dogs

    International Nuclear Information System (INIS)

    Full text: Allogenic bone marrow after transplantation into dogs irradiated with 1000 R X-rays differentiates in the normal way only for 3-4 days, afterwards transforming into lymphoid cells. This transformation is due to the antigen stimulus of the host on the grafted stem cells. The lymphoid cells, obtained from the host's blood on the 7-8th day after grafting, showed specific, immune activity under the Immune Lymphocyte Transfer test. Within a short duration of the immune response immunoblasts and immunocytes Undergo degenerative changes: destroyed mitochondria, formation of autophagic vacuoles and, finally, lysis of the cells. These changes are suggested to be the result of overloading of immune cells with antigen. Preliminary sensitization of the donor with prospective host's haemopoietic tissue does not hasten the immune transformation of haemopoiesis. Injections of bacterial pyrogen, cortisone or 6-mercaptopurine into recipients, as well as incubation of bone marrow at 37°C for 2 hours, do not prevent the immune transformation. Preliminary thymectomy of the prospective recipients prevents in some of the cases immune transformation of the bone-marrow graft. The delay of allogenic bone-marrow transplantation for 5-6 days prevents in some dogs (X-irradiated with 1000 R, but not with 1200 R) the immune transformation. Transplantation of autologic bone marrow or shielding of the legs during irradiation is accompanied with good restoration of normal haemopoiesis without lymphoid transformation. (author)

  9. Steroids prevent engraftment syndrome after autologous hematopoietic stem cell transplantation without increasing the risk of infection.

    Science.gov (United States)

    Mossad, S; Kalaycio, M; Sobecks, R; Pohlman, B; Andresen, S; Avery, R; Rybicki, L; Jarvis, J; Bolwell, B

    2005-02-01

    Engraftment syndrome (ES) following autologous hematopoietic stem cell transplantation (AHSCT) is characterized by fever and rash. In January 2002, we instituted steroid prophylaxis for ES from day +4 to +14. This study was conducted to assess whether this practice increased the risk of infection. In total, 194 consecutive patients were reviewed, 111 did not receive steroid prophylaxis (group A), and 83 did (group B). Initial antimicrobial prophylaxis was the same in both groups. There were no significant differences between groups in age, gender, race, prior radiation therapy, number of prior chemotherapy regimens, disease status at transplant, mobilization regimen, days of leukopheresis, CD34(+) cell dose, and days to platelet and neutrophil engraftment. Group B had significantly fewer patients with non-Hodgkin's lymphoma and multiple myeloma, shorter median duration from diagnosis to transplant, lower risk of ES, and shorter mean length of hospital stay. The incidence of early and late microbiologically confirmed infections was not significantly different between groups. Types of infections and types of organisms identified were similar in both groups. Hospital readmission rates were similar in both groups. Steroid prophylaxis significantly decreases the risk of ES following AHSCT, and is associated with shortened hospitalization, without increasing risk of infection. PMID:15640827

  10. First-line autologous stem cell transplantation in primary CNS lymphoma.

    Science.gov (United States)

    Brevet, M; Garidi, R; Gruson, B; Royer, B; Vaida, I; Damaj, G

    2005-10-01

    The treatment of primary central nervous system lymphoma (PCNSL) has been considerably improved over recent years. In this article, we report six cases of PCNSL treated by first-line induction chemotherapy followed by intensive chemotherapy and autologous stem cell transplantation (ASCT). Six immunocompetent patients presenting with a PCNSL, confirmed by thoraco-abdomino-pelvic computer tomography scan and bone marrow biopsy, were treated with induction chemotherapy followed by BEAM intensive chemotherapy and ASCT and radiotherapy. At the end of the treatment, all the patients were in complete remission. After a median follow-up of 41.5 months (17-70 months), four patients were alive without signs of relapse (median survival: 35.5 months). Two patients died from relapse at 19 and 23 months. The neurotoxicity was low with epilepsy in one patient and persistent left side dysesthesia in another one. These results are fairly encouraging. Other studies with greater numbers of patients and longer follow-up are needed to confirm this study. PMID:16146534

  11. Improving Outcome of Hodgkins Disease with Autologous Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Raut, Shreeniwas; Shah, Sandip; Shah, Kamalesh; Patel, Kinnari; Talati, Shailesh; Parikh, Sonia; Anand, Asha; Panchal, Harsha; Patel, Apurva; Jain, Akhil

    2016-06-01

    We report analysis of all consecutive Hodgkins disease patients undergoing autologous hematopoietic stem cell transplant from September 1999 to December 2014. Out of total 38 patients 26 were males and 12 were females. 32 were adults and 6 were pediatric (<18 years). None were elderly. Median age was 28 years (9-61). All received BEAM protocol as conditioning regimen. Median engraftment time for granulocytes was 12 and 14 days for platelets. Thirty three (86.84 %) patients achieved complete remission out of which 8 (24.24 %) had further relapse. Transplant related mortality occurred in 4 (10 %) patients. Finally 26 (78.78 %) patients were disease free at median follow up of 60 months and median disease free survival (DFS) was 35 months. DFS was 66.66 and 65 %, respectively on 3 and 5 years. While overall survival was 70.83 and 70 % on 3 and 5  years, respectively. PMID:27065579

  12. Autologous peripheral blood stem cell harvest: Collection efficiency and factors affecting it

    Directory of Open Access Journals (Sweden)

    Aseem K Tiwari

    2016-01-01

    Full Text Available Background: Harvest of hematopoietic progenitor cells via leukapheresis is being used increasingly for transplants in India. Adequate yield of cells per kilogram body weight of recipient is required for successful engraftment. Collection efficiency (CE is an objective quality parameter used to assess the quality of leukapheresis program. In this study, we calculated the CE of the ComTec cell separator (Fresenius Kabi, Germany using two different formulae (CE1 and CE2 and analyzed various patient and procedural factors, which may affect it. Materials and Methods: One hundred and one consecutive procedures in 77 autologous donors carried out over 3 years period were retrospectively reviewed. Various characteristics like gender, age, weight, disease status, hematocrit, preprocedure total leukocyte count, preprocedure CD34 positive (CD34+ cells count, preprocedure absolute CD34+ cell count and processed apheresis volume effect on CE were compared. CE for each procedure was calculated using two different formulae, and results were compared using statistical correlation and regression analysis. Results: The mean CE1 and CE2 was 41.2 and 49.1, respectively. CE2 appeared to be more accurate indicator of overall CE as it considered the impact of continued mobilization of stem cells during apheresis procedure, itself. Of all the factors affecting CE, preprocedure absolute CD34+ was the only independent factor affecting CE. Conclusion: The only factor affecting CE was preprocedure absolute CD34+ cells. Though the mean CE2 was higher than CE1, it was not statistically significant.

  13. COMPARABLE OUTCOMES IN NON-SECRETORY AND SECRETORY MULTIPLE MYELOMA AFTER AUTOLOGOUS STEM CELL TRANSPLANTATION

    Science.gov (United States)

    Kumar, Shaji; Pérez, Waleska S.; Zhang, Mei-Jie; Ballen, Karen; Bashey, Asad; To, L. Bik; Bredeson, Christopher N.; Cairo, Mitchell S.; Elfenbein, Gerald J.; Freytes, César O.; Gale, Robert Peter; Gibson, John; Kyle, Robert A.; Lacy, Martha Q.; Lazarus, Hillard M.; McCarthy, Philip L.; Milone, Gustavo A.; Moreb, Jan S.; Pavlovsky, Santiago; Reece, Donna E.; Vesole, David H.; Wiernik, Peter H.; Hari, Parameswaran

    2008-01-01

    Non-secretory myeloma (NSM) accounts for <5% of cases of multiple myeloma (MM). The outcome of these patients following autologous stem cell transplantation (ASCT) has not been evaluated in clinical trials. We compared the outcomes after ASCT for patients with NSM reported to the CIBMTR between 1989 and 2003, to a matched group of 438 patients (4 controls for each patient) with secretory myeloma (SM). The patients were matched using propensity scores calculated using age, Durie-Salmon stage, sensitivity to pre-transplant therapy, time from diagnosis to transplant and year of transplant. Disease characteristics were similar in both groups at diagnosis and at transplant except higher risk of anemia, hypoalbuminemia and marrow plasmacytosis (in SM) and plasmacytoma (more in NSM). Cumulative incidence of TRM, relapse, PFS and OS were similar between the groups. In multivariate analysis, based on a Cox model stratified on matched pairs and adjusted for covariates not considered in the propensity score, we found no difference in outcome between the NSM and SM groups. In this large cohort of patients undergoing ASCT, we found no difference in outcomes of patients with NSM compared to those with SM. PMID:18804043

  14. The Role of Wharton’s Jelly Mesenchymal Stem Cells in Skin Reconstruction

    Directory of Open Access Journals (Sweden)

    Rostamzadeh

    2015-06-01

    Full Text Available Context Stem cell therapy, especially in the segment of mesenchymal stem cells (MSCs, is one of the most promising areas of regenerative medicine. Evidence Acquisition According to research conducted by various researchers, Wharton’s Jelly mesenchymal stem cells (WJMSCs have several advantages compared to others sources, in regenerative medicine: WJMSCs are more primary cells; WJMSCs can be easily isolated and without invasive procedures; WJMSCs have no ethical problems; WJMSCs are more cost effective than other sources of MSCs. Also, WJMSCs were demonstrated to express stem cell mesenchymal markers. Results Similar to bone marrow MSCs, WJMSCs express major histocompatibility complex (MHC class I molecules. Conclusions Although the aforementioned challenges must still be addressed, the potential of WJMSCs in skin regenerative clinical treatments is promising.

  15. Cytomegalovirus infection in autologous stem cell transplant recipients in the era of rituximab.

    Science.gov (United States)

    Jain, Tania; John, Jisha; Kotecha, Aditya; Deol, Abhinav; Saliminia, Tanaz; Revankar, Sanjay; Chandrasekar, Pranatharthi

    2016-08-01

    The incidence of cytomegalovirus (CMV) reactivation/disease after autologous stem cell transplant (ASCT) is much lower than that after allogeneic stem cell transplantation. With the recent use of rituximab during cancer chemotherapy or conditioning regimens prior to transplantation, there has been an increasing concern of opportunistic infections including CMV. In the present study, we reviewed the patients undergoing ASCT from December 2007 to December 2013 to identify those developing CMV reactivation/disease. Out of the 978 patients who underwent ASCT at the Karmanos Cancer Institute, 239 patients were tested for symptomatic CMV reactivation based on clinical suspicion. Of the tested patients, 7/239 (2.9 %) were documented to have CMV reactivation within 90 days of ASCT. The median time to develop CMV viremia was 32 days from transplantation. Of the 239 patients tested, CMV viremia was detected in 3 out of 72 patients who received rituximab as compared to 4 out of 167 patients who did not. Three of these seven viremic patients were treated with anti-viral drugs; viremia resolved in all patients at a median of 24 days. Three patients were found to develop other bacterial and/or fungal infections following CMV viremia. Two of the seven patients died during 1-year follow-up, due to primary disease progression or Candida sepsis. None of the patients developed proven tissue-invasive CMV disease. The study did not evaluate the incidence of asymptomatic CMV infection/reactivation. Despite prior publications based on limited data, rituximab does not appear to contribute to an increased frequency of symptomatic CMV reactivation following ASCT. PMID:27225264

  16. A population-based cohort study of late mortality in adult autologous hematopoietic stem cell transplant recipients in Australia.

    Science.gov (United States)

    Ashton, Lesley J; Le Marsney, Renate E; Dodds, Anthony J; Nivison-Smith, Ian; Wilcox, Leonie; O'Brien, Tracey A; Vajdic, Claire M

    2014-07-01

    We assessed overall and cause-specific mortality and risk factors for late mortality in a nation-wide population-based cohort of 4547 adult cancer patients who survived 2 or more years after receiving an autologous hematopoietic stem cell transplantation (HSCT) in Australia between 1992 and 2005. Deaths after HSCT were identified from the Australasian Bone Marrow Transplant Recipient Registry and through data linkage with the National Death Index. Overall, the survival probability was 56% at 10 years from HSCT, ranging from 34% for patients with multiple myeloma to 90% for patients with testicular cancer. Mortality rates moved closer to rates observed in the age- and sex-matched Australian general population over time but remained significantly increased 11 or more years from HSCT (standardized mortality ratio, 5.9). Although the proportion of deaths from nonrelapse causes increased over time, relapse remained the most frequent cause of death for all diagnoses, 10 or more years after autologous HSCT. Our findings show that prevention of disease recurrence remains 1 of the greatest challenges for autologous HSCT recipients, while the increasing rates of nonrelapse deaths due to the emergence of second cancers, circulatory diseases, and respiratory diseases highlight the long-term health issues faced by adult survivors of autologous HSCT. PMID:24631736

  17. The Three-Dimensional Collagen Scaffold Improves the Stemness of Rat Bone Marrow Mesenchymal Stem Cells

    Institute of Scientific and Technical Information of China (English)

    Sufang Han; Yannan Zhao; Zhifeng Xiao; Jin Han; Bing Chen; Lei Chen; Jianwu Dai

    2012-01-01

    Mesenchymal stem cells (MSCs) show the great promise for the treatment of a variety of diseases because of their self-renewal and multipotential abilities.MSCs are generally cultured on two-dimensional (2D) substrate in vitro.There are indications that they may simultaneously lose their stemness and multipotentiality as the result of prolonged 2D culture.In this study,we used three-dimensional (3D) collagen scaffolds as rat MSCs carrier and compared the properties of MSCs on 3D collagen scaffolds with monolayer cultured MSCs.The results demonstrated that collagen scaffolds were suitable for rat MSCs adherence and proliferation.More importantly,compared to MSCs under 2D culture,3D MSCs significantly maintained higher expression levels of stemness genes (Oct4,Sox2,Rex-1 and Nanog),yielded high frequencies of colony-forming units-fibroblastic (CFU-F) and showed enhanced osteogenic and adipogenic differentiation efficiency upon induction.Thus,3D collagen scaffolds may be beneficial for expanding rat MSCs while maintaining the stem cell properties in vitro.

  18. Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

    International Nuclear Information System (INIS)

    Highlights: ► MSC like cells were derived from hESC by a simple and reproducible method. ► Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. ► MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.

  19. Immunology of Stem Cells and Cancer Stem Cells

    Institute of Scientific and Technical Information of China (English)

    Xiao-Feng Yang

    2007-01-01

    The capacity of pluri-potent stem cells to repair the tissues in which stem cells reside holds great promise in development of novel cell replacement therapeutics for treating chronic and degenerative diseases. However,numerous reports show that stem cell therapy, even in an autologous setting, triggers lymphocyte infiltration and inflammation. Therefore, an important question to be answered is how the host immune system responds to engrafted autologous stem cells or allogeneous stem cells. In this brief review, we summarize the progress in several related areas in this field, including some of our data, in four sections: (1) immunogenicity of stem cells; (2)strategies to inhibit immune rejection to allograft stem cells; (3) immune responses to cancer stem cells; and (4)mesenchymal stem cells in immune regulation. Improvement of our understanding on these and other aspects of immune system-stem cell interplay would greatly facilitate the development of stem cell-based therapeutics for regenerative purposes.

  20. In vitro cardiomyogenic potential of human umbilical vein-derived mesenchymal stem cells

    International Nuclear Information System (INIS)

    Cardiomyocyte loss in the ischemically injured human heart often leads to irreversible defects in cardiac function. Recently, cellular cardiomyoplasty with mesenchymal stem cells, which are multipotent cells with the ability to differentiate into specialized cells under appropriate stimuli, has emerged as a new approach for repairing damaged myocardium. In the present study, the potential of human umbilical cord-derived mesenchymal stem cells to differentiate into cells with characteristics of cardiomyocyte was investigated. Mesenchymal stem cells were isolated from endothelial/subendothelial layers of the human umbilical cords using a method similar to that of human umbilical vein endothelial cell isolation. Isolated cells were characterized by transdifferentiation ability to adipocytes and osteoblasts, and also with flow cytometry analysis. After treatment with 5-azacytidine, the human umbilical cord-derived mesenchymal stem cells were morphologically transformed into cardiomyocyte-like cells and expressed cardiac differentiation markers. During the differentiation, cells were monitored by a phase contrast microscope and their morphological changes were demonstrated. Immunostaining of the differentiated cells for sarcomeric myosin (MF20), desmin, cardiac troponin I, and sarcomeric α-actinin was positive. RT-PCR analysis showed that these differentiated cells express cardiac-specific genes. Transmission electron microscopy revealed a cardiomyocyte-like ultrastructure and typical sarcomers. These observations confirm that human umbilical cord-derived mesenchymal stem cells can be chemically transformed into cardiomyocytes and can be considered as a source of cells for cellular cardiomyoplasty

  1. Low Connexin Channel-Dependent Intercellular Communication in Human Adult Hematopoietic Progenitor/Stem Cells: Probing Mechanisms of Autologous Stem Cell Therapy

    OpenAIRE

    Yang, Jian; Darley, Richard L.; Hallett, Maurice; Evans, W. Howard

    2010-01-01

    Human bone marrow is a clinical source of autologous progenitor stem cells showing promise for cardiac repair following ischemic insult. Functional improvements following delivery of adult bone marrow CD34+ cells into heart tissue may require metabolic/electrical communication between participating cells. Since connexin43 (Cx43) channels are implicated in cardiogenesis and provide intercellular connectivity in the heart, the authors analyzed the expression of 20 connexins (Cx) in CD34+ cells ...

  2. Evaluation of transport conditions for autologous bone marrow-derived mesenchymal stromal cells for therapeutic application in horses.

    Science.gov (United States)

    Espina, Miguel; Jülke, Henriette; Brehm, Walter; Ribitsch, Iris; Winter, Karsten; Delling, Uta

    2016-01-01

    Background. Mesenchymal stromal cells (MSCs) are increasingly used for clinical applications in equine patients. For MSC isolation and expansion, a laboratory step is mandatory, after which the cells are sent back to the attending veterinarian. Preserving the biological properties of MSCs during this transport is paramount. The goal of the study was to compare transport-related parameters (transport container, media, temperature, time, cell concentration) that potentially influence characteristics of culture expanded equine MSCs. Methods. The study was arranged in three parts comparing (I) five different transport containers (cryotube, two types of plastic syringes, glass syringe, CellSeal), (II) seven different transport media, four temperatures (4 °C vs. room temperature; -20 °C vs. -80 °C), four time frames (24 h vs. 48 h; 48 h vs. 72 h), and (III) three MSC concentrations (5 × 10(6), 10 × 10(6), 20 × 10(6) MSC/ml). Cell viability (Trypan Blue exclusion; percent and total number viable cell), proliferation and trilineage differentiation capacity were assessed for each test condition. Further, the recovered volume of the suspension was determined in part I. Each condition was evaluated using samples of six horses (n = 6) and differentiation protocols were performed in duplicates. Results. In part I of the study, no significant differences in any of the parameters were found when comparing transport containers at room temperature. The glass syringe was selected for all subsequent evaluations (highest recoverable volume of cell suspension and cell viability). In part II, media, temperatures, or time frames had also no significant influence on cell viability, likely due to the large number of comparisons and small sample size. Highest cell viability was observed using autologous bone marrow supernatant as transport medium, and "transport" at 4 °C for 24 h (70.6% vs. control group 75.3%); this was not significant. Contrary, viability was unacceptably low

  3. Autologous bone marrow mesenchymal stromal cells for regeneration of injured equine ligaments and tendons: a clinical report.

    Science.gov (United States)

    Renzi, S; Riccò, S; Dotti, S; Sesso, L; Grolli, S; Cornali, M; Carlin, S; Patruno, M; Cinotti, S; Ferrari, M

    2013-08-01

    The use of Mesenchymal Stromal Cells (MSCs) in orthopedic practice has recently and rapidly acquired an important role. Therapies based on the use of MSCs for the treatment of acute injuries as well as chronic inflammatory disorders are gradually becoming clinical routine. These cells have demonstrated intriguing therapeutic potentialities (i.e.: inflammation control, tissue regeneration and pathological scar prevention), that have been taken into consideration for use in both human and veterinary medicine. In particular, horses represent high performance athletes considered models for human pathologies since musculo-skeletal disorders frequently occur in this species. In the past, repair of tendon injures were performed by different methods. In particular, clinical therapy was based on ice application, bandage, box rest and controlled exercise. An alternative approach consisted on the use of corticosteroid (inflammation reduction) and other drugs (sodium hyaluronate, polysulphated glycosaminoglycans, beta aminoproprionitrile fumarate). Furthermore, surgical treatments like accessory ligament desmotomy, local irritation by line firing or pin firing were commonly used. More recently ultrasound, laser therapy, electromagnetic field therapy have been considered. Unfortunately, they did not allow complete tissue healing and quite often animals did not regain competitiveness. In order to minimize this inconvenience, the use of MSCs has been introduced as an alternative to the traditional approach since it represents a potential tool to improve tissue regeneration. Aim of this study was to evaluate the capability of MSCs to improve the functional outcome of horses affected by tendonitis and desmitis. Thirty-three breed and activity-matched horses affected by tendonitis or desmitis, were included in clinical trial scored for lesions and subdivided into two groups. Group 1 animals were treated with autologous MSCs, associated with platelet rich plasma (group 1). Bone

  4. Treatment of multiple myeloma patients with autologous stem cell transplantation — a fresh analysis

    Directory of Open Access Journals (Sweden)

    Anna Dmoszynska

    2011-07-01

    Full Text Available Patients with multiple myeloma (MM treated with conventional chemotherapy have an average survival of approximately three years. High dose chemotherapy followed by autologous stem cell transplantation (ASCT, first introduced in the mid-1980s, is now considered the standard therapy for almost all patients with multiple myeloma, because it prolongs overall survival and disease free survival. Between November 1997 and October 2006, 122 patients with MM (58 females, 64 males, median age 51.0 years [± 7.98] range: 30–66 years were transplanted in the Department of Hematooncology and Bone Marrow Transplantation at the Medical University of Lublin: 47 patients were in complete remission or in unconfirmed complete remission, 66 patients were in partial remission, and nine had stable disease. Of these, there were 95 patients with IgG myeloma, 16 with IgA myeloma, one with IgG/IgA, one with IgM myeloma, five with non secretory type, two with solitary tumor and two with LCD myeloma. According to Durie-Salmon, 62 patients had stage III of the disease, 46 had stage II and four had stage I. Most patients (69/122 were transplanted after two or more cycles of chemotherapy, 48 patients were transplanted after one cycle of chemotherapy, one patient after surgery and rtg- -therapy and four patients had not been treated. In mobilisation procedure, the patients received a single infusion of cyclophosphamide (4–6 g/m2 or etoposide 1.6 g/m2 followed by daily administration of G-CSF until the peripheral stem cells harvest. The number of median harvest sessions was 2.0 (± 0.89 (range: 1–5. An average of 7.09 (± 33.28 × 106 CD34+ cells/kg were collected from each patient (range: 1.8–111.0 × 106/kg. Conditioning regimen consisted of high dose melphalan 60–210 mg/m2 without TBI. An average of 3.04 (± 11.59 × 106 CD34+ cells/kg were transplanted to each patient. Fatal complications occured in four patients

  5. Effects of Immobilized Glycosaminoglycans on the Proliferation and Differentiation of Mesenchymal Stem Cells

    OpenAIRE

    Uygun, Basak E.; Stojsih, Sarah E.; Matthew, Howard W.T.

    2009-01-01

    Mesenchymal stem cells (MSCs) are adult stem cells with potential for multilineage differentiation. They represent an attractive cell source alternative to embryonic stem cells for therapeutic applications. Optimal utilization of MSCs for tissue engineering requires improved biomaterials that can enhance their growth and direct differentiation. The biological activity of glycosaminoglycans (GAGs) has been previously exploited for use in tissue engineering applications. In this study, MSC prol...

  6. Investigation of toxicity of various nanoparticles on cord originated mesenchymal stem cells

    OpenAIRE

    Ersöz, Melike; Allahverdiyev, Adil

    2015-01-01

    OBJECTIVE: Some of the commonly used stem cell components are bone marrow, adipose tissue, cord blood and cord matrix. Isolated cord derived using various methods (cord matrix ) high proliferation potential of mesenchymal stem cells can be applied to toxicity studies. The purpose of this study is to investigate the effect of the nanoparticles such as titanium dioxide, titanium silver, silver and zinc on mesencyhmal stem cells obtained from cord matrix in order to be used in tissue engineering.

  7. Effects of Hypoxia and Chitosan on Equine Umbilical Cord-Derived Mesenchymal Stem Cells

    OpenAIRE

    Griffon, D. J.; Cho, J.; Wagner, J. R.; Charavaryamath, C.; Wei, J.; Wagoner Johnson, A.

    2016-01-01

    Chitosan opens new perspectives in regenerative medicine as it enhances the properties of mesenchymal stem cells (MSCs) through formation of spheroids. Hypoxia has also been proposed to enhance stemness and survival of MSCs after in vivo implantation. These characteristics are relevant to the development of an off-the-shelf source of allogenic cells for regenerative therapy of tendinopathies. Umbilical cord-derived MSCs (UCM-MSCs) offer an abundant source of immature and immunoprivileged stem...

  8. Stiffening of Human Mesenchymal Stem Cell Spheroid Microenvironments Induced by Incorporation of Gelatin Microparticles

    OpenAIRE

    Baraniak, Priya R.; Cooke, Marissa T; Saeed, Rabbia; Kinney, Melissa A.; Krista M Fridley; McDevitt, Todd C.

    2012-01-01

    Culturing multipotent adult mesenchymal stem cells as 3D aggregates augments their differentiation potential and paracrine activity. One caveat of stem cell spheroids, though, can be the limited diffusional transport barriers posed by the inherent 3D structure of the multicellular aggregates. In order to circumvent such limitations, polymeric microparticles have been incorporated into stem cell aggregates as a means to locally control the biochemical and physical properties of the 3D microenv...

  9. Heterogeneous Differentiation of Human Mesenchymal Stem Cells in Response to Extended Culture in Extracellular Matrices

    OpenAIRE

    Jose A Santiago; Pogemiller, Ryan; Ogle, Brenda M.

    2009-01-01

    Extracellular matrix proteins (ECMs) guide differentiation of adult stem cells, but the temporal distribution of differentiation (i.e., heterogeneity) in a given population has not been investigated. We tested the effect of individual ECM proteins on lineage commitment of human bone marrow–derived mesenchymal stem cells (MSCs) over time. We exposed stem cell populations to ECM proteins representing the primary tissue structures of the body (i.e., collagens type I, III, IV; laminin; and fibron...

  10. Isolation and Culture of Rabbit Marrow-derived Mesenchymal Stem Cells

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    1 IntroductionRepair of tissues like bone, cartilage, muscle, etc., is a tough problem in clinical treatment. The recent research show that there are plenty of mesenchymal stem cells (MSCs) in myeloid tissue besides hemopoietic stem cells(HSCs).Just as the pluripotential hemopoietic stem cell can give bone marrow tissue excellent hemopoietic ability and maintain the metabolism of, MSCs can give potential repair ability to bone, cartilage tissue injury~([1]).But compared with the HSCs, the content of MSCs in...

  11. Acupoint Injection of Autologous Stromal Vascular Fraction and Allogeneic Adipose-Derived Stem Cells to Treat Hip Dysplasia in Dogs

    Directory of Open Access Journals (Sweden)

    Camila Marx

    2014-01-01

    Full Text Available Stem cells isolated from adipose tissue show great therapeutic potential in veterinary medicine, but some points such as the use of fresh or cultured cells and route of administration need better knowledge. This study aimed to evaluate the effect of autologous stromal vascular fraction (SVF, n=4 or allogeneic cultured adipose-derived stem cells (ASCs, n=5 injected into acupuncture points in dogs with hip dysplasia and weak response to drug therapy. Canine ASCs have proliferation and differentiation potential similar to ASCs from other species. After the first week of treatment, clinical evaluation showed marked improvement compared with baseline results in all patients treated with autologous SVF and three of the dogs treated with allogeneic ASCs. On days 15 and 30, all dogs showed improvement in range of motion, lameness at trot, and pain on manipulation of the joints, except for one ASC-treated patient. Positive results were more clearly seen in the SVF-treated group. These results show that autologous SVF or allogeneic ASCs can be safely used in acupoint injection for treating hip dysplasia in dogs and represent an important therapeutic alternative for this type of pathology. Further studies are necessary to assess a possible advantage of SVF cells in treating joint diseases.

  12. Acupoint injection of autologous stromal vascular fraction and allogeneic adipose-derived stem cells to treat hip dysplasia in dogs.

    Science.gov (United States)

    Marx, Camila; Silveira, Maiele Dornelles; Selbach, Isabel; da Silva, Ariel Silveira; Braga, Luisa Maria Gomes de Macedo; Camassola, Melissa; Nardi, Nance Beyer

    2014-01-01

    Stem cells isolated from adipose tissue show great therapeutic potential in veterinary medicine, but some points such as the use of fresh or cultured cells and route of administration need better knowledge. This study aimed to evaluate the effect of autologous stromal vascular fraction (SVF, n = 4) or allogeneic cultured adipose-derived stem cells (ASCs, n = 5) injected into acupuncture points in dogs with hip dysplasia and weak response to drug therapy. Canine ASCs have proliferation and differentiation potential similar to ASCs from other species. After the first week of treatment, clinical evaluation showed marked improvement compared with baseline results in all patients treated with autologous SVF and three of the dogs treated with allogeneic ASCs. On days 15 and 30, all dogs showed improvement in range of motion, lameness at trot, and pain on manipulation of the joints, except for one ASC-treated patient. Positive results were more clearly seen in the SVF-treated group. These results show that autologous SVF or allogeneic ASCs can be safely used in acupoint injection for treating hip dysplasia in dogs and represent an important therapeutic alternative for this type of pathology. Further studies are necessary to assess a possible advantage of SVF cells in treating joint diseases. PMID:25180040

  13. Regenerative Effects of Mesenchymal Stem Cells: Contribution of Muse Cells, a Novel Pluripotent Stem Cell Type that Resides in Mesenchymal Cells.

    Science.gov (United States)

    Wakao, Shohei; Kuroda, Yasumasa; Ogura, Fumitaka; Shigemoto, Taeko; Dezawa, Mari

    2012-01-01

    Mesenchymal stem cells (MSCs) are easily accessible and safe for regenerative medicine. MSCs exert trophic, immunomodulatory, anti-apoptotic, and tissue regeneration effects in a variety of tissues and organs, but their entity remains an enigma. Because MSCs are generally harvested from mesenchymal tissues, such as bone marrow, adipose tissue, or umbilical cord as adherent cells, MSCs comprise crude cell populations and are heterogeneous. The specific cells responsible for each effect have not been clarified. The most interesting property of MSCs is that, despite being adult stem cells that belong to the mesenchymal tissue lineage, they are able to differentiate into a broad spectrum of cells beyond the boundary of mesodermal lineage cells into ectodermal or endodermal lineages, and repair tissues. The broad spectrum of differentiation ability and tissue-repairing effects of MSCs might be mediated in part by the presence of a novel pluripotent stem cell type recently found in adult human mesenchymal tissues, termed multilineage-differentiating stress enduring (Muse) cells. Here we review recently updated studies of the regenerative effects of MSCs and discuss their potential in regenerative medicine. PMID:24710542

  14. Regenerative Effects of Mesenchymal Stem Cells: Contribution of Muse Cells, a Novel Pluripotent Stem Cell Type that Resides in Mesenchymal Cells

    Directory of Open Access Journals (Sweden)

    Mari Dezawa

    2012-11-01

    Full Text Available Mesenchymal stem cells (MSCs are easily accessible and safe for regenerative medicine. MSCs exert trophic, immunomodulatory, anti-apoptotic, and tissue regeneration effects in a variety of tissues and organs, but their entity remains an enigma. Because MSCs are generally harvested from mesenchymal tissues, such as bone marrow, adipose tissue, or umbilical cord as adherent cells, MSCs comprise crude cell populations and are heterogeneous. The specific cells responsible for each effect have not been clarified. The most interesting property of MSCs is that, despite being adult stem cells that belong to the mesenchymal tissue lineage, they are able to differentiate into a broad spectrum of cells beyond the boundary of mesodermal lineage cells into ectodermal or endodermal lineages, and repair tissues. The broad spectrum of differentiation ability and tissue-repairing effects of MSCs might be mediated in part by the presence of a novel pluripotent stem cell type recently found in adult human mesenchymal tissues, termed multilineage-differentiating stress enduring (Muse cells. Here we review recently updated studies of the regenerative effects of MSCs and discuss their potential in regenerative medicine.

  15. Role of Wnt-5a in the Determination of Human Mesenchymal Stem Cells into Preadipocytes*

    OpenAIRE

    Bilkovski, Roman; Schulte, Dominik M.; Oberhauser, Frank; Gomolka, Matthias; Udelhoven, Michael; Hettich, Moritz M.; Roth, Bernhard; Heidenreich, Axel; Gutschow, Christian; Krone, Wilhelm; Laudes, Matthias

    2009-01-01

    Increasing adipocyte size as well as numbers is important in the development of obesity and type 2 diabetes, with adipocytes being generated from mesenchymal precursor cells. This process includes the determination of mesenchymal stem cells (MSC) into preadipocytes (PA) and the differentiation of PA into mature fat cells. Although the process of differentiation has been highly investigated, the determination in humans is poorly understood. In this study, we compared human MSC and human commit...

  16. Co-transplantation of macaque autologous Schwann cells and human embryonic nerve stem cells in treatment of macaque Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Ying Xia; Chengchuan Jiang; Zuowei Cao; Keshan Shi; Yang Wang

    2012-01-01

    Objective:To investigate the therapeutic effects of co-transplantation with Schwann cells (SCs) and human embryonic nerve stem cells (NSCs) on macaque Parkinson's disease (PD). Methods:Macaque autologous SCs and human embryonic NSCs were adopted for the treatment of macaque PD. Results: Six months after transplantation, positron emission computerized tomography showed that 18F-FP-β-CIT was significantly concentrated in the injured striatum in the co-transplanted group. Immunohistochemical staining of transplanted area tissue showed migration of tyroxine hydroxylase positive cells from the transplant area to the surrounding area was significantly increased in the co-transplanted group. Conclusions: Co-transplantation of SCs and NSCs could effectively cure PD in macaques. SCs harvested from the autologous peripheral nerves can avoid rejection and the ethics problems, so it is expected to be applied clinically.

  17. Distribution and differentiation of mesenchymal stem cells in tumor tissue

    Institute of Scientific and Technical Information of China (English)

    ZHAO Hai-feng; CHEN Jun; XU Zhi-shun; ZHANG Ke-qin

    2009-01-01

    Background Tumor has an ability to become enriched in mesenchymal stem cells (MSCs) and of guiding MSCs to migrate to tumor tissue. But there are lack of relevant reports on the distribution and differentiation of MSCs in tumor tissue and the effect on tumor growth after MSCs engrafted in tumor tissue. In this study, we observed the distribution of bone marrow MSCs in tumor tissue and the possibility of MSCs differentiating into myofibroblast under the induction of local tumor microenvironment.Methods Twenty-four New Zealand rabbits were randomly classified into the control group and the test group. MSCs were isolated and cultured for each animal, vx-2 tumor tissue was transplanted under the bladder mucosa of each animal. One week after the transplantation, the self F2 passage MSCs marked by 4',6-diamidino-2-phenylindole were transplanted into tumor tissue in the test group while only Dulbecco's modified Eagle's medium-low glucose was infused into the control group. Ultrasonography was performed for each animal 1,2, 3 and 4 week(s) after the vx-2 tumor mass was transplanted. The maximum bladder tumor diameter of each animal was recorded and the mean value of each group was calculated. One animal from each group was sacrificed in the third week and the remaining animals in the fourth week to observe the tumor development. Another animal treated the same as the test group was sacrificed to observe the distribution of MSCs in tumor tissue one week after self MSCs transplantation. Immunofluorescence was used to trace MSCs in tumor tissue. The double labeling immunofluorescence for α-smooth muscle actin (α-SMA) and vimentin was performed to identify whether the MSCs can differentiate into myofibroblast.Results The ultrasonography showed no tumor mass one week after the vx-2 tumor mass transplantation. The mean maximum tumor diameter of the control group and test group was (0.70±0.14) cm and (0.78±0.14) cm, respectively, and there was no significant difference (t=1

  18. Establishing criteria for human mesenchymal stem cell potency.

    Science.gov (United States)

    Samsonraj, Rebekah M; Rai, Bina; Sathiyanathan, Padmapriya; Puan, Kia Joo; Rötzschke, Olaf; Hui, James H; Raghunath, Michael; Stanton, Lawrence W; Nurcombe, Victor; Cool, Simon M

    2015-06-01

    This study sought to identify critical determinants of mesenchymal stem cell (MSC) potency using in vitro and in vivo attributes of cells isolated from the bone marrow of age- and sex-matched donors. Adherence to plastic was not indicative of potency, yet capacity for long-term expansion in vitro varied considerably between donors, allowing the grouping of MSCs from the donors into either those with high-growth capacity or low-growth capacity. Using this grouping strategy, high-growth capacity MSCs were smaller in size, had greater colony-forming efficiency, and had longer telomeres. Cell-surface biomarker analysis revealed that the International Society for Cellular Therapy (ISCT) criteria did not distinguish between high-growth capacity and low-growth capacity MSCs, whereas STRO-1 and platelet-derived growth factor receptor alpha were preferentially expressed on high-growth capacity MSCs. These cells also had the highest mean expression of the mRNA transcripts TWIST-1 and DERMO-1. Irrespective of these differences, both groups of donor MSCs produced similar levels of key growth factors and cytokines involved in tissue regeneration and were capable of multilineage differentiation. However, high-growth capacity MSCs produced approximately double the volume of mineralized tissue compared to low-growth capacity MSCs when assessed for ectopic bone-forming ability. The additional phenotypic criteria presented in this study when combined with the existing ISCT minimum criteria and working proposal will permit an improved assessment of MSC potency and provide a basis for establishing the quality of MSCs prior to their therapeutic application. PMID:25752682

  19. Mesenchymal stem cells secretomes' affect multiple myeloma translation initiation.

    Science.gov (United States)

    Marcus, H; Attar-Schneider, O; Dabbah, M; Zismanov, V; Tartakover-Matalon, S; Lishner, M; Drucker, L

    2016-06-01

    Bone marrow mesenchymal stem cells' (BM-MSCs) role in multiple myeloma (MM) pathogenesis is recognized. Recently, we have published that co-culture of MM cell lines with BM-MSCs results in mutual modulation of phenotype and proteome (via translation initiation (TI) factors eIF4E/eIF4GI) and that there are differences between normal donor BM-MSCs (ND-MSCs) and MM BM-MSCs (MM-MSCs) in this crosstalk. Here, we aimed to assess the involvement of soluble BM-MSCs' (ND, MM) components, more easily targeted, in manipulation of MM cell lines phenotype and TI with specific focus on microvesicles (MVs) capable of transferring critical biological material. We applied ND and MM-MSCs 72h secretomes to MM cell lines (U266 and ARP-1) for 12-72h and then assayed the cells' (viability, cell count, cell death, proliferation, cell cycle, autophagy) and TI (factors: eIF4E, teIF4GI; regulators: mTOR, MNK1/2, 4EBP; targets: cyclin D1, NFκB, SMAD5, cMyc, HIF1α). Furthermore, we dissected the secretome into >100kDa and autophagy and proliferation. The dissected secretome yielded different effects on MM cell lines phenotype and TI according to fraction (>100kDa- repressed; autophagy and TI whereas MM-MSCs MVs stimulated them. These observations highlight the very complex communication between MM and BM-MSCs and underscore its significance to major processes in the malignant cells. Studies into the influential MVs cargo are underway and expected to uncover targetable signals in the regulation of the TI/proliferation/autophagy cascade. PMID:26976208

  20. Irradiation sensitivity of human and porcine mesenchymal stem cells

    International Nuclear Information System (INIS)

    Surgical resection, chemotherapy, radiotherapy, and combinations thereof are a plethora of possible treatment modalities of head and neck malignancies. Treatment regimens including radiotherapy however put jaws at risk of subsequent osteoradionecrosis. Besides cancer cells, irradiation impacts on all tissue-inherent cells, including mesenchymal stem cells (MSCs). Since it is the bone and bone marrow MSC, which contributes to bone regeneration through proliferation and osteogenic differentiation of its progeny, the influence of irradiation on MSC viability and the respective differentiation capacity appears to be critical. However to date, only a few reports picked MSCs role out as a pivotal topic. As a first attempt, we irradiated human bone derived MSC in vitro. With increasing doses the cells self-renewal capabilities were greatly reduced. Notably however, the mitotically stalled cells were still capable of differentiating into osteoblasts and preadipocytes. Next, the mandibles of Sus scrofa domestica were irradiated with a total dose of 18 Gy. At different time points post radiatio, MSCs were isolated from bone autopsies. In comparison between irradiated and non- irradiated samples, no significant differences regarding the proliferation and osteogenic differentiation potential of tissue specific MSC became apparent Therefore, pig mandibles were irradiated with doses of 9 and 18 Gy, and MSCs were isolated immediately afterwards. No significant differences between the untreated and bone irradiated with 9 Gy with respect of proliferation and osteogenic differentiation were observed. Cells isolated from 18 Gy irradiated specimens exhibited a greatly reduced osteogenic differentiation capacity, and during the first two weeks proliferation rates of explanted cells were greatly diminished. Thereafter, cells recovered and showed proliferation behaviour comparable to control samples. These results imply that MSCs can cope with irradiation up to relatively high doses

  1. Secretion of immunoregulatory cytokines by mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Dobroslav; Kyurkchiev; Ivan; Bochev; Ekaterina; Ivanova-Todorova; Milena; Mourdjeva; Tsvetelina; Oreshkova; Kalina; Belemezova; Stanimir; Kyurkchiev

    2014-01-01

    According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells(MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when cultured under standard conditions, express a certain panel of phenotypic markers and can differentiate into osteogenic, chondrogenic and adipogenic lineages when cultured in specific inducing media. In parallel with their major role as undifferentiated cell reserves, MSCs have immunomodulatory functions which are exerted by direct cell-to-cell contacts, secretion of cytokines and/or by a combination of both mechanisms. There are no convincing data about a principal difference in the profile of cytokines secreted by MSCs isolated from different tissue sources, although some papers report some quantitative but not qualitative differences in cytokine secretion. The present review focuses on the basic cytokines secreted by MSCs as described in the literature by which the MSCs exert immunodulatory effects. It should be pointed out that MSCs themselves are objects of cytokine regulation. Hypothetical mechanisms by which the MSCs exert their immunoregulatory effects are also discussed in this review. These mechanisms may either influence the target immune cells directly or indirectly by affecting the activities of predominantly dendritic cells. Chemokines are also discussed as participants in this process by recruiting cells of the immune systems and thus making them targets of immunosuppression. This review aims to present and discuss the published data and the personal experience of the authors regarding cytokines secreted by MSCs and their effects on the cells of the immune system.

  2. Defining human mesenchymal stem cell efficacy in vivo.

    Science.gov (United States)

    Bonfield, Tracey L; Nolan Koloze, Mary T; Lennon, Donald P; Caplan, Arnold I

    2010-01-01

    Allogeneic human mesenchymal stem cells (hMSCs) can suppress graft versus host disease (GvHD) and have profound anti-inflammatory and regenerative capacity in stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of disease. There is significant clinical hMSC variability in efficacy and the ultimate response in vivo. The challenge in hMSC based therapy is defining the efficacy of hMSC in vivo. Models which may provide insight into hMSC bioactivity in vivo would provide a means to distinguish hMSCs for clinical utility. hMSC function has been described as both regenerative and trophic through the production of bioactive factors. The regenerative component involves the multi-potentiality of hMSC progenitor differentiation. The secreted factors generated by the hMSCs are milieu and injury specific providing unique niches for responses in vivo. These bioactive factors are anti-scarring, angiogenic, anti-apoptotic as well as regenerative. Further, from an immunological standpoint, hMSC's can avoid host immune response, providing xenographic applications. To study the in vivo immuno-regulatory effectiveness of hMSCs, we used the ovalbumin challenge model of acute asthma. This is a quick 3 week in vivo pulmonary inflammation model with readily accessible ways of measuring effectiveness of hMSCs. Our data show that there is a direct correlation between the traditional ceramic cube score to hMSCs attenuation of cellular recruitment due to ovalbumin challenge. The results from these studies verify the in vivo immuno-modulator effectiveness of hMSCs and support the potential use of the ovalbumin model as an in vivo model of hMSC potency and efficacy. Our data also support future directions toward exploring hMSCs as an alternative therapeutic for the treatment of airway inflammation associated with asthma. PMID:20974000

  3. Defining human mesenchymal stem cell efficacy in vivo

    Directory of Open Access Journals (Sweden)

    Lennon Donald P

    2010-10-01

    Full Text Available Abstract Allogeneic human mesenchymal stem cells (hMSCs can suppress graft versus host disease (GvHD and have profound anti-inflammatory and regenerative capacity in stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of disease. There is significant clinical hMSC variability in efficacy and the ultimate response in vivo. The challenge in hMSC based therapy is defining the efficacy of hMSC in vivo. Models which may provide insight into hMSC bioactivity in vivo would provide a means to distinguish hMSCs for clinical utility. hMSC function has been described as both regenerative and trophic through the production of bioactive factors. The regenerative component involves the multi-potentiality of hMSC progenitor differentiation. The secreted factors generated by the hMSCs are milieu and injury specific providing unique niches for responses in vivo. These bioactive factors are anti-scarring, angiogenic, anti-apoptotic as well as regenerative. Further, from an immunological standpoint, hMSC's can avoid host immune response, providing xenographic applications. To study the in vivo immuno-regulatory effectiveness of hMSCs, we used the ovalbumin challenge model of acute asthma. This is a quick 3 week in vivo pulmonary inflammation model with readily accessible ways of measuring effectiveness of hMSCs. Our data show that there is a direct correlation between the traditional ceramic cube score to hMSCs attenuation of cellular recruitment due to ovalbumin challenge. The results from these studies verify the in vivo immuno-modulator effectiveness of hMSCs and support the potential use of the ovalbumin model as an in vivo model of hMSC potency and efficacy. Our data also support future directions toward exploring hMSCs as an alternative therapeutic for the treatment of airway inflammation associated with asthma.

  4. File list: ALL.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 All antigens Cardiovascular Umbi...biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  5. File list: InP.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 Input control Cardiovascular Umbi...bc.jp/kyushu-u/hg19/assembled/InP.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  6. File list: ALL.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 All antigens Cardiovascular Umbi...biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  7. File list: ALL.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 All antigens Cardiovascular Umbi...biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  8. File list: InP.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 Input control Cardiovascular Umbi...bc.jp/kyushu-u/hg19/assembled/InP.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  9. File list: InP.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 Input control Cardiovascular Umbi...bc.jp/kyushu-u/hg19/assembled/InP.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  10. File list: ALL.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 All antigens Cardiovascular Umbi...biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  11. File list: InP.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 Input control Cardiovascular Umbi...bc.jp/kyushu-u/hg19/assembled/InP.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  12. Mesenchymal stem cells and collagen patches for anteriorcruciate ligament repair

    Institute of Scientific and Technical Information of China (English)

    Benjamin Gantenbein; Neha Gadhari; Samantha CW Chan; Sandro Kohl; Sufian S Ahmad

    2015-01-01

    AIM To investigate collagen patches seeded withmesenchymal stem cells (MSCs) and/or tenocytes (TCs)with regards to their suitability for anterior cruciateligament (ACL) repair.METHODS: Dynamic intraligamentary stabilizationutilizes a dynamic screw system to keep ACL remnantsin place and promote biological healing, supplementedby collagen patches. How these scaffolds interact withcells and what type of benefit they provide has not yetbeen investigated in detail. Primary ACL-derived TCsand human bone marrow derived MSCs were seededonto two different types of 3D collagen scaffolds,Chondro-Gide? (CG) and Novocart? (NC). Cells wereseeded onto the scaffolds and cultured for 7 d eitheras a pure populations or as "premix" containing a 1:1ratio of TCs to MSCs. Additionally, as controls, cells wereseeded in monolayers and in co-cultures on both sidesof porous high-density membrane inserts (0.4 μm). Weanalyzed the patches by real time polymerase chainreaction, glycosaminoglycan (GAG), DNA and hydroxyproline(HYP) content. To determine cell spreadingand adherence in the scaffolds microscopic imagingtechniques, i.e. , confocal laser scanning microscopy(cLSM) and scanning electron microscopy (SEM), wereapplied.RESULTS: CLSM and SEM imaging analysis confirmedcell adherence onto scaffolds. The metabolic cellactivity revealed that patches promote adherenceand proliferation of cells. The most dramatic increasein absolute metabolic cell activity was measuredfor CG samples seeded with tenocytes or a 1:1 cellpremix. Analysis of DNA content and cLSM imagingalso indicated MSCs were not proliferating as nicely astenocytes on CG. The HYP to GAG ratio significantlychanged for the premix group, resulting from a slightlylower GAG content, demonstrating that the cells aremodifying the underlying matrix. Real-time quantitative Gantenbein B et al . Mesenchymal stem cells for ACL repair polymerase chain reaction data indicated that MSCs

  13. Placenta Mesenchymal Stem Cell Derived Exosomes Confer Plasticity on Fibroblasts.

    Science.gov (United States)

    Tooi, Masayuki; Komaki, Motohiro; Morioka, Chikako; Honda, Izumi; Iwasaki, Kengo; Yokoyama, Naoki; Ayame, Hirohito; Izumi, Yuichi; Morita, Ikuo

    2016-07-01

    Mesenchymal stem cell (MSC)-conditioned medium (MSC-CM) has been reported to enhance wound healing. Exosomes contain nucleic acids, proteins, and lipids, and function as an intercellular communication vehicle for mediating some paracrine effects. However, the function of MSC-derived exosomes (MSC-exo) remains elusive. In this study, we isolated human placenta MSC (PlaMSC)-derived exosomes (PlaMSC-exo) and examined their function in vitro. PlaMSCs were isolated from human term placenta using enzymatic digestion. PlaMSC-exo were prepared from the conditioned medium of PlaMSC (PlaMSC-CM) by ultracentrifugation. The expression of stemness-related genes, such as OCT4 and NANOG, in normal adult human dermal fibroblasts (NHDF) after incubation with PlaMSC-exo was measured by real-time reverse transcriptase PCR analysis (real-time PCR). The effect of PlaMSC-exo on OCT4 transcription activity was assessed using Oct4-EGFP reporter mice-derived dermal fibroblasts. The stimulating effects of PlaMSC-exo on osteoblastic and adipocyte-differentiation of NHDF were evaluated by alkaline phosphatase (ALP), and Alizarin red S- and oil red O-staining, respectively. The expression of osteoblast- and adipocyte-related genes was also assessed by real-time PCR. The treatment of NHDF with PlaMSC-exo significantly upregulated OCT4 and NANOG mRNA expression. PlaMSC-exo also enhanced OCT4 transcription. The NHDF treated with PlaMSC-exo exhibited osteoblastic and adipocyte-differentiation in osteogenic and adipogenic induction media. PlaMSC-exo increase the expression of OCT4 and NANOG mRNA in fibroblasts. As a result, PlaMSC-exo influence the differentiation competence of fibroblasts to both osteoblastic and adipocyte-differentiation. It shows a new feature of MSCs and the possibility of clinical application of MSC-exo. J. Cell. Biochem. 117: 1658-1670, 2016. © 2015 Wiley Periodicals, Inc. PMID:26640165

  14. Migration capacity of human umbilical cord mesenchymal stem cells towards glioma in vivo*

    Institute of Scientific and Technical Information of China (English)

    Cungang Fan; Dongliang Wang; Qingjun Zhang; Jingru Zhou

    2013-01-01

    High-grade glioma is the most common malignant primary brain tumor in adults. The poor prognosis of glioma, combined with a resistance to currently available treatments, necessitates the ment of more effective tumor-selective therapies. Stem cel-based therapies are emerging as novel cel-based delivery vehicle for therapeutic agents. In the present study, we successful y isolated human umbilical cord mesenchymal stem cel s by explant culture. The human umbilical cord senchymal stem cel s were adherent to plastic surfaces, expressed specific surface phenotypes of mesenchymal stem cel s as demonstrated by flow cytometry, and possessed multi-differentiation potentials in permissive induction media in vitro. Furthermore, human umbilical cord mesenchymal stem cel s demonstrated excel ent glioma-specific targeting capacity in established rat glioma models after intratumoral injection or contralateral ventricular administration in vivo. The excellent glioma-specific targeting ability and extensive intratumoral distribution of human umbilical cord mesenchymal stem cel s indicate that they may serve as a novel cel ular vehicle for delivering the-rapeutic molecules in glioma therapy.

  15. Umbilical cord mesenchymal stem cell transplantation for the treatment of Duchenne muscular dystrophy

    Institute of Scientific and Technical Information of China (English)

    Xiaofeng Yang; Yanxiang Wu; Xinping Liu; Yifeng Xu; Naiwu Lü; Yibin Zhang; Hongmei Wang; Xin Lü; Jiping Cui; Jinxu Zhou; Hong Shan

    2011-01-01

    Due to their relative abundance, stable biological properties and excellent reproductive activity,umbilical cord mesenchymal stem cells have previously been utilized for the treatment of Duchenne muscular dystrophy, which is a muscular atrophy disease. Three patients who were clinically and pathologically diagnosed with Duchenne muscular dystrophy were transplanted with umbilical cord mesenchymal stem cells by intravenous infusion, in combination with multi-point intramuscular injection. They were followed up for 12 months after cell transplantation. Results showed that clinical symptoms significantly improved, daily living activity and muscle strength were enhanced,the sero-enzyme, electromyogram, and MRI scans showed improvement, and dystrophin was expressed in the muscle cell membrane. Hematoxylin-eosin staining of a muscle biopsy revealed that muscle fibers were well arranged, fibrous degeneration was alleviated, and fat infiltration was improved. These pieces of evidence suggest that umbilical cord mesenchymal stem cell transplantation can be considered as a new regimen for Duchenne muscular dystrophy.

  16. Gene expression profiles of human bone marrow derived mesenchymal stem cells and tendon cells

    Institute of Scientific and Technical Information of China (English)

    胡庆柳; 朴英杰; 邹飞

    2003-01-01

    Objective To study the gene expression profiles of human bone marrow derived mesenchymal stem cells and tendon cells.Methods Total RNA extracted from human bone marrow derived mesenchymal stem cells and tendon cells underwent reverse transcription, and the products were labeled with α-32P dCTP. The cDNA probes of total RNA were hybridized to cDNA microarray with 1176 genes, and then the signals were analyzed by AtlasImage analysis software Version 1.01a.Results Fifteen genes associated with cell proliferation and signal transduction were up-regulated, and one gene that takes part in cell-to-cell adhesion was down-regulated in tendon cells.Conclusion The 15 up-regulated and one down-regulated genes may be beneficial to the orientational differentiation of mesenchymal stem cells into tendon cells.

  17. Quality of life before autologous stem cells transplantation as prognostic factor in patients with malignant lymphomas

    Directory of Open Access Journals (Sweden)

    Yu. L. Shevchenko

    2014-01-01

    Full Text Available Currently high-doses chemotherapy (HD-PCT + autologous hematopoietic stem cells transplantation (auto-HSCT is the treatment ofchoice in patients with recurrent and progressive lymphomas. Most of quality of life (QoL studies in lymphomas patients received HSCT limited on parameters dynamics assessment in the early and late post-transplant period. Aim of this study was to evaluate the QoL parameters and their prognostic significance in lymphoma patients before transplantation. 124 patients with lymphomas (non-Hodgkin lymphomas – 45 patients, Hodgkin's lymphoma – 79 patients who received HD-PCT + auto-HSCT were included in the study: men – 42.7 % (n = 53, women – 57.3 % (n = 71, median age – 34 years (19–65 years. Patients’ heterogeneity before transplantation regarding quality of life has been revealed. Almost 1/3 of patients showed a significant reduction in the integral index of QoL. Insignificant differences between patients with chemosensitivity and chemoresistant lymphomas regarding QoL before HD-PCT + auto-HSCT were shown. We also analyzed the outcomes of studied patients received HD-PCT + auto-HSCT. With a median follow-up of 18 months, overall survival after transplantation was 72 % (95 % CI 56–84; event-free survival – 64 % (95 % CI 53,3–73,2.Overall and event-free survivals were significantly higher in patients with chemosensitive lymphoma compared with chemoresistance tumor. Differences in the survival rates between patients with no or negligible decrease of QoL integral index and with significant reduction of it also were found. Revealed differences in overall and event-free survival between the groups allowed the first group considered as patients with a favorable prognosis, and the second group – as patients with poor prognosis regarding the transplantation outcome.

  18. Quality of life before autologous stem cells transplantation as prognostic factor in patients with malignant lymphomas

    Directory of Open Access Journals (Sweden)

    Yu. L. Shevchenko

    2014-07-01

    Full Text Available Currently high-doses chemotherapy (HD-PCT + autologous hematopoietic stem cells transplantation (auto-HSCT is the treatment ofchoice in patients with recurrent and progressive lymphomas. Most of quality of life (QoL studies in lymphomas patients received HSCT limited on parameters dynamics assessment in the early and late post-transplant period. Aim of this study was to evaluate the QoL parameters and their prognostic significance in lymphoma patients before transplantation. 124 patients with lymphomas (non-Hodgkin lymphomas – 45 patients, Hodgkin's lymphoma – 79 patients who received HD-PCT + auto-HSCT were included in the study: men – 42.7 % (n = 53, women – 57.3 % (n = 71, median age – 34 years (19–65 years. Patients’ heterogeneity before transplantation regarding quality of life has been revealed. Almost 1/3 of patients showed a significant reduction in the integral index of QoL. Insignificant differences between patients with chemosensitivity and chemoresistant lymphomas regarding QoL before HD-PCT + auto-HSCT were shown. We also analyzed the outcomes of studied patients received HD-PCT + auto-HSCT. With a median follow-up of 18 months, overall survival after transplantation was 72 % (95 % CI 56–84; event-free survival – 64 % (95 % CI 53,3–73,2.Overall and event-free survivals were significantly higher in patients with chemosensitive lymphoma compared with chemoresistance tumor. Differences in the survival rates between patients with no or negligible decrease of QoL integral index and with significant reduction of it also were found. Revealed differences in overall and event-free survival between the groups allowed the first group considered as patients with a favorable prognosis, and the second group – as patients with poor prognosis regarding the transplantation outcome.

  19. Spontaneous transformation of adult mesenchymal stem cells from cynomolgus macaques in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Zhenhua [Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing (China); Key Laboratory of Neurodegeneration, Ministry of Education, Beijing (China); Department of Anatomy, Anhui Medical University, Hefei, 230032 (China); Wang, Jiayin; Zhu, Wanwan; Guan, Yunqian; Zou, Chunlin [Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing (China); Key Laboratory of Neurodegeneration, Ministry of Education, Beijing (China); Chen, Zhiguo, E-mail: chenzhiguo@gmail.com [Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing (China); Key Laboratory of Neurodegeneration, Ministry of Education, Beijing (China); Stanford Institute for Stem Cell Biology and Regenerative Medicine and Department of Neurosurgery, Stanford, CA (United States); Zhang, Y. Alex, E-mail: yaz@bjsap.org [Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing (China); Key Laboratory of Neurodegeneration, Ministry of Education, Beijing (China)

    2011-12-10

    Mesenchymal stem cells (MSCs) have shown potential clinical utility in cell therapy and tissue engineering, due to their ability to proliferate as well as to differentiate into multiple lineages, including osteogenic, adipogenic, and chondrogenic specifications. Therefore, it is crucial to assess the safety of MSCs while extensive expansion ex vivo is a prerequisite to obtain the cell numbers for cell transplantation. Here we show that MSCs derived from adult cynomolgus monkey can undergo spontaneous transformation following in vitro culture. In comparison with MSCs, the spontaneously transformed mesenchymal cells (TMCs) display significantly different growth pattern and morphology, reminiscent of the characteristics of tumor cells. Importantly, TMCs are highly tumorigenic, causing subcutaneous tumors when injected into NOD/SCID mice. Moreover, no multiple differentiation potential of TMCs is observed in vitro or in vivo, suggesting that spontaneously transformed adult stem cells may not necessarily turn into cancer stem cells. These data indicate a direct transformation of cynomolgus monkey MSCs into tumor cells following long-term expansion in vitro. The spontaneous transformation of the cultured cynomolgus monkey MSCs may have important implications for ongoing clinical trials and for models of oncogenesis, thus warranting a more strict assessment of MSCs prior to cell therapy. -- Highlights: Black-Right-Pointing-Pointer Spontaneous transformation of cynomolgus monkey MSCs in vitro. Black-Right-Pointing-Pointer Transformed mesenchymal cells lack multipotency. Black-Right-Pointing-Pointer Transformed mesenchymal cells are highly tumorigenic. Black-Right-Pointing-Pointer Transformed mesenchymal cells do not have the characteristics of cancer stem cells.

  20. Mesenchymal traits are selected along with stem features in breast cancer cells grown as mammospheres

    Science.gov (United States)

    Borgna, Silvia; Armellin, Michela; di Gennaro, Alessandra; Maestro, Roberta; Santarosa, Manuela

    2012-01-01

    Increasing evidence indicates that invasive properties of breast cancers rely on gain of mesenchymal and stem features, which has suggested that the dual targeting of these phenotypes may represent an appealing therapeutic strategy. It is known that the fraction of stem cells can be enriched by culturing breast cancer cells as mammospheres (MS), but whether these pro-stem conditions favor also the expansion of cells provided of mesenchymal features is still undefined. In the attempt to shed light on this issue, we compared the phenotypes of a panel of 10 breast cancer cell lines representative of distinct subtypes (luminal, HER2-positive, basal-like and claudin-low), grown in adherent conditions and as mammospheres. Under MS-proficient conditions, the increment in the fraction of stem-like cells was associated to upregulation of the mesenchymal marker Vimentin and downregulation of the epithelial markers expressed by luminal cells (E-cadherin, KRT18, KRT19, ESR1). Luminal cells tended also to upregulate the myoepithelial marker CD10. Taken together, our data indicate that MS-proficient conditions do favor mesenchymal/myoepithelial features, and indicate that the use of mammospheres as an in vitro tumor model may efficiently allow the exploitation of therapeutic approaches aimed at targeting aggressive tumors that have undergone epithelial-to-mesenchymal transition. PMID:23095640

  1. Spontaneous transformation of adult mesenchymal stem cells from cynomolgus macaques in vitro

    International Nuclear Information System (INIS)

    Mesenchymal stem cells (MSCs) have shown potential clinical utility in cell therapy and tissue engineering, due to their ability to proliferate as well as to differentiate into multiple lineages, including osteogenic, adipogenic, and chondrogenic specifications. Therefore, it is crucial to assess the safety of MSCs while extensive expansion ex vivo is a prerequisite to obtain the cell numbers for cell transplantation. Here we show that MSCs derived from adult cynomolgus monkey can undergo spontaneous transformation following in vitro culture. In comparison with MSCs, the spontaneously transformed mesenchymal cells (TMCs) display significantly different growth pattern and morphology, reminiscent of the characteristics of tumor cells. Importantly, TMCs are highly tumorigenic, causing subcutaneous tumors when injected into NOD/SCID mice. Moreover, no multiple differentiation potential of TMCs is observed in vitro or in vivo, suggesting that spontaneously transformed adult stem cells may not necessarily turn into cancer stem cells. These data indicate a direct transformation of cynomolgus monkey MSCs into tumor cells following long-term expansion in vitro. The spontaneous transformation of the cultured cynomolgus monkey MSCs may have important implications for ongoing clinical trials and for models of oncogenesis, thus warranting a more strict assessment of MSCs prior to cell therapy. -- Highlights: ► Spontaneous transformation of cynomolgus monkey MSCs in vitro. ► Transformed mesenchymal cells lack multipotency. ► Transformed mesenchymal cells are highly tumorigenic. ► Transformed mesenchymal cells do not have the characteristics of cancer stem cells.

  2. Autologous stem cell therapy to treat chronic ulcer in heifer- A case study

    Directory of Open Access Journals (Sweden)

    Jayakrushna Das

    Full Text Available Aim: The study was conducted to reveal the efficacy of Bone marrow derived mesenchymal stem cells (BM-MSCs based therapy in healing of chronic non-healing and ulcerative wound in bovine species. Materials and Methods: One 2 years old Jersey heifer affected with chronic ulcerative wound involving full thickness skin and under lying muscle at dorsal side of lumbar region since four months at the time of presentation. Bone marrow was collected from tibia, cultured and grown and after achievement of optimum confluence it was applied at the site. Different parameters of clinical, physiological, haematological, biochemical, histochemical, histological, tensile strength and photographic evaluations were done during the study period. Results: The estimated values of above mentioned parameters on zero day and after healing (18 days showed significant difference (P<0.05 in relation to collagen content, tensile strength and physical characteristics of wound like extent of wound, size of wound, type of exudates and photography. But clinical, haematological and biochemical data showed no significant difference. Conclusion: The BM-MSCs were the main pioneers to bring the chronic ulcerative wound towards healing. The procedure is simple, safe and effective in bringing out healing without showing any adverse effect on host. [Vet World 2012; 5(12.000: 771-774

  3. Effects of high glucose on mesenchymal stem cell proliferation and differentiation

    DEFF Research Database (Denmark)

    Li, Yu-Ming; Schilling, Tatjana; Benisch, Peggy;

    2007-01-01

    High glucose (HG) concentrations impair cellular functions and induce apoptosis. Exposition of mesenchymal stem cells (MSC) to HG was reported to reduce colony forming activity and induce premature senescence. We characterized the effects of HG on human MSC in vitro using telomerase-immortalized ......High glucose (HG) concentrations impair cellular functions and induce apoptosis. Exposition of mesenchymal stem cells (MSC) to HG was reported to reduce colony forming activity and induce premature senescence. We characterized the effects of HG on human MSC in vitro using telomerase...

  4. Autologous bone marrow stem cell transplantation in patients with liver failure: a meta-analytic review.

    Science.gov (United States)

    Wang, Kewei; Chen, Xiaopan; Ren, Jinma

    2015-01-15

    Autologous bone marrow stem cell (ABMSC) transplantation has been utilized in clinical practice to treat patients with liver failure, but the therapeutic effect remains to be defined. A meta-analysis is essential to assess clinical advantages of ABMSC transplantation in patients with liver failure. A systematic search of published works [eg, PubMed, Medline, Embase, Chin J Clinicians (Electronic edition), and Science Citation Index] was conducted to compare clinical outcomes of ABMSC transplantation in patients with liver failure. Meta-analytic results were tested by fixed-effects model or random-effects model, dependent on the characteristics of variables. A total of 534 patients from seven studies were included in final meta-analysis. Subsequent to ABMSC transplantation, there was no significant improvement in general symptom and signs such as loss of appetite, fatigue, and ascites. Activities of serum ALT were not significantly decreased with weighted mean difference (WMD) of -19.36 and 95% confidence interval (CI) -57.53 to 18.80 (P=0.32). Postoperative level of albumin (ALB) was expectedly enhanced by stem cell transplantation (WMD 2.97, 95% CI 0.52 to 5.43, P<0.05, I(2)=84%). Coagulation function was improved as demonstrated by a short prothrombin time (PT) (WMD -1.18, 95% CI -2.32 to -0.03, P<0.05, I(2)=6%), but was not reflected by prothrombin activity (PTA) (P=0.39). Total bilirubin (TBIL) was drastically diminished after ABMSC therapy (WMD -14.85, 95% CI -20.39 to -9.32, P<0.01, I(2)=73%). Model for end-stage liver disease (MELD) scores were dramatically reduced (WMD -2.27, 95% CI -3.53 to -1.02, P<0.01, I(2)=0%). The advantage of ABMSC transplantation could be maintained more than 24 weeks as displayed by time-courses of ALB, TBIL, and MELD score. ABMSC transplantation does provide beneficial effects for patients with liver failure. Therapeutic effects can last for 6 months. However, long-term effects need to be determined. PMID:25356526

  5. Tbo-Filgrastim versus Filgrastim during Mobilization and Neutrophil Engraftment for Autologous Stem Cell Transplantation.

    Science.gov (United States)

    Elayan, Mohammed M; Horowitz, Justin G; Magraner, Jose M; Shaughnessy, Paul J; Bachier, Carlos

    2015-11-01

    There are limited data available supporting the use of the recombinant granulocyte colony-stimulating factor (G-CSF), tbo-filgrastim, rather than traditionally used filgrastim to mobilize peripheral blood stem cells (PBSC) or to accelerate engraftment after autologous stem cell transplantation (ASCT). We sought to compare the efficacy and cost of tbo-filgrastim to filgrastim in these settings. Patients diagnosed with lymphoma or plasma cell disorders undergoing G-CSF mobilization, with or without plerixafor, were included in this retrospective analysis. The primary outcome was total collected CD34(+) cells/kg. Secondary mobilization endpoints included peripheral CD34(+) cells/μL on days 4 and 5 of mobilization, adjunctive use of plerixafor, CD34(+) cells/kg collected on day 5, number of collection days and volumes processed, number of collections reaching 5 million CD34(+) cells/kg, and percent reaching target collection goal in 1 day. Secondary engraftment endpoints included time to neutrophil and platelet engraftment, number of blood product transfusions required before engraftment, events of febrile neutropenia, and length of stay. A total of 185 patients were included in the final analysis. Patients receiving filgrastim (n = 86) collected a median of 5.56 × 10(6) CD34(+) cells/kg, compared with a median of 5.85 × 10(6) CD34(+) cells/kg in the tbo-filgrastim group (n = 99; P = .58). There were no statistically significant differences in all secondary endpoints with the exception of apheresis volumes processed (tbo-filgrastim, 17.0 liters versus filgrastim, 19.7 liters; P units versus filgrastim, 1.4 units; P = .04). In conclusion, tbo-filgrastim demonstrated similar CD34(+) yield compared with filgrastim in mobilization and post-transplantation settings, with no clinically meaningful differences in secondary efficacy and safety endpoints. Furthermore, tbo-filgrastim utilization was associated with cost savings of approximately $1406 per patient

  6. Instant stem cell therapy: Characterization and concentration of human mesenchymal stem cells in vitro

    Directory of Open Access Journals (Sweden)

    P Kasten

    2008-10-01

    Full Text Available In regenerative medicine, there is an approach to avoid expansion of the mesenchymal stem cell (MSC before implantation. The aim of this study was to compare methods for instant MSC therapy by use of a portable, automatic and closed system centrifuge that allows for the concentration of MSCs. The main outcome measures were the amount of MSCs per millilitre of bone marrow (BM, clusters of differentiation (CD, proliferation and differentiation capacities of the MSC. A volume reduction protocol was compared to the traditional laboratory methods of isolation using a Ficoll gradient and native BM. Fifty millilitres of BM were obtained from haematologically healthy male Caucasians (n=10, age 8 to 49 years. The number of colony forming units-fibroblast (CFU-F/ml BM was highest in the centrifuge volume reduction protocol, followed by the native BM (not significant, the centrifuge Ficoll (p=0.042 and the manual Ficoll procedure (p=0.001. The MSC of all groups could differentiate into the mesenchymal lineages without significant differences between the groups. The CD pattern was identical for all groups: CD13+; CD 44+; CD73 +; CD90+; CD105+; HLA-A,B,C+; CD14-; CD34-; CD45-; CD271-; HLA-DR-. In a further clinical pilot study (n=5 with 297 ml BM (SD 18.6, the volume reduction protocol concentrated the MSC by a factor of 14: there were 1.08 x 102 MSC/ml BM (standard deviation (SD 1.02 x 102 before concentration, 14.8 x 102 MSC/ ml BM (SD 12.4 x 102 after concentration, and on average 296 x 102 MSC (SD 248.9 x 102, range 86.4-691.5 x 102 were available for MSC therapy. The volume reduction protocol of the closed centrifuge allows for the highest concentration of the MSC, and therefore, is a promising candidate for instant stem cell therapy.

  7. Overexpression of microRNA-124 promotes the neuronal differentiation of bone marrow-derived mesenchymal stem cells

    OpenAIRE

    Zou, Defeng; Chen, Yi; Han, Yaxin; Lv, Chen; Tu, Guanjun

    2014-01-01

    microRNAs (miRNAs) play an important regulatory role in the self-renewal and differentiation of stem cells. In this study, we examined the effects of miRNA-124 (miR-124) overexpression in bone marrow-derived mesenchymal stem cells. In particular, we focused on the effect of overexpression on the differentiation of bone marrow-derived mesenchymal stem cells into neurons. First, we used GeneChip technology to analyze the expression of miRNAs in bone marrow-derived mesenchymal stem cells, neural...

  8. Prognostic Value of EMT-Circulating Tumor Cells in Metastatic Breast Cancer Patients Undergoing High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Michal Mego, Hui Gao, Bang-Ning Lee, Evan N. Cohen, Sanda Tin, Antonio Giordano, Qiong Wu, Ping Liu, Yago Nieto, Richard E. Champlin, Gabriel N. Hortobagyi, Massimo Cristofanilli, Naoto T. Ueno, James M. Reuben

    2012-01-01

    Full Text Available Background: Circulating tumor cells (CTCs are an independent prognostic factor in metastatic breast cancer (MBC patients treated by conventional dose chemotherapy. The aim of this study was to determine the role of CTCs and CTCs undergoing epithelial-mesenchymal transition (EMT in metastatic breast cancer. We used the platform of high-dose chemotherapy (HDCT and autologous hematopoietic stem cell transplantation (AHSCT to study the CTCs and CTCs with EMT.Patients and methods: CTCs were enumerated in 21 MBC patients before apheresis and 1 month after AHSCT. CD34-depleted apheresis products were analyzed for CD326+ epithelial and Aldefluor+ cancer stem cells (CSC by flow cytometry and were depleted of CD45+ cells and assessed for EMT-inducing transcription factors (EMT-TF by quantitative RT-PCR.Results: Patients with ≥ 5 CTCs/7.5 mL of peripheral blood 1 month after AHSCT had shorter progression-free survival (PFS (P=0.02 and overall survival (OS (P=0.02. Patients with apheresis products containing high percentages of CD326+ epithelial cells or overexpressing EMT-TF had shorter PFS. In multivariate analysis, low percentage of CD326+ epithelial cells and response to HDCT with AHSCT were associated with longer PFS, whereas lower CTCs after AHSCT was associated with longer OS. High CTCs, 1 month after AHSCT correlated with shorter PFS and OS in MBC patients undergoing HDCT and AHSCT, while CTCs with EMT and CSCs phenotype in apheresis products are associated with relapse.Conclusion: Our data suggest that CTC and CTCs with EMT are prognostic in MBC patients undergoing HDCT followed by AHSCT.

  9. Outcomes and costs of autologous stem cell mobilization with chemotherapy plus G-CSF versus G-CSF alone

    OpenAIRE

    Sung, Anthony D.; Grima, Daniel T; Bernard, Lisa M.; Brown, Stephen; Carrum, George; Holmberg, Leona; Horwitz, Mitchell E.; Liesveld, Jane L.; Kanda, Junya; McClune, Brian; Shaughnessy, Paul; Tricot, Guido J.; Nelson J Chao

    2013-01-01

    Chemotherapy plus granulocyte colony stimulating factor (G-CSF) (C+G) and G-CSF alone are two of the most common methods of mobilizing CD34+ cells for autologous hematopoietic stem cell transplantation (AHSCT). In order to compare and determine real-world outcomes and costs of these strategies, we performed a retrospective study of 226 consecutive patients at 11 medical centers (64 lymphoma, 162 multiple myeloma), of whom 55% and 66% received C+G. Patients with C+G collected more CD34+ cells/...

  10. Effect of Remission Status and Induction Chemotherapy Regimen on Outcome of Autologous Stem Cell Transplantation for Mantle Cell Lymphoma

    OpenAIRE

    Till, Brian G.; Gooley, Theodore A.; Crawford, Nathan; Gopal, Ajay K.; Maloney, David G; Petersdorf, Stephen H.; Pagel, John M.; Holmberg, Leona; Bensinger, William; Press, Oliver W.

    2008-01-01

    We analyzed the outcomes of autologous stem cell transplantation (ASCT) following high-dose therapy with respect to remission status at the time of transplantation and induction regimen used in 56 consecutive patients with mantle cell lymphoma (MCL). Twenty-one patients received induction chemotherapy with HyperCVAD with or without rituximab (±R) followed by ASCT in first complete or partial remission (CR1/PR1), 15 received CHOP (±R) followed by ASCT in CR1/PR1, and 20 received ASCT following...

  11. Autologous stem cell transplantation versus novel drugs or conventional chemotherapy for patients with relapsed multiple myeloma after previous ASCT

    DEFF Research Database (Denmark)

    Grövdal, M; Nahi, H; Gahrton, G;

    2015-01-01

    High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) is the most common first-line treatment for patients with multiple myeloma (MM) under 65 years of age. A second ASCT at first relapse is frequently used but is challenged by the use of novel drugs. We retrospectively....... A second ASCT also resulted in a significantly longer second time to progression and a significantly longer time to next treatment. We conclude that, irrespective of the addition of novel drugs, MM patients in first relapse after ASCT still appear to benefit from a second ASCT. A second ASCT should...

  12. High-dose carboplatin, thiotepa, and etoposide with autologous stem cell rescue for patients with previously irradiated recurrent medulloblastoma†

    OpenAIRE

    Dunkel, Ira J.; Gardner, Sharon L.; Garvin, James H.; Goldman, Stewart; Shi, Weiji; Finlay, Jonathan L.

    2010-01-01

    Recurrent medulloblastoma is highly lethal in previously irradiated patients. Previously irradiated patients with M-0–M-3 recurrences who achieved a minimal disease state prior to protocol enrollment received carboplatin (Calvert formula with area under the curve = 7 mg/mL min, maximum 500 mg/m2/day) on days −8 to −6, and thiotepa (300 mg/m2/day) and etoposide (250 mg/m2/day) on days −5 to −3, followed by autologous stem cell rescue (ASCR) on day 0. Twenty-five patients, aged 7.6–44.7 years (...

  13. Autologous stem cell transplantation for adult acute leukemia in 2015: time to rethink? Present status and future prospects.

    Science.gov (United States)

    Gorin, N-C; Giebel, S; Labopin, M; Savani, B N; Mohty, M; Nagler, A

    2015-12-01

    The use of autologous stem cell transplantation (ASCT) as consolidation therapy for adult patients with acute leukemia has declined over time. However, multiple randomized studies in the past have reported lower relapse rates after autologous transplantation compared with chemotherapy and lower non-relapse mortality rates compared with allogeneic transplantation. In addition, quality of life of long-term survivors is better after autologous transplantation than after allogeneic transplantation. Further, recent developments may improve outcomes of autograft recipients. These include the use of IV busulfan and the busulfan+melphalan combination, better detection of minimal residual disease (MRD) with molecular biology techniques, the introduction of targeted therapies and post-transplant maintenance therapy. Therefore, ASCT may nowadays be reconsidered for consolidation in the following patients if and when they reach a MRD-negative status: good- and at least intermediate-1 risk acute myelocytic leukemia in first CR, acute promyelocytic leukemia in second CR, Ph-positive acute lymphocytic leukemia. Conversely, patients with MRD-positive status or high-risk leukemia should not be considered for consolidation with ASCT. PMID:26281031

  14. Effect of silver nanoparticles on human mesenchymal stem cell differentiation

    Directory of Open Access Journals (Sweden)

    Christina Sengstock

    2014-11-01

    Full Text Available Background: Silver nanoparticles (Ag-NP are one of the fastest growing products in nano-medicine due to their enhanced antibacterial activity at the nanoscale level. In biomedicine, hundreds of products have been coated with Ag-NP. For example, various medical devices include silver, such as surgical instruments, bone implants and wound dressings. After the degradation of these materials, or depending on the coating technique, silver in nanoparticle or ion form can be released and may come into close contact with tissues and cells. Despite incorporation of Ag-NP as an antibacterial agent in different products, the toxicological and biological effects of silver in the human body after long-term and low-concentration exposure are not well understood. In the current study, we investigated the effects of both ionic and nanoparticulate silver on the differentiation of human mesenchymal stem cells (hMSCs into adipogenic, osteogenic and chondrogenic lineages and on the secretion of the respective differentiation markers adiponectin, osteocalcin and aggrecan.Results: As shown through laser scanning microscopy, Ag-NP with a size of 80 nm (hydrodynamic diameter were taken up into hMSCs as nanoparticulate material. After 24 h of incubation, these Ag-NP were mainly found in the endo-lysosomal cell compartment as agglomerated material. Cytotoxicity was observed for differentiated or undifferentiated hMSCs treated with high silver concentrations (≥20 µg·mL−1 Ag-NP; ≥1.5 µg·mL−1 Ag+ ions but not with low-concentration treatments (≤10 µg·mL−1 Ag-NP; ≤1.0 µg·mL−1 Ag+ ions. Subtoxic concentrations of Ag-NP and Ag+ ions impaired the adipogenic and osteogenic differentiation of hMSCs in a concentration-dependent manner, whereas chondrogenic differentiation was unaffected after 21 d of incubation. In contrast to aggrecan, the inhibitory effect of adipogenic and osteogenic differentiation was confirmed by a decrease in the secretion of

  15. Incidence of interstitial pneumonia after hyperfractionated total body irradiation before autologous bone marrow/stem cell transplantation

    International Nuclear Information System (INIS)

    Purpose/Objectives Interstitial pneumonia (IP) is a severe complication after allogenic bone marrow transplantation (BMT) with incidence rates between 10 % and 40 % in different series. It is a polyetiologic disease that occurs depending on age, graft vs. host disease (GvHD), CMV-status, total body irradiation (TBI) and immunosuppressive therapy after BMT. The effects of fractionation and dose rate are not entirely clear. This study evaluates the incidence of lethal IP after hyperfractionated TBI for autologous BMT or stem cell transplantation. Materials and Methods Between 1982 and 1992, 182 patients (60 % male, 40 % female) were treated with hyperfractionated total body irradiation (TBI) before autologous bone marrow transplantation. Main indications were leukemias and lymphomas (53 % AML, 21 % ALL, 22 % NHL, 4 % others) Median age was 30 ys (15 - 55 ys). A total dose of 14.4 Gy was applied using lung blocks (12 fractions of 1.2 Gy in 4 days, dose rate 7-18 cGy/min, lung dose 9 - 9.5 Gy). TBI was followed by cyclophosphamide (200 mg/kg). 72 % were treated with bone marrow transplantation, 28 % were treated with stem cell transplantation. Interstitial pneumonia was diagnosed clinically, radiologically and by autopsy. Results 4 patients died most likely of interstitial pneumonia. For another 12 patients interstitial pneumonia was not the most likely cause of death but could not be excluded. Thus, the incidence of lethal IP was at least 2.2 % but certainly below 8.8 %. Conclusion Lethal interstitial pneumonia is a rare complication after total body irradiation before autologous bone marrow transplantation in this large, homogeously treated series. In the autologous setting, total doses of 14.4 Gy can be applied with a low risk for developing interstitial pneumonia if hyperfractionation and lung blocks are used. This falls in line with data from series with identical twins or t-cell depleted marrow and smaller, less homogeneous autologous transplant studies. Thus

  16. Therapeutic Use of Stem Cell Transplantation for Cell Replacement or Cytoprotective Effect of Microvesicle Released from Mesenchymal Stem Cell

    Science.gov (United States)

    Choi, Moonhwan; Ban, Taehyun; Rhim, Taiyoun

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is the most common and severe type of idiopathic interstitial pneumonias (IIP), and which is currently no method was developed to restore normal structure and function. There are several reports on therapeutic effects of adult stem cell transplantations in animal models of pulmonary fibrosis. However, little is known about how mesenchymal stem cell (MSC) can repair the IPF. In this study, we try to provide the evidence to show that transplanted mesenchymal stem cells directly replace fibrosis with normal lung cells using IPF model mice. As results, transplanted MSC successfully integrated and differentiated into type II lung cell which express surfactant protein. In the other hand, we examine the therapeutic effects of microvesicle treatment, which were released from mesenchymal stem cells. Though the therapeutic effects of MV treatment is less than that of MSC treatment, MV treat-ment meaningfully reduced the symptom of IPF, such as collagen deposition and inflammation. These data suggest that stem cell transplantation may be an effective strategy for the treatment of pulmonary fibrosis via replacement and cytoprotective effect of microvesicle released from MSCs. PMID:24598998

  17. Stemness gene expression profile analysis in human umbilical cord mesenchymal stem cells.

    Science.gov (United States)

    Meng, Ming-Yao; Pang, Wei; Jiang, Li-Hong; Liu, Yun-Hong; Wei, Chuan-Yu; Xie, Yan-Hua; Yu, Hai-Dong; Hou, Zong-Liu

    2012-06-01

    Umbilical cord mesenchymal stem cells (UC-MSCs) have several advantages for clinical therapy: the material is easily obtainable, the donation procedure is painless and there is low risk of viral contamination. UC-MSCs play important roles in tissue regeneration, tissue damage repair, autoimmune disease and graft-versus-host disease. In this study, we investigated the normal mRNA expression profile of UC-MSCs, and analyzed the candidate proteins responsible for the signaling pathway that may affect the differentiation characteristics of UC-MSCs. UC-MSCs were isolated by mincing UC samples into fragments and placing them in growth medium in a six-well plate. The immunophenotype characteristics and multilineage differentiation potential of the UC-MSCs were measured by flow cytometry and immunohistochemical assays. In addition, the pathway-focused gene expression profile of UC-MSCs was compared with those of normal or tumorous cells by realtime quantitative polymerase chain reaction. We successfully isolated and cultured UC-MSCs and analyzed the appropriate surface markers and their capacity for osteogenic, adipogenic and neural differentiation. In total, 168 genes focusing on signal pathways were examined. We found that the expression levels of some genes were much higher or lower than those of control cells, either normal or tumorous. UC-MSCs exhibit a unique mRNA expression profile of pathway-focused genes, especially some stemness genes, which warrants further investigation. PMID:22728706

  18. Superparamagnetic iron oxide nanoparticles label human bone marrow and umbilical cord mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Ma Yan; Zhang De-qing; Chen Le; Wang Jian; Zhang Xue; Hou Yan; Bi Xiao-juan; Yang Rong; Hu An-hua

    2012-01-01

      BACKGROUND: Nowadays, it is becoming more and more important to optimize safety of human derived cel s, label cel s efficiently and track cel s after cel s transplantation both in basic research and clinic application. OBJECTIVE: To compare the cel viability, labeling efficiency and imaging effect of the T2* weight image (WI) magnetic resonance (MR) between the human bone marrow and umbilical cord derived mesenchymal stem cel s labeled with the superparamaganetic iron oxide nanoparticles, as wel as to optimize their treatment efficiency. METHODS: The third generation of human bone marrow and umbilical cord derived mesenchymal stem cel s were cultured, and labeled with 5-30 mg/L Feridex Ⅳ and protamine sulfate. RESULTS AND CONCLUSION: The viability of human bone marrow mesenchymal stromal cel s was similar with human umbilical cord derived mesenchymal stem cel s (P >0.05). There was no significant difference of labeling rate between the bone marrow msenchymal stem cel s labeled with 5-30 mg/L Feridex Ⅳ(P >0.05); while there was significant difference of labeling rate between the umbilical cord derived mesenchymal stem cel s labeled with 5 mg/L Feridex Ⅳ and 20 and 30 mg/L Feridex Ⅳ(P <0.05); the positive labeling rate of umbilical cord derived mesenchymal stem cel s was lower than that of bone marrow msenchymal stem cel s after labeled with 10 mg/L FeridexⅣ(P <0.05). When two sources of cel s were labeled with Feridex Ⅳ more than 2 mg/L, the iron oxide particles were found in the cel suspension and could not be removed by elution and filtration. The signal intensity from 3.0T MR GRE T2*WI scan was decreased with the increasing of Feridex Ⅳ concentration in both cel types. It is safe and effective to label the two tissue-derived mesenchymal stem cel s with 10 mg/L Feridex Ⅳ-protamine sulfate complex, and can be observed with T2*WI MR.

  19. A Comparative Study of the Therapeutic Potential of Mesenchymal Stem Cells and Limbal Epithelial Stem Cells for Ocular Surface Reconstruction

    Czech Academy of Sciences Publication Activity Database

    Holáň, Vladimír; Trošan, Peter; Čejka, Čestmír; Javorková, Eliška; Zajícová, Alena; Heřmánková, Barbora; Chudičková, Milada; Čejková, Jitka

    2015-01-01

    Roč. 4, č. 9 (2015), s. 1052-1063. ISSN 2157-6564 R&D Projects: GA ČR(CZ) GA14-12580S; GA MZd NT14102; GA MŠk(CZ) LO1309; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378041 Keywords : limbal stem cells * mesenchymal stem cells * alkali-injured ocular surface * corneal regeneration * stem cell-based therapy Subject RIV: FF - HEENT, Dentistry Impact factor: 5.709, year: 2014

  20. Chinese preparation Xuesaitong promotes the mobilization of bone marrow mesenchymal stem cells in rats with cerebral infarction

    OpenAIRE

    Bao-xia Zhang; Jin-sheng Zhang; Mei-mei Du; Xiao-ya Wang; Wei Li

    2016-01-01

    After cerebral ischemia, bone marrow mesenchymal stem cells are mobilized and travel from the bone marrow through peripheral circulation to the focal point of ischemia to initiate tissue regeneration. However, the number of bone marrow mesenchymal stem cells mobilized into peripheral circulation is not enough to exert therapeutic effects, and the method by which blood circulation is promoted to remove blood stasis influences stem cell homing. The main ingredient of Xuesaitong capsules is Pana...

  1. All-trans retinoic acid promotes smooth muscle cell differentiation of rabbit bone marrow-derived mesenchymal stem cells*

    OpenAIRE

    Su, Zhong-yuan; Ying LI; Zhao, Xiao-Li; Zhang, Ming

    2010-01-01

    Bone marrow-derived mesenchymal stem cells are multipotent stem cells, an attractive resource for regenerative medicine. Accumulating evidence suggests that all-trans retinoic acid plays a key role in the development and differentiation of smooth muscle cells. In the present study, we demonstrate, for the first time, that rabbit bone marrow-derived mesenchymal stem cells differentiate into smooth muscle cells upon the treatment with all-trans retinoic acid. All-trans retinoic acid increased t...

  2. Expression of mesenchymal stem cell marker CD90 on dermal sheath cells of the anagen hair follicle in canine species

    OpenAIRE

    Gargiulo, A.M.; Pedini, V.; C. Dall’Aglio; Ceccarelli, P.; L. Pascucci; F Mercati

    2009-01-01

    The dermal sheath (DS) of the hair follicle is comprised by fibroblast-like cells and extends along the follicular epithelium, from the bulb up to the infundibulum. From this structure, cells with stem characteristics were isolated: they have a mesenchymal origin and express CD90 protein, a typical marker of mesenchymal stem cells. It is not yet really clear in which region of hair follicle these cells are located but some experimental evidence suggests that dermal stem cells are localized pr...

  3. Combination of fibrin-agarose hydrogels and adipose-derived mesenchymal stem cells for peripheral nerve regeneration

    Science.gov (United States)

    Carriel, Víctor; Garrido-Gómez, Juan; Hernández-Cortés, Pedro; Garzón, Ingrid; García-García, Salomé; Sáez-Moreno, José Antonio; Sánchez-Quevedo, María del Carmen; Campos, Antonio; Alaminos, Miguel

    2013-04-01

    Objective. The objective was to study the effectiveness of a commercially available collagen conduit filled with fibrin-agarose hydrogels alone or with fibrin-agarose hydrogels containing autologous adipose-derived mesenchymal stem cells (ADMSCs) in a rat sciatic nerve injury model. Approach. A 10 mm gap was created in the sciatic nerve of 48 rats and repaired using saline-filled collagen conduits or collagen conduits filled with fibrin-agarose hydrogels alone (acellular conduits) or with hydrogels containing ADMSCs (ADMSC conduits). Nerve regeneration was assessed in clinical, electrophysiological and histological studies. Main results. Clinical and electrophysiological outcomes were more favorable with ADMSC conduits than with the acellular or saline conduits, evidencing a significant recovery of sensory and motor functions. Histological analysis showed that ADMSC conduits produce more effective nerve regeneration by Schwann cells, with higher remyelination and properly oriented axonal growth that reached the distal areas of the grafted conduits, and with intensely positive expressions of S100, neurofilament and laminin. Extracellular matrix was also more abundant and better organized around regenerated nerve tissues with ADMSC conduits than those with acellular or saline conduits. Significance. Clinical, electrophysiological and histological improvements obtained with tissue-engineered ADMSC conduits may contribute to enhancing axonal regeneration by Schwann cells.

  4. Visual bone marrow mesenchymal stem cell transplantation in the repair of spinal cord injury

    OpenAIRE

    Rui-ping Zhang; Cheng Xu; Yin Liu; Jian-ding Li; Jun Xie

    2015-01-01

    An important factor in improving functional recovery from spinal cord injury using stem cells is maximizing the number of transplanted cells at the lesion site. Here, we established a contusion model of spinal cord injury by dropping a weight onto the spinal cord at T 7-8 . Superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells were transplanted into the injured spinal cord via the subarachnoid space. An outer magnetic field was used to successfully guide the labeled cells to...

  5. Absence of Nucks1 enhances mesenchymal stem cells mediated cardiac protection

    OpenAIRE

    Chiu, Sin-ming; 趙善明

    2013-01-01

    Despite major advances in diagnosis and prevention of coronary artery disease (CAD), the development of therapies to regenerate functional cardiomyocytes after myocardial infarction (MI) is very challenging. Studies have demonstrated that bone marrow derived mesenchymal stem cells (BM-MSCs) secrete a panel of growth factors and anti-inflammatory cytokines to activate resident cardiomyocytes and cardiac stem cells in myocardial repair after MI. However, the mechanisms of modulating BM-MSC secr...

  6. Mesenchymal Stem Cells in Immune-Mediated Bone Marrow Failure Syndromes

    OpenAIRE

    Maria-Christina Kastrinaki; Konstantia Pavlaki; Batsali, Aristea K.; Elisavet Kouvidi; Irene Mavroudi; Charalampos Pontikoglou; Papadaki, Helen A

    2013-01-01

    Immune-mediated bone marrow failure syndromes (BMFS) are characterized by ineffective marrow haemopoiesis and subsequent peripheral cytopenias. Ineffective haemopoiesis is the result of a complex marrow deregulation including genetic, epigenetic, and immune-mediated alterations in haemopoietic stem/progenitor cells, as well as abnormal haemopoietic-to-stromal cell interactions, with abnormal release of haemopoietic growth factors, chemokines, and inhibitors. Mesenchymal stem/stromal cells (MS...

  7. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche

    OpenAIRE

    Méndez-Ferrer, Simón; Michurina, Tatyana V.; Ferraro, Francesca; Amin R Mazloom; MacArthur, Ben D; Lira, Sergio A.; Scadden, David T.; Ma’ayan, Avi; Enikolopov, Grigori N.; Frenette, Paul S.

    2010-01-01

    The cellular constituents forming the haematopoietic stem cell (HSC) niche in the bone marrow are unclear, with studies implicating osteoblasts, endothelial and perivascular cells. Here we demonstrate that mesenchymal stem cells (MSCs), identified using nestin expression, constitute an essential HSC niche component. Nestin+ MSCs contain all the bone-marrow colony-forming-unit fibroblastic activity and can be propagated as non-adherent ‘mesenspheres’ that can self-renew and expand in serial tr...

  8. 12 hours after cerebral ischemia is the optimal time for bone marrow mesenchymal stem cell transplantation

    OpenAIRE

    Seyed Mojtaba Hosseini; Mohammad Farahmandnia; Zahra Razi; Somayeh Delavarifar; Benafsheh Shakibajahromi

    2015-01-01

    Cell therapy using stem cell transplantation against cerebral ischemia has been reported. However, it remains controversial regarding the optimal time for cell transplantation and the transplantation route. Rat models of cerebral ischemia were established by occlusion of the middle cerebral artery. At 1, 12 hours, 1, 3, 5 and 7 days after cerebral ischemia, bone marrow mesenchymal stem cells were injected via the tail vein. At 28 days after cerebral ischemia, rat neurological function was eva...

  9. Environmental parameters influence non-viral transfection of human mesenchymal stem cells for tissue engineering applications

    OpenAIRE

    King, William J.; Kouris, Nicholas A.; Choi, Siyoung; Ogle, Brenda M.; Murphy, William L.

    2012-01-01

    Non-viral transfection is a promising technique which could be used to increase the therapeutic potential of stem cells. The purpose of this study was to explore practical culture parameters of relevance in potential human mesenchymal stem cell (hMSC) clinical and tissue engineering applications, including type of polycationic transfection reagent, N/P ratio and dose of polycation/pDNA polyplexes, cell passage number, cell density, and cell proliferation. The non-viral transfection efficiency...

  10. Pelvic Organ Distribution of Mesenchymal Stem Cells Injected Intravenously after Simulated Childbirth Injury in Female Rats

    OpenAIRE

    Michelle Cruz; Charuspong Dissaranan; Anne Cotleur; Matthew Kiedrowski; Marc Penn; Margot Damaser

    2011-01-01

    The local route of stem cell administration utilized presently in clinical trials for stress incontinence may not take full advantage of the capabilities of these cells. The goal of this study was to evaluate if intravenously injected mesenchymal stem cells (MSCs) home to pelvic organs after simulated childbirth injury in a rat model. Female rats underwent either vaginal distension (VD) or sham VD. All rats received 2 million GFP-labeled MSCs intravenously 1 hour after injury. Four or 10 days...

  11. Cardiogenic and Myogenic Gene Expression in Mesenchymal Stem Cells After 5-Azacytidine Treatment

    OpenAIRE

    Aungkura Supokawej; Pakpoom Kheolamai; Kuneerat Nartprayut; Yaowalak U-pratya; Sirikul Manochantr; Methichit Chayosumrit; Surapol Issaragrisil

    2013-01-01

    Objective: 5-Azacytidine is a hypomethylating agent that is used for the treatment of myelodysplastic syndrome. This histone modifier is widely employed and plays a nonspecific role in influencing the differentiation capability of stem cells. The ability of bone marrow mesenchymal stem cells to differentiate into cardiomyocyte- and myocyte-like cells after exposure to 3 different doses of 5-azacytidine has been evaluated and compared. The aim of the study was to optimize the effective dose of...

  12. Reconstruction of the corneal epithelium with induced marrow mesenchymal stem cells in rats

    OpenAIRE

    Jiang, Ting-Shuai; Cai, Li; Ji, Wei-Ying; Hui, Yan-Nian; Wang, Yu-Sheng; Hu, Dan; Zhu, Jie

    2010-01-01

    Purpose To explore the feasibility of bone marrow mesenchymal stem cells (MSCs) transdifferentiating into corneal epithelial cells in a limbal stem cell deficiency (LSCD) model in rats. Methods Rat MSCs were isolated and purified using a gradient isolation procedure. The cells were induced by rat corneal stromal cells (CSCs) in a transwell co-culture system. The induced MSCs were identified by immunofluorescence staining, flow cytometry, and scanning electron microscopy (SEM). A corneal LSCD ...

  13. Characterization and clinical application of mesenchymal stem cells from equine umbilical cord blood

    OpenAIRE

    Kang, Jun-gu; Park, Sang-Bum; Seo, Min-Soo; Kim, Hyung-Sik; Chae, Joon-Seok; Kang, Kyung-Sun

    2013-01-01

    Tendinitis of the superficial digital flexor tendon (SDFT) is a significant cause of lameness in horses; however, recent studies have shown that stem cells could be useful in veterinary regenerative medicine. Therefore, we isolated and characterized equine umbilical cord blood mesenchymal stem cells (eUCB-MSCs) from equine umbilical cord blood obtained from thoroughbred mares during the foaling period. Horses that had tendinitis of the SDFT were treated with eUCB-MSCs to confirm the therapeut...

  14. BONE MARROW MESENCHYMAL STEM CELLS ARE PROGENITORS IN VITRO FOR INNER EAR HAIR CELLS

    OpenAIRE

    Jeon, Sang-Jun; Oshima, Kazuo; Heller, Stefan; Edge, Albert S. B.

    2006-01-01

    Stem cells have been demonstrated in the inner ear but they do not spontaneously divide to replace damaged sensory cells. Mesenchymal stem cells (MSC) from bone marrow have been reported to differentiate into multiple lineages including neurons, and we therefore asked whether MSCs could generate sensory cells. Overexpression of the prosensory transcription factor, Math1, in sensory epithelial precursor cells induced expression of myosin VIIa, espin, Brn3c, p27Kip, and jagged2, indicating diff...

  15. Tissue-based Identification of Stem Cells and Epithelial-to-Mesenchymal Transition in Breast Cancer

    OpenAIRE

    Anwar, Talha; Kleer, Celina G.

    2013-01-01

    Pathologists have recognized breast cancer heterogeneity for decades, but its causes were unknown. In recent years, basic science and translational studies have demonstrated that cancer stem cells contribute to the heterogeneous histological and functional characteristics of breast cancer. Even more recently, the ability of breast epithelial cells to undergo an epithelial to mesenchymal (EMT) transition has been linked to the acquisition of stem cells properties, and enhanced tumor invasion, ...

  16. Stem cells of the suture mesenchyme in craniofacial bone development, repair and regeneration

    OpenAIRE

    Maruyama, Takamitsu; Jeong, Jaeim; Sheu, Tzong-jen; Hsu, Wei

    2016-01-01

    The suture mesenchyme serves as a growth centre for calvarial morphogenesis and has been postulated to act as the niche for skeletal stem cells. Aberrant gene regulation causes suture dysmorphogenesis resulting in craniosynostosis, one of the most common craniofacial deformities. Owing to various limitations, especially the lack of suture stem cell isolation, reconstruction of large craniofacial bone defects remains highly challenging. Here we provide the first evidence for an Axin2-expressin...

  17. Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Angiogenesis: Potencial Clinical Application

    OpenAIRE

    Merino-González, Consuelo; Zuñiga, Felipe A.; Escudero, Carlos; Ormazabal, Valeska; Reyes, Camila; Nova-Lamperti, Estefanía; Salomón, Carlos; Aguayo, Claudio

    2016-01-01

    Mesenchymal stem cells (MSCs) are adult multipotent stem cells that are able to differentiate into multiple specialized cell types including osteocytes, adipocytes, and chondrocytes. MSCs exert different functions in the body and have recently been predicted to have a major clinical/therapeutic potential. However, the mechanisms of self-renewal and tissue regeneration are not completely understood. It has been shown that the biological effect depends mainly on its paracrine action. Furthermor...

  18. PET/CT before autologous stem cell transplantation predicts outcome in refractory/relapsed follicular lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Alcantara, Marion; Tilly, Herve [Universite de Rouen, Service d' Hematologie, Centre Henri Becquerel, Rouen (France); Dupuis, Jehan; Haioun, Corinne [CHU Henri Mondor et Universite Paris-Est, Assistance Publique - Hopitaux de Paris, Unite Hemopathies Lymphoides, Marechal de Lattre de Tassigny (France); Mareschal, Sylvain; Dubois, Sydney [Centre Henri Becquerel, IRIB, Unite Inserm U918, Rouen (France); Julian, Anne [CHU Purpan, Service de Medecine Nucleaire, Toulouse (France); Cottereau, Anne Segolene; Becker, Stephanie [Centre Henri Becquerel, Service de Medecine Nucleaire, Rouen (France); Oberic, Lucie; Huynh, Anne; Laurent, Guy; Ysebaert, Loic [IUCT-Oncopole, Departement d' Hematologie, Toulouse (France); Meignan, Michel [CHU Henri-Mondor, Service de Medecine Nucleaire, Paris (France)

    2014-09-20

    Salvage of young patients with follicular lymphoma (FL) after R-CHOP includes salvage immunochemotherapy followed by autologous stem cell transplantation (ASCT). Previous studies dealing with relapsed Hodgkin lymphoma have shown the prognostic value of PET/CT prior to ASCT. We retrospectively analysed 59 patients with refractory/relapsed FL after first-line R-CHOP who were chemosensitive (as evaluated by CT) to the salvage treatment and who proceeded to ASCT. The role of PET/CT in this setting to define chemosensitivity is not definitely established. So we focused on the prognostic value of PET/CT performed after salvage treatment, before ASCT. The estimated 3-year progression-free survival (PFS) and overall survival were 63.1 % (50.9-78.3 %) and 90.5 % (82.8 - 98.8 %), respectively, and did not differ significantly according to their Follicular Lymphoma International Prognostic Index at relapse, conditioning regimen, or type of salvage. PFS was significantly lower in PET/CT-positive patients, according to the International Harmonization Project revised response criteria, with a 3-year PFS of 45.5 % (26.6 - 77.8 %) versus 72.6 % (58.5 - 90.0 %; p = 0.039). To better refine prognosis, we applied two types of thresholds: a Deauville five-point scale positive threshold of ≥3 (3-year PFS of 74.9 %, range 61.0 - 92.1 % %, versus 42.8 %, range 24.7 - 74.4 %; p = 0.02), and a ≥70 % ∇SUV{sub max} threshold between presalvage and pre-ASCT PET/CT (3-year PFS of 72.4 %, range 57.5 - 91.3 % versus 13.3 %, 2.2 - 81.7 %; p < 10{sup -3}). The PET/CT findings before ASCT were independently correlated with PFS in our series. PET/CT negativity before ASCT is a desirable and achievable goal in the management of chemosensitive FL relapsing after first-line R-CHOP. (orig.)

  19. In vitro mesenchymal stem cell response to a CO2 laser modified polymeric material.

    Science.gov (United States)

    Waugh, D G; Hussain, I; Lawrence, J; Smith, G C; Cosgrove, D; Toccaceli, C

    2016-10-01

    With an ageing world population it is becoming significantly apparent that there is a need to produce implants and platforms to manipulate stem cell growth on a pharmaceutical scale. This is needed to meet the socio-economic demands of many countries worldwide. This paper details one of the first ever studies in to the manipulation of stem cell growth on CO2 laser surface treated nylon 6,6 highlighting its potential as an inexpensive platform to manipulate stem cell growth on a pharmaceutical scale. Through CO2 laser surface treatment discrete changes to the surfaces were made. That is, the surface roughness of the nylon 6,6 was increased by up to 4.3μm, the contact angle was modulated by up to 5° and the surface oxygen content increased by up to 1atom %. Following mesenchymal stem cell growth on the laser treated samples, it was identified that CO2 laser surface treatment gave rise to an enhanced response with an increase in viable cell count of up to 60,000cells/ml when compared to the as-received sample. The effect of surface parameters modified by the CO2 laser surface treatment on the mesenchymal stem cell response is also discussed along with potential trends that could be identified to govern the mesenchymal stem cell response. PMID:27287173

  20. Stiffening of Human Mesenchymal Stem Cell Spheroid Microenvironments Induced by Incorporation of Gelatin Microparticles

    Science.gov (United States)

    Baraniak, Priya R.; Cooke, Marissa T.; Saeed, Rabbia; Kinney, Melissa A.; Fridley, Krista M.; McDevitt, Todd C.

    2012-01-01

    Culturing multipotent adult mesenchymal stem cells as 3D aggregates augments their differentiation potential and paracrine activity. One caveat of stem cell spheroids, though, can be the limited diffusional transport barriers posed by the inherent 3D structure of the multicellular aggregates. In order to circumvent such limitations, polymeric microparticles have been incorporated into stem cell aggregates as a means to locally control the biochemical and physical properties of the 3D microenvironment. However, the introduction of biomaterials to the 3D stem cell microenvironment could alter the mechanical forces sensed by cells within aggregates, which in turn could impact various cell behaviors and overall spheroid mechanics. Therefore, the objective of this study was to determine the acute effects of biomaterial incorporation within mesenchymal stem cell spheroids on aggregate structure and mechanical properties. The results of this study demonstrate that although gelatin microparticle incorporation results in similar multi-cellular organization within human mesenchymal stem cell spheroids, the introduction of gelatin materials significantly impacts spheroid mechanical properties. The marked differences in spheroid mechanics induced by microparticle incorporation may hold major implications for in vitro directed differentiation strategies and offer a novel route to engineer the mechanical properties of tissue constructs ex vivo. PMID:22658155