Persistence of Yellow Fever vaccine-induced antibodies after cord blood stem cell transplant.

Science.gov (United States)

Avelino-Silva, Vivian Iida; Freire, Marcos da Silva; Rocha, Vanderson; Rodrigues, Celso Arrais; Novis, Yana Sarkis; Sabino, Ester C; Kallas, Esper Georges

2016-04-02

We report the case of a cord blood haematopoietic stem cell transplant recipient who was vaccinated for Yellow Fever (YF) 7 days before initiating chemotherapy and had persistent YF antibodies more than 3 years after vaccination. Since the stem cell donor was never exposed to wild YF or to the YF vaccine, and our patient was not exposed to YF or revaccinated, this finding strongly suggests the persistence of recipient immunity. We briefly discuss potential consequences of incomplete elimination of recipient's leukocytes following existing haematopoietic cancer treatments.

Banking on cord blood stem cells.

Science.gov (United States)

Sullivan, Michael J

2008-07-01

Umbilical cord blood gifted to non-profit public cord blood banks is now routinely used as an alternative source of haematopoietic stem cells for allogeneic transplantation for children and adults with cancer, bone marrow failure syndromes, haemoglobinopathies and many genetic metabolic disorders. Because of the success and outcomes of public cord banking, many companies now provide private cord banking services. However, in the absence of any published transplant evidence to support autologous and non-directed family banking, commercial cord banks currently offer a superfluous service.

Imaging in haematopoietic stem cell transplantation

International Nuclear Information System (INIS)

Evans, A.; Steward, C.G.; Lyburn, I.D.; Grier, D.J.

2003-01-01

Haematopoietic stem cell transplantation (SCT) is used to treat a wide range of malignant and non-malignant haematological conditions, solid malignancies, and metabolic and autoimmune diseases. Although imaging has a limited role before SCT, it is important after transplantation when it may support the clinical diagnosis of a variety of complications. It may also be used to monitor the effect of therapy and to detect recurrence of the underlying disease if the transplant is unsuccessful. We present a pictorial review of the imaging of patients who have undergone SCT, based upon 15 years experience in a large unit performing both adult and paediatric transplants

Imaging in haematopoietic stem cell transplantation

Energy Technology Data Exchange (ETDEWEB)

Evans, A.; Steward, C.G.; Lyburn, I.D.; Grier, D.J

2003-03-01

Haematopoietic stem cell transplantation (SCT) is used to treat a wide range of malignant and non-malignant haematological conditions, solid malignancies, and metabolic and autoimmune diseases. Although imaging has a limited role before SCT, it is important after transplantation when it may support the clinical diagnosis of a variety of complications. It may also be used to monitor the effect of therapy and to detect recurrence of the underlying disease if the transplant is unsuccessful. We present a pictorial review of the imaging of patients who have undergone SCT, based upon 15 years experience in a large unit performing both adult and paediatric transplants.

Promotion of haematopoietic activity in embryonic stem cells by the aorta-gonad-mesonephros microenvironment

International Nuclear Information System (INIS)

Krassowska, Anna; Gordon-Keylock, Sabrina; Samuel, Kay; Gilchrist, Derek; Dzierzak, Elaine; Oostendorp, Robert; Forrester, Lesley M.; Ansell, John D.

2006-01-01

We investigated whether the in vitro differentiation of ES cells into haematopoietic progenitors could be enhanced by exposure to the aorta-gonadal-mesonephros (AGM) microenvironment that is involved in the generation of haematopoietic stem cells (HSC) during embryonic development. We established a co-culture system that combines the requirements for primary organ culture and differentiating ES cells and showed that exposure of differentiating ES cells to the primary AGM region results in a significant increase in the number of ES-derived haematopoietic progenitors. Co-culture of ES cells on the AM20-1B4 stromal cell line derived from the AGM region also increases haematopoietic activity. We conclude that factors promoting the haematopoietic activity of differentiating ES cells present in primary AGM explants are partially retained in the AM20.1B4 stromal cell line and that these factors are likely to be different to those required for adult HSC maintenance

Haematopoietic ESL-1 enables stem cell proliferation in the bone marrow by limiting TGFβ availability.

Science.gov (United States)

Leiva, Magdalena; Quintana, Juan A; Ligos, José M; Hidalgo, Andrés

2016-01-08

The life-long maintenance of haematopoietic stem and progenitor cells (HSPCs) critically relies on environmental signals produced by cells that constitute the haematopoietic niche. Here we report a cell-intrinsic mechanism whereby haematopoietic cells limit proliferation within the bone marrow, and show that this pathway is repressed by E-selectin ligand 1 (ESL-1). Mice deficient in ESL-1 display aberrant HSPC quiescence, expansion of the immature pool and reduction in niche size. Remarkably, the traits were transplantable and dominant when mutant and wild-type precursors coexisted in the same environment, but were independent of E-selectin, the vascular receptor for ESL-1. Instead, quiescence is generated by unrestrained production of the cytokine TGFβ by mutant HSPC, and in vivo or in vitro blockade of the cytokine completely restores the homeostatic properties of the haematopoietic niche. These findings reveal that haematopoietic cells, including the more primitive compartment, can actively shape their own environment.

The Haematopoietic Stem Cell Niche: New Insights into the Mechanisms Regulating Haematopoietic Stem Cell Behaviour

Directory of Open Access Journals (Sweden)

Andrew J. Lilly

2011-01-01

Full Text Available The concept of the haematopoietic stem cell (HSC niche was formulated by Schofield in the 1970s, as a region within the bone marrow containing functional cell types that can maintain HSC potency throughout life. Since then, ongoing research has identified numerous cell types and a plethora of signals that not only maintain HSCs, but also dictate their behaviour with respect to homeostatic requirements and exogenous stresses. It has been proposed that there are endosteal and vascular niches within the bone marrow, which are thought to regulate different HSC populations. However, recent data depicts a more complicated picture, with functional crosstalk between cells in these two regions. In this review, recent research into the endosteal/vascular cell types and signals regulating HSC behaviour are considered, together with the possibility of a single subcompartmentalised niche.

Socially disadvantaged parents of children treated with allogeneic haematopoietic stem cell transplantation (HSCT)

DEFF Research Database (Denmark)

Larsen, Hanne Bækgaard; Heilmann, Carsten; Johansen, Christoffer

2013-01-01

PURPOSE: This study was undertaken to test a daily Family Navigator Nurse (FNN) conducted intervention program, to support parents during the distressful experience of their child's Allogeneic Haematopoietic Stem Cell Transplantation (HSCT). METHODS: A qualitative analysis of the supportive...

Pneumonia Caused by Moraxella Catarrhalis in Haematopoietic ...

African Journals Online (AJOL)

Two patients with haematopoietic stem cell transplant who developed pneumonia caused by M. catarrhalis at King Faisal Specialist Hospital and Research Centre in Riyadh are reported and the literature is reviewed. To our knowledge, these are the first case reports of M. catarrhalis pneumonia in haematopoietic stem cell ...

Distinct bone marrow blood vessels differentially regulate haematopoiesis.

Science.gov (United States)

Itkin, Tomer; Gur-Cohen, Shiri; Spencer, Joel A; Schajnovitz, Amir; Ramasamy, Saravana K; Kusumbe, Anjali P; Ledergor, Guy; Jung, Yookyung; Milo, Idan; Poulos, Michael G; Kalinkovich, Alexander; Ludin, Aya; Kollet, Orit; Shakhar, Guy; Butler, Jason M; Rafii, Shahin; Adams, Ralf H; Scadden, David T; Lin, Charles P; Lapidot, Tsvee

2016-04-21

Bone marrow endothelial cells (BMECs) form a network of blood vessels that regulate both leukocyte trafficking and haematopoietic stem and progenitor cell (HSPC) maintenance. However, it is not clear how BMECs balance these dual roles, and whether these events occur at the same vascular site. We found that mammalian bone marrow stem cell maintenance and leukocyte trafficking are regulated by distinct blood vessel types with different permeability properties. Less permeable arterial blood vessels maintain haematopoietic stem cells in a low reactive oxygen species (ROS) state, whereas the more permeable sinusoids promote HSPC activation and are the exclusive site for immature and mature leukocyte trafficking to and from the bone marrow. A functional consequence of high permeability of blood vessels is that exposure to blood plasma increases bone marrow HSPC ROS levels, augmenting their migration and differentiation, while compromising their long-term repopulation and survival. These findings may have relevance for clinical haematopoietic stem cell transplantation and mobilization protocols.

State-of-the-art fertility preservation in children and adolescents undergoing haematopoietic stem cell transplantation

DEFF Research Database (Denmark)

Dalle, J-H; Lucchini, G; Balduzzi, A

2017-01-01

Nowadays, allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a well-established treatment procedure and often the only cure for many patients with malignant and non-malignant diseases. Decrease in short-term complications has substantially contributed to increased survival. Theref...

Polycomb Cbx family members mediate the balance between haematopoietic stem cell self-renewal and differentiation

DEFF Research Database (Denmark)

Klauke, Karin; Radulović, Višnja; Broekhuis, Mathilde

2013-01-01

The balance between self-renewal and differentiation of adult stem cells is essential for tissue homeostasis. Here we show that in the haematopoietic system this process is governed by polycomb chromobox (Cbx) proteins. Cbx7 is specifically expressed in haematopoietic stem cells (HSCs), and its...... overexpression enhances self-renewal and induces leukaemia. This effect is dependent on integration into polycomb repressive complex-1 (PRC1) and requires H3K27me3 binding. In contrast, overexpression of Cbx2, Cbx4 or Cbx8 results in differentiation and exhaustion of HSCs. ChIP-sequencing analysis shows that Cbx......7 and Cbx8 share most of their targets; we identified approximately 200 differential targets. Whereas genes targeted by Cbx8 are highly expressed in HSCs and become repressed in progenitors, Cbx7 targets show the opposite expression pattern. Thus, Cbx7 preserves HSC self-renewal by repressing...

Angiocrine factors from Akt-activated endothelial cells balance self-renewal and differentiation of haematopoietic stem cells

Science.gov (United States)

Kobayashi, Hideki; Butler, Jason M.; O'Donnell, Rebekah; Kobayashi, Mariko; Ding, Bi-Sen; Bonner, Bryant; Chiu, Vi K.; Nolan, Daniel J.; Shido, Koji; Benjamin, Laura; Rafii, Shahin

2010-01-01

Endothelial cells establish an instructive vascular niche that reconstitutes haematopoietic stem and progenitor cells (HSPCs) through release of specific paracrine growth factors, known as angiocrine factors. However, the mechanism by which endothelial cells balance the rate of proliferation and lineage-specific differentiation of HSPCs is unknown. Here, we demonstrate that Akt activation in endothelial cells, through recruitment of mTOR, but not the FoxO pathway, upregulates specific angiocrine factors that support expansion of CD34−Flt3− KLS HSPCs with long-term haematopoietic stem cell (LT-HSC) repopulation capacity. Conversely, co-activation of Akt-stimulated endothelial cells with p42/44 MAPK shifts the balance towards maintenance and differentiation of the HSPCs. Selective activation of Akt1 in the endothelial cells of adult mice increased the number of colony forming units in the spleen and CD34−Flt3− KLS HSPCs with LT-HSC activity in the bone marrow, accelerating haematopoietic recovery. Therefore, the activation state of endothelial cells modulates reconstitution of HSPCs through the upregulation of angiocrine factors, with Akt–mTOR-activated endothelial cells supporting the self-renewal of LT-HSCs and expansion of HSPCs, whereas MAPK co-activation favours maintenance and lineage-specific differentiation of HSPCs. PMID:20972423

Differential cytokine contributions of perivascular haematopoietic stem cell niches.

Science.gov (United States)

Asada, Noboru; Kunisaki, Yuya; Pierce, Halley; Wang, Zichen; Fernandez, Nicolas F; Birbrair, Alexander; Ma'ayan, Avi; Frenette, Paul S

2017-03-01

Arterioles and sinusoids of the bone marrow (BM) are accompanied by stromal cells that express nerve/glial antigen 2 (NG2) and leptin receptor (LepR), and constitute specialized niches that regulate quiescence and proliferation of haematopoietic stem cells (HSCs). However, how niche cells differentially regulate HSC functions remains unknown. Here, we show that the effects of cytokines regulating HSC functions are dependent on the producing cell sources. Deletion of chemokine C-X-C motif ligand 12 (Cxcl12) or stem cell factor (Scf) from all perivascular cells marked by nestin-GFP dramatically depleted BM HSCs. Selective Cxcl12 deletion from arteriolar NG2 + cells, but not from sinusoidal LepR + cells, caused HSC reductions and altered HSC localization in BM. By contrast, deletion of Scf in LepR + cells, but not NG2 + cells, led to reductions in BM HSC numbers. These results uncover distinct contributions of cytokines derived from perivascular cells in separate vascular niches to HSC maintenance.

Repopulation dynamics of single haematopoietic stem cells in mouse transplantation experiments: Importance of stem cell composition in competitor cells.

Science.gov (United States)

Ema, Hideo; Uchinomiya, Kouki; Morita, Yohei; Suda, Toshio; Iwasa, Yoh

2016-04-07

The transplantation of blood tissues from bone marrow into a lethally irradiated animal is an experimental procedure that is used to study how the blood system is reconstituted by haematopoietic stem cells (HSC). In a competitive repopulation experiment, a lethally irradiated mouse was transplanted with a single HSC as a test cell together with a number of bone marrow cells as competitor cells, and the fraction of the test cell progeny (percentage of chimerism) was traced over time. In this paper, we studied the stem cell kinetics in this experimental procedure. The balance between symmetric self-renewal and differentiation divisions in HSC determined the number of cells which HSC produce and the length of time for which HSC live after transplantation. The percentage of chimerism depended on the type of test cell (long-, intermediate-, or short-term HSC), as well as the type and number of HSC included in competitor cells. We next examined two alternative HSC differentiation models, one-step and multi-step differentiation models. Although these models differed in blood cell production, the percentage of chimerism appeared very similar. We also estimated the numbers of different types of HSC in competitor cells. Based on these results, we concluded that the experimental results inevitably include stochasticity with regard to the number and the type of HSC in competitor cells, and that, in order to detect different types of HSC, an appropriate number of competitor cells needs to be used in transplantation experiments. Copyright © 2016. Published by Elsevier Ltd.

Platelet-biased stem cells reside at the apex of the haematopoietic stem-cell hierarchy.

Science.gov (United States)

Sanjuan-Pla, Alejandra; Macaulay, Iain C; Jensen, Christina T; Woll, Petter S; Luis, Tiago C; Mead, Adam; Moore, Susan; Carella, Cintia; Matsuoka, Sahoko; Bouriez Jones, Tiphaine; Chowdhury, Onima; Stenson, Laura; Lutteropp, Michael; Green, Joanna C A; Facchini, Raffaella; Boukarabila, Hanane; Grover, Amit; Gambardella, Adriana; Thongjuea, Supat; Carrelha, Joana; Tarrant, Paul; Atkinson, Deborah; Clark, Sally-Ann; Nerlov, Claus; Jacobsen, Sten Eirik W

2013-10-10

The blood system is maintained by a small pool of haematopoietic stem cells (HSCs), which are required and sufficient for replenishing all human blood cell lineages at millions of cells per second throughout life. Megakaryocytes in the bone marrow are responsible for the continuous production of platelets in the blood, crucial for preventing bleeding--a common and life-threatening side effect of many cancer therapies--and major efforts are focused at identifying the most suitable cellular and molecular targets to enhance platelet production after bone marrow transplantation or chemotherapy. Although it has become clear that distinct HSC subsets exist that are stably biased towards the generation of lymphoid or myeloid blood cells, we are yet to learn whether other types of lineage-biased HSC exist or understand their inter-relationships and how differently lineage-biased HSCs are generated and maintained. The functional relevance of notable phenotypic and molecular similarities between megakaryocytes and bone marrow cells with an HSC cell-surface phenotype remains unclear. Here we identify and prospectively isolate a molecularly and functionally distinct mouse HSC subset primed for platelet-specific gene expression, with enhanced propensity for short- and long-term reconstitution of platelets. Maintenance of platelet-biased HSCs crucially depends on thrombopoietin, the primary extrinsic regulator of platelet development. Platelet-primed HSCs also frequently have a long-term myeloid lineage bias, can self-renew and give rise to lymphoid-biased HSCs. These findings show that HSC subtypes can be organized into a cellular hierarchy, with platelet-primed HSCs at the apex. They also demonstrate that molecular and functional priming for platelet development initiates already in a distinct HSC population. The identification of a platelet-primed HSC population should enable the rational design of therapies enhancing platelet output.

Tug of war in the haematopoietic stem cell niche: do myeloma plasma cells compete for the HSC niche?

Science.gov (United States)

Noll, J E; Williams, S A; Purton, L E; Zannettino, A C W

2012-09-14

In the adult mammal, normal haematopoiesis occurs predominantly in the bone marrow, where primitive haematopoietic stem cells (HSC) and their progeny reside in specialised microenvironments. The bone marrow microenvironment contains specific anatomical areas (termed niches) that are highly specialised for the development of certain blood cell types, for example HSCs. The HSC niche provides important cell-cell interactions and signalling molecules that regulate HSC self-renewal and differentiation processes. These same signals and interactions are also important in the progression of haematological malignancies, such as multiple myeloma (MM). This review provides an overview of the bone marrow microenvironment and its involvement in normal, physiological HSC maintenance and plasma cell growth throughout MM disease progression.

Polylox barcoding reveals haematopoietic stem cell fates realized in vivo

Science.gov (United States)

Rössler, Jens; Wang, Xi; Postrach, Daniel; Busch, Katrin; Rode, Immanuel; Klapproth, Kay; Dietlein, Nikolaus; Quedenau, Claudia; Chen, Wei; Sauer, Sascha; Wolf, Stephan; Höfer, Thomas; Rodewald, Hans-Reimer

2017-01-01

Developmental deconvolution of complex organs and tissues at the level of individual cells remains challenging. Non-invasive genetic fate mapping1 has been widely used, but the low number of distinct fluorescent marker proteins limits its resolution. Much higher numbers of cell markers have been generated using viral integration sites2, viral barcodes3, and strategies based on transposons4 and CRISPR/Cas9 genome editing5; however, temporal and tissue-specific induction of barcodes in situ has not been achieved. Here we report the development of an artificial DNA recombination locus (termed Polylox) that enables broadly applicable endogenous barcoding based on the Cre-loxP recombination system6,7. Polylox recombination in situ reaches a practical diversity of several hundred thousand barcodes, allowing tagging of single cells. We have used this experimental system, combined with fate mapping, to assess haematopoietic stem cell (HSC) fates in vivo. Classical models of haematopoietic lineage specification assume a tree with few major branches. More recently, driven in part by the development of more efficient single-cell assays and improved transplantation efficiencies, different models have been proposed, in which unilineage priming may occur in mice and humans at the level of HSCs8–10. We have introduced barcodes into HSC progenitors in embryonic mice, and found that the adult HSC compartment is a mosaic of embryo-derived HSC clones, some of which are unexpectedly large. Most HSC clones gave rise to multilineage or oligolineage fates, arguing against unilineage priming, and suggesting coherent usage of the potential of cells in a clone. The spreading of barcodes, both after induction in embryos and in adult mice, revealed a basic split between common myeloid-erythroid development and common lymphocyte development, supporting the long-held but contested view of a tree-like haematopoietic structure. PMID:28813413

Polylox barcoding reveals haematopoietic stem cell fates realized in vivo.

Science.gov (United States)

Pei, Weike; Feyerabend, Thorsten B; Rössler, Jens; Wang, Xi; Postrach, Daniel; Busch, Katrin; Rode, Immanuel; Klapproth, Kay; Dietlein, Nikolaus; Quedenau, Claudia; Chen, Wei; Sauer, Sascha; Wolf, Stephan; Höfer, Thomas; Rodewald, Hans-Reimer

2017-08-24

Developmental deconvolution of complex organs and tissues at the level of individual cells remains challenging. Non-invasive genetic fate mapping has been widely used, but the low number of distinct fluorescent marker proteins limits its resolution. Much higher numbers of cell markers have been generated using viral integration sites, viral barcodes, and strategies based on transposons and CRISPR-Cas9 genome editing; however, temporal and tissue-specific induction of barcodes in situ has not been achieved. Here we report the development of an artificial DNA recombination locus (termed Polylox) that enables broadly applicable endogenous barcoding based on the Cre-loxP recombination system. Polylox recombination in situ reaches a practical diversity of several hundred thousand barcodes, allowing tagging of single cells. We have used this experimental system, combined with fate mapping, to assess haematopoietic stem cell (HSC) fates in vivo. Classical models of haematopoietic lineage specification assume a tree with few major branches. More recently, driven in part by the development of more efficient single-cell assays and improved transplantation efficiencies, different models have been proposed, in which unilineage priming may occur in mice and humans at the level of HSCs. We have introduced barcodes into HSC progenitors in embryonic mice, and found that the adult HSC compartment is a mosaic of embryo-derived HSC clones, some of which are unexpectedly large. Most HSC clones gave rise to multilineage or oligolineage fates, arguing against unilineage priming, and suggesting coherent usage of the potential of cells in a clone. The spreading of barcodes, both after induction in embryos and in adult mice, revealed a basic split between common myeloid-erythroid development and common lymphocyte development, supporting the long-held but contested view of a tree-like haematopoietic structure.

Haematopoietic stem cell niches: new insights inspire new questions

Science.gov (United States)

Ugarte, Fernando; Forsberg, E Camilla

2013-01-01

Haematopoietic stem cell (HSC) niches provide an environment essential for life-long HSC function. Intense investigation of HSC niches both feed off and drive technology development to increase our capability to assay functionally defined cells with high resolution. A major driving force behind the desire to understand the basic biology of HSC niches is the clear implications for clinical therapies. Here, with particular emphasis on cell type-specific deletion of SCL and CXCL12, we focus on unresolved issues on HSC niches, framed around some very recent advances and novel discoveries on the extrinsic regulation of HSC maintenance. We also provide ideas for possible paths forward, some of which are clearly within reach while others will require both novel tools and vision. PMID:24022369

Management of adenovirus infection in patients after haematopoietic stem cell transplantation: State-of-the-art and real-life current approach: A position statement on behalf of the Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation.

Science.gov (United States)

Hiwarkar, Prashant; Kosulin, Karin; Cesaro, Simone; Mikulska, Malgorzata; Styczynski, Jan; Wynn, Robert; Lion, Thomas

2018-05-01

The important insights gained over the past years in diagnosis and treatment of invasive adenoviral infections provide new paradigms for the monitoring and clinical management of these life-threatening complications. A meeting was held to discuss and subsequently disseminate the current advances in our understanding of the aetiology/pathogenesis and future treatment options facilitating effective control or prevention of adenovirus-related diseases in the allogeneic haematopoietic stem cell transplant setting. Invited experts in the field discussed recent progress with leading members of the Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation at the "State-of-the-art" Meeting in Poznan, Poland, in October 2017. In this review article, the panel of experts presents a concise summary of the current evidence based on published data from the last 15 years and on recent achievements resulting from real-life practice. The present position statement reflects an expert opinion on current approaches to clinical management of adenovirus infections in patients undergoing allogeneic haematopoietic stem cell transplant and provides graded recommendations of the panel for diagnostic approaches and preemptive therapy reflecting the present state of knowledge. Copyright © 2018 John Wiley & Sons, Ltd.

An Analysis of Blood Utilization for Stem Cell Transplant Patients in a Tertiary Care Hospital.

Science.gov (United States)

Ali, Natasha

2017-05-30

Haematopoietic stem cell transplant is a potentially curative treatment option in various benign and malignant haematological diseases. Patients undergoing stem cell transplant procedure require blood transfusion on a daily basis. Currently, there is paucity of data from developing countries on transfusion practices. This audit was undertaken to determine the consumption of packed red blood cells (PRBCs) transfusion in the bone marrow transplant unit of the Aga Khan University Hospital. A retrospective audit was conducted for packed red cell transfusion ordering practice over a period from June 2014∼June 2015. All consecutive patients, admitted for stem cell transplant procedure for various underlying diseases were included. Outcome measures used in this study were (i) cross match to transfusion (C: T) ratio and (ii) transfusion trigger. During the study period, n=25 patients underwent haematopoietic stem cell transplant. There were n=19 males and n=6 females. One patient was less than 15 years of age while rests were adults. Median age±SD was 26.5±14.5 years (12∼54 years). The underlying diagnosis included Aplastic anemia (n=8), Thalassemia major (n=3), Multiple Myeloma (n=4), Acute leukemia (n=5), Hodgkin's lymphoma (n=4), PRCA (n=1). Grand total consumption of PRBCs during the study period was 204 while 258 products were crossmatch. The C:T ratio was 1.26. The transfusion trigger was Hb level of less than 8 gms/dl. The results of our BMT unit indicate that the C:T ratio and transfusion trigger is comparable to the international benchmark.

Oral complaints and dental care of haematopoietic stem cell transplant patients: a qualitative survey of patients and their dentists

NARCIS (Netherlands)

Bos-den Braber, J.; Potting, C.M.J.; Bronkhorst, E.M.; Huysmans, M.C.D.N.J.M.; Blijlevens, N.M.A.

2015-01-01

PURPOSE: Little is known about the understanding of the oral and dental needs of haematopoietic stem cell transplant (HSCT) patients or about dentists' views and experiences regarding this patient group. This information is essential if we want to improve the standard of peri-HSCT dental care. The

T cell reconstitution in allogeneic haematopoietic stem cell transplantation

DEFF Research Database (Denmark)

Kielsen, K; Jordan, K K; Uhlving, H H

2015-01-01

Infections and acute graft-versus-host disease (aGVHD) are major causes of treatment-related mortality and morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). Both complications depend on reconstitution of the T-lymphocyte population based on donor T cells. Although...... it is well established that Interleukin-7 (IL-7) is a cytokine essential for de novo T cell development in the thymus and homoeostatic peripheral expansion of T cells, associations between circulating levels of IL-7 and T cell reconstitution following HSCT have not been investigated previously. We...... in patients treated with anti-thymocyte globulin (ATG) compared with those not treated with ATG (P = 0.0079). IL-7 levels at day +7 were negatively associated with T cell counts at day +30 to +60 (at day +60: CD3(+) : β = -10.6 × 10(6) cells/l, P = 0.0030; CD8(+) : β = -8.4 × 10(6) cells/l, P = 0.061; CD4...

Therapeutic potential of ex vivo expansion of haematopoietic precursors for the treatment of accidental irradiation-induced aplasia

International Nuclear Information System (INIS)

Nguyen-Neildez, T.M.A.; Vetillard, J.; Thierry, D.; Nenot, J.C.; Parmentier, C.

1996-01-01

After whole body overexposure, the key issue is the therapeutic decision, i.e. the choice between bone marrow transplantation and other strategies. The indications of bone marrow transplantation cover only a short range of doses, provided the exposure is distributed uniformly within the body; a rare event in accidental settings. The results of the clinical trials for Granulocyte-Colony Stimulating Factor: G-CSF, Granulocyte/Macrophage Colony Stimulating Factor: GM-CSF or Interleukin 3: IL-3, in vivo and in vitro radiobiology experiments suggest that growth factor therapy could be of use after most accidental overexposures to evidence and to stimulate the remaining haematopoietic stem cells in order to shorten the duration of aplasia, although questions have been raised about growth factor infusion real clinical efficiency. Ex vivo expansion of haematopoietic precursor, stem cells and differentiated cells is a new approach of growth factor therapy, which may be of interest for the treatment of patients with accidental radiation-induced aplasia. These studies aim to expand the pool of progenitors and stem cells for transplantation or to expand differentiated cells (mainly granulocytes but also megakaryocytes) for transfusion. This is made possible due to the development of techniques allowing the selection of a population of haematopoietic progenitors and stem cells from the blood (with stimulation by growth factors prior stem cell harvesting) or bone marrow using immature cell positive selection. The next step consisting in their culture with combination of growth factors or additional stroma cells is also under development. Autologous progenitor cells generated ex vivo has been recently used with some success for reconstitution of haematopoiesis after high-dose chemotherapy. (author)

Pneumonia Caused by Moraxella Catarrhalis in Haematopoietic ...

African Journals Online (AJOL)

Moraxella catarrhalis is a gram negative diplococcus that causes a variety of upper and lower respiratory tract infections. Patients with malignant, hematological disorders treated with intensive cytotoxic chemotherapy, and recipients of various forms of haematopoietic stem cell transplant receiving immunosuppressive ...

Impact of oral gut decontamination on Staphylococcus aureus colonisation in patients undergoing allogeneic haematopoietic stem cell transplantation.

Science.gov (United States)

Wilk, C Matthias; Weber, Isabel; Seidl, Kati; Rachmühl, Carole; Holzmann-Bürgel, Anne; Müller, Antonia M S; Kuster, Stefan P; Schanz, Urs; Zinkernagel, Annelies S

2017-12-01

Recipients of allogeneic haematopoietic stem cell transplantation (allo-HSCT) are severely immunocompromised and are at increased risk of infection. In this prospective, observational, single-centre study including 110 allo-HSCT recipients, the rate of Staphylococcus aureus colonisation was reduced from 11.8% to 0% (P <0.001) following peritransplant oral gut decontamination. No invasive S. aureus infections were observed. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Urological management (medical and surgical of BK-virus associated haemorrhagic cystitis in children following haematopoietic stem cell transplantation

Directory of Open Access Journals (Sweden)

Nikhil Vasdev

2013-10-01

Full Text Available Aim: Haemorrhagic cystitis (HC is uncommon and in its severe form potentially life threatening complication of Haematopoietic stem cell transplantation (HSCT in children. We present our single centre experience in the urological management of this clinically challenging condition. Patients and Methods: Fourteen patients were diagnosed with BK-Virus HC in our centre. The mean age at diagnosis was 8.8 years (range, 3.2-18.4 years. The mean number of days post-BMT until onset of HC was 20.8 (range, 1 – 51. While all patients tested urine positive for BKV at the clinical onset of HC, only four patients had viral quantification, with viral loads ranging from 97,000 to >1 billion/ml. 8 patients had clinical HC. Ten patients experienced acute GVHD (grade I: 6 patients, grade II: 3 patients, grade 4: 1 patient.Results: Four patients received medical management for their HC. Treatments included hyperhydration, MESNA, blood and platelet transfusion, premarin and oxybutynin (Table 6.  Two patients received both medical and surgical management which included cystoscopy with clot evacuation, bladder irrigation and supra-pubic catheter insertion. One patient received exclusive surgical management. Seven patients were treated conservatively. Conclusion: There is limited available evidence for other potential therapeutic strategies highlighting the need for more research into the pathophysiology of HSCT-associated HC. Commonly used interventions with possible clinical benefit (e.g. cidofovir, ciprofloxacin still require to be evaluated in multi-centre, high-quality studies. Potential future preventative and therapeutic options, such as modulation of conditioning, immunosuppression and engraftment, new antiviral and anti-inflammatory and less nephrotoxic agents need to be assessed.---------------------------Cite this article as:Vasdev N, Davidson A, Harkensee C, Slatter M, Gennery A, Willetts I, Thorpe A.Urological management (medical and surgical of BK

Prognosis of Allogeneic Haematopoietic Stem Cell Recipients Admitted to the Intensive Care Unit

DEFF Research Database (Denmark)

Lindgaard, Sidsel Christy; Nielsen, Jonas; Lindmark, Anders

2016-01-01

BACKGROUND: Allogeneic haematopoietic stem cell transplantation (HSCT) is a procedure with inherent complications and intensive care may be necessary. We evaluated the short- and long-term outcomes of the HSCT recipients requiring admission to the intensive care unit (ICU). METHODS: We...... ventilation had a statistically significant effect on in-ICU (p = 0.02), 6-month (p = 0.049) and 1-year (p = 0.014) mortality. Renal replacement therapy also had a statistically significant effect on in-hospital (p = 0.038) and 6-month (p = 0.026) mortality. Short ICU admissions, i.e. ... to the ICU was confirmed in our study. Mechanical ventilation, renal replacement therapy and an ICU admission of ≥10 days were each risk factors for mortality in the first year after ICU admission....

Proliferative kinetics of the haematopoietic stem cells of the mouse after several weeks of reconvalescence of an irradiation attack

International Nuclear Information System (INIS)

Huebner, G.

1980-01-01

The 125 IDU(iodo-deoxyuridine) tracer-technique was applied for investigating proliferative kinetics. The intention was to reveal a possible persistent irradiation damage in the haematopoietic stem-cells of the mouse. The three following methodically differing arrangements were made: 1. 35 days after irradiation with 450 rad no difference is found between the measured turnover of incorporated 125 IUD in the bone marrow and not irradiated mice. However, there is a splenic cell population which unambiguously transfers its activity slowlier. A dose-response relationship exists to a limited extent. 2. By four transplantations at different instants the donors were marked first, and then the turnover of the early haematopoietic precursor cells in the bone marrow was detected. It resulted that 35 days after irradiation with 450 rad the turnover takes place slightly slowlier than in not irradiated early precursor cells. Iodised water, which is administered before the tracer technique is applied, seems to have a stimulating effect, particularly on the turnover of irradiated stem cells; the marking with a specific activity of 2000 Ci/mol seems to have a slightly toxic effect. 3. A test was developed, by which the proliferation velocity of stem cells and their descendants is measured when there is a very high proliferation stimulus. Differing amounts of bone marrow cells are transfused to lethally irradiated receivers. Within the logarithmic phase of the 125 IDU incorporation the relative cellular proliferation, originating in the stem cells being in the spleen, is determined for the interval between day 3 and day 5. It results very clearly that the descendants of those stem cells irradiated with 450 rad after a reconvalescence time of 35 days present a lower degree of rapid proliferative ability than the not irradiated cells. (orig./MG) [de

Menstrual patterns, fertility and main pregnancy outcomes after allogeneic haematopoietic stem cell transplantation.

Science.gov (United States)

Chiodi, Sandra; Spinelli, Simonetta; Bruzzi, Paolo; Anserini, Paola; Di Grazia, Carmen; Bacigalupo, Andrea

2016-08-01

Two-hundred and sixty-nine females aged ≤42 and undergoing an allogeneic stem cell transplant were retrospectively studied to assess the effect of age, conditioning regimen and chronic graft-versus-host disease (cGVHD) on resumption of stable menstrual cyclicity. Overall, a stable menstrual cyclicity was observed in 22% of cases. The cumulative probability of menses resumption was significantly age and conditioning regimen related. A statistically significant inverse correlation between cGVHD severity and menses resumption was observed only in univariate analysis. In patients with residual ovarian function, infertility was found in 43% and early menopause in 45%. An increased incidence of prematurity and low birth weight (LBW) was observed among the single spontaneous pregnancies. Follicle-stimulating hormone (FSH) and 17 beta-oestradiol levels were found to be inadequate to detect both early signs of menses resumption and menstrual stability. Our study confirms the crucial role of full dose total body irradiation (TBI) and age on menses recovery and fertility after haematopoietic stem cell transplantation (HSCT). The impact of severe cGVHD remains unclear.

Protection from UV light is an evolutionarily conserved feature of the haematopoietic niche

Science.gov (United States)

Kapp, Friedrich G.; Perlin, Julie R.; Hagedorn, Elliott J.; Gansner, John M.; Schwarz, Daniel E.; O'Connell, Lauren A.; Johnson, Nicholas; Amemiya, Chris; Fisher, David E.; Wolfle, Ute; Trompouki, Eirini; Niemeyer, Charlotte M.; Driever, Wolfgang; Zon, Leonard I.

2018-01-01

Haematopoietic stem and progenitor cells (HSPCs) require a specific microenvironment, the haematopoietic niche, which regulates HSPC behaviour. The location of this niche varies across species, but the evolutionary pressures that drive HSPCs to different microenvironments remain unknown. The niche is located in the bone marrow in adult mammals, whereas it is found in other locations in non-mammalian vertebrates, for example, in the kidney marrow in teleost fish. Here we show that a melanocyte umbrella above the kidney marrow protects HSPCs against ultraviolet light in zebrafish. Because mutants that lack melanocytes have normal steady-state haematopoiesis under standard laboratory conditions, we hypothesized that melanocytes above the stem cell niche protect HSPCs against ultraviolet-light-induced DNA damage. Indeed, after ultraviolet-light irradiation, unpigmented larvae show higher levels of DNA damage in HSPCs, as indicated by staining of cyclobutane pyrimidine dimers and have reduced numbers of HSPCs, as shown by cmyb (also known as myb) expression. The umbrella of melanocytes associated with the haematopoietic niche is highly evolutionarily conserved in aquatic animals, including the sea lamprey, a basal vertebrate. During the transition from an aquatic to a terrestrial environment, HSPCs relocated into the bone marrow, which is protected from ultraviolet light by the cortical bone around the marrow. Our studies reveal that melanocytes above the haematopoietic niche protect HSPCs from ultraviolet-light-induced DNA damage in aquatic vertebrates and suggest that during the transition to terrestrial life, ultraviolet light was an evolutionary pressure affecting the location of the haematopoietic niche.

Comparison of Amicus and COBE Spectra for allogenic peripheral blood stem cell harvest: Study from tertiary care centre in India.

Science.gov (United States)

Setia, Rasika Dhawan; Arora, Satyam; Handoo, Anil; Dadu, Tina; Choudhary, Dharma; Sharma, Sajeev Kumar; Kharya, Gaurav; Khandelwal, Vipin; Sachdeva, Prerna; Doval, Divya; Bakliwal, Anamika; Kapoor, Meenu; Bajaj, Shalu; Bachchas, Virendra; Singh, Praveen

2017-06-01

Most common source of stem cell graft for both autologous and allogenic haematopoietic transplants are peripheral blood haematopoietic progenitor stem cells. Adequate collection of the CD34+ cells and safety of the allogenic donor during the leukapheresis are of prime importance to an apheresis physician. Our retrospective analysis is a comparison between of two platforms namely, COBE Spectra and Amicus, for CD34+ mononuclear cell collection. The study included the data of GSCF (Granulocyte-Colony-Stimulating Factor) mobilized allogenic PBSC collections at our centre from January 2015 to June 2016. The apheresis platforms used were COBE Spectra and Amicus. Blood cell counts were done using LH750 Beckman Coulter (Florida, Miami, USA). CD45+ & CD34+ cell counts were done using BD FACS Canto-II Flow-Cytometer by ISHAGE guidelines. A total of 170 PBSC (100 COBE Spectra & 70 Amicus) harvests were done on 143 donors, of which 116 completed the collection in a single session and 27 required a second session. Demographic details and pre harvest peripheral blood counts for both the groups did not show any statistical differences. Amicus processed higher blood volume with higher ACD exposure and procedure time compared to COBE Spectra. Higher platelets loss was with COBE Spectra harvests with higher product volumes collection. Collection efficiency (CE2), collection ratio, CD34+ cells dose was similar on both the platforms. RBC contamination, absolute lymphocyte and monocytes counts were significantly higher with Amicus harvest product compared with COBE Spectra. A total of 14 (8.2%; citrate toxicity) adverse reactions were reported out of 170 allogenic PBSC collections. Our study suggests that both Amicus and COBE Spectra platforms offer comparable results for allogenic PBSC collections. Amicus offers a concentrated PBSC product with lesser volume and platelets loss but higher RBC contamination. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cord blood banking and transplantation: advances and controversies.

Science.gov (United States)

Yoder, Mervin C

2014-04-01

A review of articles published since January 2012 on the topic of cord blood banking and cord blood stem cell transplantation was conducted for this the 25th anniversary year of the first cord blood transplant performed in a human. Cord blood banking is performed throughout the world. Umbilical cord blood (UCB) transplantation is recognized as an acceptable alternative stem cell source for paediatric and adults requiring a haematopoietic transplant, particularly for patients of racial and ethnic minorities. To further advance the use of UCB, methods to enhance UCB stem cell expansion, engraftment and maintenance may be required. Controversy on the most effective and economically sustainable model for banking and storing an optimal UCB product continues to persist. Cord blood banking and transplantation of cord blood stem cells has advanced rapidly over the initial 25 years, as more than 30 ,000 patients have benefited from the therapy. New concepts on the use of methods to expand UCB stem cells for transplantation and use for nonhaematopoietic indications may increase demand for UCB over the next few decades.

Effects of extracellular matrix proteins on the growth of haematopoietic progenitor cells

Energy Technology Data Exchange (ETDEWEB)

Celebi, Betuel; Pineault, Nicolas [Hema-Quebec, Research and Development Department, Quebec City, G1V 5C3, PQ (Canada); Mantovani, Diego, E-mail: nicolas.pineault@hema-quebec.qc.ca [Laboratory for Biomaterials and Bioengineering, Department of Materials Engineering and University Hospital Research Center, Laval University, Quebec City, G1V 0A6, PQ (Canada)

2011-10-15

Umbilical cord blood (UCB) transplantation and haematological recovery are currently limited by the amount of haematopoietic progenitor cells (HPCs) present in each unit. HPCs and haematopoietic stem cells (HSCs) normally interact with cells and extracellular matrix (ECM) proteins present within the endosteal and vascular niches. Hence, we investigated whether coating of culture surfaces with ECM proteins normally present in the marrow microenvironment could benefit the ex vivo expansion of HPCs. Towards this, collagen types I and IV (COL I and IV), laminin (LN) and fibronectin (FN) were tested individually or as component of two ECM-mix complexes. Individually, ECM proteins had both common and unique properties on the growth and differentiation of UCB CD34+ cells; some ECM proteins favoured the differentiation of some lineages over that of others (e.g. FN for erythroids), some the expansion of HPCs (e.g. LN and megakaryocyte (MK) progenitor) while others had less effects. Next, two ECM-mix complexes were tested; the first one contained all four ECM proteins (4ECMp), while the second 'basement membrane-like structure' was without COL I (3ECMp). Removal of COL I led to strong reductions in cell growth and HPCs expansion. Interestingly, the 4ECMp-mix complex reproducibly increased CD34+ (1.3-fold) and CD41+ (1.2-fold) cell expansions at day 6 (P < 0.05) versus control, and induced greater myeloid progenitor expansion (P < 0.05) than 3ECMp. In conclusion, these results suggest that optimization of BM ECM protein complexes could provide a better environment for the ex vivo expansion of haematopoietic progenitors than individual ECM protein.

Effects of extracellular matrix proteins on the growth of haematopoietic progenitor cells

International Nuclear Information System (INIS)

Celebi, Betuel; Pineault, Nicolas; Mantovani, Diego

2011-01-01

Umbilical cord blood (UCB) transplantation and haematological recovery are currently limited by the amount of haematopoietic progenitor cells (HPCs) present in each unit. HPCs and haematopoietic stem cells (HSCs) normally interact with cells and extracellular matrix (ECM) proteins present within the endosteal and vascular niches. Hence, we investigated whether coating of culture surfaces with ECM proteins normally present in the marrow microenvironment could benefit the ex vivo expansion of HPCs. Towards this, collagen types I and IV (COL I and IV), laminin (LN) and fibronectin (FN) were tested individually or as component of two ECM-mix complexes. Individually, ECM proteins had both common and unique properties on the growth and differentiation of UCB CD34+ cells; some ECM proteins favoured the differentiation of some lineages over that of others (e.g. FN for erythroids), some the expansion of HPCs (e.g. LN and megakaryocyte (MK) progenitor) while others had less effects. Next, two ECM-mix complexes were tested; the first one contained all four ECM proteins (4ECMp), while the second 'basement membrane-like structure' was without COL I (3ECMp). Removal of COL I led to strong reductions in cell growth and HPCs expansion. Interestingly, the 4ECMp-mix complex reproducibly increased CD34+ (1.3-fold) and CD41+ (1.2-fold) cell expansions at day 6 (P < 0.05) versus control, and induced greater myeloid progenitor expansion (P < 0.05) than 3ECMp. In conclusion, these results suggest that optimization of BM ECM protein complexes could provide a better environment for the ex vivo expansion of haematopoietic progenitors than individual ECM protein.

Non-circadian rhythm in proliferation of haematopoietic stem cells

International Nuclear Information System (INIS)

Necas, E.; Znojil, V.

1988-01-01

The proportion of haematopoietic stem cells (CFU-s) engaged in DNA synthesis was determined by means of the [ 3 H]-thymidine ([ 3 H]TdR) suicide technique during recovery of bone marrow from the damage caused by a sublethal total body irradiation. In contrast with previous reports the [ 3 H]TdR suicide rate was not permanently increased. It was observed that CFU-s passed through S phase in synchronous waves, following a dose of irradiation of 1.5 Gy. After a dose of 2.6 Gy, there was only one initial wave of increased CFU-s sensitivity to the action of [ 3 H]TdR. Following the depression occurring 26 hr after the irradiation with 2.6 Gy, the proportion of CFU-s killed by the [ 3 H]TdR was permanently increased until 5-6 days after irradiation. Thereafter large differences in the [ 3 H]TdR suicide data were observed among individual mice. Evidence was obtained that individual mice, which had been irradiated by a dose of 2.6 Gy 8-9 days before, had identical values of the CFU-s [ 3 H]TdR suicide rate in the bone marrow from different bones of the lower extremities. The recurrence of the synchronous waves in CFU-s passage through the cell cycle was recorded when the CFU-s population regenerated to only about 10% of its normal value. It is concluded that the synchronous waves in which CFU-s proliferation occurred reflected the action of the control mechanism on CFU-s proliferation. (author)

Non-circadian rhythm in proliferation of haematopoietic stem cells

Energy Technology Data Exchange (ETDEWEB)

Necas, E; Znojil, V [Charles Univ., Prague (Czechoslovakia). Faculty of Medicine

1988-03-01

The proportion of haematopoietic stem cells (CFU-s) engaged in DNA synthesis was determined by means of the (/sup 3/H)-thymidine ((/sup 3/H)TdR) suicide technique during recovery of bone marrow from the damage caused by a sublethal total body irradiation. In contrast with previous reports the (/sup 3/H)TdR suicide rate was not permanently increased. It was observed that CFU-s passed through S phase in synchronous waves, following a dose of irradiation of 1.5 Gy. After a dose of 2.6 Gy, there was only one initial wave of increased CFU-s sensitivity to the action of (/sup 3/H)TdR. Following the depression occurring 26 hr after the irradiation with 2.6 Gy, the proportion of CFU-s killed by the (/sup 3/H)TdR was permanently increased until 5-6 days after irradiation. Thereafter large differences in the (/sup 3/H)TdR suicide data were observed among individual mice. Evidence was obtained that individual mice, which had been irradiated by a dose of 2.6 Gy 8-9 days before, had identical values of the CFU-s (/sup 3/H)TdR suicide rate in the bone marrow from different bones of the lower extremities. The recurrence of the synchronous waves in CFU-s passage through the cell cycle was recorded when the CFU-s population regenerated to only about 10% of its normal value. It is concluded that the synchronous waves in which CFU-s proliferation occurred reflected the action of the control mechanism on CFU-s proliferation. (author).

Donating Peripheral Blood Stem Cells

Science.gov (United States)

... Print this page My Cart Donating peripheral blood stem cells Peripheral blood stem cell (PBSC) donation is a nonsurgical procedure to collect ... Donating bone marrow Donor experiences videos Peripheral blood stem cell (PBSC) donation is one of two methods of ...

Persistent response of Fanconi anemia haematopoietic stem and progenitor cells to oxidative stress.

Science.gov (United States)

Li, Yibo; Amarachintha, Surya; Wilson, Andrew F; Li, Xue; Du, Wei

2017-06-18

Oxidative stress is considered as an important pathogenic factor in many human diseases including Fanconi anemia (FA), an inherited bone marrow failure syndrome with extremely high risk of leukemic transformation. Members of the FA protein family are involved in DNA damage and other cellular stress responses. Loss of FA proteins renders cells hypersensitive to oxidative stress and cancer transformation. However, how FA cells respond to oxidative DNA damage remains unclear. By using an in vivo stress-response mouse strain expressing the Gadd45β-luciferase transgene, we show here that haematopoietic stem and progenitor cells (HSPCs) from mice deficient for the FA gene Fanca or Fancc persistently responded to oxidative stress. Mechanistically, we demonstrated that accumulation of unrepaired DNA damage, particularly in oxidative damage-sensitive genes, was responsible for the long-lasting response in FA HSPCs. Furthermore, genetic correction of Fanca deficiency almost completely abolished the persistent oxidative stress-induced G 2 /M arrest and DNA damage response in vivo. Our study suggests that FA pathway is an integral part of a versatile cellular mechanism by which HSPCs respond to oxidative stress.

Pentraxin 3 plasma levels at graft-versus-host disease onset predict disease severity and response to therapy in children given haematopoietic stem cell transplantation

OpenAIRE

Dander, Erica; De Lorenzo, Paola; Bottazzi, Barbara; Quarello, Paola; Vinci, Paola; Balduzzi, Adriana; Masciocchi, Francesca; Bonanomi, Sonia; Cappuzzello, Claudia; Prunotto, Giulia; Pavan, Fabio; Pasqualini, Fabio; Sironi, Marina; Cuccovillo, Ivan; Leone, Roberto

2016-01-01

Acute Graft-versus-Host Disease (GvHD) remains a major complication of allogeneic haematopoietic stem cell transplantation, with a significant proportion of patients failing to respond to first-line systemic corticosteroids. Reliable biomarkers predicting disease severity and response to treatment are warranted to improve its management. Thus, we sought to determine whether pentraxin 3 (PTX3), an acute-phase protein produced locally at the site of inflammation, could represent a novel acute G...

Pancreas developing markers expressed on human mononucleated umbilical cord blood cells

International Nuclear Information System (INIS)

Pessina, A.; Eletti, B.; Croera, C.; Savalli, N.; Diodovich, C.; Gribaldo, L.

2004-01-01

Haematopoietic system represents the main source of haematopoietic stem cells and probably of multipotential adult progenitor cells and mesenchimal stem cells at first described as colony forming unit-fibroblast. Whereas there are many studies on the gene expression profile of the different precursors along their haematopoietic differentiation, few data (sometimes conflicting) have been reported about the phenotype of the cells (present in bone marrow and possibly in cord blood) able to differentiate into non-haematopoietic cells. As both postnatal bone marrow and umbilical cord blood contain nestin positive cells able to proliferate and differentiate into the main neural phenotype (neuron, astroglia and oligodendroglia) many authors considered nestin a neuroepithelial precursor marker that seems to be essential also in multipotential progenitor cells of pancreas present both in rat and in human pancreatic islets (called nestin positive islet derived progenitors). Although the importance of nestin in these cells appears to be evident, it remains yet to clarify the number and the sequential expression of the genes coding all the transcription factors essential for beta cells differentiation and therefore the conditions able to induce the expression of many important transcription factors genes such as isl-1, pax-4, pdx-1 and ngn-3. Among them pdx-1 is a gene essential for pancreas development which is able to control ngn-3 in activating the expression of other differentiation factors for endocrine cells. Here, we describe for the first time in human umbilical cord blood cells (UCB) the pattern of expression of a panel of markers (nestin, CK-8, CK-18) and transcription factors (Isl-1, Pdx-1, Pax-4, Ngn-3) considered important for beta cells differentiation. Our data demonstrate that UCB contains a cell population having a phenotype very similar to endocrine cell precursors in transition to beta cells

Clonal reversal of ageing-associated stem cell lineage bias via a pluripotent intermediate

DEFF Research Database (Denmark)

Wahlestedt, Martin; Erlandsson, Eva; Kristiansen, Trine

2017-01-01

Ageing associates with significant alterations in somatic/adult stem cells and therapies to counteract these might have profound benefits for health. In the blood, haematopoietic stem cell (HSC) ageing is linked to several functional shortcomings. However, besides the recent realization...... with the generation of induced pluripotent stem (iPS) cells. This allows us to specifically focus on aged HSCs presenting with a pronounced lineage skewing, a hallmark of HSC ageing. Functional and molecular evaluations reveal haematopoiesis from these iPS clones to be indistinguishable from that associating...

Different mutations of the human c-mpl gene indicate distinct haematopoietic diseases.

Science.gov (United States)

He, Xin; Chen, Zhigang; Jiang, Yangyan; Qiu, Xi; Zhao, Xiaoying

2013-01-25

The human c-mpl gene (MPL) plays an important role in the development of megakaryocytes and platelets as well as the self-renewal of haematopoietic stem cells. However, numerous MPL mutations have been identified in haematopoietic diseases. These mutations alter the normal regulatory mechanisms and lead to autonomous activation or signalling deficiencies. In this review, we summarise 59 different MPL mutations and classify these mutations into four different groups according to the associated diseases and mutation rates. Using this classification, we clearly distinguish four diverse types of MPL mutations and obtain a deep understand of their clinical significance. This will prove to be useful for both disease diagnosis and the design of individual therapy regimens based on the type of MPL mutations.

A survey of fertility and sexual health following allogeneic haematopoietic stem cell transplantation in New South Wales, Australia.

Science.gov (United States)

Dyer, Gemma; Gilroy, Nicole; Bradford, Jennifer; Brice, Lisa; Kabir, Masura; Greenwood, Matt; Larsen, Stephen R; Moore, John; Hertzberg, Mark; Kwan, John; Brown, Louisa; Hogg, Megan; Huang, Gillian; Tan, Jeff; Ward, Christopher; Kerridge, Ian

2016-02-01

Four hundred and twenty-one adult allogeneic haematopoietic stem cell transplant (HSCT) survivors participated in a cross-sectional study to assess sexual dysfunction and infertility post-transplant. Survey instruments included the Sydney Post-Blood and Marrow Transplant (BMT) Survey, Functional Assessment of Cancer Treatment (FACT) - BMT, the Depression, Anxiety, Stress Scales (DASS 21), the Chronic Graft-versus-Host Disease (cGVHD) Activity Assessment- Patient Self Report (Form B), the Lee cGVHD Symptom Scale and The Post-Traumatic Growth Inventory. Most HSCT survivors reported sexual difficulties (51% of males; 66% of females). Men reported erectile dysfunction (79%) and decreased libido (61·6%) and women reported loss of libido (83%), painful intercourse (73%) and less enjoyment of sex (68%). Women also commonly reported vaginal dryness (73%), vaginal narrowing (34%) and vaginal irritation (26%). Woman had much higher rates of genital cGvHD than men (22% vs. 5%). Age and cGVHD were significantly associated with sexual dysfunction. Few survivors had children following transplant (3·3%). However, for those of reproductive age at HSCT, 22% reported trying to conceive, with 10·3% reporting success. This study is the largest to date exploring sexual function in survivors of allo-HSCT. This data provides the basis for health service reform to better meet the needs of HSCT survivors, including evidence to support counselling and education both pre- and post-transplant. © 2015 John Wiley & Sons Ltd.

Blood-Forming Stem Cell Transplants

Science.gov (United States)

... to Ask about Your Treatment Research Blood-Forming Stem Cell Transplants On This Page What are bone marrow ... Considering becoming a bone marrow or a blood stem cell donor? View this video on YouTube. Follow a ...

Radioprotective potency of ginseng on some haematopoietic and physiological parameters in irradiated rats

International Nuclear Information System (INIS)

Ashry, O.M.; Hussein, E.M.

2007-01-01

Currently, investigations focus on co administration of natural products with radiation treatment. The present study was assessed to investigate the potency of ginseng as a radioprotective agent on haematopoietic cell recovery, the content of reduced glutathione (GSH) and malonaldehyde (MDA) level in addition to physiological bio markers. Panax ginseng was intraperitoneally injected (100 mg/ kg) to female rats 24 h before gamma irradiation of 7 Gy which is liable to disturb the haematopoietic system and the organs involved as the bone marrow and spleen. Animals were investigated after 5 and 9 days from irradiation, ginseng or dual treatments. Irradiation caused significant wt loss of the body and spleen, decrease in bone marrow (B.M.) viable cells, significant depression in leukocytes with its differential counts, significant drop in erythrocytes, haemoglobin and haematocrite values besides elevation in MCV. Gamma-irradiation treatment resulted in significant increase in serum MDA and glucose as well as significant reduction in blood GSH. Significant elevations in transaminases (ALT and AST) and alkaline phosphatase (ALP) activities were recorded after gamma irradiation. Preservation of body wt, B.M. viable cells, spleen wt and haematopoietic cell recovery was evident upon ginseng pre-administration. It ameliorated the depression in GSH content and the elevation in MDA level. ALT, AST and ALP were depressed approaching the control level after 9 days from dual treatments and blood sugar level was maintained. The study points out the promising positive role played by ginseng as a nontoxic natural product to reduce the time necessary for reconstituting haematopoietic cells and protecting vital physiological processes after irradiation

Second neoplasms in adult patients submitted to haematopoietic stem cell transplantation.

Science.gov (United States)

Torrent, Anna; Ferrá, Christelle; Morgades, Mireia; Jiménez, María-José; Sancho, Juan-Manuel; Vives, Susana; Batlle, Montserrat; Moreno, Miriam; Xicoy, Blanca; Oriol, Albert; Ibarra, Gladys; Ribera, Josep-Maria

2018-06-08

Patients submitted to haematopoietic stem cell transplantation (HSCT) are at increased risk of late complications, such as second neoplasm (SN). The incidence and risk factors of SN in patients receiving HSCT at a single centre were analysed. The follow-up of adult patients who received a first HSCT (autologous [auto-HSCT] or allogeneic [allo-HSCT]) between January 2000 and December 2015 was reviewed. We collected their demographic characteristics, the primary disease and type of HSCT, and analysed the cumulative incidence of SN and their risk factors. Of 699 transplanted patients (auto-HSCT, n=451; allo-HSCT, n=248), 42 (6%) developed SN (17 haematological and 25 solid), 31 post-auto-HSCT and 11 post-allo-HSCT. Haematologic SN were more frequent after auto-HSCT than after allo-HSCT. The median time between HSCT and SN was 4.09 years [range 0.07-13.15], with no differences between auto-HSCT and allo-HSCT. The cumulative incidence of SN was 5% (95% CI 3-6) at 5 years, 7% (95% CI 5-10) at 10 years and 11% (95% CI 8-15) at 15 years, without differences according to the type of HSCT. Only the age over 40 years correlated with an increased risk of SN. In this series, the incidence of post-HSCT SN was similar to that previously described. Patients submitted to an auto-HSCT showed a higher frequency of haematologic SN. A higher incidence of SN was detected in patients older than 40 at the time of HSCT. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Allogeneic peripheral blood stem cell transplantation in patients with haematological malignancies

International Nuclear Information System (INIS)

Shamsi, T.S.; Irfan, M.; Ansari, S.H.; Farzana, T.; Kahlid, M.Z.; Panwani, V.K.; Baig, M.I.; Shakoor, N.

2004-01-01

Objective: To report the initial data on allogeneic peripheral blood stem cell transplantation for haematogical malignancies in Pakistan. Patients and Methods: Patients with haematological malignancies were included who had received allogeneic PBSC transplantation of Filgrastim (rhG-CSF) mobilized peripheral blood stem cells from HLA-identical siblings (except one 5/6 antigen sibling) with Busulphan and Cyclophosphamide standard conditioning therapy in all patients. No patient received antibiotics for gut decontamination. Empirical antibiotics included Ceftriaxone and Amikacin for febrile neutropenia, oral Itraconazole for antifungal prophylaxis while oral acyclovir was used for antiviral prophylaxis. All donors and recipients were CMV IgG positive Cyclosporin A / Methotrexate were given for graft versus host disease (GvHD) prophylaxis. Stem cells were harvested using Haemonetics MCS+ cell separator. All patients received G-CSF starting from day +4 until their neutrophil count rose to normal. Results: There were 21 patients with age range of 8-38 years and male to female ratio of 2:1. Engraftment was achieved in all patients; median time to absolute neutrophil count of > 0.5 x 10/sup 9/I was 10 days (range 8 -12 days) and platelet count of > 20 x 10/sup 9/1 was 14 days (12-17 days). Acute graft versus host disease (aGvHD) was seen in 7 patients; one patient had grade IV skin and hepatic GvHD; another patient had grade III gut GvHD, grade II GvHD was seen in 3 patients while grade I skin aGvHD was seen in 2 patients. Median hospital stay was 34 days. Treatment related mortality was seen in 3 patients (18%). Chronic GvHD was seen in 5 patients. Four more patients died during the follow-up period. Malaria was seen in 2 while tuberculosis developed in one case. Relapse was seen in 2 patients. The estimated probability of survival at one hundred day, at one year and five years was 82, 47 and 40 percent respectively. Conclusion: Haematopoietic stem cell transplant

Residual haematopoietic damage in adult and 8 day-old mice exposed to 7 Gy of x-rays

International Nuclear Information System (INIS)

Grande, T.; Bueren, J.A.; Gaitan, S.; Tejero, C.

1993-01-01

The authors' experiments have focused on the analysis of residual haematopoietic damage in 8-day-old and 12-week-old mice X-irradiated with a single dose of 7 Gy. In the case of adult mice, analysis of femoral and splenic CFU-S, CFU-GM and BFU-E showed a persistent depletion of these haematopoietic progenitor cells after irradiation. In contrast, in 1-week-old irradiated mice, a progressive recovery of the femoral haematopoietic progenitors was observed, achieving essentially normal values 1 year after irradiation. The spleens of these mice, however, contained significantly less haematopoietic progenitors than the control group, mainly as a consequence of the size reduction of this organ. In the peripheral blood, normal cellularity values were observed in most cases, although in the adult group a decline in numbers or circulating cells was noted after the first year following irradiation. (author)

NK cells and other innate lymphoid cells in haematopoietic stem cell transplantation

Directory of Open Access Journals (Sweden)

Paola eVacca

2016-05-01

Full Text Available Natural Killer (NK cells play a major role in the T-cell depleted haploidentical haematopoietic stem cell transplantation (haplo-HSCT to cure high-risk leukemias. NK cells belong to the expanding family of innate lymphoid cells (ILC. At variance with NK cells, the other ILC populations (ILC1/2/3 are non-cytolytic, while they secrete different patterns of cytokines. ILC provide host defences against viruses, bacteria and parasites, drive lymphoid organogenesis, and contribute to tissue remodelling. In haplo-HSCT patients, the extensive T-cell depletion is required to prevent graft-versus-host disease (GvHD but increases risks of developing a wide range of life-threatening infections. However, these patients may rely on innate defences that are reconstituted more rapidly than the adaptive ones. In this context, ILC may represent important players in the early phases following transplantation. They may contribute to tissue homeostasis/remodelling and lymphoid tissue reconstitution. While the reconstitution of NK cell repertoire and its role in haplo-HSCT have been largely investigated, little information is available on ILC. Of note, CD34+ cells isolated from different sources of HSC, may differentiate in vitro towards various ILC subsets. Moreover, cytokines released from leukemia blasts (e.g. IL-1β may alter the proportions of NK cells and ILC3, suggesting the possibility that leukemia may skew the ILC repertoire. Further studies are required to define the timing of ILC development and their potential protective role after HSCT.

Legal implications of translational promises of unproven stem cell ...

African Journals Online (AJOL)

2015-08-02

Aug 2, 2015 ... multipotent stem cells are haematopoietic stem cells (HSCs), which give rise ... include diseases such as arthritis, heart attacks, multiple sclerosis, diabetes ... regard to autologous stem cell therapy, where a patient's own stem.

The lived experience of autologous stem cell-transplanted patients: Post-transplantation and before discharge.

Science.gov (United States)

Alnasser, Qasem; Abu Kharmah, Salahel Deen; Attia, Manal; Aljafari, Akram; Agyekum, Felicia; Ahmed, Falak Aftab

2018-04-01

To explore the lived experience of the patients post-haematopoietic stem cell transplantation and specifically after engraftment and before discharge. Patients post-stem cell transplantation experience significant changes in all life aspects. Previous studies carried out by other researchers focused mainly on the postdischarge experience, where patients reported their perceptions that have always been affected by the life post-transplantation and influenced by their surroundings. The lived experience of patients, specifically after engraftment and prior to discharge (the "transition" phase), has not been adequately explored in the literature. Doing so might provide greater insight into the cause of change post-haematopoietic stem cell transplantation. This study is a phenomenological description of the participants' perception about their lived experience post-haematopoietic stem cell transplantation. The study used Giorgi's method of analysis. Through purposive sampling, 15 post-haematopoietic stem cell transplantation patients were recruited. Data were collected by individual interviews. Data were then analysed based on Giorgi's method of analysis to reveal the meaning of a phenomenon as experienced through the identification of essential themes. The analysis process revealed 12 core themes covered by four categories that detailed patients lived experience post-haematopoietic stem cell transplantation. The four categories were general transplant experience, effects of transplantation, factors of stress alleviation and finally life post-transplantation. This study showed how the haematopoietic stem cell transplantation affected the patients' physical, psychological and spiritual well-being. Transplantation also impacted on the patients' way of thinking and perception of life. Attending to patients' needs during transplantation might help to alleviate the severity of the effects and therefore improve experience. Comprehensive information about transplantation needs

Cost effectiveness of cord blood versus bone marrow and peripheral blood stem cells

Directory of Open Access Journals (Sweden)

Thomas Bart

2010-10-01

Full Text Available Thomas BartSwiss Blood Stem Cells, Bern, SwitzerlandAbstract: Umbilical cord blood (CB has become, since its first successful use more than two decades ago, an increasingly important source of blood stem cells. In this light, an overview of current usage of CB in the field of unrelated hematopoietic blood stem cell transplantation (HSCT is given. The three main sources of hematopoietic stem cells: bone marrow (BM, peripheral blood stem cells (PBSC, and cord blood (CB are compared as regards their current quantitative usage in HSCT. A cost analysis of the named three hematopoietic blood stem cell (HSC sources, taking into account various factors, is undertaken. The health economical comparison shows significant differences between CB on the one side, and BM and PBSC on the other. The consequences for the public health side and propositions for a possible health care policy, especially regarding future resource allocation towards the different choices for HSCT products, are discussed. An outlook on the possible future usage of BM, PBSC, and CB and its implications on health systems, donor registries, and CB banks is given.Keywords: health economy, cord blood, hematopoietic stem cell transplantation

Immune ablation and stem-cell therapy in autoimmune disease: Clinical experience

OpenAIRE

Tyndall, Alan; Gratwohl, Alois

2000-01-01

In the past 5 years, around 350 patients have received haematopoietic stem cell (HSC) transplantation for an autoimmune disease, with 275 of these registered in an international data base in Basel under the auspices of the European League Against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation(EBMT). Most patients had either a progressive form of multiple sclerosis (MS; n = 88) or scleroderma (now called systemic sclerosis; n = 55). Other diseases were rheumatoi...

Second allogeneic stem cell transplant for aplastic anaemia: a retrospective study by the Severe Aplastic Anaemia Working Party of the European Society for Blood and Marrow Transplantation.

Science.gov (United States)

Cesaro, Simone; Peffault de Latour, Regis; Tridello, Gloria; Pillon, Marta; Carlson, Kristina; Fagioli, Franca; Jouet, Jean-Pierre; Koh, Mickey B C; Panizzolo, Irene Sara; Kyrcz-Krzemien, Slawomira; Maertens, Johan; Rambaldi, Alessandro; Strahm, Brigitte; Blaise, Didier; Maschan, Alexei; Marsh, Judith; Dufour, Carlo

2015-11-01

We analysed the outcome of a second allogeneic haematopoietic stem cell transplant (alloHSCT) in 162 patients reported to the European Society for Blood and Marrow Transplantation between 1998 and 2009. Donor origin was a sibling in 110 and an unrelated donor in 52 transplants, respectively. The stem cell source was bone marrow in 31% and peripheral blood in 69% of transplants. The same donor as for the first alloHSCT was used in 81% of transplants whereas a change in the choice of stem cell source was reported in 56% of patients, mainly from bone marrow to peripheral blood. Neutrophil and platelet engraftment occurred in 85% and 72% of patients, after a median time of 15 and 17 days, respectively. Grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD occurred in 21% and 37% of patients, respectively. Graft failure (GF) occurred in 42 patients (26%). After a median follow-up of 3·5 years, the 5-year overall survival (OS) was 60·7%. In multivariate analysis, the only factor significantly associated with a better outcome was a Karnofsky/Lansky score ≥80 (higher OS). We conclude that a second alloHSCT is feasible rescue option for GF in SAA, with a successful outcome in 60% of cases. © 2015 John Wiley & Sons Ltd.

RNA-based, transient modulation of gene expression in human haematopoietic stem and progenitor cells

Science.gov (United States)

Diener, Yvonne; Jurk, Marion; Kandil, Britta; Choi, Yeong-Hoon; Wild, Stefan; Bissels, Ute; Bosio, Andreas

2015-01-01

Modulation of gene expression is a useful tool to study the biology of haematopoietic stem and progenitor cells (HSPCs) and might also be instrumental to expand these cells for therapeutic approaches. Most of the studies so far have employed stable gene modification by viral vectors that are burdensome when translating protocols into clinical settings. Our study aimed at exploring new ways to transiently modify HSPC gene expression using non-integrating, RNA-based molecules. First, we tested different methods to deliver these molecules into HSPCs. The delivery of siRNAs with chemical transfection methods such as lipofection or cationic polymers did not lead to target knockdown, although we observed more than 90% fluorescent cells using a fluorochrome-coupled siRNA. Confocal microscopic analysis revealed that despite extensive washing, siRNA stuck to or in the cell surface, thereby mimicking a transfection event. In contrast, electroporation resulted in efficient, siRNA-mediated protein knockdown. For transient overexpression of proteins, we used optimised mRNA molecules with modified 5′- and 3′-UTRs. Electroporation of mRNA encoding GFP resulted in fast, efficient and persistent protein expression for at least seven days. Our data provide a broad-ranging comparison of transfection methods for hard-to-transfect cells and offer new opportunities for DNA-free, non-integrating gene modulation in HSPCs. PMID:26599627

Mumps virus encephalomyelitis in a 19-year old male patient with an undefined severe combined immunodeficiency post-haematopoietic bone marrow transplantation: a rare fatal complication.

Science.gov (United States)

Eyre, Toby A; Pelosi, Emanuela; McQuaid, Stephen; Richardson, Deborah; Newman, Joan; Hill, Kate; Veys, Paul; Davies, Graham; Orchard, Kim H

2013-06-01

We describe a rare case of fatal mumps encephalomyelitis occurring in 19-year old male following matched unrelated donor peripheral blood haematopoietic stem cell transplantation (HSCT). The indication for HSCT was for an undefined form of severe combined immunodeficiency (SCID). Molecular typing of the mumps viral RNA isolated from neural tissue indicated that the infection was acquired at the time of a mumps outbreak in England and Wales that occurred between 2004 and 2006. This case highlights the importance of considering mumps in the differential diagnosis of central nervous system infection in highly immunosuppressed patients. Copyright © 2013 Elsevier B.V. All rights reserved.

Ethnicity, equity and public benefit: a critical evaluation of public umbilical cord blood banking in Australia.

Science.gov (United States)

Samuel, G N; Kerridge, I H; Vowels, M; Trickett, A; Chapman, J; Dobbins, T

2007-10-01

Over the past decade umbilical cord blood (UCB) has been increasingly used as a source of haematopoietic stem cells (HSCs) for patients who require a HSC transplant but do not have an HLA-matched donor. It was anticipated that using UCB as an alternative source of HSCs would increase the chance of finding a donor, particularly for the otherwise underrepresented ethnic minority groups. To evaluate the effectiveness of the Australian public UCB banks to increase the ethnic diversity of available HSC donations, this paper analyses the ethnic diversity of the Sydney Cord Blood Bank (SCBB), comparing this diversity to that of the Australian Bone Marrow Donor Registry (ABMDR). It also examines the ethnic diversity of those patients who, after requesting a haematopoietic stem cell transplantation in the 2-year period between 2003 and 2005, managed to find a suitably matched bone marrow or UCB donor. We show that the ethnic mix of donors to the SCBB has remained generally broad in source, is comparative to the Australian population, and is more diverse than the ABMDR. This, however, may still not be sufficient to substantially increase the likelihood of finding a donor for some ethnic minority groups.

In vitro expansion of Lin+ and Lin− mononuclear cells from human peripheral blood

International Nuclear Information System (INIS)

Norhaiza, H. Siti; Zarina, Z. A. Intan; Hisham, Z. A. Shahrul; Rohaya, M. A. W.

2013-01-01

Haematopoietic stem cells (HSCs) are used in the therapy of blood disorders due to the ability of these cells to reconstitute haematopoietic lineage cells when transplanted into myeloablative recipients. However, substantial number of cells is required in order for the reconstitution to take place. Since HSCs present in low frequency, larger number of donor is required to accommodate the demand of transplantable HSCs. Therefore, in vitro expansion of HSCs will have profound impact on clinical purposes. The aim of this study was to expand lineage negative (Lin − ) stem cells from human peripheral blood. Total peripheral blood mononuclear cells (PBMNCs) were fractionated from human blood by density gradient centrifugation. Subsequently, PBMNCs were subjected to magnetic assisted cell sorter (MACS) which depletes lineage positive (Lin + ) mononuclear cells expressing lineage positive markers such as CD2, CD3, CD11b, CD14, CD15, CD16, CD19, CD56, CD123, and CD235a to obtained Lin − cell population. The ability of Lin + and Lin − to survive in vitro was explored by culturing both cell populations in complete medium consisting of Alpha-Minimal Essential Medium (AMEM) +10% (v/v) Newborn Calf Serum (NBCS)+ 2% (v/v) pen/strep. In another experiment, Lin + and Lin − were cultured with complete medium supplemented with 10ng/mL of the following growth factors: stem cell factor (SCF), interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF), 2IU/mL of Erythropoietin (Epo) and 20ng/mL of IL-6. Three samples were monitored in static culture for 22 days. The expansion potential was assessed by the number of total viable cells, counted by trypan blue exclusion assay. It was found that Lin + mononuclear cells were not able to survive either in normal proliferation medium or proliferation medium supplemented with cytokines. Similarly, Lin − stem cells were not able to survive in proliferation medium however, addition of cytokines into the proliferation

In vitro expansion of Lin+ and Lin- mononuclear cells from human peripheral blood

Science.gov (United States)

Norhaiza, H. Siti; Rohaya, M. A. W.; Zarina, Z. A. Intan; Hisham, Z. A. Shahrul

2013-11-01

Haematopoietic stem cells (HSCs) are used in the therapy of blood disorders due to the ability of these cells to reconstitute haematopoietic lineage cells when transplanted into myeloablative recipients. However, substantial number of cells is required in order for the reconstitution to take place. Since HSCs present in low frequency, larger number of donor is required to accommodate the demand of transplantable HSCs. Therefore, in vitro expansion of HSCs will have profound impact on clinical purposes. The aim of this study was to expand lineage negative (Lin-) stem cells from human peripheral blood. Total peripheral blood mononuclear cells (PBMNCs) were fractionated from human blood by density gradient centrifugation. Subsequently, PBMNCs were subjected to magnetic assisted cell sorter (MACS) which depletes lineage positive (Lin+) mononuclear cells expressing lineage positive markers such as CD2, CD3, CD11b, CD14, CD15, CD16, CD19, CD56, CD123, and CD235a to obtained Lin- cell population. The ability of Lin+ and Lin- to survive in vitro was explored by culturing both cell populations in complete medium consisting of Alpha-Minimal Essential Medium (AMEM) +10% (v/v) Newborn Calf Serum (NBCS)+ 2% (v/v) pen/strep. In another experiment, Lin+ and Lin- were cultured with complete medium supplemented with 10ng/mL of the following growth factors: stem cell factor (SCF), interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF), 2IU/mL of Erythropoietin (Epo) and 20ng/mL of IL-6. Three samples were monitored in static culture for 22 days. The expansion potential was assessed by the number of total viable cells, counted by trypan blue exclusion assay. It was found that Lin+ mononuclear cells were not able to survive either in normal proliferation medium or proliferation medium supplemented with cytokines. Similarly, Lin- stem cells were not able to survive in proliferation medium however, addition of cytokines into the proliferation medium support Lin

Dietary restriction ameliorates haematopoietic ageing independent of telomerase, whilst lack of telomerase and short telomeres exacerbates the ageing phenotype.

Science.gov (United States)

Al-Ajmi, Nouf; Saretzki, Gabriele; Miles, Colin; Spyridopoulos, Ioakim

2014-10-01

Ageing is associated with an overall decline in the functional capacity of tissues and stem cells, including haematopoietic stem and progenitor cells (HSPCs), as well as telomere dysfunction. Dietary restriction (DR) is a recognised anti-ageing intervention that extends lifespan and improves health in several organisms. To investigate the role of telomeres and telomerase in haematopoietic ageing, we compared the HSPC profile and clonogenic capacity of bone marrow cells from wild type with telomerase-deficient mice and the effect of DR on these parameters. Compared with young mice, aged wild type mice demonstrated a significant accumulation of HSPCs (1.3% vs 0.2%, P=0.002) and elevated numbers of granulocyte/macrophage colony forming units (CFU-GM, 26.4 vs 17.3, P=0.0037) consistent with myeloid "skewing" of haematopoiesis. DR was able to restrict the increase in HSPC number as well as the myeloid "skewing" in aged wild type mice. In order to analyse the influence of short telomeres on the ageing phenotype we examined mice lacking the RNA template for telomerase, TERC(-/-). Telomere shortening resulted in a similar bone marrow phenotype to that seen in aged mice, with significantly increased HSPC numbers and an increased formation of all myeloid colony types but at a younger age than wild type mice. However, an additional increase in erythroid colonies (BFU-E) was also evident. Mice lacking telomerase reverse transcriptase without shortened telomeres, TERT(-/-), also presented with augmented haematopoietic ageing which was ameliorated by DR, demonstrating that the effect of DR was not dependent on the presence of telomerase in HSPCs. We conclude that whilst shortened telomeres mimic some aspects of haematopoietic ageing, both shortened telomeres and the lack of telomerase produce specific phenotypes, some of which can be prevented by dietary restriction. Copyright © 2014 Elsevier Inc. All rights reserved.

Bone marrow adipocytes promote the regeneration of stem cells and haematopoiesis by secreting SCF.

Science.gov (United States)

Zhou, Bo O; Yu, Hua; Yue, Rui; Zhao, Zhiyu; Rios, Jonathan J; Naveiras, Olaia; Morrison, Sean J

2017-08-01

Endothelial cells and leptin receptor + (LepR + ) stromal cells are critical sources of haematopoietic stem cell (HSC) niche factors, including stem cell factor (SCF), in bone marrow. After irradiation or chemotherapy, these cells are depleted while adipocytes become abundant. We discovered that bone marrow adipocytes synthesize SCF. They arise from Adipoq-Cre/ER + progenitors, which represent ∼5% of LepR + cells, and proliferate after irradiation. Scf deletion using Adipoq-Cre/ER inhibited haematopoietic regeneration after irradiation or 5-fluorouracil treatment, depleting HSCs and reducing mouse survival. Scf from LepR + cells, but not endothelial, haematopoietic or osteoblastic cells, also promoted regeneration. In non-irradiated mice, Scf deletion using Adipoq-Cre/ER did not affect HSC frequency in long bones, which have few adipocytes, but depleted HSCs in tail vertebrae, which have abundant adipocytes. A-ZIP/F1 'fatless' mice exhibited delayed haematopoietic regeneration in long bones but not in tail vertebrae, where adipocytes inhibited vascularization. Adipocytes are a niche component that promotes haematopoietic regeneration.

Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine synergize to enhance haematopoietic reconstitution in irradiated mice

Energy Technology Data Exchange (ETDEWEB)

Pospisil, M.; Hofer, M.; Netikova, J.; Hola, J.; Vacek, A. [Academy of Sciences of the Czech Republic, Inst. of Biophysics, Brno (Czech Republic); Znojil, V.; Vacha, J. [Masaryk Univ., Medical Faculty, Brno (Czech Republic)

1998-03-01

The activation of adenosine receptors has recently been demonstrated to stimulate haematopoiesis. In the present study, we investigated the ability of drugs elevating extracellular adenosine to influence curative effects of granulocyte colony-stimulating factor (G-CSF) in mice exposed to a sublethal dose of 4 Gy of {sup 60}Co radiation. Elevation of extracellular adenosine in mice was induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole plus AMP, and G-CSF, administered either alone or in combination, were evaluated. The drugs were injected to mice in a 4-d treatment regimen starting on d 3 after irradiation and the haematopoietic response was evaluated on d 7, 10, 14, 18 and 24 after irradiation. While the effects of G-CSF on the late maturation stages of blood cells, appearing shortly after the completion of the treatment, were not influenced by dipyridamole plus AMP, positive effects of the combination therapy occurred in the post-irradiation recovery phase which is dependent on the repopulation of haematopoietic stem cells. This was indicated by the significant elevation of counts of granulocyte-macrophage progenitor cells (GM-CFC) and granulocytic cells in the bone marrow (d 14), of GM-CFC (d 14), granulocytic and erythroid cells (d 14 and 18) in the spleen, and of neutrophils (d 18), monocytes (d 14 and 18) and platelets (d 18) in the peripheral blood. These effects suggest that the repopulation potential of the combination therapy lies in a common multi-lineage cell population. The results of this study implicate the promising possibility to enhance the curative effects of G-CSF under conditions of myelosuppressive state induced by radiation exposure. (au) 43 refs.

Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine synergize to enhance haematopoietic reconstitution in irradiated mice

International Nuclear Information System (INIS)

Pospisil, M.; Hofer, M.; Netikova, J.; Hola, J.; Vacek, A.; Znojil, V.; Vacha, J.

1998-01-01

The activation of adenosine receptors has recently been demonstrated to stimulate haematopoiesis. In the present study, we investigated the ability of drugs elevating extracellular adenosine to influence curative effects of granulocyte colony-stimulating factor (G-CSF) in mice exposed to a sublethal dose of 4 Gy of 60 Co radiation. Elevation of extracellular adenosine in mice was induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole plus AMP, and G-CSF, administered either alone or in combination, were evaluated. The drugs were injected to mice in a 4-d treatment regimen starting on d 3 after irradiation and the haematopoietic response was evaluated on d 7, 10, 14, 18 and 24 after irradiation. While the effects of G-CSF on the late maturation stages of blood cells, appearing shortly after the completion of the treatment, were not influenced by dipyridamole plus AMP, positive effects of the combination therapy occurred in the post-irradiation recovery phase which is dependent on the repopulation of haematopoietic stem cells. This was indicated by the significant elevation of counts of granulocyte-macrophage progenitor cells (GM-CFC) and granulocytic cells in the bone marrow (d 14), of GM-CFC (d 14), granulocytic and erythroid cells (d 14 and 18) in the spleen, and of neutrophils (d 18), monocytes (d 14 and 18) and platelets (d 18) in the peripheral blood. These effects suggest that the repopulation potential of the combination therapy lies in a common multi-lineage cell population. The results of this study implicate the promising possibility to enhance the curative effects of G-CSF under conditions of myelosuppressive state induced by radiation exposure. (au)

Haematopoietic Stem Cell Transplantation Arrests the Progression of Neurodegenerative Disease in Late-Onset Tay-Sachs Disease.

Science.gov (United States)

Stepien, Karolina M; Lum, Su Han; Wraith, J Edmond; Hendriksz, Christian J; Church, Heather J; Priestman, David; Platt, Frances M; Jones, Simon; Jovanovic, Ana; Wynn, Robert

2017-12-07

Tay-Sachs disease is a rare metabolic disease caused by a deficiency of hexosaminidase A that leads to accumulation of GM2 gangliosides predominantly in neural tissue. Late-onset Tay-Sachs disease variant is associated with a higher level of residual HexA activity. Treatment options are limited, and there are a few described cases who have undergone haematopoietic stem cell transplantation (HSCT) with variable outcome.We describe a case of a 23-year-old male patient who presented with a long-standing tremor since 7 years of age. He had gait ataxia, a speech stammer and swallowing problems. His condition had had a static course apart from his tremor that had been gradually deteriorating. Because of the deterioration in his neurological function, the patient had an uneventful, matched-sibling donor bone marrow transplant at the age of 15 years. Eight years post-HSCT, at the age of 23, he retains full donor engraftment, and his white cell beta-HexA of 191 nmol/mg/h is comparable to normal controls (in-assay control = 187). He continues to experience some intentional tremor that is tolerable for daily life and nonprogressive since HSCT. HSCT is a potential treatment option which might arrest neurodegeneration in patients with LOTS.

Life coaching following haematopoietic stem cell transplantation: a mixed-method investigation of feasibility and acceptability.

Science.gov (United States)

Kenyon, M; Young, F; Mufti, G J; Pagliuca, A; Lim, Z; Ream, E

2015-07-01

Haematopoietic stem cell transplantation (HSCT) cures many haematological cancers. Recovery post-HSCT is physically and psychologically challenging, lasting several months. Beyond the first post-transplant year, a fifth report difficulties encompassing practical, social and emotional domains, including finance and employment. We investigated the feasibility, acceptability and impact of a life coaching intervention designed to address psychosocial 'survivor' concerns of HSCT recipients and facilitate transition to life post-treatment. A concurrent embedded experimental mixed-method design was employed. Pre- and post-intervention data collection comprised qualitative semi-structured telephone interviews and quantitative postal questionnaires. Seven purposively sampled HSCT recipients (life coaching delivered by a professional life coach fortnightly over 8 weeks. Participants reported less anxiety, depression and fewer survivor concerns post-intervention, with a trend for lower social difficulties and increased functional well-being. Perceived self-efficacy was unchanged. Life coaching was feasible to deliver and acceptable to the participants who indicated it was a positive experience, with benefits described in diverse areas including work, lifestyle and hobbies. Life coaching within cancer services potentially offers the means to address psychosocial concerns and support transition to life after treatment, enabling patients to reach their potential, e.g. returning to employment and financial independence. Further investigation of this intervention in cancer survivors is warranted. © 2015 John Wiley & Sons Ltd.

How much blood is needed?

Science.gov (United States)

Seifried, E; Klueter, H; Weidmann, C; Staudenmaier, T; Schrezenmeier, H; Henschler, R; Greinacher, A; Mueller, M M

2011-01-01

Demographic changes in developed countries as their populations age lead to a steady increase in the consumption of standard blood components. Complex therapeutic procedures like haematopoietic stem cell transplantation, cardiovascular surgery and solid organ transplantation are options for an increasing proportion of older patients nowadays. This trend is likely to continue in coming years. On the other hand, novel aspects in transplant regimens, therapies for malignant diseases, surgical procedures and perioperative patient management have led to a moderate decrease in blood product consumption per individual procedure. The ageing of populations in developed countries, intra-society changes in the attitude towards blood donation as an important altruistic behaviour and the overall alterations in our societies will lead to a decline in regular blood donations over the next decades in many developed countries. Artificial blood substitutes or in vitro stem cell-derived blood components might also become alternatives in the future. However, such substitutes are still in early stages of development and will therefore probably not alleviate this problem within the next few years. Taken together, a declining donation rate and an increase in the consumption of blood components require novel approaches on both sides of the blood supply chain. Different blood donor groups require specific approaches and, for example, inactive or deferred donors must be re-activated. Optimal use of blood components requires even more attention. © 2010 The Author(s). Vox Sanguinis © 2010 International Society of Blood Transfusion.

Risk Adapted Management of Febrile Neutrepenia and Early Cessation of Empirical Antibiotherapy in Hematopoietic Stem Cell Transplantation Setting

Directory of Open Access Journals (Sweden)

Ali Hakan Kaya

2017-04-01

Full Text Available Background: Haematopoietic stem cell transplantation is a curative treatment option for many haematological disorders. Infection following haematopoietic stem cell transplantation is one of the major causes of mortality. Aims: To investigate the outcomes of early cessation of empirical antibiotic treatment per protocol in febrile neutropenia patients who have undergone haematopoietic stem cell transplantation at our clinic. Study Design: Descriptive study. Methods: The present study retrospectively evaluated febrile neutropenia attacks in haematopoietic stem cell transplantation recipients during the period June 2014 - January 2015 at our haematopoietic stem cell transplantation clinic. Results: A total of 72 febrile neutropenia attacks were evaluated in 53 patients. In 46 febrile neutropenia attacks, microbiologic cultures revealed positive results. In culture-positive febrile neutropenia episodes a single bacterium was isolated in 32 cases and multiple strains were isolated in 14. In 15 patients, empirical antibiotic therapy was discontinued after 72 hours. These patients were clinically stable, without evident focus of infection and had negative culture results. Only 4 recurrent episodes were observed (27% after cessation of antibiotherapy. No patient died as a result of recurrent infection. The 30-day and 100-day post-transplantation mortality rates of patients with febrile neutropenia episodes were 11.3% (6/53 and 3.8% (2/53, respectively. Infection-related 30-day and 100-day mortality rates were 7.5% (4/53 and 0% (0/53, respectively. Conclusion: The main message of our study is that early cessation of empirical antibiotherapy seems to be feasible in eligible patients without increasing febrile neutropenia mortality rates

Religious perspectives on umbilical cord blood banking.

Science.gov (United States)

Jordens, Christopher F C; O'Connor, Michelle A C; Kerridge, Ian H; Stewart, Cameron; Cameron, Andrew; Keown, Damien; Lawrence, Rabbi Jeremy; McGarrity, Andrew; Sachedina, Abdulaziz; Tobin, Bernadette

2012-03-01

Umbilical cord blood is a valuable source of haematopoietic stem cells. There is little information about whether religious affiliations have any bearing on attitudes to and decisions about its collection, donation and storage. The authors provided information about umbilical cord blood banking to expert commentators from six major world religions (Catholicism, Anglicanism, Islam, Judaism, Hinduism and Buddhism) and asked them to address a specific set of questions in a commentary. The commentaries suggest there is considerable support for umbilical cord blood banking in these religions. Four commentaries provide moral grounds for favouring public donation over private storage. None attach any particular religious significance to the umbilical cord or to the blood within it, nor place restrictions on the ethnicity or religion of donors and recipients. Views on ownership of umbilical cord blood vary. The authors offer a series of general points for those who seek a better understanding of religious perspectives on umbilical cord blood banking.

Current practices for screening, consent and care of related donors in France: Haematopoietic stem cell transplantation coordinator nurses' perceptions.

Science.gov (United States)

Polomeni, A; Bompoint, C; Gomez, A; Brissot, E; Ruggeri, A; Belhocine, R; Mohty, M

2017-11-01

Haematopoietic stem cell transplantation-coordinating nurses (HSCT-CNs) play an important role in informing related donors (RDs) and in organising human leucocyte antigen (HLA) tests, pre-donation workup and stem cells collection. Our pilot study aimed to explore French HSCT-CNs' perceptions of RD care issues. Twenty-nine French HSCT adult units were sent a questionnaire on the subject of donation procedures, HSCT-CNs' data and their professional experience of related donation issues. Twenty-two HSCT-CNs returned a completed questionnaire, and 90% of HSCT units were involved to some degree in both patient and donor care. Responses indicated that the provision of information to potential donors prior to HLA tests was insufficient, while donors were given a medical consultation only during the pre-donation workup. Questions were raised about the consent and voluntary status of RDs. None of the HSCT teams organised a post-donation consultation, while 57% provided follow-up by phone or via a questionnaire. Our results draw attention to the conflict of interest experienced by HSCT-CNs when caring simultaneously for patients and donors. The specific psychosocial difficulties associated with becoming an RD are also highlighted. French HSCT-CNs' perceptions of related donation reveal many ethical and clinical problems that have yet to be fully explored. Data on this topic remain scarce, and our pilot study may contribute to the current debate on the organisation of RD care. © 2016 John Wiley & Sons Ltd.

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

. 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 38.5o......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...

Haematopoietic stem cell transplantation survivorship and quality of life: is it a small world after all?

Science.gov (United States)

Brice, Lisa; Gilroy, Nicole; Dyer, Gemma; Kabir, Masura; Greenwood, Matt; Larsen, Stephen; Moore, John; Kwan, John; Hertzberg, Mark; Brown, Louisa; Hogg, Megan; Huang, Gillian; Tan, Jeff; Ward, Christopher; Gottlieb, David; Kerridge, Ian

2017-02-01

The aim of this qualitative study was to gain a rich understanding of the impact that haematopoietic stem cell transplantation (HSCT) has on long-term survivor's quality of life (QoL). Participants included 441 survivors who had undergone HSCT for a malignant or non-malignant disease. Data were obtained by a questionnaire positing a single open-ended question asking respondents to list the three issues of greatest importance to their QoL in survivorship. Responses were analysed and organised into QoL themes and subthemes. Major themes identified included the following: the failing body and diminished physical effectiveness, the changed mind, the loss of social connectedness, the loss of the functional self and the patient for life. Each of these themes manifests different ways in which HSCT survivor's world and opportunities had diminished compared to the unhindered and expansive life that they enjoyed prior to the onset of disease and subsequent HSCT. HSCT has a profound and pervasive impact on the life of survivors-reducing their horizons and shrinking various parts of their worlds. While HSCT survivors can describe the ways in which their life has changed, many of their fears, anxieties, regrets and concerns are existential in nature and are ill-defined-making it exceeding unlikely that they would be adequately captured by standard psychometric measures of QoL post HSCT.

Stem cells of umbilical blood cord – therapeutic use

Directory of Open Access Journals (Sweden)

Beata Bielec

2015-07-01

Full Text Available For many years, the transplantation of hematopoietic stem cells has been used to treat some diseases of the hematopoietic system. For a very long time, only bone marrow was used as a source of hematopoietic stem cells for this method of treatment. However, to comply with allogeneic bone marrow transplantation, an antigenically compatible donor is necessary. Transplantations from unrelated donors are associated with increased risk of a graft-versus-host reaction, transplant rejection and, consequently, increased mortality. Many years ago, it was found that umbilical cord blood as well as bone marrow and peripheral blood contains hematopoietic stem cells and mesenchymal cells able to differentiate into different cell types and that the umbilical cord blood can be a source of stem cells for transplantation. Following this discovery, numerous attempts were made for its potential use in the treatment of hematologic diseases, metabolic diseases as well as regenerative medicine. Umbilical cord blood stem cells exhibit intermediate characteristics between embryonic and adult stem cells. They are distinguished from the latter by telomere length, telomerase activity, and lower risk of accumulation of DNA mutations or chromosomal aberrations. The only transplantation limitation appears to be the amount of cord blood collected, which on average is sufficient for transplantation in a 40-50 kg child. Collection of cord blood is a simple, short-lasting treatment, not causing any danger for a newborn or the mother. Umbilical cord blood is obtained during labor, and then frozen and stored at cord blood banks all over the world.

Ginsenoside Rg1 improves bone marrow haematopoietic activity via extramedullary haematopoiesis of the spleen.

Science.gov (United States)

Liu, Hua-Hsing; Chen, Fei-Peng; Liu, Rong-Kai; Lin, Chun-Lin; Chang, Ko-Tung

2015-11-01

Cyclophosphamide (CY) is a chemotherapeutic agent used for cancer and immunological diseases. It induces cytotoxicity of bone marrow and causes myelosuppression and extramedullary haematopoiesis (EMH) in treated patients. EMH is characterized with the emergence of multipotent haematopoietic progenitors most likely in the spleen and liver. Previous studies indicated that a Chinese medicine, ginsenoside Rg1, confers a significant effect to elevate the number of lineage (Lin(-) ) Sca-1(+) c-Kit(+) haematopoietic stem and progenitor cells (HSPCs) and restore the function of bone marrow in CY-treated myelosuppressed mice. However, whether the amelioration of bone marrow by Rg1 accompanies an alleviation of EMH in the spleen was still unknown. In our study, the cellularity and weight of the spleen were significantly reduced after Rg1 treatment in CY-treated mice. Moreover, the number of c-Kit(+) HSPCs was significantly decreased but not as a result of apoptosis, indicating that Rg1 alleviated EMH of the spleen induced by CY. Unexpectedly, the proliferation activity of c-Kit(+) HSPCs was only up-regulated in the spleen, but not in the bone marrow, after Rg1 treatment in CY-treated mice. We also found that a fraction of c-Kit(+) /CD45(+) HSPCs was simultaneously increased in the circulation after Rg1 treatment. Interestingly, the effects of Rg1 on the elevation of HSPCs in bone marrow and in the peripheral blood were suppressed in CY-treated splenectomized mice. These results demonstrated that Rg1 improves myelosuppression induced by CY through its action on the proliferation of HSPCs in EMH of the spleen and migration of HSPCs from the spleen to the bone marrow. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Multicentre standardisation of a clinical grade procedure for the preparation of allogeneic platelet concentrates from umbilical cord blood

Science.gov (United States)

Rebulla, Paolo; Pupella, Simonetta; Santodirocco, Michele; Greppi, Noemi; Villanova, Ida; Buzzi, Marina; De Fazio, Nicola; Grazzini, Giuliano

2016-01-01

Background In addition to a largely prevalent use for bleeding prophylaxis, platelet concentrates from adult blood have also been used for many years to prepare platelet gels for the repair of topical skin ulcers. Platelet gel can be obtained by activation of fresh, cryopreserved, autologous or allogeneic platelet concentrates with calcium gluconate, thrombin and/or batroxobin. The high content of tissue regenerative factors in cord blood platelets and the widespread availability of allogeneic cord blood units generously donated for haematopoietic transplant but unsuitable for this use solely because of low haematopoietic stem cell content prompted us to develop a national programme to standardise the production of allogeneic cryopreserved cord blood platelet concentrates (CBPC) suitable for later preparation of clinical-grade cord blood platelet gel. Materials and methods Cord blood units collected at public banks with total nucleated cell counts 150×109/L and volume >50 mL, underwent soft centrifugation within 48 hours of collection. Platelet-rich plasma was centrifuged at high speed to obtain a CBPC with target platelet concentration of 800–1,200×109/L, which was cryopreserved, without cryoprotectant, below −40 °C. Results During 14 months, 13 banks produced 1,080 CBPC with mean (± standard deviation) volume of 11.4±4.4 mL and platelet concentration of 1,003±229×109/L. Total platelet count per CBPC was 11.3±4.9×109. Platelet recovery from cord blood was 47.7±17.8%. About one-third of cord blood units donated for haematopoietic transplant could meet the requirements for preparation of CBPC. The cost of preparation was € 160.92/CBPC. About 2 hours were needed for one technician to prepare four CBPC. Discussion This study yielded valuable scientific and operational information regarding the development of clinical trials using allogeneic CBPC. PMID:26509822

Long-Term Effects of Haematopoietic Stem Cell Transplantation after Pediatric Cancer: A Qualitative Analysis of Life Experiences and Adaptation Strategies

Directory of Open Access Journals (Sweden)

Magali Lahaye

2017-05-01

Full Text Available Haematopoietic stem cell transplantation (HSCT improves the survival rate of children and adolescents with malignant and non-malignant conditions; however, the physical, psychological and social burden of such a procedure is considerable both during and after treatment. The present qualitative study investigated the long-term effects of HSCT after pediatric cancer. Thirty adolescent and young adult (AYA survivors (Mage = 23.61 years, SD = 5.21 participated in individual interviews and were invited to speak about their life experiences following their treatment and strategies they use to deal with their past medical experiences and the long-term sequelae. Our results showed the presence of ongoing physical and psychosocial consequences of their past illness and its treatments with wide ranging psychosocial impacts, such as affected self-image, social withdrawal, sense of lack of choice, and need for specific attention. Different strategies were reported to overcome these consequences, such as talking about illness, giving a sense to their past medical experiences, and developing meaningful social relationships. Clinical and research implications are also discussed.

Defibrotide: a review of its use in severe hepatic veno-occlusive disease following haematopoietic stem cell transplantation.

Science.gov (United States)

Keating, Gillian M

2014-12-01

Defibrotide (Defitelio(®)) was recently approved in the EU for the treatment of severe hepatic veno-occlusive disease (VOD), also known as sinusoidal obstructive syndrome, in haematopoietic stem cell transplantation (HSCT) therapy. It is indicated in adults, adolescents, children and infants over 1 month of age. Defibrotide is also available in the US via an expanded-access protocol. Defibrotide is thought to protect endothelial cells and restore the thrombo-fibrinolytic balance in VOD. In a multicentre, phase III trial, the complete response rate by day +100 (primary endpoint) was significantly higher, and mortality at day +100 was significantly lower, in patients with severe hepatic VOD and multiorgan failure following HSCT who received intravenous defibrotide 6.25 mg/kg every 6 h than in a group of historical controls. The efficacy of defibrotide in severe hepatic VOD following HSCT was also supported by findings from a phase II dose-finding study, compassionate-use data and information provided from an independent transplant registry. Intravenous defibrotide was generally well tolerated in patients with severe hepatic VOD following HSCT, and was not associated with an increased risk of haemorrhagic adverse events. In conclusion, defibrotide is the only agent approved (in the EU) for use in severe hepatic VOD following HSCT and represents a useful advance in the treatment of this condition.

In vitro expansion of Lin{sup +} and Lin{sup −} mononuclear cells from human peripheral blood

Energy Technology Data Exchange (ETDEWEB)

Norhaiza, H. Siti; Zarina, Z. A. Intan; Hisham, Z. A. Shahrul [School of Bioscience and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600, Selangor (Malaysia); Rohaya, M. A. W. [Department of Orthodontics, Faculty of Dentistry, Universiti Kebangsaan Malaysia, 50300, Kuala Lumpur (Malaysia)

2013-11-27

Haematopoietic stem cells (HSCs) are used in the therapy of blood disorders due to the ability of these cells to reconstitute haematopoietic lineage cells when transplanted into myeloablative recipients. However, substantial number of cells is required in order for the reconstitution to take place. Since HSCs present in low frequency, larger number of donor is required to accommodate the demand of transplantable HSCs. Therefore, in vitro expansion of HSCs will have profound impact on clinical purposes. The aim of this study was to expand lineage negative (Lin{sup −}) stem cells from human peripheral blood. Total peripheral blood mononuclear cells (PBMNCs) were fractionated from human blood by density gradient centrifugation. Subsequently, PBMNCs were subjected to magnetic assisted cell sorter (MACS) which depletes lineage positive (Lin{sup +}) mononuclear cells expressing lineage positive markers such as CD2, CD3, CD11b, CD14, CD15, CD16, CD19, CD56, CD123, and CD235a to obtained Lin{sup −} cell population. The ability of Lin{sup +} and Lin{sup −} to survive in vitro was explored by culturing both cell populations in complete medium consisting of Alpha-Minimal Essential Medium (AMEM) +10% (v/v) Newborn Calf Serum (NBCS)+ 2% (v/v) pen/strep. In another experiment, Lin{sup +} and Lin{sup −} were cultured with complete medium supplemented with 10ng/mL of the following growth factors: stem cell factor (SCF), interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF), 2IU/mL of Erythropoietin (Epo) and 20ng/mL of IL-6. Three samples were monitored in static culture for 22 days. The expansion potential was assessed by the number of total viable cells, counted by trypan blue exclusion assay. It was found that Lin{sup +} mononuclear cells were not able to survive either in normal proliferation medium or proliferation medium supplemented with cytokines. Similarly, Lin{sup −} stem cells were not able to survive in proliferation medium however

Legislation governing pluripotent stem cells in South Africa

Directory of Open Access Journals (Sweden)

Michael Pepper

2015-09-01

Full Text Available One of the most exciting areas of medical research involves the use of stem cells for the treatment of patients with a variety of diseases and for tissue repair. Although stem cell research is accelerating rapidly in many countries, it has in the past been limited in South Africa (SA; very little has been done in this country to explore the great potential offered by stem cells to address the high disease burden. Stem cell therapy has however been practised for many years, in SA and worldwide, in the form of haematopoietic stem cell transplantation, mainly for haematological malignancies. From a therapeutic perspective, two types of stem cells can be defined: pluripotent stem cells and adult stem cells. Pluripotent cells derived from the inner cell mass of blastocysts (either from in vitro fertilisation or following somatic cell nuclear transfer are called embryonic stem (ES cells, while those derived by reprogramming adult cells are called induced pluripotent stem (iPS cells. Adult stem cells include haematopoietic, mesenchymal and neural stem cells.The purpose of this article is to critically examine the SA legislation with regard to elements that impact on pluripotent stem cell research and the use of pluripotent stem cells for therapeutic purposes. This includes (but is not limited to legislation from the National Health Act (Chapter 8 in particular and its regulations, and deals with matters related to research on embryos in the stem cell context, somatic cell nuclear transfer, reproductive and therapeutic cloning and the generation and therapeutic use of iPS and ES cells.

Characterization Of Bovine Adipose-Derived Stem Cells

OpenAIRE

Daniel Cebo

2017-01-01

Bovine adipose-derived stem cells were obtained from the subcutaneous abdominal adipose tissue. The cells were cultured by the modified tissue-explants method developed in our laboratory and then analyzed using optical microscopy and flow cytometry. These cells were able to replicate in our cell culture conditions. cell Flow cytometry showed that bovine adipose-derived stem cells expressed mesenchymal stem cell markers CD73 and CD90. Meanwhile haematopoietic markers CD45 and CD34 are absent f...

Haematopoietic stem cell transplantation: activities (2014 report) in a ...

African Journals Online (AJOL)

PROMOTING ACCESS TO AFRICAN RESEARCH ... Introduction: Hematopoietic Stem Cell transplantation (HSCT) is the only curative therapy for ... Activities: The stem cell transplant centre at the University of Benin Teaching Hospital Edo ...

File list: Pol.Bld.50.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Bld.50.AllAg.Peripheral_blood_stem_cells hg19 RNA polymerase Blood Peripheral b...lood stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Bld.50.AllAg.Peripheral_blood_stem_cells.bed ...

File list: Pol.Bld.20.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Bld.20.AllAg.Peripheral_blood_stem_cells hg19 RNA polymerase Blood Peripheral b...lood stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Bld.20.AllAg.Peripheral_blood_stem_cells.bed ...

File list: Unc.Bld.50.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Bld.50.AllAg.Peripheral_blood_stem_cells hg19 Unclassified Blood Peripheral blo...od stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.50.AllAg.Peripheral_blood_stem_cells.bed ...

File list: Pol.Bld.05.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Bld.05.AllAg.Peripheral_blood_stem_cells hg19 RNA polymerase Blood Peripheral b...lood stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Bld.05.AllAg.Peripheral_blood_stem_cells.bed ...

File list: Unc.Bld.05.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Bld.05.AllAg.Peripheral_blood_stem_cells hg19 Unclassified Blood Peripheral blo...od stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.05.AllAg.Peripheral_blood_stem_cells.bed ...

File list: Unc.Bld.10.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Bld.10.AllAg.Peripheral_blood_stem_cells hg19 Unclassified Blood Peripheral blo...od stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.10.AllAg.Peripheral_blood_stem_cells.bed ...

File list: Unc.Bld.20.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Bld.20.AllAg.Peripheral_blood_stem_cells hg19 Unclassified Blood Peripheral blo...od stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.20.AllAg.Peripheral_blood_stem_cells.bed ...

File list: Pol.Bld.10.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Bld.10.AllAg.Peripheral_blood_stem_cells hg19 RNA polymerase Blood Peripheral b...lood stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Bld.10.AllAg.Peripheral_blood_stem_cells.bed ...

Effect of Induced Pluripotent Stem Cell Technology in Blood Banking

Science.gov (United States)

Focosi, Daniele

2016-01-01

Summary Population aging has imposed cost-effective alternatives to blood donations. Artificial blood is still at the preliminary stages of development, and the need for viable cells seems unsurmountable. Because large numbers of viable cells must be promptly available for clinical use, stem cell technologies, expansion, and banking represent ideal tools to ensure a regular supply. Provided key donors can be identified, induced pluripotent stem cell (iPSC) technology could pave the way to a new era in transfusion medicine, just as it is already doing in many other fields of medicine. The present review summarizes the current state of research on iPSC technology in the field of blood banking, highlighting hurdles, and promises. Significance The aging population in Western countries is causing a progressive reduction of blood donors and a constant increase of blood recipients. Because blood is the main therapeutic option to treat acute hemorrhage, cost-effective alternatives to blood donations are being actively investigated. The enormous replication capability of induced pluripotent stem cells and their promising results in many other fields of medicine could be an apt solution to produce the large numbers of viable cells required in transfusion and usher in a new era in transfusion medicine. The present report describes the potentiality, technological hurdles, and promises of induced pluripotent stem cells to generate red blood cells by redifferentiation. PMID:26819256

Incidence of human herpes virus-6 and human cytomegalovirus infections in donated bone marrow and umbilical cord blood hematopoietic stem cells

Directory of Open Access Journals (Sweden)

Behzad-Behbahani A

2008-01-01

Full Text Available This study examined the incidence of human herpes virus-6 (HHV-6 and human cytomegalovirus (HCMV infections that are potentially transmitted to haematopoietic stem cells (HSC transplant recipients via bone marrow (BM or umbilical cord blood (UCB. Bone marrow progenitor cells were collected from 30 allogenic BM donors. UCB HSC were collected from 34 subjects. The extracted DNA was then processed using nested polymerase chain reaction (nPCR technique. HCMV and HHV-6 serological status were determined by enzyme immunoassay (EIA. Nested PCR identified HCMV in 22 (73% of 30 samples of BM progenitor cells but in only eight (23.5% of 34 samples of UBC HSC ( P = 0.001. HHV-6 DNA was detected in 11 (36.6% of 30 BM progenitor cells and in only one (2.9% of 34 UBC cells ( P = 0.002. Both HHV-6 and HCMV infections were determined in nine (26.5% of 34 bone marrow samples. The results indicate that, the risk of HCMV and HHV-6 via BM progenitor cells is higher than transmission by UCB cells ( P= 0.04.

File list: Oth.Bld.05.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Bld.05.AllAg.Peripheral_blood_stem_cells hg19 TFs and others Blood Peripheral b...lood stem cells SRX1036365 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.05.AllAg.Peripheral_blood_stem_cells.bed ...

File list: DNS.Bld.20.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Bld.20.AllAg.Peripheral_blood_stem_cells hg19 DNase-seq Blood Peripheral blood ...stem cells SRX838173,SRX838174 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Bld.20.AllAg.Peripheral_blood_stem_cells.bed ...

File list: DNS.Bld.10.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Bld.10.AllAg.Peripheral_blood_stem_cells hg19 DNase-seq Blood Peripheral blood ...stem cells SRX838173,SRX838174 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Bld.10.AllAg.Peripheral_blood_stem_cells.bed ...

File list: Oth.Bld.10.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Bld.10.AllAg.Peripheral_blood_stem_cells hg19 TFs and others Blood Peripheral b...lood stem cells SRX1036365 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.10.AllAg.Peripheral_blood_stem_cells.bed ...

File list: Oth.Bld.50.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Bld.50.AllAg.Peripheral_blood_stem_cells hg19 TFs and others Blood Peripheral b...lood stem cells SRX1036365 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.50.AllAg.Peripheral_blood_stem_cells.bed ...

File list: DNS.Bld.50.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Bld.50.AllAg.Peripheral_blood_stem_cells hg19 DNase-seq Blood Peripheral blood ...stem cells SRX838174,SRX838173 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Bld.50.AllAg.Peripheral_blood_stem_cells.bed ...

File list: Oth.Bld.20.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Bld.20.AllAg.Peripheral_blood_stem_cells hg19 TFs and others Blood Peripheral b...lood stem cells SRX1036365 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.20.AllAg.Peripheral_blood_stem_cells.bed ...

File list: DNS.Bld.05.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Bld.05.AllAg.Peripheral_blood_stem_cells hg19 DNase-seq Blood Peripheral blood ...stem cells SRX838173,SRX838174 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Bld.05.AllAg.Peripheral_blood_stem_cells.bed ...

Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger.

Science.gov (United States)

Wang, Gang G; Song, Jikui; Wang, Zhanxin; Dormann, Holger L; Casadio, Fabio; Li, Haitao; Luo, Jun-Li; Patel, Dinshaw J; Allis, C David

2009-06-11

Histone H3 lysine 4 methylation (H3K4me) has been proposed as a critical component in regulating gene expression, epigenetic states, and cellular identities1. The biological meaning of H3K4me is interpreted by conserved modules including plant homeodomain (PHD) fingers that recognize varied H3K4me states. The dysregulation of PHD fingers has been implicated in several human diseases, including cancers and immune or neurological disorders. Here we report that fusing an H3K4-trimethylation (H3K4me3)-binding PHD finger, such as the carboxy-terminal PHD finger of PHF23 or JARID1A (also known as KDM5A or RBBP2), to a common fusion partner nucleoporin-98 (NUP98) as identified in human leukaemias, generated potent oncoproteins that arrested haematopoietic differentiation and induced acute myeloid leukaemia in murine models. In these processes, a PHD finger that specifically recognizes H3K4me3/2 marks was essential for leukaemogenesis. Mutations in PHD fingers that abrogated H3K4me3 binding also abolished leukaemic transformation. NUP98-PHD fusion prevented the differentiation-associated removal of H3K4me3 at many loci encoding lineage-specific transcription factors (Hox(s), Gata3, Meis1, Eya1 and Pbx1), and enforced their active gene transcription in murine haematopoietic stem/progenitor cells. Mechanistically, NUP98-PHD fusions act as 'chromatin boundary factors', dominating over polycomb-mediated gene silencing to 'lock' developmentally critical loci into an active chromatin state (H3K4me3 with induced histone acetylation), a state that defined leukaemia stem cells. Collectively, our studies represent, to our knowledge, the first report that deregulation of the PHD finger, an 'effector' of specific histone modification, perturbs the epigenetic dynamics on developmentally critical loci, catastrophizes cellular fate decision-making, and even causes oncogenesis during mammalian development.

File list: His.Bld.05.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Bld.05.AllAg.Peripheral_blood_stem_cells hg19 Histone Blood Peripheral blood st...em cells SRX879221,SRX879209,SRX879208,SRX879210 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.05.AllAg.Peripheral_blood_stem_cells.bed ...

File list: His.Bld.20.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Bld.20.AllAg.Peripheral_blood_stem_cells hg19 Histone Blood Peripheral blood st...em cells SRX879208,SRX879221,SRX879210,SRX879209 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.20.AllAg.Peripheral_blood_stem_cells.bed ...

File list: His.Bld.50.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Bld.50.AllAg.Peripheral_blood_stem_cells hg19 Histone Blood Peripheral blood st...em cells SRX879208,SRX879221,SRX879210,SRX879209 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.50.AllAg.Peripheral_blood_stem_cells.bed ...

File list: His.Bld.10.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Bld.10.AllAg.Peripheral_blood_stem_cells hg19 Histone Blood Peripheral blood st...em cells SRX879208,SRX879221,SRX879210,SRX879209 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.10.AllAg.Peripheral_blood_stem_cells.bed ...

SEVERE (GRADE III-IV ACUTE GRAFT VERSUS HOST DISEASE AFTER ALLOGENEIC HAEMATOPOIETIC STEM CELL TRANSPLANTATION

Directory of Open Access Journals (Sweden)

Irena Preložnik-Zupan

2002-09-01

Full Text Available Background. Beside greater susceptibility to infections, acute graft host disease is a consequence of the activation of donor T-cells against host antigens. Most common target organs are skin, liver and intestinal mucosis.Methods. In the 6-year period between January 1995 and December 2000, 49 patients were treated with allogeneic haematopoietic stem cell transplantation (allo-HSCT in Transplant unit, Department of Hematology, Clinical Centre Ljubljana. The standard GVHD prophylaxis regimen consisted of cyclosporine and short-course methotrexate. Severe, grade III-IV aGVHD with skin and/or gastrointestinal and/or liver involvement appeared in 16 (32% of the 49 patients.Results. Among the 16 patients with severe aGVHD, 14 had liver involvement, ten gastrointestinal and eight skin involvement. One patient had skin involvement only, the rest of them had combined involvement of two or three organ systems. Routine first-line treatment for aGVHD, given to all 16 pts with severe forms of the disease, was methylprednisolone (MP 2mg/ kg. Six patients with predominant skin involvement responded to MP. Other ten patients with mainly liver and gastrointestinal involvement needed second or even third line aGVHD treatment. These were anti-thymocyte globulin (ATG and/or monoclonal antibodies (OKT3 and/or mycophenolate mofetil (MMF and/or FK506 (tacrolimus. Seven patients died of advanced aGVHD and treatment related infection.Conclusions. Based on our experiences, we conclude that in critically ill patients with severe aGVHD, neutropenia and high risk for opportunistic infection, each day of ineffective MP therapy may have fatal consequences. Simultaneous institution of a combination of corticosteroids and a second-line drug might prove more appropriate for patients with a severe form of aGVHD.

Haematopoietic stem cell transplantation for Diamond Blackfan anaemia: a report from the Italian Association of Paediatric Haematology and Oncology Registry.

Science.gov (United States)

Fagioli, Franca; Quarello, Paola; Zecca, Marco; Lanino, Edoardo; Corti, Paola; Favre, Claudio; Ripaldi, Mimmo; Ramenghi, Ugo; Locatelli, Franco; Prete, Arcangelo

2014-06-01

Allogeneic haematopoietic stem cell transplantation (HSCT) is the only curative option for patients with Diamond Blackfan anaemia (DBA). We report the transplantation outcome of 30 Italian DBA patients referred to the Italian Association of Paediatric Haematology and Oncology Registry between 1990 and 2012. This is one of the largest national registry cohorts of transplanted DBA patients. Most patients (83%) were allografted after 2000. A matched sibling donor was employed in 16 patients (53%), the remaining 14 patients (47%) were transplanted from matched unrelated donors. Twenty-eight of the 30 patients engrafted. One patient died at day +6 due to veno-occlusive disease without achieving neutrophil recovery and another patient remained transfusion-dependent despite the presence of a full donor chimerism. The 5-year overall survival and transplant-related mortality was 74·4% and 25·6%, respectively. Patients younger than 10 years as well as those transplanted after 2000 showed a significantly higher overall survival and a significantly lower risk of transplant-related mortality. No difference between donor type was observed. Our data suggest that allogeneic HSCT from a related or unrelated donor was a reasonable alternative to transfusion therapy in young and well chelated DBA patients. © 2014 John Wiley & Sons Ltd.

Genetic and serological typing of European infectious haematopoietic necrosis virus (IHNV) isolates

DEFF Research Database (Denmark)

Johansson, Tove; Einer-Jensen, Katja; Batts, William

2009-01-01

Infectious haematopoietic necrosis virus (IHNV) causes the lethal disease infectious haematopoietic necrosis (IHN) in juvenile salmon and trout. The nucleocapsid (N) protein gene and partial glycoprotein (G) gene (nucleotides 457 to 1061) of the European isolates IT-217A, FR-32/87, DE-DF 13/98 11...

Allogeneic Peripheral Blood Stem Cell Harvest

Indian Academy of Sciences (India)

First page Back Continue Last page Overview Graphics. Allogeneic Peripheral Blood Stem Cell Harvest. Mobilization protocol. G-CSF 10 mcg/Kg / day for 5 days. Pheresis. Cobe Spectra; Haemonetics mcs+. Enumeration. CD34 counts; Cfu-GM assays.

The partition coefficients of 133Xe between blood and bone

International Nuclear Information System (INIS)

Lahtinen, T.; Karjalainen, P.; Vaeaenaenen, A.; Lahtinen, R.; Alhava, E.M.

1981-01-01

The partition coefficients of 133 Xe between blood and haematopoietic bone marrow and homogenised bone have been determined in vitro. The partition coefficient lambda 1 corresponding to haematopoietic marrow was 0.95 ml g -1 while that corresponding to homogenised bone was a function of age, lambda 2 = 3.11 + 0.049(age)(ml g -1 ). These data can be used for calculating regional blood flow in healthy human femur by means of a simple 133 Xe radionuclide method. (author)

File list: NoD.Bld.05.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Bld.05.AllAg.Peripheral_blood_stem_cells hg19 No description Blood Peripheral b...lood stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Bld.05.AllAg.Peripheral_blood_stem_cells.bed ...

File list: InP.Bld.10.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Bld.10.AllAg.Peripheral_blood_stem_cells hg19 Input control Blood Peripheral bl...ood stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Bld.10.AllAg.Peripheral_blood_stem_cells.bed ...

File list: NoD.Bld.20.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Bld.20.AllAg.Peripheral_blood_stem_cells hg19 No description Blood Peripheral b...lood stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Bld.20.AllAg.Peripheral_blood_stem_cells.bed ...

File list: NoD.Bld.10.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Bld.10.AllAg.Peripheral_blood_stem_cells hg19 No description Blood Peripheral b...lood stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Bld.10.AllAg.Peripheral_blood_stem_cells.bed ...

File list: NoD.Bld.50.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Bld.50.AllAg.Peripheral_blood_stem_cells hg19 No description Blood Peripheral b...lood stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Bld.50.AllAg.Peripheral_blood_stem_cells.bed ...

File list: InP.Bld.05.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Bld.05.AllAg.Peripheral_blood_stem_cells hg19 Input control Blood Peripheral bl...ood stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Bld.05.AllAg.Peripheral_blood_stem_cells.bed ...

File list: InP.Bld.50.AllAg.Peripheral_blood_stem_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Bld.50.AllAg.Peripheral_blood_stem_cells hg19 Input control Blood Peripheral bl...ood stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Bld.50.AllAg.Peripheral_blood_stem_cells.bed ...

Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs

OpenAIRE

Phinney, Donald G.; Di Giuseppe, Michelangelo; Njah, Joel; Sala, Ernest; Shiva, Sruti; St Croix, Claudette M.; Stolz, Donna B.; Watkins, Simon C.; Di, Y. Peter; Leikauf, George D.; Kolls, Jay; Riches, David W. H.; Deiuliis, Giuseppe; Kaminski, Naftali; Boregowda, Siddaraju V.

2015-01-01

Mesenchymal stem cells (MSCs) and macrophages are fundamental components of the stem cell niche and function coordinately to regulate haematopoietic stem cell self-renewal and mobilization. Recent studies indicate that mitophagy and healthy mitochondrial function are critical to the survival of stem cells, but how these processes are regulated in MSCs is unknown. Here we show that MSCs manage intracellular oxidative stress by targeting depolarized mitochondria to the plasma membrane via arres...

Mesenchymal stem cells attenuate blood-brain barrier leakage after cerebral ischemia in mice.

Science.gov (United States)

Cheng, Zhuo; Wang, Liping; Qu, Meijie; Liang, Huaibin; Li, Wanlu; Li, Yongfang; Deng, Lidong; Zhang, Zhijun; Yang, Guo-Yuan

2018-05-03

Ischemic stroke induced matrixmetallo-proteinase-9 (MMP-9) upregulation, which increased blood-brain barrier permeability. Studies demonstrated that mesenchymal stem cell therapy protected blood-brain barrier disruption from several cerebrovascular diseases. However, the underlying mechanism was largely unknown. We therefore hypothesized that mesenchymal stem cells reduced blood-brain barrier destruction by inhibiting matrixmetallo-proteinase-9 and it was related to intercellular adhesion molecule-1 (ICAM-1). Adult ICR male mice (n = 118) underwent 90-min middle cerebral artery occlusion and received 2 × 10 5 mesenchymal stem cell transplantation. Neurobehavioral outcome, infarct volume, and blood-brain barrier permeability were measured after ischemia. The relationship between myeloperoxidase (MPO) activity and ICAM-1 release was further determined. We found that intracranial injection of mesenchymal stem cells reduced infarct volume and improved behavioral function in experimental stroke models (p mesenchymal stem cell-treated mice compared to the control group following ischemia (p cells and myeloperoxidase activity were decreased in mesenchymal stem cell-treated mice (p mesenchymal stem cell therapy attenuated blood-brain barrier disruption in mice after ischemia. Mesenchymal stem cells attenuated the upward trend of MMP-9 and potentially via downregulating ICAM-1 in endothelial cells. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway may influence MMP-9 expression of neutrophils and resident cells, and ICAM-1 acted as a key factor in the paracrine actions of mesenchymal stem cell.

76 FR 11491 - Advisory Council on Blood Stem Cell Transplantation; Request for Nominations for Voting Members

Science.gov (United States)

2011-03-02

... transplantation, Program priorities, research priorities, and the scope and design of the Stem Cell Therapeutic... Council on Blood Stem Cell Transplantation; Request for Nominations for Voting Members AGENCY: Health... on Blood Stem Cell Transplantation. The Advisory Council on Blood Stem Cell Transplantation was...

The influence of prenatal exposure to trans-fatty acids for development of childhood haematopoietic neoplasms (EnTrance): a natural societal experiment and a case-control study.

Science.gov (United States)

Specht, Ina Olmer; Huybrechts, Inge; Frederiksen, Peder; Steliarova-Foucher, Eva; Chajes, Veronique; Heitmann, Berit Lilienthal

2018-01-24

Little is known about the causes of childhood cancer, partly as not many children develop cancer, although childhood cancer is a leading cause of death by disease in the young. The young age of the children suggests that risk factors for childhood cancer may be present during pregnancy. Previous studies have shown that exposure to trans-fat, a type of unsaturated fat common in industrially produced foods (iTFA), has adverse health effects in adults, including the risk of developing cancer. Haematopoietic neoplasms are the most common cancer types among European children under the age of 15 years. This study will bring new knowledge as to whether trans-fat and other fatty acids may also increase the risk of developing haematopoietic neoplasms during childhood. We will investigate if the Danish iTFA legislation ban, which radically reduced the use of iTFA in foodstuffs, influenced the risk of childhood haematopoietic neoplasms in children born either before or after the change in legislation, adjusting for relevant secular trends. Further, in a case-control study, we will examine if levels of fatty acids in dried blood spots from newborns can predict the risk of developing childhood haematopoietic neoplasms. Permission from the Danish Data Protection Agency and the Ethical Committee has been granted. The results from this study will provide important information about fatty acids in the mother's diet as a contributor to development of haematopoietic neoplasms during childhood, which may result in relevant preventive action. Not relevant.

Cord blood banking - bio-objects on the borderlands between community and immunity.

Science.gov (United States)

Brown, Nik; Williams, Rosalind

2015-01-01

Umbilical cord blood (UCB) has become the focus of intense efforts to collect, screen and bank haematopoietic stem cells (HSCs) in hundreds of repositories around the world. UCB banking has developed through a broad spectrum of overlapping banking practices, sectors and institutional forms. Superficially at least, these sectors have been widely distinguished in bioethical and policy literature between notions of the 'public' and the 'private', the commons and the market respectively. Our purpose in this paper is to reflect more critically on these distinctions and to articulate the complex practical and hybrid nature of cord blood as a 'bio-object' that straddles binary conceptions of the blood economies. The paper draws upon Roberto Esposito's reflections on biopolitics and his attempt to transcend the dualistic polarisations of immunity and community, or the private and the public. We suggest that his thoughts on immunitary hospitality resonate with many of the actual features and realpolitik of a necessarily internationalised and globally distributed UCB 'immunitary regime'.

Earlier defibrotide initiation post-diagnosis of veno-occlusive disease/sinusoidal obstruction syndrome improves Day +100 survival following haematopoietic stem cell transplantation.

Science.gov (United States)

Richardson, Paul G; Smith, Angela R; Triplett, Brandon M; Kernan, Nancy A; Grupp, Stephan A; Antin, Joseph H; Lehmann, Leslie; Miloslavsky, Maja; Hume, Robin; Hannah, Alison L; Nejadnik, Bijan; Soiffer, Robert J

2017-07-01

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a progressive, potentially fatal complication of conditioning for haematopoietic stem cell transplant (HSCT). The VOD/SOS pathophysiological cascade involves endothelial-cell activation and damage, and a prothrombotic-hypofibrinolytic state. Severe VOD/SOS (typically characterized by multi-organ dysfunction) may be associated with >80% mortality. Defibrotide is approved for treating severe hepatic VOD/SOS post-HSCT in the European Union, and for hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the United States. Previously, defibrotide (25 mg/kg/day in 4 divided doses for a recommended ≥21 days) was available through an expanded-access treatment protocol for patients with VOD/SOS. Data from this study were examined post-hoc to determine if the timing of defibrotide initiation post-VOD/SOS diagnosis affected Day +100 survival post-HSCT. Among 573 patients, defibrotide was started on the day of VOD/SOS diagnosis in approximately 30%, and within 7 days in >90%. The relationship between Day +100 survival and treatment initiation before/after specific days post-diagnosis showed superior survival when treatment was initiated closer to VOD/SOS diagnosis with a statistically significant trend over time for better outcomes with earlier treatment initiation (P defibrotide should not be delayed after diagnosis of VOD/SOS. © 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Identification of resident and inflammatory bone marrow derived cells in the sclera by bone marrow and haematopoietic stem cell transplantation.

Science.gov (United States)

Hisatomi, Toshio; Sonoda, Koh-hei; Ishikawa, Fumihiko; Qiao, Hong; Nakazawa, Takahiro; Fukata, Mitsuhiro; Nakamura, Toru; Noda, Kousuke; Miyahara, Shinsuke; Harada, Mine; Kinoshita, Shigeru; Hafezi-Moghadam, Ali; Ishibashi, Tatsuro; Miller, Joan W

2007-04-01

To characterise bone marrow derived cells in the sclera under normal and inflammatory conditions, we examined their differentiation after transplantation from two different sources, bone marrow and haematopoietic stem cells (HSC). Bone marrow and HSC from green fluorescent protein (GFP) transgenic mice were transplanted into irradiated wild-type mice. At 1 month after transplantation, mice were sacrificed and their sclera examined by histology, immunohistochemistry (CD11b, CD11c, CD45), and transmission and scanning electron microscopy. To investigate bone marrow derived cell recruitment under inflammatory conditions, experimental autoimmune uveitis (EAU) was induced in transplanted mice. GFP positive cells were distributed in the entire sclera and comprised 22.4 (2.8)% (bone marrow) and 28.4 (10.9)% (HSC) of the total cells in the limbal zone and 18.1 (6.7)% (bone marrow) and 26.3 (3.4)% (HSC) in the peripapillary zone. Immunohistochemistry showed that GFP (+) CD11c (+), GFP (+) CD11b (+) cells migrated in the sclera after bone marrow and HSC transplantation. Transmission and scanning electron microscopy revealed antigen presenting cells among the scleral fibroblasts. In EAU mice, vast infiltration of GFP (+) cells developed into the sclera. We have provided direct and novel evidence for the migration of bone marrow and HSC cells into the sclera differentiating into macrophages and dendritic cells. Vast infiltration of bone marrow and HSC cells was found to be part of the inflammatory process in EAU.

Extracorporeal irradiation of dog blood: the effects of a radiostrontium irradiator on blood stem cells (CFU-C)

Energy Technology Data Exchange (ETDEWEB)

Szemere, P.; Fliedner, T.M.; Nothdurft, W.; Breitig, D.

1982-07-01

The radiation sensitivity of dog blood stem cells was measured in vitro and in an extracorporeal circulation passing through a radiation field. It was established that the calculated D/sub 0/ was as low as 0.45 Gy. Investigating the cell killing rate in our equipment (Buchler type /sup 90/Sr device for extracorporeal irradiation), we found an overkill situation; the dose delivered was in excess of that which would be required for the total eradication of all stem cells in the peripheral blood passing through the radiation field. Various other types of devices used for extracorporeal irradiation of blood are also reviewed.

Biological characteristics of human menstrual blood-derived endometrial stem cells.

Science.gov (United States)

Liu, Yanli; Niu, Rongcheng; Yang, Fen; Yan, Yan; Liang, Shengying; Sun, Yuliang; Shen, Ping; Lin, Juntang

2018-03-01

Successful isolation of human endometrial stem cells from menstrual blood, namely menstrual blood-derived endometrial stem cells (MenSCs), has provided enticing alternative seed cells for stem cell-based therapy. MenSCs are enriched in the self-regenerative tissue, endometrium, which shed along the periodic menstrual blood and thus their acquisition involves no physical invasiveness. However, the impact of the storage duration of menstrual blood prior to stem cell isolation, the age of the donor, the number of passages on the self-renewing of MenSCs, the paracrine production of biological factors in MenSCs and expression of adhesion molecules on MenSCs remain elusive. In this study, we confirmed that MenSCs reside in shedding endometrium, and documented that up to 3 days of storage at 4°C has little impact on MenSCs, while the age of the donor and the number of passages are negatively associated with proliferation capacity of MenSCs. Moreover, we found that MenSCs were actually immune-privileged and projected no risk of tumour formation. Also, we documented a lung- and liver-dominated, spleen- and kidney-involved organic distribution profile of MenSC 3 days after intravenous transfer into mice. At last, we suggested that MenSCs may have potentially therapeutic effects on diseases through paracrine effect and immunomodulation. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Pregnant women's knowledge and attitudes about stem cells and cord blood banking.

Science.gov (United States)

Dinç, H; Sahin, N H

2009-06-01

This study was to determine pregnant women's knowledge and attitudes towards stem cells and cord blood banking in Istanbul, Turkey. Stem cell research is one of the most important and, at the same time, the most controversial topics of science and technology today. Nurses need to understand stem cell research so they can enter the debate on this issue. They can become important sources of information in order to help parents understand the issues. This exploratory descriptive study was conducted in two antenatal outpatient clinics in Istanbul. The sample consisted of 334 pregnant women during routine prenatal visits. Data were collected in interviews by using an interview form developed by the researchers according to the literature. The form included demographic characteristics of participants and 20 questions about stem cells, storing cord blood and banking and 10 independent attitude statements. The majority of the participants had a lack of knowledge about stem cells and cord blood banking and wanted more information. Before pregnancy, they received some information through the media (newspaper, Internet, television, etc.), but unintentionally. It was determined that they wanted information before becoming pregnant, more from their obstetrician but also from nurses and midwives. The majority also wanted to store their infants' cord blood and stated that they would be more likely to choose a public cord blood bank. Those giving ante- and perinatal care need to offer accurate and scientific counselling services on this subject to parents who need to be informed.

Four decades of stem cell transplantation for Fanconi anaemia in the Netherlands

NARCIS (Netherlands)

Smetsers, Stephanie E.; Smiers, Frans J.; Bresters, Dorine; Sonnevelt, Martine C.; Bierings, Marc B.

2016-01-01

This article presents the haematopoietic stem cell transplantation (SCT) results of the complete Dutch Fanconi anaemia (FA) patient cohort. Sixty-eight Dutch FA patients have been transplanted since 1972. In total, 63 (93%) patients engrafted, 54 after first SCT and 9 after second SCT. Fludarabine

Neuroprotective properties of a novel, non-haematopoietic agonist of the erythropoietin receptor

DEFF Research Database (Denmark)

Pankratova, Stanislava; Kiryushko, Dar'Ya; Sonn, Katrin

2010-01-01

they are involved in tissue protection. However, the use of erythropoietin as a neuroprotective agent may be hampered by its erythropoietic activity. Therefore, developing non-haematopoietic erythropoietin mimetics is important. Based on the crystal structure of the complex of erythropoietin and its receptor, we...... attenuated seizures, decreased mortality and reduced neurodegeneration in an in vivo model of kainic acid-induced neurotoxicity. In contrast to erythropoietin, Epotris did not stimulate erythropoiesis upon chronic administration. Thus, Epotris is a novel neuroprotective non-haematopoietic erythropoietin...

Concise review: stem cell-derived erythrocytes as upcoming players in blood transfusion.

Science.gov (United States)

Zeuner, Ann; Martelli, Fabrizio; Vaglio, Stefania; Federici, Giulia; Whitsett, Carolyn; Migliaccio, Anna Rita

2012-08-01

Blood transfusions have become indispensable to treat the anemia associated with a variety of medical conditions ranging from genetic disorders and cancer to extensive surgical procedures. In developed countries, the blood supply is generally adequate. However, the projected decline in blood donor availability due to population ageing and the difficulty in finding rare blood types for alloimmunized patients indicate a need for alternative red blood cell (RBC) transfusion products. Increasing knowledge of processes that govern erythropoiesis has been translated into efficient procedures to produce RBC ex vivo using primary hematopoietic stem cells, embryonic stem cells, or induced pluripotent stem cells. Although in vitro-generated RBCs have recently entered clinical evaluation, several issues related to ex vivo RBC production are still under intense scrutiny: among those are the identification of stem cell sources more suitable for ex vivo RBC generation, the translation of RBC culture methods into clinical grade production processes, and the development of protocols to achieve maximal RBC quality, quantity, and maturation. Data on size, hemoglobin, and blood group antigen expression and phosphoproteomic profiling obtained on erythroid cells expanded ex vivo from a limited number of donors are presented as examples of the type of measurements that should be performed as part of the quality control to assess the suitability of these cells for transfusion. New technologies for ex vivo erythroid cell generation will hopefully provide alternative transfusion products to meet present and future clinical requirements. Copyright © 2012 AlphaMed Press.

78 FR 47714 - Advisory Council on Blood Stem Cell Transplantation; Notice of Meeting

Science.gov (United States)

2013-08-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration Advisory Council on Blood Stem Cell Transplantation; Notice of Meeting In accordance with section 10(a)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), notice is hereby given of the following meeting: Name: Advisory Council on Blood Stem Cell...

78 FR 23571 - Advisory Council on Blood Stem Cell Transplantation; Notice of Meeting

Science.gov (United States)

2013-04-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration Advisory Council on Blood Stem Cell Transplantation; Notice of Meeting In accordance with section 10(a)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), notice is hereby given of the following meeting: Name: Advisory Council on Blood Stem Cell...

75 FR 14175 - Advisory Council on Blood Stem Cell Transplantation; Notice of Meeting

Science.gov (United States)

2010-03-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration Advisory Council on Blood Stem Cell Transplantation; Notice of Meeting In accordance with section 10(a)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), notice is hereby given of the following meeting: Name: Advisory Council on Blood Stem Cell...

77 FR 22791 - Advisory Council on Blood Stem Cell Transplantation; Notice of Meeting

Science.gov (United States)

2012-04-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration Advisory Council on Blood Stem Cell Transplantation; Notice of Meeting In accordance with section 10(a)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), notice is hereby given of the following meeting: Name: Advisory Council on Blood Stem Cell...

76 FR 62814 - Advisory Council on Blood Stem Cell Transplantation; Notice of Meeting

Science.gov (United States)

2011-10-11

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration Advisory Council on Blood Stem Cell Transplantation; Notice of Meeting In accordance with section 10(a)(2) of the Federal Advisory Committee Act (Public Law 92-463), notice is hereby given of the following meeting: Name: Advisory Council on Blood Stem Cell...

Radiation response of haematopoietic cell lines of human origin

International Nuclear Information System (INIS)

Lehnert, S.; Rybka, W.B.; Suissa, S.; Giambattisto, D.

1986-01-01

Six human haematopoietic cell lines, five of leukaemic origin, including cells with myeloid, lymphoid and undifferentiated phenotype have been studied with respect to radiation response. The intrinsic radio-sensitivity of the cells varied widely, the D 0 s ranging from 0.53 to 1.39 Gy. Five of the cell lines showed some capacity to accumulate sublethal damage; in three of these, enhanced survival was demonstrated in split-dose experiments. One cell line (HL-60) was anomalous in that although little accumulation of sublethal damage was demonstrable, survival was enhanced by fractionation of the dose. Five of the six cell lines studied were of leukaemic origin. The results support the belief that, in contrast to the almost constant radiosensitivity of normal haematopoietic cell progenitors, leukaemic cell progenitors may show a wide range of radiosensitivities. (author)

Umbilical Cord Blood Stem Cells. Who has the right word?

Directory of Open Access Journals (Sweden)

Gisela Laporta

2014-12-01

Full Text Available In this article we analyze bioethical and legal aspects related to the cryopreservation of cord blood stem cells in Argentina. To unify definitions, the concept and variety of stem cells, together with the understanding of the means to obtain and store umbilical cord blood stem cells, are provided.  Options that arise in our country, mainly analyzing the conceptual differences underlying legal body and parts by public and private biobanks, are described. Additionally, the current Argentinean legislation and circumstances arising from a resolution which INCUCAI sought to regulate private biobanks, is analyzed. This analysis leads to thoughts on the way conflicts are solved when the health and life of people are judicialized. In this particular case, the appearance of a complex new topic which gives rise to new social and healthcare scenarios, must be further understood.

Lethal giant larvae 1 tumour suppressor activity is not conserved in models of mammalian T and B cell leukaemia.

Directory of Open Access Journals (Sweden)

Edwin D Hawkins

Full Text Available In epithelial and stem cells, lethal giant larvae (Lgl is a potent tumour suppressor, a regulator of Notch signalling, and a mediator of cell fate via asymmetric cell division. Recent evidence suggests that the function of Lgl is conserved in mammalian haematopoietic stem cells and implies a contribution to haematological malignancies. To date, direct measurement of the effect of Lgl expression on malignancies of the haematopoietic lineage has not been tested. In Lgl1⁻/⁻ mice, we analysed the development of haematopoietic malignancies either alone, or in the presence of common oncogenic lesions. We show that in the absence of Lgl1, production of mature white blood cell lineages and long-term survival of mice are not affected. Additionally, loss of Lgl1 does not alter leukaemia driven by constitutive Notch, c-Myc or Jak2 signalling. These results suggest that the role of Lgl1 in the haematopoietic lineage might be restricted to specific co-operating mutations and a limited number of cellular contexts.

Lethal Giant Larvae 1 Tumour Suppressor Activity Is Not Conserved in Models of Mammalian T and B Cell Leukaemia

Science.gov (United States)

Hawkins, Edwin D.; Oliaro, Jane; Ramsbottom, Kelly M.; Ting, Stephen B.; Sacirbegovic, Faruk; Harvey, Michael; Kinwell, Tanja; Ghysdael, Jacques; Johnstone, Ricky W.; Humbert, Patrick O.; Russell, Sarah M.

2014-01-01

In epithelial and stem cells, lethal giant larvae (Lgl) is a potent tumour suppressor, a regulator of Notch signalling, and a mediator of cell fate via asymmetric cell division. Recent evidence suggests that the function of Lgl is conserved in mammalian haematopoietic stem cells and implies a contribution to haematological malignancies. To date, direct measurement of the effect of Lgl expression on malignancies of the haematopoietic lineage has not been tested. In Lgl1−/− mice, we analysed the development of haematopoietic malignancies either alone, or in the presence of common oncogenic lesions. We show that in the absence of Lgl1, production of mature white blood cell lineages and long-term survival of mice are not affected. Additionally, loss of Lgl1 does not alter leukaemia driven by constitutive Notch, c-Myc or Jak2 signalling. These results suggest that the role of Lgl1 in the haematopoietic lineage might be restricted to specific co-operating mutations and a limited number of cellular contexts. PMID:24475281

78 FR 54257 - Advisory Council on Blood Stem Cell Transplantation; Request for Nominations for Voting Members

Science.gov (United States)

2013-09-03

...; Program priorities; research priorities; and the scope and design of the Stem Cell Therapeutic Outcomes... Council on Blood Stem Cell Transplantation; Request for Nominations for Voting Members AGENCY: Health... on the Advisory Council on Blood Stem Cell Transplantation (ACBSCT). The ACBSCT was established...

Imaging of hepatic toxicity of systemic therapy in a tertiary cancer centre: chemotherapy, haematopoietic stem cell transplantation, molecular targeted therapies, and immune checkpoint inhibitors.

Science.gov (United States)

Alessandrino, F; Tirumani, S H; Krajewski, K M; Shinagare, A B; Jagannathan, J P; Ramaiya, N H; Di Salvo, D N

2017-07-01

The purpose of this review is to familiarise radiologists with the spectrum of hepatic toxicity seen in the oncology setting, in view of the different systemic therapies used in cancer patients. Drug-induced liver injury can manifest in various forms, and anti-neoplastic agents are associated with different types of hepatotoxicity. Although chemotherapy-induced liver injury can present as hepatitis, steatosis, sinusoidal obstruction syndrome, and chronic parenchymal damages, molecular targeted therapy-associated liver toxicity ranges from mild liver function test elevation to fulminant life-threatening acute liver failure. The recent arrival of immune checkpoint inhibitors in oncology has introduced a new range of immune-related adverse events, with differing mechanisms of liver toxicity and varied imaging presentation of liver injury. High-dose chemotherapy regimens for haematopoietic stem cell transplantation are associated with sinusoidal obstruction syndrome. Management of hepatic toxicity depends on the clinical scenario, the drug in use, and the severity of the findings. In this article, we will (1) present the most common types of oncological drugs associated with hepatic toxicity and associated liver injuries; (2) illustrate imaging findings of hepatic toxicities and the possible differential diagnosis; and (3) provide a guide for management of these conditions. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Transplantation? Peripheral Stem Cell/Bone Marrow/Cord Blood

Directory of Open Access Journals (Sweden)

Itır Sirinoglu Demiriz

2012-01-01

Full Text Available The introduction of peripheral stem cell (PSC and cord blood (CB as an alternative to bone marrow (BM recently has caused important changes on hematopoietic stem cell transplantation (HSCT practice. According to the CIBMTR data, there has been a significant decrease in the use of bone marrow and increase in the use of PSC and CB as the stem cell source for HSCT performed during 1997–2006 period for patients under the age of 20. On the other hand, the stem cell source in 70% of the HSCT procedures performed for patients over the age of 20 was PSC and the second most preferred stem cell source was bone marrow. CB usage is very limited for the adult population. Primary disease, stage, age, time and urgency of transplantation, HLA match between the patient and the donor, stem cell quantity, and the experience of the transplantation center are some of the associated factors for the selection of the appropriate stem cell source. Unfortunately, there is no prospective randomized study aimed to facilitate the selection of the correct source between CB, PSC, and BM. In this paper, we would like to emphasize the data on stem cell selection in light of the current knowledge for patient populations according to their age and primary disease.

Donating umbilical cord blood to a public bank or storing it in a private bank: knowledge and preference of blood donors and of pregnant women.

Science.gov (United States)

Screnci, Maria; Murgi, Emilia; Pirrè, Guglielma; Valente, Elisabetta; Gesuiti, Paola; Corona, Francesca; Girelli, Gabriella

2012-07-01

Umbilical cord blood (UCB) is a source of stem cells for allogeneic haematopoietic transplantation in paediatric and adult patients with haematological malignancies and other indications. Voluntary donation is the basis for the success of unrelated UCB transplantation programmes. In the last few years a growing number of private banks offer their services to expectant parents, to store UCB for future use. The debate concerning UCB donation and private preservation has been ongoing for several years. The aims of this single centre study were to explore knowledge about UCB stem cells and attitudes towards voluntary UCB donation or private UCB preservation among both blood donors and pregnant women. This study was conducted at the "Sapienza" University of Rome. Two types of anonymous questionnaires were prepared: one type was administered to 1,000 blood donors while the other type was distributed to 300 pregnant women. Most blood donors as well as the majority of pregnant women had some general knowledge about UCB (89% and 93%, respectively) and were aware of the possibility of donating it (82% and 95%). However, the level of knowledge regarding current therapeutic use resulted generally low, only 91 (10%) among informed blood donors and 69 (31%) among informed pregnant women gave a correct answer. The survey revealed a preference for voluntary donation both among blood donors (76%) and among pregnant woman (55%). Indeed, a minority of blood donors (6.5%) and of pregnant women (9%) would opt to store UCB for private use. The study raises the following considerations: (i) the large support for UCB donation expressed by blood donors and by pregnant women suggests that UCB preservation does not represent an obstacle to the expansion of UCB donation and to development of unrelated transplantation programmes; (ii) information about UCB donation and preservation should be carefully given by professionals and institutions.

Autologous blood cell therapies from pluripotent stem cells

Science.gov (United States)

Lengerke, Claudia; Daley, George Q.

2010-01-01

Summary The discovery of human embryonic stem cells (hESCs) raised promises for a universal resource for cell based therapies in regenerative medicine. Recently, fast-paced progress has been made towards the generation of pluripotent stem cells (PSCs) amenable for clinical applications, culminating in reprogramming of adult somatic cells to autologous PSCs that can be indefinitely expanded in vitro. However, besides the efficient generation of bona fide, clinically safe PSCs (e.g. without the use of oncoproteins and gene transfer based on viruses inserting randomly into the genome), a major challenge in the field remains how to efficiently differentiate PSCs to specific lineages and how to select for cells that will function normally upon transplantation in adults. In this review, we analyse the in vitro differentiation potential of PSCs to the hematopoietic lineage discussing blood cell types that can be currently obtained, limitations in derivation of adult-type HSCs and prospects for clinical application of PSCs-derived blood cells. PMID:19910091

Real-world costs of autologous and allogeneic stem cell transplantations for haematological diseases: a multicentre study.

NARCIS (Netherlands)

Blommestein, H.M.; Verelst, S.G.; Huijgens, P.C.; Blijlevens, N.M.A.; Cornelissen, J.J.; Uyl-de Groot, C.A.

2012-01-01

Haematopoietic stem cell transplantation (SCT) is an expensive lifesaving procedure, which is increasingly performed in patients with haematological diseases. Developments in the protocol for SCT have resulted in cost estimates that require updating. We aimed to calculate actual costs for SCT and to

Cord Blood Stem Cell Procurement in Minority Donors

National Research Council Canada - National Science Library

Ratanatharathorn, Voravit

2008-01-01

... of building minority CBU inventory. This final annual report is to give the report of the transplantation outcomes of African/American CBU recipients compared with other racial groups. This analysis is limited to those patients who have received an allogeneic cord blood stem cell transplantation at Karmanos Cancer Center.

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...

Harvesting, processing and inventory management of peripheral blood stem cells

Directory of Open Access Journals (Sweden)

Mijovic Aleksandar

2007-01-01

Full Text Available By 2003, 97% autologous transplants and 65% of allogeneic transplants in Europe used mobilised peripheral blood stem cells (PBSC. Soon after their introduction in the early 1990′s, PBSC were associated with faster haemopoietic recovery, fewer transfusions and antibiotic usage, and a shorter hospital stay. Furthermore, ease and convenience of PBSC collection made them more appealing than BM harvests. Improved survival has hitherto been demonstrated in patients with high risk AML and CML. However, the advantages of PBSC come at a price of a higher incidence of extensive chronic GVHD. In order to be present in the blood, stem cells undergo the process of "mobilisation" from their bone marrow habitat. Mobilisation, and its reciprocal process - homing - are regulated by a complex network of molecules on the surface of stem cells and stromal cells, and enzymes and cytokines released from granulocytes and osteoclasts. Knowledge of these mechanisms is beginning to be exploited for clinical purposes. In current practice, stem cell are mobilised by use of chemotherapy in conjunction with haemopoietic growth factors (HGF, or with HGF alone. Granulocyte colony stimulating factor has emerged as the single most important mobilising agent, due to its efficacy and a relative paucity of serious side effects. Over a decade of use in healthy donors has resulted in vast experience of optimal dosing and administration, and safety matters. PBSC harvesting can be performed on a variety of cell separators. Apheresis procedures are nowadays routine, but it is important to be well versed in the possible complications in order to avoid harm to the patient or donor. To ensure efficient collection, harvesting must begin when sufficient stem cells have been mobilised. A rapid, reliable, standardized blood test is essential to decide when to begin harvesting; currently, blood CD34+ cell counting by flow cytometry fulfils these criteria. Blood CD34+ cell counts strongly

[THE USE AND STORAGE OF STEM CELLS AND CORD BLOOD: FRENCH AND ENGLISH LAW COMPARATIVE APPROACH].

Science.gov (United States)

Madanamoothoo, Allane

2015-07-01

Becoming parents is one of the greatest wishes of a lot of couples. When their dreams come true, prior to the birth of the child, parents have to face several points: the choice of the name, place of delivery, breast or bottle feeding, etc. Recently, they have to face the issues of cord blood stem cells. Researchers and cord blood banks are also interested in those cells. In many countries a lot of advertising is made around umbilical cord blood stem cells. In France as in England, the use and preservation of cord blood are regulated by the legislators without necessarily having the same approach. The objective of this paper is to present English and French law approaches' on cord blood stem cells.

Peripheral blood stem cell collection for allogeneic hematopoietic stem cell transplantation: Practical implications after 200 consequent transplants.

Science.gov (United States)

Goren Sahin, Deniz; Arat, Mutlu

2017-12-01

Proper stem cell mobilization is one of the most important steps in hematopoietic stem cell transplantation (HSCT). The aim of this paper is to share our 6 years' experience and provide practical clinical approaches particularly for stem cell mobilization and collection within the series of more than 200 successive allogeneic HSCT at our transplant center. Two hundred and seven consecutive patients who underwent allogeneic peripheral blood stem cell transplantation were included in this study. Age, sex, weight, complete blood counts, CD34 + cell counts, total collected amount of CD34 + cells, CD34 + cells per 10l processed, mobilization failure and adverse events were reviewed. Median age was 40.2±12.9 (21-68) years and 46.4±13.4 (17-67) years for donors and patients, respectively. The number of donors who had undergone adequate CD34 + cell harvesting and completed the procedure on the fourth day was 67 (32.8% of all patients). Only 12 patients required cell apheresis both on day 5 and 6. Apheresis was completed on day 4 and/or day 5 in 94.2% of all our donors. There was no significant association between CD34 + stem cell volume and age, gender and weight values of donors. Mobilization failure was not seen in our series. G-CSF is highly effective in 1/3 of the donors on the 4th day in order to collect enough number of stem cells. We propose that peripheral stem cell collection might start on day 4th of G-CSF treatment for avoiding G-CSF related side effects and complications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of umbilical cord blood stem cells on healing factors for diabetic foot injuries.

Science.gov (United States)

Çil, N; Oğuz, E O; Mete, E; Çetinkaya, A; Mete, G A

2017-01-01

The use of stem or progenitor cells from bone marrow, or peripheral or umbilical cord blood is becoming more common for treatment of diabetic foot problems. These cells promote neovascularization by angiogenic factors and they promote epithelium formation by stimulating cell replication and migration under certain pathological conditions. We investigated the role of CD34 + stem cells from human umbilical cord blood in wound healing using a rat model. Rats were randomly divided into a control group and two groups with diabetes induced by a single dose of 55 mg/kg intraperitoneal streptozocin. Scarred areas 5 mm in diameter were created on the feet of all rats. The diabetic rats constituted the diabetes control group and a diabetes + stem cell group with local injection into the wound site of 0.5 × 106 CD34 + stem cells from human umbilical cord blood. The newly formed skin in the foot wounds following CD34 + stem cell treatment showed significantly improvement by immunohistochemistry and TUNEL staining, and were closer to the wound healing of the control group than the untreated diabetic animals. The increase in FGF expression that accompanied the local injection of CD34 + stem cells indicates that FGF stimulation helped prevent apoptosis. Our findings suggest a promising new treatment approach to diabetic wound healing.

Effectiveness of structured teaching programme on knowledge regarding menstrual blood stem cells banking among nursing students

OpenAIRE

Neelam Hans; Sandeep Kaur

2016-01-01

Background: Menstrual blood banking enables women to store their menstrual blood under required conditions and preserve it for future. Stem cells present in the menstrual blood have the remarkable potential to develop into many different cell types in the body. The objective of the study was to assess the effectiveness of structured teaching programme on knowledge regarding menstrual blood stem cells banking among nursing students studying in selected nursing college of Amritsar, Punjab. M...

Stem cells: progressions and applications in clinical medicine

Directory of Open Access Journals (Sweden)

Ali Hosseini Bereshneh

2016-05-01

Full Text Available Stem cells are undifferentiated and multi pluripotent cells which can differentiate into a variety of mature cells and tissues such as nervous tissue, muscle tissue, epithelial tissue, skeletal tissue and etc. Stem cells from all different source have three unique features: 1 Proliferative capability: Stem cells are capable of self dividing and self renewing for long periods or more than six months at least that called immortalization. 2 Undifferentiated nature: It’s considered as one of the essential characteristics of stem cell, so it doesn't have any tissue-specific construction. 3 Differentiation to the different cells from all organs: This ability can Induced by tissue specific transcription factors. Because of that, they are so important in prevention and treatment of human disease. Depending on the sources from which they derive, they have different types which can be used to produce special cells and tissues. The most significant types of stem cells are; embryonic stem cells (ESCs which are derived from embryos, adult stem cells (ASCs which are derived from differentiated cells in a specific tissue, induced pluripotent stem cells (iPSs which are produced from adult differentiated cells that have been genetically reprogrammed to act resemble to an embryonic stem cell and cord blood stem cells which contains haematopoietic stem cells and derived from the umbilical cord after gestation. By providing a medium containing of special growth factor, it is possible to orientated stem cell differentiation pathway and gained certain cells from them. The important uses of stem cells includes damaged heart tissue cells improvements and bone tissue repairing, cancer treatment, damaged neurological and spinal tissue repairing, improving burns and injuries and the treatment of diabetes, infertility and spermatogenesis dysfunction. Furthermore, the application of them in gene therapy is an important issue in the modern medicine science due to the role

Platelet-Rich Blood Derivatives for Stem Cell-Based Tissue Engineering and Regeneration

NARCIS (Netherlands)

Masoudi, E.A.; Ribas, J.; Kaushik, G.; Leijten, Jeroen Christianus Hermanus; Khademhosseini, A.

2016-01-01

Platelet-rich blood derivatives have been widely used in different fields of medicine and stem cell-based tissue engineering. They represent natural cocktails of autologous growth factors, which could provide an alternative for recombinant protein-based approaches. Platelet-rich blood derivatives,

Photo-transfection of mouse embryonic stem cells with plasmid DNA using femtosecond laser pulses

CSIR Research Space (South Africa)

Thobakgale, Lebogang

2017-01-01

Full Text Available disease- iPS, dopaminergic neurons Transplantation • Autologous- bone marrow, tissue defects, leukemia • Haematopoietic- blood dieases, autoimmune disorders • Mesenchymal- neurological disorders Phototransfection • Transfection refers...

Concise review: stem cell-based approaches to red blood cell production for transfusion.

Science.gov (United States)

Shah, Siddharth; Huang, Xiaosong; Cheng, Linzhao

2014-03-01

Blood transfusion is a common procedure in modern medicine, and it is practiced throughout the world; however, many countries report a less than sufficient blood supply. Even in developed countries where the supply is currently adequate, projected demographics predict an insufficient supply as early as 2050. The blood supply is also strained during occasional widespread disasters and crises. Transfusion of blood components such as red blood cells (RBCs), platelets, or neutrophils is increasingly used from the same blood unit for multiple purposes and to reduce alloimmune responses. Even for RBCs and platelets lacking nuclei and many antigenic cell-surface molecules, alloimmunity could occur, especially in patients with chronic transfusion requirements. Once alloimmunization occurs, such patients require RBCs from donors with a different blood group antigen combination, making it a challenge to find donors after every successive episode of alloimmunization. Alternative blood substitutes such as synthetic oxygen carriers have so far proven unsuccessful. In this review, we focus on current research and technologies that permit RBC production ex vivo from hematopoietic stem cells, pluripotent stem cells, and immortalized erythroid precursors.

Generation of Human Induced Pluripotent Stem Cells from Peripheral Blood Mononuclear Cells Using Sendai Virus.

Science.gov (United States)

Soares, Filipa A C; Pedersen, Roger A; Vallier, Ludovic

2016-01-01

This protocol describes the efficient isolation of peripheral blood mononuclear cells from circulating blood via density gradient centrifugation and subsequent generation of integration-free human induced pluripotent stem cells. Peripheral blood mononuclear cells are cultured for 9 days to allow expansion of the erythroblast population. The erythroblasts are then used to derive human induced pluripotent stem cells using Sendai viral vectors, each expressing one of the four reprogramming factors Oct4, Sox2, Klf4, and c-Myc.

Genetic and haematopoietic effects of long-term tritiated water ingestion in mice

International Nuclear Information System (INIS)

Carsten, A.L.; Cronkite, E.P.

1976-01-01

The effect of large amounts of tritiated water (HTO) from reactors on the environment is evaluated. Randomly bred mice of the Hale-Stoner-Brookhaven strain have been maintained on HTO (3 μCi/mlitre) for extended periods. First-generation animals on HTO from four weeks of age have been evaluated for changes in growth pattern, and second-generation animals (also on HTO) for breeding efficiency, dominant lethal mutation rate and bone-marrow integrity. A total of 18831 embryos were examined. Statistical analysis of these results using either Student's ''t'' test or Kruskal and Wallis rank test indicates that there was a significant (p<0.01) reduction in viable embryos and an increase in early deaths in matings involving animals drinking HTO. Beginning at eight weeks of age and monthly thereafter, the haematopoietic stem cell content of the bone marrow was determined using the exogenous spleen colony technique. Although the total cellularity of the bone marrow remains comparable in the control and treated groups, the total number of stem cells (CFU) was reduced beginning after approximately 12-20 weeks on the tritium regime. These findings indicate a reduction in the total number of pluripotent stem cells in the marrow together with the ability of this reduced number of cells to maintain normal levels of total cellularity in the bone marrow. Thus, continuous ingestion of HTO at a concentration of 3 μCi/mlitre by mice results in: (1) Reduction in number of viable embryos present in the female at late pregnancy from matings when either the female or both parents have been on HTO; (2) Increase in number of early post-implantation deaths when both parents are on HTO; (3) Reduction in bone-marrow stem cell content after 12 weeks or longer on HTO; (4) No apparent effect on breeding efficiency (percentage of females pregnant) or body weight. These results are discussed in relation to the accumulated radiation dose

Human haemato-endothelial precursors: cord blood CD34+ cells produce haemogenic endothelium.

Directory of Open Access Journals (Sweden)

Elvira Pelosi

Full Text Available Embryologic and genetic evidence suggest a common origin of haematopoietic and endothelial lineages. In the murine embryo, recent studies indicate the presence of haemogenic endothelium and of a common haemato-endothelial precursor, the haemangioblast. Conversely, so far, little evidence supports the presence of haemogenic endothelium and haemangioblasts in later stages of development. Our studies indicate that human cord blood haematopoietic progenitors (CD34+45+144-, triggered by murine hepatocyte conditioned medium, differentiate into adherent proliferating endothelial precursors (CD144+CD105+CD146+CD31+CD45- capable of functioning as haemogenic endothelium. These cells, proven to give rise to functional vasculature in vivo, if further instructed by haematopoietic growth factors, first switch to transitional CD144+45+ cells and then to haematopoietic cells. These results highlight the plasticity of haemato-endhothelial precursors in human post-natal life. Furthermore, these studies may provide highly enriched populations of human post-fetal haemogenic endothelium, paving the way for innovative projects at a basic and possibly clinical level.

Evaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model.

Science.gov (United States)

Shah, Sandeep N; Gelderman, Monique P; Lewis, Emily M A; Farrel, John; Wood, Francine; Strader, Michael Brad; Alayash, Abdu I; Vostal, Jaroslav G

2016-01-01

Reliance on volunteer blood donors can lead to transfusion product shortages, and current liquid storage of red blood cells (RBCs) is associated with biochemical changes over time, known as 'the storage lesion'. Thus, there is a need for alternative sources of transfusable RBCs to supplement conventional blood donations. Extracorporeal production of stem cell-derived RBCs (stemRBCs) is a potential and yet untapped source of fresh, transfusable RBCs. A number of groups have attempted RBC differentiation from CD34+ cells. However, it is still unclear whether these stemRBCs could eventually be effective substitutes for traditional RBCs due to potential differences in oxygen carrying capacity, viability, deformability, and other critical parameters. We have generated ex vivo stemRBCs from primary human cord blood CD34+ cells and compared them to donor-derived RBCs based on a number of in vitro parameters. In vivo, we assessed stemRBC circulation kinetics in an animal model of transfusion and oxygen delivery in a mouse model of exercise performance. Our novel, chronically anemic, SCID mouse model can evaluate the potential of stemRBCs to deliver oxygen to tissues (muscle) under resting and exercise-induced hypoxic conditions. Based on our data, stem cell-derived RBCs have a similar biochemical profile compared to donor-derived RBCs. While certain key differences remain between donor-derived RBCs and stemRBCs, the ability of stemRBCs to deliver oxygen in a living organism provides support for further development as a transfusion product.

Evaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model.

Directory of Open Access Journals (Sweden)

Sandeep N Shah

Full Text Available Reliance on volunteer blood donors can lead to transfusion product shortages, and current liquid storage of red blood cells (RBCs is associated with biochemical changes over time, known as 'the storage lesion'. Thus, there is a need for alternative sources of transfusable RBCs to supplement conventional blood donations. Extracorporeal production of stem cell-derived RBCs (stemRBCs is a potential and yet untapped source of fresh, transfusable RBCs. A number of groups have attempted RBC differentiation from CD34+ cells. However, it is still unclear whether these stemRBCs could eventually be effective substitutes for traditional RBCs due to potential differences in oxygen carrying capacity, viability, deformability, and other critical parameters. We have generated ex vivo stemRBCs from primary human cord blood CD34+ cells and compared them to donor-derived RBCs based on a number of in vitro parameters. In vivo, we assessed stemRBC circulation kinetics in an animal model of transfusion and oxygen delivery in a mouse model of exercise performance. Our novel, chronically anemic, SCID mouse model can evaluate the potential of stemRBCs to deliver oxygen to tissues (muscle under resting and exercise-induced hypoxic conditions. Based on our data, stem cell-derived RBCs have a similar biochemical profile compared to donor-derived RBCs. While certain key differences remain between donor-derived RBCs and stemRBCs, the ability of stemRBCs to deliver oxygen in a living organism provides support for further development as a transfusion product.

Optimising methods of red cell sedimentation from cord blood to maximise nucleated cell recovery prior to cryopreservation.

Science.gov (United States)

Madkaikar, M; Gupta, M; Ghosh, K; Swaminathan, S; Sonawane, L; Mohanty, D

2007-01-01

Human cord blood is now an established source of stem cells for haematopoietic reconstitution. Red blood cell (RBC) depletion is required to reduce the cord blood unit volume for commercial banking. Red cell sedimentation using hydroxy ethyl starch (HES) is a standard procedure in most cord blood banks. However, while standardising the procedure for cord blood banking, a significant loss of nucleated cells (NC) may be encountered during standard HES sedimentation protocols. This study compares four procedures for cord blood processing to obtain optimal yield of nucleated cells. Gelatin, dextran, 6% HES and 6% HES with an equal volume of phosphate-buffered saline (PBS) were compared for RBC depletion and NC recovery. Dilution of the cord blood unit with an equal volume of PBS prior to sedimentation with HES resulted in maximum NC recovery (99% [99.5 +/- 1.3%]). Although standard procedures using 6% HES are well established in Western countries, they may not be applicable in India, as a variety of factors that can affect RBC sedimentation (e.g., iron deficiency, hypoalbuminaemia, thalassaemia trait, etc.) may reduce RBC sedimentation and thus reduce NC recovery. While diluting cord blood with an equal volume of PBS is a simple method to improve the NC recovery, it does involve an additional processing step.

Radiation responses of stem cells: targeted and non-targeted effects

International Nuclear Information System (INIS)

Kavanagh, J.N.; Waring, E.J.; Prise, K.M.

2015-01-01

Stem cells are fundamental to the development of any tissue or organism via their ability to self-renew, which is aided by their unlimited proliferative capacity and their ability to produce fully differentiated offspring, often from multiple lineages. Stems cells are long lived and have the potential to accumulate mutations, including in response to radiation exposure. It is thought that stem cells have the potential to be induced into a cancer stem cell phenotype and that these may play an important role in resistance to radiotherapy. For radiation-induced carcinogenesis, the role of targeted and non-targeted effects is unclear with tissue or origin being important. Studies of genomic instability and bystander responses have shown consistent effects in haematopoietic models. Several models of radiation have predicted that stem cells play an important role in tumour initiation and that bystander responses could play a role in proliferation and self-renewal. (authors)

Sustained release of stem cell factor in a double network hydrogel for ex vivo culture of cord blood-derived CD34+ cells.

Science.gov (United States)

Zhang, Yuanhao; Pan, Xiuwei; Shi, Zhen; Cai, Haibo; Gao, Yun; Zhang, Weian

2018-04-01

Stem cell factor (SCF) is considered as a commonly indispensable cytokine for proliferation of haematopoietic stem cells (HSCs), which is used in large dosages during ex vivo culture. The work presented here aimed to reduce the consumption of SCF by sustained release but still support cells proliferation and maintain the multipotency of HSCs. Stem cell factor was physically encapsulated within a hyaluronic acid/gelatin double network (HGDN) hydrogel to achieve a slow release rate. CD34 + cells were cultured within the SCF-loaded HGDN hydrogel for 14 days. The cell number, phenotype and functional capacity were investigated after culture. The HGDN hydrogels had desirable properties and encapsulated SCF kept being released for more than 6 days. SCF remained the native bioactivity, and the proliferation of HSCs within the SCF-loaded HGDN hydrogel was not affected, although the consumption of SCF was only a quarter in comparison with the conventional culture. Moreover, CD34 + cells harvested from the SCF-loaded HGDN hydrogels generated more multipotent colony-forming units (CFU-GEMM). The data suggested that the SCF-loaded HGDN hydrogel could support ex vivo culture of HSCs, thus providing a cost-effective culture protocol for HSCs. © 2017 John Wiley & Sons Ltd.

Immune ablation and stem-cell therapy in autoimmune disease. Clinical experience.

Science.gov (United States)

Tyndall, A; Gratwohl, A

2000-01-01

In the past 5 years, around 350 patients have received haematopoietic stem cell (HSC) transplantation for an autoimmune disease, with 275 of these registered in an international data base in Basel under the auspices of the European League Against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation(EBMT). Most patients had either a progressive form of multiple sclerosis (MS; n = 88) or scleroderma (now called systemic sclerosis; n = 55). Other diseases were rheumatoid arthritis (Ra n = 40), juvenile idiopathic arthritis (JIA; n = 30), systemic lupus erythematosus (SLE; n = 20), idiopathic thrombocytopenic purpura (ITP; n = 7) and others. The procedure-related mortality was around 9%, with between-disease differences, being higher in systemic sclerosis and JIA and lower in RA (one death only). Benefit has been seen in around two-thirds of cases. No one regimen was clearly superior to another, with a trend toward more infectious complications with more intense regimens. Prospective, controlled randomized trials are indicated and being planned.

klf2ash317 Mutant Zebrafish Do Not Recapitulate Morpholino-Induced Vascular and Haematopoietic Phenotypes.

Directory of Open Access Journals (Sweden)

Peter Novodvorsky

Full Text Available The zinc-finger transcription factor Krϋppel-like factor 2 (KLF2 transduces blood flow into molecular signals responsible for a wide range of responses within the vasculature. KLF2 maintains a healthy, quiescent endothelial phenotype. Previous studies report a range of phenotypes following morpholino antisense oligonucleotide-induced klf2a knockdown in zebrafish. Targeted genome editing is an increasingly applied method for functional assessment of candidate genes. We therefore generated a stable klf2a mutant zebrafish and characterised its cardiovascular and haematopoietic development.Using Transcription Activator-Like Effector Nucleases (TALEN we generated a klf2a mutant (klf2ash317 with a 14bp deletion leading to a premature stop codon in exon 2. Western blotting confirmed loss of wild type Klf2a protein and the presence of a truncated protein in klf2ash317 mutants. Homozygous klf2ash317 mutants exhibit no defects in vascular patterning, survive to adulthood and are fertile, without displaying previously described morphant phenotypes such as high-output cardiac failure, reduced haematopoetic stem cell (HSC development or impaired formation of the 5th accessory aortic arch. Homozygous klf2ash317 mutation did not reduce angiogenesis in zebrafish with homozygous mutations in von Hippel Lindau (vhl, a form of angiogenesis that is dependent on blood flow. We examined expression of three klf family members in wildtype and klf2ash317 zebrafish. We detected vascular expression of klf2b (but not klf4a or biklf/klf4b/klf17 in wildtypes but found no differences in expression that might account for the lack of phenotype in klf2ash317 mutants. klf2b morpholino knockdown did not affect heart rate or impair formation of the 5th accessory aortic arch in either wildtypes or klf2ash317 mutants.The klf2ash317 mutation produces a truncated Klf2a protein but, unlike morpholino induced klf2a knockdown, does not affect cardiovascular development.

Peripheral blood CD34+ cell count as a predictor of adequacy of hematopoietic stem cell collection for autologous transplantation

Directory of Open Access Journals (Sweden)

Combariza, Juan F.

2016-10-01

Full Text Available Introduction: In order to carry out an autologous transplantation, hematopoietic stem cells should be mobilized to peripheral blood and later collected by apheresis. The CD34+ cell count is a tool to establish the optimal time to begin the apheresis procedure. Objective: To evaluate the association between peripheral blood CD34+ cell count and the successful collection of hematopoietic stem cells. Materials and methods: A predictive test evaluation study was carried out to establish the usefulness of peripheral blood CD34+ cell count as a predictor of successful stem cell collection in patients that will receive an autologous transplantation. Results: 77 patients were included (median age: 49 years; range: 5-66. The predominant baseline diagnosis was lymphoma (53.2 %. The percentage of patients with successful harvest of hematopoietic stem cells was proportional to the number of CD34+cells in peripheral blood at the end of the mobilization procedure. We propose that more than 15 CD34+cells/μL must be present in order to achieve an adequate collection of hematopoietic stem cells. Conclusion: Peripheral blood CD34+ cell count is a useful tool to predict the successful collection of hematopoietic stem cells.

Is there any reason to prefer cord blood instead of adult donors for hematopoietic stem cell transplants?

Directory of Open Access Journals (Sweden)

Meral eBeksac

2016-01-01

Full Text Available As cord blood (CB enables rapid access and tolerance to HLA mismatches, number of unrelated cord blood transplants have reached 30 000. Such transplant activity has been the result of international accreditation programs maintaining highly qualified CBUs reaching more than 600 000 CBUs stored worldwide. Efforts to increase stem cell content or engraftment rate of the graft by ex vivo expansion, modulation by molecules such as fucose, Prostaglandin E2 derivative, complement, CD26 inhibitors or CXCR4/CXCL12 axis have been able to accelerate engraftment speed and rate. Furthermore introduction of reduced intensity conditioning protocols, better HLA matching and recognition of the importance of HLA-C have improved CBT success by decreasing Transplant Related Mortality (TRM. Cord blood progenitor/stem cell content has been compared with adult stem cells revealing higher long-term repopulating capacity compared to BM-MSC and less oncogenic potential than Induced Progenitor Stem Cells. This chapter summarizes the advantage and disadvantages of CB compared to adult stem cells within the context of stem cell biology and transplantation.

Oral complaints and dental care of haematopoietic stem cell transplant patients: a qualitative survey of patients and their dentists.

Science.gov (United States)

Bos-den Braber, Jacolien; Potting, Carin M J; Bronkhorst, Ewald M; Huysmans, Marie-Charlotte D N J M; Blijlevens, Nicole M A

2015-01-01

Little is known about the understanding of the oral and dental needs of haematopoietic stem cell transplant (HSCT) patients or about dentists' views and experiences regarding this patient group. This information is essential if we want to improve the standard of peri-HSCT dental care. The primary objective of this qualitative survey was to explore the following: (1) The understanding of dental care pre- and post-HSCT (2) The subjective oral complaints of HSCT patients both short- and long-term (3) The relationship of these oral complaints to the severity of oral mucositis during hospitalization The secondary objective was to explore the opinions of dentists regarding dental care before and after HSCT. All adult patients who survived HSCT at the Radboud University Medical Centre between 2010 and 2011 (n = 101) received a questionnaire. During hospitalization, mucositis scores were recorded daily in the patient's chart. The patients' dentist (n = 88) was also sent a questionnaire after permission of the patient. Ninety-six out of 101 patients (95%) responded. The average period since HSCT was 19 months (range 8-31 months). The overall mean maximum mucositis score was 6.6 (sd = 3.3). Only eight patients reported not having visited a dentist pre-HSCT. The majority of the patients (59%) reported short-term oral complaints, and 28% reported long-term oral complaints. Fifty-two dentists responded (59%). Nine had not performed pre-HSCT screening and eight dentists reported screening their patients but could not complete the necessary treatments. Only 44 dentists succeeded in completing the required treatments. The most important advice of the dentist was to reinforce the importance of regular dental care. Most patients report short-term and/or long-term oral complaints after HSCT. Most dentists stress the importance of regular dental care before and after HSCT but report not being familiar with the particular dental care needs of this patient group. The high

Guideline for the prevention of oral and oropharyngeal mucositis in children receiving treatment for cancer or undergoing haematopoietic stem cell transplantation.

Science.gov (United States)

Sung, Lillian; Robinson, Paula; Treister, Nathaniel; Baggott, Tina; Gibson, Paul; Tissing, Wim; Wiernikowski, John; Brinklow, Jennifer; Dupuis, L Lee

2017-03-01

To develop an evidence-based clinical practice guideline for the prevention of oral mucositis in children (0-18 years) receiving treatment for cancer or undergoing haematopoietic stem cell transplantation (HSCT). The Mucositis Prevention Guideline Development Group was interdisciplinary and included internationally recognised experts in paediatric mucositis. For the evidence review, we included randomised controlled trials (RCTs) conducted in either children or adults evaluating the following interventions selected according to prespecified criteria: cryotherapy, low level light therapy (LLLT) and keratinocyte growth factor (KGF). We also examined RCTs of any intervention conducted in children. For all systematic reviews, we synthesised the occurrence of severe oral mucositis. The Grades of Recommendation, Assessment, Development and Evaluation approach was used to describe quality of evidence and strength of recommendations. We suggest cryotherapy or LLLT may be offered to cooperative children receiving chemotherapy or HSCT conditioning with regimens associated with a high rate of mucositis. We also suggest KGF may be offered to children receiving HSCT conditioning with regimens associated with a high rate of severe mucositis. However, KGF use merits caution as there is a lack of efficacy and toxicity data in children, and a lack of long-term follow-up data in paediatric cancers. No other interventions were recommended for oral mucositis prevention in children. All three specific interventions evaluated in this clinical practice guideline were associated with a weak recommendation for use. There may be important organisational and cost barriers to the adoption of LLLT and KGF. Considerations for implementation and key research gaps are highlighted. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Induced pluripotent stem cell-derived gamete-associated proteins incite rejection of induced pluripotent stem cells in syngeneic mice.

Science.gov (United States)

Kim, Eun-Mi; Manzar, Gohar; Zavazava, Nicholas

2017-06-01

The safety of induced pluripotent stem cells (iPSCs) in autologous recipients has been questioned after iPSCs, but not embryonic stem cells (ESCs), were reported to be rejected in syngeneic mice. This important topic has remained controversial because there has not been a mechanistic explanation for this phenomenon. Here, we hypothesize that iPSCs, but not ESCs, readily differentiate into gamete-forming cells that express meiotic antigens normally found in immune-privileged gonads. Because peripheral blood T cells are not tolerized to these antigens in the thymus, gamete-associated-proteins (GAPs) sensitize T cells leading to rejection. Here, we provide evidence that GAPs expressed in iPSC teratomas, but not in ESC teratomas, are responsible for the immunological rejection of iPSCs. Furthermore, silencing the expression of Stra8, 'the master regulator of meiosis', in iPSCs, using short hairpin RNA led to significant abrogation of the rejection of iPSCs, supporting our central hypothesis that GAPs expressed after initiation of meiosis in iPSCs were responsible for rejection. In contrast to iPSCs, iPSC-derivatives, such as haematopoietic progenitor cells, are able to engraft long-term into syngeneic recipients because they no longer express GAPs. Our findings, for the first time, provide a unifying explanation of why iPSCs, but not ESCs, are rejected in syngeneic recipients, ending the current controversy on the safety of iPSCs and their derivatives. © 2017 John Wiley & Sons Ltd.

Transplantation of cord blood mesenchymal stem cells as spheroids enhances vascularization.

Science.gov (United States)

Bhang, Suk Ho; Lee, Seahyoung; Shin, Jung-Youn; Lee, Tae-Jin; Kim, Byung-Soo

2012-10-01

Despite promising results from the therapeutic use of stem cells for treating ischemic diseases, the poor survival of cells transplanted into ischemic regions is one of the major problems that undermine the efficacy of stem cell therapy. Cord blood mononuclear cells (CBMNCs) are an alternative source of mesenchymal stem cells (MSCs) without disadvantages, such as the painful and invasive harvesting procedure, of MSCs derived from bone marrow or adipose tissue. In the present study, we investigated whether the angiogenic efficacy of cord blood mesenchymal stem cells (CBMSCs) can be enhanced by grafting as spheroids in a mouse hindlimb ischemia model. Human CBMSC (hCBMSC) spheroids were prepared by using the hanging-drop method. Mouse hindlimb ischemia was induced by excising the femoral artery and its branches. After surgery, the animals were divided into no-treatment, dissociated hCBMSC, and spheroid hCBMSC groups (n=8 per group) and received corresponding hCBMSC treatments. After surgery, the ischemic hindlimbs were monitored for 4 weeks, and then, the ischemic hindlimb muscles were harvested for histological analysis. Apoptotic signaling, angiogenesis-related signal pathways, and blood vessel formation were investigated in vitro and/or in vivo. The transplantation of hCBMSCs as spheroids into mouse ischemic hindlimbs significantly improved the survival of the transplanted cells by suppressing apoptotic signaling while activating antiapoptotic signaling. Furthermore, the transplantation of hCBMSCs as spheroids significantly increased the number of microvessels and smooth muscle α-actin-positive vessels in the ischemic limbs of mice, and attenuated limb loss and necrosis. Human CBMNC can be considered an alternative source of MSC, and spheroid-based hCBMSC delivery can be considered a simple and effective strategy for enhancing the therapeutic efficacy of hCBMSCs.

Incorporating placental tissue in cord blood banking for stem cell transplantation.

Science.gov (United States)

Teofili, Luciana; Silini, Antonietta R; Bianchi, Maria; Valentini, Caterina Giovanna; Parolini, Ornella

2018-06-01

Human term placenta is comprised of various tissues from which different cell populations can be obtained, including hematopoietic stem cells and mesenchymal stem/stromal cells (MSCs). Areas covered: This review will discuss the possibility to incorporate placental tissue cells in cord blood banking. It will discuss general features of human placenta, with a brief review of the immune cells at the fetal-maternal interface and the different cell populations isolated from placenta, with a particular focus on MSCs. It will address the question as to why placenta-derived MSCs should be banked with their hematopoietic counterparts. It will discuss clinical trials which are studying safety and efficacy of placenta tissue-derived MSCs in selected diseases, and preclinical studies which have proven their therapeutic properties in other diseases. It will discuss banking of umbilical cord blood and raise several issues for improvement, and the applications of cord blood cells in non-malignant disorders. Expert Commentary: Umbilical cord blood banking saves lives worldwide. The concomitant banking of non-hematopoietic cells from placenta, which could be applied therapeutically in the future, alone or in combination to their hematopoietic counterparts, could exploit current banking processes while laying the foundation for clinical trials exploring placenta-derived cell therapies in regenerative medicine.

Human umbilical cord blood stem cells and brain-derived neurotrophic factor for optic nerve injury: a biomechanical evaluation

Directory of Open Access Journals (Sweden)

Zhong-jun Zhang

2015-01-01

Full Text Available Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 μg brain-derived neurotrophic factor or 1 × 10 6 human umbilical cord blood stem cells. After 30 days, the maximum load, maximum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neurotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These findings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, improve biomechanical properties, and contribute to the recovery after injury.

The Assessment of Parameters Affecting the Quality of Cord Blood by the Appliance of the Annexin V Staining Method and Correlation with CFU Assays

Directory of Open Access Journals (Sweden)

Teja Falk Radke

2013-01-01

Full Text Available The assessment of nonviable haematopoietic cells by Annexin V staining method in flow cytometry has recently been published by Duggleby et al. Resulting in a better correlation with the observed colony formation in methylcellulose assays than the standard ISHAGE protocol, it presents a promising method to predict cord blood potency. Herein, we applied this method for examining the parameters during processing which potentially could affect cord blood viability. We could verify that the current standards regarding time and temperature are sufficient, since no significant difference was observed within 48 hours or in storage at 4°C up to 26°C. However, the addition of DMSO for cryopreservation alone leads to an inevitable increase in nonviable haematopoietic stem cells from initially 14.8% ± 4.3% to at least 30.6% ± 5.5%. Furthermore, CFU-assays with varied seeding density were performed in order to evaluate the applicability as a quantitative method. The results revealed that only in a narrow range reproducible clonogenic efficiency (ClonE could be assessed, giving at least a semiquantitative estimation. We conclude that both Annexin V staining method and CFU-assays with defined seeding density are reliable means leading to a better prediction of the final potency. Especially Annexin V, due to its fast readout, is a practical tool for examining and optimising specific steps in processing, while CFU-assays add a functional confirmation.

Optimisation of a quantitative polymerase chain reaction-based strategy for the detection and quantification of human herpesvirus 6 DNA in patients undergoing allogeneic haematopoietic stem cell transplantation

Directory of Open Access Journals (Sweden)

Miriam YH Ueda

2015-06-01

Full Text Available Human herpesvirus 6 (HHV-6 may cause severe complications after haematopoietic stem cell transplantation (HSCT. Monitoring this virus and providing precise, rapid and early diagnosis of related clinical diseases, constitute essential measures to improve outcomes. A prospective survey on the incidence and clinical features of HHV-6 infections after HSCT has not yet been conducted in Brazilian patients and the impact of this infection on HSCT outcome remains unclear. A rapid test based on real-time quantitative polymerase chain reaction (qPCR has been optimised to screen and quantify clinical samples for HHV-6. The detection step was based on reaction with TaqMan® hydrolysis probes. A set of previously described primers and probes have been tested to evaluate efficiency, sensitivity and reproducibility. The target efficiency range was 91.4% with linearity ranging from 10-106 copies/reaction and a limit of detection of five copies/reaction or 250 copies/mL of plasma. The qPCR assay developed in the present study was simple, rapid and sensitive, allowing the detection of a wide range of HHV-6 loads. In conclusion, this test may be useful as a practical tool to help elucidate the clinical relevance of HHV-6 infection and reactivation in different scenarios and to determine the need for surveillance.

Molecular Profiling of Peripheral Blood Cells from Patients with Polycythemia Vera and Related Neoplasms: Identification of Deregulated Genes of Significance for Inflammation and Immune Surveillance

DEFF Research Database (Denmark)

Skov, Vibe; Larsen, Thomas Stauffer; Thomassen, Mads

2012-01-01

Essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) are haematopoietic stem cell neoplasms that may be associated with autoimmune or chronic inflammatory disorders. Earlier gene expression profiling studies have demonstrated aberrant expression of genes involved...

Isoform-specific potentiation of stem and progenitor cell engraftment by AML1/RUNX1.

Directory of Open Access Journals (Sweden)

Shinobu Tsuzuki

2007-05-01

Full Text Available AML1/RUNX1 is the most frequently mutated gene in leukaemia and is central to the normal biology of hematopoietic stem and progenitor cells. However, the role of different AML1 isoforms within these primitive compartments is unclear. Here we investigate whether altering relative expression of AML1 isoforms impacts the balance between cell self-renewal and differentiation in vitro and in vivo.The human AML1a isoform encodes a truncated molecule with DNA-binding but no transactivation capacity. We used a retrovirus-based approach to transduce AML1a into primitive haematopoietic cells isolated from the mouse. We observed that enforced AML1a expression increased the competitive engraftment potential of murine long-term reconstituting stem cells with the proportion of AML1a-expressing cells increasing over time in both primary and secondary recipients. Furthermore, AML1a expression dramatically increased primitive and committed progenitor activity in engrafted animals as assessed by long-term culture, cobblestone formation, and colony assays. In contrast, expression of the full-length isoform AML1b abrogated engraftment potential. In vitro, AML1b promoted differentiation while AML1a promoted proliferation of progenitors capable of short-term lymphomyeloid engraftment. Consistent with these findings, the relative abundance of AML1a was highest in the primitive stem/progenitor compartment of human cord blood, and forced expression of AML1a in these cells enhanced maintenance of primitive potential both in vitro and in vivo.These data demonstrate that the "a" isoform of AML1 has the capacity to potentiate stem and progenitor cell engraftment, both of which are required for successful clinical transplantation. This activity is consistent with its expression pattern in both normal and leukaemic cells. Manipulating the balance of AML1 isoform expression may offer novel therapeutic strategies, exploitable in the contexts of leukaemia and also in cord blood

Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015.

Science.gov (United States)

Sureda, A; Bader, P; Cesaro, S; Dreger, P; Duarte, R F; Dufour, C; Falkenburg, J H F; Farge-Bancel, D; Gennery, A; Kröger, N; Lanza, F; Marsh, J C; Nagler, A; Peters, C; Velardi, A; Mohty, M; Madrigal, A

2015-08-01

This is the sixth special report that the European Society for Blood and Marrow Transplantation regularly publishes on the current practice and indications for haematopoietic SCT for haematological diseases, solid tumours and immune disorders in Europe. Major changes have occurred in the field of haematopoietic SCT over the last years. Cord blood units as well as haploidentical donors have been increasingly used as stem cell sources for allo-SCT, thus, augmenting the possibility of finding a suitable donor for a patient. Continuous refinement of conditioning strategies has also expanded not only the number of potential indications but also has permitted consideration of older patients or those with co-morbidity for a transplant. There is accumulating evidence of the role of haematopoietic SCT in non-haematological disorders such as autoimmune diseases. On the other hand, the advent of new drugs and very effective targeted therapy has challenged the role of SCT in some instances or at least, modified its position in the treatment armamentarium of a given patient. An updated report with revised tables and operating definitions is presented.

Enhanced humoral and HLA-A2-restricted dengue virus-specific T-cell responses in humanized BLT NSG mice

Science.gov (United States)

Jaiswal, Smita; Pazoles, Pamela; Woda, Marcia; Shultz, Leonard D; Greiner, Dale L; Brehm, Michael A; Mathew, Anuja

2012-01-01

Dengue is a mosquito-borne viral disease of humans, and animal models that recapitulate human immune responses or dengue pathogenesis are needed to understand the pathogenesis of the disease. We recently described an animal model for dengue virus (DENV) infection using humanized NOD-scid IL2rγnull mice (NSG) engrafted with cord blood haematopoietic stem cells. We sought to further improve this model by co-transplantation of human fetal thymus and liver tissues into NSG (BLT-NSG) mice. Enhanced DENV-specific antibody titres were found in the sera of BLT-NSG mice compared with human cord blood haematopoietic stem cell-engrafted NSG mice. Furthermore, B cells generated during the acute phase and in memory from splenocytes of immunized BLT-NSG mice secreted DENV-specific IgM antibodies with neutralizing activity. Human T cells in engrafted BLT-NSG mice secreted interferon-γ in response to overlapping DENV peptide pools and HLA-A2 restricted peptides. The BLT-NSG mice will allow assessment of human immune responses to DENV vaccines and the effects of previous immunity on subsequent DENV infections. PMID:22384859

Dipeptide species regulate p38MAPK–Smad3 signalling to maintain chronic myelogenous leukaemia stem cells

Science.gov (United States)

Naka, Kazuhito; Jomen, Yoshie; Ishihara, Kaori; Kim, Junil; Ishimoto, Takahiro; Bae, Eun-Jin; Mohney, Robert P.; Stirdivant, Steven M.; Oshima, Hiroko; Oshima, Masanobu; Kim, Dong-Wook; Nakauchi, Hiromitsu; Takihara, Yoshihiro; Kato, Yukio; Ooshima, Akira; Kim, Seong-Jin

2015-01-01

Understanding the specific survival of the rare chronic myelogenous leukaemia (CML) stem cell population could provide a target for therapeutics aimed at eradicating these cells. However, little is known about how survival signalling is regulated in CML stem cells. In this study, we survey global metabolic differences between murine normal haematopoietic stem cells (HSCs) and CML stem cells using metabolomics techniques. Strikingly, we show that CML stem cells accumulate significantly higher levels of certain dipeptide species than normal HSCs. Once internalized, these dipeptide species activate amino-acid signalling via a pathway involving p38MAPK and the stemness transcription factor Smad3, which promotes CML stem cell maintenance. Importantly, pharmacological inhibition of dipeptide uptake inhibits CML stem cell activity in vivo. Our results demonstrate that dipeptide species support CML stem cell maintenance by activating p38MAPK–Smad3 signalling in vivo, and thus point towards a potential therapeutic target for CML treatment. PMID:26289811

Stem Cells and Blood: Where have we come from... and where are we going?

International Nuclear Information System (INIS)

Bueren, J. A.

2011-01-01

Since 1961, they year when the first trial that characterized the behaviour of a stem cell in mice exposed to high doses of radiation was described, research in this field has proceeded at an unpredictable place. Knowledge of the function of hematopoietic stem cells which are responsible for forming blood cells facilitated the development of therapies based on the transplant of bone marrow and other cell source, e. g. blood from the umbilical cord. These breakthroughs, together with the progress of molecular biology and virology, made it possible to manipulate the genome of hematopoietic stem cells so effectively and safely that the transplant of genetically modified cells has become a variable therapeutic alternative for the treatment of certain genetic diseases and also cancer. This brief article describes some of the contributions that our Hematopoiesis and Gene Therapy Division of the CIEMAT and the CIBER for Rare Diseases has been developing in this fascinating field of stem cells and gene therapy, in the context of the international research being carried out in this area. (Author) 34 refs.

2-(trimethylammonium)ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate promotes megakaryocytic differentiation of myeloid leukaemia cells and primary human CD34⁺ haematopoietic stem cells.

Science.gov (United States)

Limb, Jin-Kyung; Song, Doona; Jeon, Mijeong; Han, So-Yeop; Han, Gyoonhee; Jhon, Gil-Ja; Bae, Yun Soo; Kim, Jaesang

2015-04-01

In this study we showed that 2-(trimethylammonium)ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient differentiation of megakaryocytes. Specifically, (R)-TEMOSPho induces cell cycle arrest, cell size increase and polyploidization from K562 and HEL cells, which are used extensively to model megakaryocytic differentiation. In addition, megakaryocyte-specific cell surface markers showed a dramatic increase in expression in response to (R)-TEMOSPho treatment. Importantly, we demonstrated that such megakaryocytic differentiation can also be induced from primary human CD34(+) haematopoietic stem cells. Activation of the PI3K-AKT pathway and, to a lesser extent, the MEK-ERK pathway appears to be required for this process, as blocking with specific inhibitors interferes with the differentiation of K562 cells. A subset of (R)-TEMOSPho-treated K562 cells undergoes spontaneous apoptosis and produces platelets that are apparently functional, as they bind to fibrinogen, express P-selectin and aggregate in response to SFLLRN and AYPGFK, the activating peptides for the PAR1 and PAR4 receptors, respectively. Taken together, these results indicate that (R)-TEMOSPho will be useful for dissecting the molecular mechanisms of megakaryocytic differentiation, and that this class of compounds represents potential therapeutic reagents for thrombocytopenia. Copyright © 2012 John Wiley & Sons, Ltd.

Cord blood stem cell banking: a snapshot of the Italian situation.

Science.gov (United States)

Capone, Francesca; Lombardini, Letizia; Pupella, Simonetta; Grazzini, Giuliano; Costa, Alessandro Nanni; Migliaccio, Giovanni

2011-09-01

In Italy, the law does not permit the setting up of private banks to preserve cord blood (CB) stem cells for personal use. However, since 2007 the right to export and preserve them in private laboratories located outside Italy has existed, and an increasing number of women are requesting this collection of umbilical CB at delivery to enable storage of stem cells for autologous use. Since private banks recruit clients mainly via the Internet, we examined the content of 24 Italian-language websites that offer stem cells storage (from CB or amniotic fluid), to assess what information is available. We found that the majority of private banks give no clear information about the procedures of collection, processing, and banking of CB units and that the standards offered by private CB banks strongly differ in terms of exclusion or acceptance criteria from the public banks. These factors may well influence the overall quality of the CB units stored in private CB banks. Of note, during the period 2007 to 2009, the number collected for autologous use did not create a downward trend on the number of units stored in public CB banks for allogeneic use. CB is a valuable community resource but expectant parents should be better informed as to the quality variables necessary for its storage, both by institutions and by professionals. Currently, most of the advertising is insufficient to justify the expense and the hopes pinned on autologous use of CB stem cells. © 2011 American Association of Blood Banks.

Generation of glucose-responsive, insulin-producing cells from human umbilical cord blood-derived mesenchymal stem cells.

Science.gov (United States)

Prabakar, Kamalaveni R; Domínguez-Bendala, Juan; Molano, R Damaris; Pileggi, Antonello; Villate, Susana; Ricordi, Camillo; Inverardi, Luca

2012-01-01

We sought to assess the potential of human cord blood-derived mesenchymal stem cells (CB-MSCs) to derive insulin-producing, glucose-responsive cells. We show here that differentiation protocols based on stepwise culture conditions initially described for human embryonic stem cells (hESCs) lead to differentiation of cord blood-derived precursors towards a pancreatic endocrine phenotype, as assessed by marker expression and in vitro glucose-regulated insulin secretion. Transplantation of these cells in immune-deficient animals shows human C-peptide production in response to a glucose challenge. These data suggest that human cord blood may be a promising source for regenerative medicine approaches for the treatment of diabetes mellitus.

Blood on the tracks: hematopoietic stem cell-endothelial cell interactions in homing and engraftment.

Science.gov (United States)

Perlin, Julie R; Sporrij, Audrey; Zon, Leonard I

2017-08-01

Cells of the hematopoietic system undergo rapid turnover. Each day, humans require the production of about one hundred billion new blood cells for proper function. Hematopoietic stem cells (HSCs) are rare cells that reside in specialized niches and are required throughout life to produce specific progenitor cells that will replenish all blood lineages. There is, however, an incomplete understanding of the molecular and physical properties that regulate HSC migration, homing, engraftment, and maintenance in the niche. Endothelial cells (ECs) are intimately associated with HSCs throughout the life of the stem cell, from the specialized endothelial cells that give rise to HSCs, to the perivascular niche endothelial cells that regulate HSC homeostasis. Recent studies have dissected the unique molecular and physical properties of the endothelial cells in the HSC vascular niche and their role in HSC biology, which may be manipulated to enhance hematopoietic stem cell transplantation therapies.

Immunophenotype of hematopoietic stem cells from placental/umbilical cord blood after culture

Directory of Open Access Journals (Sweden)

P. Pranke

2005-12-01

Full Text Available Identification and enumeration of human hematopoietic stem cells remain problematic, since in vitro and in vivo stem cell assays have different outcomes. We determined if the altered expression of adhesion molecules during stem cell expansion could be a reason for the discrepancy. CD34+CD38- and CD34+CD38+ cells from umbilical cord blood were analyzed before and after culture with thrombopoietin (TPO, FLT-3 ligand (FL and kit ligand (KL; or stem cell factor in different combinations: TPO + FL + KL, TPO + FL and TPO, at concentrations of 50 ng/mL each. Cells were immunophenotyped by four-color fluorescence using antibodies against CD11c, CD31, CD49e, CD61, CD62L, CD117, and HLA-DR. Low-density cord blood contained 1.4 ± 0.9% CD34+ cells, 2.6 ± 2.1% of which were CD38-negative. CD34+ cells were isolated using immuno-magnetic beads and cultured for up to 7 days. The TPO + FL + KL combination presented the best condition for maintenance of stem cells. The total cell number increased 4.3 ± 1.8-fold, but the number of viable CD34+ cells decreased by 46 ± 25%. On the other hand, the fraction of CD34+CD38- cells became 52.0 ± 29% of all CD34+ cells. The absolute number of CD34+CD38- cells was expanded on average 15 ± 12-fold when CD34+ cells were cultured with TPO + FL + KL for 7 days. The expression of CD62L, HLA-DR and CD117 was modulated after culture, particularly with TPO + FL + KL, explaining differences between the adhesion and engraftment of primary and cultured candidate stem cells. We conclude that culture of CD34+ cells with TPO + FL + KL results in a significant increase in the number of candidate stem cells with the CD34+CD38- phenotype.

[Mobilization of peripheral blood stem cells with plerixafor in poor mobilizer patients].

Science.gov (United States)

Sancho, Juan-Manuel; Duarte, Rafael; Medina, Laura; Querol, Sergi; Marín, Pedro; Sureda, Anna

2016-09-02

Poor mobilization of peripheral blood stem cells (CD34(+) cells) from bone marrow is a frequent reason for not reaching the autologous stem cell trasplantation (SCT) procedure in patients diagnosed with lymphoma or myeloma. Plerixafor, a reversible inhibitor of the binding of stromal cell-derived factor 1 to its cognate receptor CXCR4, has demonstrated a higher capacity for the mobilization of peripheral blood stem cells in combination with granulocyte colony stimulating factor (G-CSF) compared with G-CSF alone. For this reason, plerixafor is now indicated for poor mobilizer myeloma or lymphoma patients. Some studies have recently indicated that a pre-emptive strategy of plerixafor use during first mobilization, according to the number of CD34(+) mobilized cells in peripheral blood or to the harvested CD34(+) cells after first apheresis, could avoid mobilization failures and re-mobilizations, as well as the delay of autologous SCT. The aim of this consensus was to perform a review of published studies on pre-emptive strategy and to establish common recommendations for hospitals in Catalonia and Balearics on the use of pre-emptive plerixafor. For the Consensus, physicians from participant hospitals met to review previous studies as well as previous own data about plerixafor use. The GRADE system was used to qualify the available evidence and to establish recommendations on the use of pre-emptive plerixafor. After a review of the literature, the expert consensus recommended the administration of pre-emptive plerixafor for multiple myeloma or lymphoma patients with a CD34+ cell count lower than 10 cells/μL in peripheral blood (measured in the morning of day 4 of mobilization with G-CSF or after haematopietic recovery in the case of mobilization with chemotherapy plus G-CSF). Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Is There Any Reason to Prefer Cord Blood Instead of Adult Donors for Hematopoietic Stem Cell Transplants?

Science.gov (United States)

Beksac, Meral

2015-01-01

As cord blood (CB) enables rapid access and tolerance to HLA mismatches, a number of unrelated CB transplants have reached 30,000. Such transplant activity has been the result of international accreditation programs maintaining highly qualified cord blood units (CBUs) reaching more than 600,000 CBUs stored worldwide. Efforts to increase stem cell content or engraftment rate of the graft by ex vivo expansion, modulation by molecules such as fucose, prostaglandin E2 derivative, complement CD26 inhibitors, or CXCR4/CXCL12 axis have been able to accelerate engraftment speed and rate. Furthermore, introduction of reduced intensity conditioning protocols, better HLA matching, and recognition of the importance of HLA-C have improved CB transplants success by decreasing transplant-related mortality. CB progenitor/stem cell content has been compared with adult stem cells revealing higher long-term repopulating capacity compared to bone marrow-mesenchymal stromal cells and lesser oncogenic potential than progenitor-induced stem cells. This chapter summarizes the advantages and disadvantages of CB compared to adult stem cells within the context of stem cell biology and transplantation.

Evaluation of two different protocols for peripheral blood stem cell collection with the Fresenius AS 104 blood cell separator.

Science.gov (United States)

Menichella, G; Lai, M; Pierelli, L; Vittori, M; Serafini, R; Ciarli, M; Foddai, M L; Salerno, G; Sica, S; Scambia, G; Leone, G; Bizzi, B

1997-01-01

Reconstitution of hematopoiesis by means of peripheral blood stem cells is a valid alternative to autologous bone marrow transplantation. The aim of this investigation was to increase the efficiency of collection of circulating blood progenitor cells and to obtain a purer product for transplant. We carried out leukapheresis procedures with the Fresenius AS 104 blood cell separator, using two different protocols, the previously used PBSC-LYM and a new mononuclear cell collection program. Both programs were highly effective in collecting mononuclear cells (MNC) and CD34+ cells. Some differences were found, especially regarding MNC yield and efficiencies. There are remarkable differences in the efficiency of collection of CD34+ cells (62.38% with the new program as opposed to 31.69% with the older one). Linear regression analysis showed a negative correlation between blood volume processed and MNC efficiency only for the PBSC-LYM program. Differences were also observed in the degree of inverse correlation existing in both programs between patients' white blood cell precount and MNC collection efficiency. The inverse correlation was stronger for the PBSC-LYM program. Seven patients with solid tumors and hematologic malignancies received high dose chemotherapy and were subsequently transplanted with peripheral blood stem cells collected using the new protocol. All patients obtained a complete and stable engraftment with the reinfusion product collected with one or two leukapheresis procedures. High efficiencies and yields were observed in the new protocol for MNC and CD34+ cells. These were able to effect rapid and complete bone marrow recovery after myeloablative chemotherapy.

Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs.

Science.gov (United States)

Phinney, Donald G; Di Giuseppe, Michelangelo; Njah, Joel; Sala, Ernest; Shiva, Sruti; St Croix, Claudette M; Stolz, Donna B; Watkins, Simon C; Di, Y Peter; Leikauf, George D; Kolls, Jay; Riches, David W H; Deiuliis, Giuseppe; Kaminski, Naftali; Boregowda, Siddaraju V; McKenna, David H; Ortiz, Luis A

2015-10-07

Mesenchymal stem cells (MSCs) and macrophages are fundamental components of the stem cell niche and function coordinately to regulate haematopoietic stem cell self-renewal and mobilization. Recent studies indicate that mitophagy and healthy mitochondrial function are critical to the survival of stem cells, but how these processes are regulated in MSCs is unknown. Here we show that MSCs manage intracellular oxidative stress by targeting depolarized mitochondria to the plasma membrane via arrestin domain-containing protein 1-mediated microvesicles. The vesicles are then engulfed and re-utilized via a process involving fusion by macrophages, resulting in enhanced bioenergetics. Furthermore, we show that MSCs simultaneously shed micro RNA-containing exosomes that inhibit macrophage activation by suppressing Toll-like receptor signalling, thereby de-sensitizing macrophages to the ingested mitochondria. Collectively, these studies mechanistically link mitophagy and MSC survival with macrophage function, thereby providing a physiologically relevant context for the innate immunomodulatory activity of MSCs.

Regulation of human umbilical cord blood-derived multi-potent stem cells by autogenic osteoclast-based niche-like structure

International Nuclear Information System (INIS)

Sun, Bo; Jeong, Yun-Hyeok; Jung, Ji-Won; Seo, Kwangwon; Lee, Yong-Soon; Kang, Kyung-Sun

2007-01-01

Stem cell niches provide the micro-environment for the development of stem cells. Under our culturing regimen, a kind of osteoclast-centralized structure supports the proliferation of MSCs, derived from human cord blood, once they reside on osteoclasts. MSCs in this structure expressed Oct4 which is a marker of embryonic stem cells. Floating daughter cells of MSCs colony showed abilities to differentiate into osteocyte, adipocyte, and neuronal progenitor cells. Compared with the easy senescence of MSCs without this niche-like structure in vitro, these results suggested that osteoclasts might play an important role the development and maintenance of Umbilical cord blood (UCB)-derived MSCs and might provide a means to expand UCB-MSCs in vitro, more easily, through a stem cell niche-like structure

The in Vitro Assessment of Biochemical Factors in Hepatocyte like Cells Derived from Umbilical Cord Blood Stem Cells

Directory of Open Access Journals (Sweden)

A KHoramroodi

2009-10-01

Full Text Available Introduction & Objective: Umbilical cord blood (UCB is a source of Hematopoietic Stem Cells (HSC and progenitor cells that can reconstitute the hematopoietic system in patients with malignant and nonmalignant disorders. Mesenchymal stem cell-derived from umbilical cord blood (UCB have been differentiated to some kind of cells, such as osteobblast, adipoblast and chondroblast in Vitro. This study examined the differentiation of Umbilical Cord Blood (UCB derived stem cells to functional hepatocytes. Materials & Methods: The present study was an experimental study which was carried out in the Payam-e-Noor University of Tehran in cooperation with Hamedan University of Medical Sciences in 2008. Umbilical cord blood (UCB was obtained from Fatemieh hospital (Hamadan, Iran. Stem cells were isolated from the cord blood by combining density gradient centrifugation with plastic adherence. When the isolated cells reached 80% confluence, they differentiated to hepatocyte like cells. The medium which was used was consists of DMEM and 10% Fetal Bovine Serum (FBS supplemented with 20 ng/mL Hepatocyte Growth Factor (HGF, 10 ng/mL basic Fibroblast Growth Factor (bFGF and 20 ng/mL Oncostatin M (OSM.The medium was changed every 3 days and stored for Albumin (ALB, Alpha Fetoprotein (AFP, Alkaline Phosphatase (ALP, and urea assay. Finally PAS stain was done to study Glycogen storage in the differentiated cell. Results: Measurement of biochemical factors in different days showed that concentration of albumin (ALB, alpha fetoprotein (AFP, alkaline phosphatase (ALP, and Urea gradually increased. Also, PAS staining showed the storage of glycogen in these cells. Conclusion: Stem cell-derived from human umbilical cord blood (HUCB is a new source of cell types for cell transplantation therapy of hepatic diseases and under certain conditions these cells can differentiate into liver cells.

Cord Blood

Directory of Open Access Journals (Sweden)

Saeed Abroun

2014-05-01

Full Text Available   Stem cells are naïve or master cells. This means they can transform into special 200 cell types as needed by body, and each of these cells has just one function. Stem cells are found in many parts of the human body, although some sources have richer concentrations than others. Some excellent sources of stem cells, such as bone marrow, peripheral blood, cord blood, other tissue stem cells and human embryos, which last one are controversial and their use can be illegal in some countries. Cord blood is a sample of blood taken from a newborn baby's umbilical cord. It is a rich source of stem cells, umbilical cord blood and tissue are collected from material that normally has no use following a child’s birth. Umbilical cord blood and tissue cells are rich sources of stem cells, which have been used in the treatment of over 80 diseases including leukemia, lymphoma and anemia as bone marrow stem cell potency.  The most common disease category has been leukemia. The next largest group is inherited diseases. Patients with lymphoma, myelodysplasia and severe aplastic anemia have also been successfully transplanted with cord blood. Cord blood is obtained by syringing out the placenta through the umbilical cord at the time of childbirth, after the cord has been detached from the newborn. Collecting stem cells from umbilical blood and tissue is ethical, pain-free, safe and simple. When they are needed to treat your child later in life, there will be no rejection or incompatibility issues, as the procedure will be using their own cells. In contrast, stem cells from donors do have these potential problems. By consider about cord blood potency, cord blood banks (familial or public were established. In IRAN, four cord blood banks has activity, Shariati BMT center cord blood bank, Royan familial cord blood banks, Royan public cord blood banks and Iranian Blood Transfusion Organ cord blood banks. Despite 50,000 sample which storage in these banks, but the

Therapeutic Potential of Umbilical Cord Blood Stem Cells on Brain Damage of a Model of Stroke

Directory of Open Access Journals (Sweden)

Mohammad Reza Nikravesh

2011-11-01

Full Text Available Introduction: Human cord blood-derived stem cells are a rich source of stem cells as well as precursors. With regard to the researchers have focused on the therapeutic potential of stem cell in the neurological disease such as stroke, the aim of this study was the investiga-tion of the therapeutic effects of human cord blood-derived stem cells in cerebral ischemia on rat. Methods: This study was carried out on young rats. Firstly, to create a laboratory model of ischemic stroke, carotid artery of animals was occluded for 30 minutes. Then, umbilical cord blood cells were isolated and labeled using bromodeoxyuridine and 2×105 cells were injected into the experimental group via the tail vein. Rats with hypoxic condi-tions were used as a sham group. A group of animals did not receive any injection or sur-geries were used as a control. Results: Obtained results were evaluated based on behavior-al responses and immunohistochemistry, with emphasis on areas of putamen and caudate nucleus in the control, sham and experimental groups. Our results indicated that behavioral recovery was observed in the experimental group compared to the either the sham or the control group. However, histological studies demonstrated a low percent of tissue injury in the experimental group in comparison with the sham group. Conclusion: Stem cell trans-plantation is beneficial for the brain tissue reparation after hypoxic ischemic cell death.

A novel monoclonal antibody of human stem cell factor inhibits umbilical cord blood stem cell ex vivo expansion

Directory of Open Access Journals (Sweden)

Fan Jie

2012-12-01

Full Text Available Abstract Stem cell factor (SCF activates hematopoietic stem cell (HSC self-renewal and is being used to stimulate the ex vivo expansion of HSCs. The mechanism by which SCF supports expansion of HSCs remains poorly understood. In cord blood ex vivo expansion assays, a newly produced anti-SCF monoclonal antibody (clone 23C8 was found to significantly inhibit the expansion of CD34+ cells. This antibody appears to bind directly to a part of SCF that is critical for biological activity toward expansion of CD34+ cells, which is located in the first 104 amino acids from the NH2-terminus.

[Stem and progenitor cells in biostructure of blood vessel walls].

Science.gov (United States)

Korta, Krzysztof; Kupczyk, Piotr; Skóra, Jan; Pupka, Artur; Zejler, Paweł; Hołysz, Marcin; Gajda, Mariusz; Nowakowska, Beata; Barć, Piotr; Dorobisz, Andrzej T; Dawiskiba, Tomasz; Szyber, Piotr; Bar, Julia

2013-09-18

Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, "anchored" in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC). Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as "subendothelial or vasculogenic zones". Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

Stem and progenitor cells in biostructure of blood vessel walls

Directory of Open Access Journals (Sweden)

Krzysztof Korta

2013-09-01

Full Text Available Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, “anchored” in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC. Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as “subendothelial or vasculogenic zones”. Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

Human Umbilical Cord Blood Stem Cells: Rational for Use as a Neuroprotectant in Ischemic Brain Disease

Directory of Open Access Journals (Sweden)

Hadar Arien-Zakay

2010-09-01

Full Text Available The use of stem cells for reparative medicine was first proposed more than three decades ago. Hematopoietic stem cells from bone marrow, peripheral blood and human umbilical cord blood (CB have gained major use for treatment of hematological indications. CB, however, is also a source of cells capable of differentiating into various non-hematopoietic cell types, including neural cells. Several animal model reports have shown that CB cells may be used for treatment of neurological injuries. This review summarizes the information available on the origin of CB-derived neuronal cells and the mechanisms proposed to explain their action. The potential use of stem/progenitor cells for treatment of ischemic brain injuries is discussed. Issues that remain to be resolved at the present stage of preclinical trials are addressed.

Factors affecting autologous peripheral blood hematopoietic stem cell collections by large-volume leukapheresis: a single center experience

Directory of Open Access Journals (Sweden)

Araci Massami Sakashita

2011-06-01

Full Text Available Objective: To evaluate factors affecting peripheral bloodhematopoietic stem cell yield in patients undergoing large-volumeleukapheresis for autologous peripheral blood stem cell collection.Methods: Data from 304 consecutive autologous peripheral bloodstem cell donors mobilized with hematopoietic growth factor (usually G-CSF, associated or not with chemotherapy, at Hospital Israelita Albert Einstein between February 1999 and June 2010 were retrospectively analyzed. The objective was to obtain at least 2 x 106CD34+ cells/kg of body weight. Pre-mobilization factors analyzedincluded patient’s age, gender and diagnosis. Post mobilizationparameters evaluated were pre-apheresis peripheral white bloodcell count, immature circulating cell count, mononuclear cell count,peripheral blood CD34+ cell count, platelet count, and hemoglobinlevel. The effect of pre and post-mobilization factors on hematopoietic stem cell collection yield was investigated using logistic regression analysis (univariate and multivariate approaches. Results: Premobilization factors correlating to poor CD34+ cell yield in univariate analysis were acute myeloid leukemia (p = 0.017 and other hematological diseases (p = 0.023. Significant post-mobilization factors included peripheral blood immature circulating cells (p = 0.001, granulocytes (p = 0.002, hemoglobin level (p = 0.016, and CD34+ cell concentration (p < 0.001 in the first harvesting day. However, according to multivariate analysis, peripheral blood CD34+ cell content (p < 0.001 was the only independent factor that significantly correlated to poor hematopoietic stem cell yield. Conclusion: In this study, peripheral blood CD34+ cell concentration was the only factor significantly correlated to yield in patients submitted to for autologous collection.

Establishing a public umbilical cord blood stem cell bank for South Africa: an enquiry into public acceptability.

Science.gov (United States)

Meissner-Roloff, Madelein; Pepper, Michael S

2013-12-01

South Africa (SA) faces a large unmet need for bone marrow (BM) transplantation, which could be alleviated in part by establishing a public umbilical cord blood stem cell bank (UCB SCB). Umbilical cord blood is an increasingly utilised source of hematopoietic stem cells for BM transplantation in addition to BM or mobilized peripheral blood stem cells. Establishing a public UCB SCB would therefore be a positive step towards improving the quality of health care in SA by providing for an important unmet need. This study takes the form of an enquiry into the acceptability of establishing a public bank through an interview with and questionnaire completed by mothers-to-be in the antenatal clinic of a large public hospital in SA. Initial results are positive, with 85 % of the participants in favour of establishing a public UCB SCB in SA. This initial probe will serve as a model for a more comprehensive national enquiry into public support and acceptability in different clinics, hospitals and provinces in SA.

Mechanisms of adhesion and subsequent actions of a haematopoietic stem cell line, HPC-7, in the injured murine intestinal microcirculation in vivo.

Directory of Open Access Journals (Sweden)

Dean P J Kavanagh

Full Text Available Although haematopoietic stem cells (HSCs migrate to injured gut, therapeutic success clinically remains poor. This has been partially attributed to limited local HSC recruitment following systemic injection. Identifying site specific adhesive mechanisms underpinning HSC-endothelial interactions may provide important information on how to enhance their recruitment and thus potentially improve therapeutic efficacy. This study determined (i the integrins and inflammatory cyto/chemokines governing HSC adhesion to injured gut and muscle (ii whether pre-treating HSCs with these cyto/chemokines enhanced their adhesion and (iii whether the degree of HSC adhesion influenced their ability to modulate leukocyte recruitment.Adhesion of HPC-7, a murine HSC line, to ischaemia-reperfused (IR injured mouse gut or cremaster muscle was monitored intravitally. Critical adhesion molecules were identified by pre-treating HPC-7 with blocking antibodies to CD18 and CD49d. To identify cyto/chemokines capable of recruiting HPC-7, adhesion was monitored following tissue exposure to TNF-α, IL-1β or CXCL12. The effects of pre-treating HPC-7 with these cyto/chemokines on surface integrin expression/clustering, adhesion to ICAM-1/VCAM-1 and recruitment in vivo was also investigated. Endogenous leukocyte adhesion following HPC-7 injection was again determined intravitally.IR injury increased HPC-7 adhesion in vivo, with intestinal adhesion dependent upon CD18 and muscle adhesion predominantly relying on CD49d. Only CXCL12 pre-treatment enhanced HPC-7 adhesion within injured gut, likely by increasing CD18 binding to ICAM-1 and/or CD18 surface clustering on HPC-7. Leukocyte adhesion was reduced at 4 hours post-reperfusion, but only when local HPC-7 adhesion was enhanced using CXCL12.This data provides evidence that site-specific molecular mechanisms govern HPC-7 adhesion to injured tissue. Importantly, we show that HPC-7 adhesion is a modulatable event in IR injury and

Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs

Science.gov (United States)

Phinney, Donald G.; Di Giuseppe, Michelangelo; Njah, Joel; Sala, Ernest; Shiva, Sruti; St Croix, Claudette M.; Stolz, Donna B.; Watkins, Simon C.; Di, Y. Peter; Leikauf, George D.; Kolls, Jay; Riches, David W. H.; Deiuliis, Giuseppe; Kaminski, Naftali; Boregowda, Siddaraju V.; McKenna, David H.; Ortiz, Luis A.

2015-01-01

Mesenchymal stem cells (MSCs) and macrophages are fundamental components of the stem cell niche and function coordinately to regulate haematopoietic stem cell self-renewal and mobilization. Recent studies indicate that mitophagy and healthy mitochondrial function are critical to the survival of stem cells, but how these processes are regulated in MSCs is unknown. Here we show that MSCs manage intracellular oxidative stress by targeting depolarized mitochondria to the plasma membrane via arrestin domain-containing protein 1-mediated microvesicles. The vesicles are then engulfed and re-utilized via a process involving fusion by macrophages, resulting in enhanced bioenergetics. Furthermore, we show that MSCs simultaneously shed micro RNA-containing exosomes that inhibit macrophage activation by suppressing Toll-like receptor signalling, thereby de-sensitizing macrophages to the ingested mitochondria. Collectively, these studies mechanistically link mitophagy and MSC survival with macrophage function, thereby providing a physiologically relevant context for the innate immunomodulatory activity of MSCs. PMID:26442449

Selective interactions between epithelial tumour cells and bone marrow mesenchymal stem cells

OpenAIRE

Hombauer, H; Minguell, J J

2000-01-01

This work is a comparative study on the features displayed by an epithelial metastatic breast cancer cell line (MCF-7) when set in co-culture with human bone marrow mesenchymal stem cells (MSC) or a feeder layer of 3T3 fibroblasts. MSC, a subset of non-haematopoietic cells in the marrow stroma, display a potential for self-renewal, proliferation and differentiation into precursors for bone, cartilage, connective and muscular tissue. Adhesion of MCF-7 cells to monolayers of MSC or 3T3 was high...

The impact of preapheresis white blood cell count on autologous peripheral blood stem cell collection efficiency and HSC infusion side effect rate.

Science.gov (United States)

Sakashita, Araci M; Kondo, Andrea T; Yokoyama, Ana Paula H; Lira, Sanny M C; Bub, Carolina B; Souza, Aline M; Cipolletta, Andrea N F; Alvarez, Kelen C; Hamerschlak, Nelson; Kutner, Jose M; Chiattone, Carlos S

2018-01-19

Autologous peripheral blood hematopoietic stem cell (PBSC) collection efficiency (CE) is reportedly affected by the patient's blood properties; however, studies to identify factors correlated with CE have shown inconsistent results. Additionally, variables such as stem cell graft granulocyte content and patient age, sex, and underlying disease, may be associated with hematopietic stem cell (HSC) infusion-related adverse reactions. In this study, we evaluated the correlation of preleukapheresis PB granulocyte count and PBSC harvest variables with CD34 + collection yield and efficiency, and thawed HSC infusion side effect occurrence. We evaluated data from 361 patients who had undergone autologous PBSC transplant. Large volume leukapheresis was the method for PBSC collection. Complete Blood Count and CD34 + cell enumeration were performed in the preapheresis PB and the apheresis product sample. The PBSC grafts were submitted to non-controlled rate freezing after addition of 5% DMSO plus 6% hidroxyethylstarch as a cryoprotectant solution. The cryopreserved graft was thawed in a 37°C water bath and then infused without further manipulation. The CD34 + yield was associated with preapheresis PB CD34 + count and immature granulocyte count. The PBSC CE was negatively correlated with preapheresis white blood cell (WBC), immature granulocyte and granulocyte count. The leukapheresis product total nucleated cell (TNC) and granulocyte content was correlated with the thawed graft infusion side effect occurrence. This study has shown that preapheresis PB WBC and granulocyte counts were associated with leukapheresis CE. Additionally, the leukapheresis product TNC and granulocyte content was correlated with thawed graft infusion side effect occurrence. © 2018 Wiley Periodicals, Inc.

Autologous blood stem-cell transplantation in patients with advanced Hodgkin's disease and prior radiation to the pelvic site

International Nuclear Information System (INIS)

Koerbling, M.H.; Holle, R.; Haas, R.; Knauf, W.; Doerken, B.H.; Ho, A.D.; Kuse, R.; Pralle, H.; Fliedner, T.M.; Hunstein, W.

1990-01-01

Patients with relapsed Hodgkin's disease who respond to salvage therapy are successfully treated with cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) followed by autologus bone marrow transplantation (ABMT). Because of heavy pretreatment including radiation to the pelvic site, marrow harvest was not feasible in those patients. We therefore used blood-derived hemopoietic precursor cells as an alternative stem-cell source to rescue them after superdose chemotherapy. Hemopoietic precursor cells were mobilized into the peripheral blood either by chemotherapeutic induction of transient myelosuppression followed by an overshooting of blood stem-cell concentration, or by continuous intravenous (IV) granulocyte-macrophage colony-stimulating factor (GM-CSF) administration. The median time to reach 1,000 WBC per microliter, 500 polymorphonuclear cells (PMN) per microliter, or 20,000 platelets per microliter was 10, 20.5, and 38 days, respectively, for 50% of all patients. The platelet counts of two patients never dropped below 20,000/microL following autologous blood stem-cell transplantation (ABSCT), whereas two other patients had to be supported with platelets for 75 and 86 days posttransplant until a stable peripheral platelet count of 20,000/microL was attained. Among the 11 assessable patients, seven are in unmaintained complete remission (CR) at a median follow-up of 318 days. This is a first report on a series of ABSCTs in patients with advanced Hodgkin's disease proving that, despite prior damage to the marrow site, the circulating stem-cell pool is still a sufficient source of hemopoietic precursor cells for stem-cell rescue

Genetic modification of haematopoietic cells for combined resistance to podophyllotoxins, other agents covered by MDR1-mediated efflux activity and nitrosoureas.

Science.gov (United States)

Baum, C; Peinert, S; Carpinteiro, A; Eckert, H G; Fairbairn, L J

2000-05-01

Genetic transfer and expression of drug-resistance functions into haematopoietic stem and progenitor cells is a promising means to overcome both the acute and longterm side-effects of cytotoxic drugs in bone marrow. Here, we describe a functional analysis of a retroviral vector that co-expresses human cDNAs for multidrug resistance 1/P-glycoprotein (MDR1) and a double mutant of O(6)-alkylguanine-alkyltransferase (hATPA/GA) to high levels. The hATPA/GA protein contains two amino acid substitutions that render it resistant to compounds such as O(6)-benzylguanine that inhibit the wild-type protein which is often overexpressed in resistant tumour cells. Evidence for simultaneous drug resistance of genetically modified primary murine progenitor cells to colchicine or the podophyllotoxin etoposide, both covered by MDR1-mediated efflux activity, and the nitrosourea BCNU, which is counteracted by hATPA/GA, is presented using in vitro colony assays.

Mobilization of peripheral blood stem cells in CLL patients after front-line fludarabine treatment.

Science.gov (United States)

Lysak, D; Koza, V; Steinerova, K; Jindra, P; Vozobulova, V; Schutzova, M

2005-07-01

Autologous peripheral blood stem cell transplantation is performed in an increasing number of chronic lymphocytic leukaemia (CLL) patients who are in the first remission following fludarabine treatment. There are contradictory data about the adverse impact of fludarabine on stem cell harvest. We analysed retrospectively mobilization results in 56 poor-risk CLL patients (median age: 56 years) who underwent first-line treatment with fludarabine and cyclophosphamide. The mobilization, consisting of cyclophosphamide 3 g/m(2) and granulocyte colony-stimulating factor (G-CSF) 10 microg/kg per day, was performed with a median of 77 days following the last fludarabine course. The target yield was >or=2.0x10(6) CD34+ cells/kg. The procedure was successful in 23 (41%) patients. A median of 3.3x10(6) CD34+ cells/kg was collected per patient. The successful mobilization was associated with a longer interval from the last chemotherapy (>2 months). The mobilization result was not influenced by the number of fludarabine cycles. No correlation was found in other parameters such as disease stage at diagnosis, disease status at stimulation or age. The poorly mobilized patients had significantly lower prestimulation blood counts (platelets, WBC and haemoglobin). Our data show that fludarabine does not generally prevent the stem cell mobilization; nevertheless, mechanisms related to the impact of fludarabine on stem cell harvest must be further investigated.

Human mesenchymal stem cells promote CD34+ hematopoietic stem cell proliferation with preserved red blood cell differentiation capacity.

Science.gov (United States)

Lau, Show Xuan; Leong, Yin Yee; Ng, Wai Hoe; Ng, Albert Wee Po; Ismail, Ida Shazrina; Yusoff, Narazah Mohd; Ramasamy, Rajesh; Tan, Jun Jie

2017-06-01

Studies showed that co-transplantation of mesenchymal stem cells (MSCs) and cord blood-derived CD34 + hematopoietic stem cells (HSCs) offered greater therapeutic effects but little is known regarding the effects of human Wharton's jelly derived MSCs on HSC expansion and red blood cell (RBC) generation in vitro. This study aimed to investigate the effects of MSCs on HSC expansion and differentiation. HSCs were co-cultured with MSCs or with 10% MSCs-derived conditioned medium, with HSCs cultured under standard medium served as a control. Cell expansion rates, number of mononuclear cell post-expansion and number of enucleated cells post-differentiation were evaluated. HSCs showed superior proliferation in the presence of MSC with mean expansion rate of 3.5 × 10 8  ± 1.8 × 10 7 after day 7 compared to the conditioned medium and the control group (8.9 × 10 7  ± 1.1 × 10 8 and 7.0 × 10 7  ± 3.3 × 10 6 respectively, P cell was greater compared to earlier passages, indicating successful RBC differentiation. Cord blood-derived CD34 + HSCs can be greatly expanded by co-culturing with MSCs without affecting the RBC differentiation capability, suggesting the importance of direct MSC-HSCs contact in HSC expansion and RBC differentiation. © 2017 International Federation for Cell Biology.

Three-dimensional wet-electrospun poly(lactic acid)/multi-wall carbon nanotubes scaffold induces differentiation of human menstrual blood-derived stem cells into germ-like cells.

Science.gov (United States)

Eyni, Hossein; Ghorbani, Sadegh; Shirazi, Reza; Salari Asl, Leila; P Beiranvand, Shahram; Soleimani, Masoud

2017-09-01

Infertility caused by the disruption or absence of germ cells is a major and largely incurable medical problem. Germ cells (i.e., sperm or egg) play a key role in the transmission of genetic and epigenetic information across generations. Generation of gametes derived in vitro from stem cells hold promising prospects which could potentially help infertile men and women. Menstrual blood-derived stem cells are a unique stem cell source. Evidence suggests that menstrual blood-derived stem cells exhibit a multi-lineage potential and have attracted extensive attention in regenerative medicine. To maintain the three-dimensional structure of natural extra cellular matrices in vitro, scaffolds can do this favor and mimic a microenvironment for cell proliferation and differentiation. According to previous studies, poly(lactic acid) and multi-wall carbon nanotubes have been introduced as novel and promising biomaterials for the proliferation and differentiation of stem cells. Some cell types have been successfully grown on a matrix containing carbon nanotubes in tissue engineering but there is no report for this material to support stem cells differentiation into germ cells lineage. This study designed a 3D wet-electrospun poly(lactic acid) and poly(lactic acid)/multi-wall carbon nanotubes composite scaffold to compare infiltration, proliferation, and differentiation potential of menstrual blood-derived stem cells toward germ cell lineage with 2D culture. Our primary data revealed that the fabricated scaffold has mechanical and biological suitable qualities for supporting and attachments of stem cells. The differentiated menstrual blood-derived stem cells tracking in scaffolds using scanning electron microscopy confirmed cell attachment, aggregation, and distribution on the porous scaffold. Based on the differentiation assay by RT-PCR analysis, stem cells and germ-like cells markers were expressed in 3D groups as well as 2D one. It seems that poly(lactic acid

Centre characteristics and procedure-related factors have an impact on outcomes of allogeneic transplantation for patients with CLL: a retrospective analysis from the European Society for Blood and Marrow Transplantation (EBMT)

NARCIS (Netherlands)

Schetelig, J.; Wreede, L.C. de; Andersen, N.S.; Moreno, C.; Gelder, M. van; Vitek, A.; Karas, M.; Michallet, M.; Machaczka, M.; Gramatzki, M.; Beelen, D.; Finke, J.; Delgado, J.; Volin, L.; Passweg, J.; Dreger, P.; Schaap, N.P.; Wagner, E.; Henseler, A.; Biezen, A. van; Bornhauser, M.; Iacobelli, S.; Putter, H.; Schonland, S.O.; Kroger, N.

2017-01-01

The best approach for allogeneic haematopoietic stem cell transplantations (alloHCT) in patients with chronic lymphocytic leukaemia (CLL) is unknown. We therefore analysed the impact of procedure- and centre-related factors on 5-year event-free survival (EFS) in a large retrospective study. Data of

Stem cell migration after irradiation

International Nuclear Information System (INIS)

Nothdurft, W.; Fliedner, T.M.

1979-01-01

The survival rate of irradiated rodents could be significantly improved by shielding only the small parts of hemopoietic tissues during the course of irradiation. The populations of circulating stem cells in adult organisms are considered to be of some importance for the homeostasis between the many sites of blood cell formation and for the necessary flexibility of hemopoietic response in the face of fluctuating demands. Pluripotent stem cells are migrating through peripheral blood as has been shown for several mammalian species. Under steady state conditions, the exchange of stem cells between the different sites of blood cell formation appears to be restricted. Their presence in blood and the fact that they are in balance with the extravascular stem cell pool may well be of significance for the surveilance of the integrity of local stem cell populations. Any decrease of stem cell population in blood below a critical size results in the rapid immigration of circulating stem cells in order to restore local stem cell pool size. Blood stem cells are involved in the regeneration after whole-body irradiation if the stem cell population in bone marrows is reduced to less than 10% of the normal state. In the animals subjected to partial-body irradiation, the circulating stem cells appear to be the only source for the repopulation of the heavily irradiated, aplastic sites of hemopoietic organs. (Yamashita, S.)

The stem cell secretome and its role in brain repair.

Science.gov (United States)

Drago, Denise; Cossetti, Chiara; Iraci, Nunzio; Gaude, Edoardo; Musco, Giovanna; Bachi, Angela; Pluchino, Stefano

2013-12-01

Compelling evidence exists that non-haematopoietic stem cells, including mesenchymal (MSCs) and neural/progenitor stem cells (NPCs), exert a substantial beneficial and therapeutic effect after transplantation in experimental central nervous system (CNS) disease models through the secretion of immune modulatory or neurotrophic paracrine factors. This paracrine hypothesis has inspired an alternative outlook on the use of stem cells in regenerative neurology. In this paradigm, significant repair of the injured brain may be achieved by injecting the biologics secreted by stem cells (secretome), rather than implanting stem cells themselves for direct cell replacement. The stem cell secretome (SCS) includes cytokines, chemokines and growth factors, and has gained increasing attention in recent years because of its multiple implications for the repair, restoration or regeneration of injured tissues. Thanks to recent improvements in SCS profiling and manipulation, investigators are now inspired to harness the SCS as a novel alternative therapeutic option that might ensure more efficient outcomes than current stem cell-based therapies for CNS repair. This review discusses the most recent identification of MSC- and NPC-secreted factors, including those that are trafficked within extracellular membrane vesicles (EVs), and reflects on their potential effects on brain repair. It also examines some of the most convincing advances in molecular profiling that have enabled mapping of the SCS. Copyright © 2013 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Umbilical cord blood banking in the worldwide hematopoietic stem cell transplantation system: perspectives for Ukraine.

Science.gov (United States)

Kalynychenko, T O

2017-09-01

Significant progress in the promotion of procedural technologies associated with the transplantation of hematopoietic stem cells caused a rapid increase in activity. The exchange of hematopoietic stem cells for unrelated donor transplantations is now much easier due to the relevant international professional structures and organizations established to support cooperation and standard setting, as well as rules for the functioning of both national donor registries and cord blood banks. These processes are increasing every year and are contributing to the outpacing rates of development in this area. Products within their country should be regulated by the competent government authorities. This study analyzes the work of international and national levels of support for transplantation activity in the field of unrelated hematopoietic stem cell transplantation, the standardization order of technologies, as well as data that justify the need to create a network of donated umbilical cord blood banks in Ukraine as a factor in the development of allogeneic transplantation. This will promote the accessibility of international standards for the treatment of serious diseases for Ukrainian citizens.

76 FR 19101 - Advisory Council on Blood Stem Cell Transplantation; Notice of Meeting

Science.gov (United States)

2011-04-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration Advisory Council on Blood Stem Cell Transplantation; Notice of Meeting In accordance with section 10(a)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), notice is hereby given of the following meeting: [[Page 19102

Radiation effects on haematopoietic stem cells in vitro: possible role of stromal niches in the stem cell hierarchy

International Nuclear Information System (INIS)

Sharp, J.G.; Crouse, D.A.; Jackson, J.D.; Schmidt, C.M.; Ritter, E.K.; Udeaja, G.C.; Mann, S.L.

1986-01-01

The authors describe experiments which attempt to elucidate the nature of haemopoietic stem cell and microenvironmental stromal cell interactions which might explain anomalies in explanations of the differential effects of radiation on HSC versus MSC. In particular, there is an attempt to demonstrate the existence of stromal niches. (UK)

Generation of human induced pluripotent stem cells from a Bombay individual: Moving towards 'universal-donor' red blood cells

International Nuclear Information System (INIS)

Seifinejad, Ali; Taei, Adeleh; Totonchi, Mehdi; Vazirinasab, Hamed; Hassani, Seideh Nafiseh; Aghdami, Nasser; Shahbazi, Ebrahim; Yazdi, Reza Salman; Salekdeh, Ghasem Hosseini; Baharvand, Hossein

2010-01-01

Bombay phenotype is one of the rare phenotypes in the ABO blood group system that fails to express ABH antigens on red blood cells. Nonsense or missense mutations in fucosyltransfrase1 (FUT1) and fucosyltransfrase2 (FUT2) genes are known to create this phenotype. This blood group is compatible with all other blood groups as a donor, as it does not express the H antigen on the red blood cells. In this study, we describe the establishment of human induced pluripotent stem cells (iPSCs) from the dermal fibroblasts of a Bombay blood-type individual by the ectopic expression of established transcription factors Klf4, Oct4, Sox2, and c-Myc. Sequence analyses of fibroblasts and iPSCs revealed a nonsense mutation 826C to T (276 Gln to Ter) in the FUT1 gene and a missense mutation 739G to A (247 Gly to Ser) in the FUT2 gene in the Bombay phenotype under study. The established iPSCs resemble human embryonic stem cells in morphology, passaging, surface and pluripotency markers, normal karyotype, gene expression, DNA methylation of critical pluripotency genes, and in-vitro differentiation. The directed differentiation of the iPSCs into hematopoietic lineage cells displayed increased expression of the hematopoietic lineage markers such as CD34, CD133, RUNX1, KDR, α-globulin, and γ-globulin. Such specific stem cells provide an unprecedented opportunity to produce a universal blood group donor, in-vitro, thus enabling cellular replacement therapies, once the safety issue is resolved.

Exploiting endogenous fibrocartilage stem cells to regenerate cartilage and repair joint injury

Science.gov (United States)

Embree, Mildred C.; Chen, Mo; Pylawka, Serhiy; Kong, Danielle; Iwaoka, George M.; Kalajzic, Ivo; Yao, Hai; Shi, Chancheng; Sun, Dongming; Sheu, Tzong-Jen; Koslovsky, David A.; Koch, Alia; Mao, Jeremy J.

2016-01-01

Tissue regeneration using stem cell-based transplantation faces many hurdles. Alternatively, therapeutically exploiting endogenous stem cells to regenerate injured or diseased tissue may circumvent these challenges. Here we show resident fibrocartilage stem cells (FCSCs) can be used to regenerate and repair cartilage. We identify FCSCs residing within the superficial zone niche in the temporomandibular joint (TMJ) condyle. A single FCSC spontaneously generates a cartilage anlage, remodels into bone and organizes a haematopoietic microenvironment. Wnt signals deplete the reservoir of FCSCs and cause cartilage degeneration. We also show that intra-articular treatment with the Wnt inhibitor sclerostin sustains the FCSC pool and regenerates cartilage in a TMJ injury model. We demonstrate the promise of exploiting resident FCSCs as a regenerative therapeutic strategy to substitute cell transplantation that could be beneficial for patients suffering from fibrocartilage injury and disease. These data prompt the examination of utilizing this strategy for other musculoskeletal tissues. PMID:27721375

Fifteen-year follow-up of a patient with beta thalassaemia and extramedullary haematopoietic tissue compressing the spinal cord

International Nuclear Information System (INIS)

Niggemann, P.; Krings, T.; Thron, A.; Hans, F.

2005-01-01

A long-term follow-up of a patient with beta thalassaemia with intra- and extraspinal extramedullary haematopoietic tissue compressing the spinal cord is presented. Extramedullary haematopoietic nodules are a rare cause of spinal cord compression and should be included in the differential diagnosis, especially in patients from Mediterranean countries. Treatment with radiation therapy solely failed, giving rise to the need of surgical intervention. Surgical decompression of the spine and the removal of the culprit lesion compressing the spine were performed. Postinterventional radiation therapy was applied to the spine. A relapse had to be treated again by surgical means combined with postinterventional radiation therapy. A complete relief of the symptoms and control of the lesion could be obtained

Fifteen-year follow-up of a patient with beta thalassaemia and extramedullary haematopoietic tissue compressing the spinal cord

Energy Technology Data Exchange (ETDEWEB)

Niggemann, P.; Krings, T.; Thron, A. [Dept. of Neuroradiology, RWTH-Aachen Hosital (Germany); Hans, F. [Dept. of Neurosurgery, RWTH Aachen Hospital (Germany); 1

2005-04-01

A long-term follow-up of a patient with beta thalassaemia with intra- and extraspinal extramedullary haematopoietic tissue compressing the spinal cord is presented. Extramedullary haematopoietic nodules are a rare cause of spinal cord compression and should be included in the differential diagnosis, especially in patients from Mediterranean countries. Treatment with radiation therapy solely failed, giving rise to the need of surgical intervention. Surgical decompression of the spine and the removal of the culprit lesion compressing the spine were performed. Postinterventional radiation therapy was applied to the spine. A relapse had to be treated again by surgical means combined with postinterventional radiation therapy. A complete relief of the symptoms and control of the lesion could be obtained.

Biosimilar G-CSF based mobilization of peripheral blood hematopoietic stem cells for autologous and allogeneic stem cell transplantation.

Science.gov (United States)

Schmitt, Michael; Publicover, Amy; Orchard, Kim H; Görlach, Matthias; Wang, Lei; Schmitt, Anita; Mani, Jiju; Tsirigotis, Panagiotis; Kuriakose, Reeba; Nagler, Arnon

2014-01-01

The use of granulocyte colony stimulating factor (G-CSF) biosimilars for peripheral blood hematopoietic stem cell (PBSC) mobilization has stimulated an ongoing debate regarding their efficacy and safety. However, the use of biosimilar G-CSF was approved by the European Medicines Agency (EMA) for all the registered indications of the originator G-CSF (Neupogen (®) ) including mobilization of stem cells. Here, we performed a comprehensive review of published reports on the use of biosimilar G-CSF covering patients with hematological malignancies as well as healthy donors that underwent stem cell mobilization at multiple centers using site-specific non-randomized regimens with a biosimilar G-CSF in the autologous and allogeneic setting. A total of 904 patients mostly with hematological malignancies as well as healthy donors underwent successful autologous or allogeneic stem cell mobilization, respectively, using a biosimilar G-CSF (520 with Ratiograstim®/Tevagrastim, 384 with Zarzio®). The indication for stem cell mobilization in hematology patients included 326 patients with multiple myeloma, 273 with Non-Hodgkin's lymphoma (NHL), 79 with Hodgkin's lymphoma (HL), and other disease. 156 sibling or volunteer unrelated donors were mobilized using biosimilar G-CSF. Mobilization resulted in good mobilization of CD34+ stem cells with side effects similar to originator G-CSF. Post transplantation engraftment did not significantly differ from results previously documented with the originator G-CSF. The side effects experienced by the patients or donors mobilized by biosimilar G-CSF were minimal and were comparable to those of originator G-CSF. In summary, the efficacy of biosimilar G-CSFs in terms of PBSC yield as well as their toxicity profile are equivalent to historical data with the reference G-CSF.

Being a haematopoietic stem cell donor for a sick sibling: Adult donors' experiences prior to donation.

Science.gov (United States)

Kisch, Annika; Bolmsjö, Ingrid; Lenhoff, Stig; Bengtsson, Mariette

2015-10-01

There is a lack of knowledge about sibling stem cell donors' experiences pre-donation and the waiting period before the donation might have been long. The donors and their corresponding sibling recipients were simultaneously included in two different interview studies. The results from the recipient study have been presented in a separate paper. The aim was to explore the experiences of being a stem cell donor for a sibling, prior to donation. Ten adult sibling donors were interviewed prior to stem cell donation. The interviews were digitally recorded, transcribed verbatim and subjected to qualitative content analysis. The main theme Being a cog in a big wheel describes the complex process of being a sibling donor prior to donation, covering a mixture of emotions and thoughts. The four subthemes Being available, Being anxious, Being concerned and Being obliged cover the various experiences. The sibling donors' experiences are influenced by the quality of the relationship with the sick sibling. Sibling stem cell donors go through a complex process once they have accidentally got involved in. They have been asked to become a donor; it was not a voluntary choice. In caring for sibling stem cell donors the nurses should be aware of the complexity of the process they experience and take into consideration their personal situation and needs. Providing optimal care for both sibling donors and their corresponding recipients is a challenge, and further improvement and exploration are needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Ethical aspects of human embryonic stem cell use and commercial umbilical cord blood stem cell banking. Ethical reflections on the occasion of the regulation of the European Council and Parliament on advanced therapy medicinal products].

Science.gov (United States)

Virt, G

2010-01-01

The regulation of the European Council and Parliament on advanced therapy medicinal products also includes therapies with human embryonic stem cells. The use of these stem cells is controversially and heavily discussed. Contrary to the use of adult stem cells, medical and ethical problems concerning the use of human embryonic stem cells persists, because this use is based on the destruction of human life at the very beginning. The regulation foresees, therefore, subsidiarity within the European Member States. Although there are no ethical problems in principle with the use of stem cells from the umbilical cord blood, there are social ethical doubts with the banking of these stem cells for autologous use without any currently foreseeable medical advantage by commercial blood banks. Also in this case subsidiarity is valid.

Targeting the bone marrow: applications in stem cell transplantation

International Nuclear Information System (INIS)

Orchard, K.; Cooper, M.

2004-01-01

Therapeutic doses of radiation cab be selectively directed to the bone marrow either directly using vectors that bind to myeloid and/or lymphoid specific antigens or indirectly by targeting bone matrix. The combination of an accessible target tissue and relatively radiation sensitive malignant cells favours the use of targeted radiotherapy in the treatment of haematopoietic malignancies. Dose escalation of targeted radiation can increase tumour cell destruction and has led to the use of myelosuppressive and possibly myeloablative doses of targeted radiation. A natural development has been the use of targeted radiation in conditioning prior to haematopoietic stem cell transplantation (HSCT). Several groups are actively exploring the use of targeted radiotherapy in the context of HSCT as treatment for haematological malignancies. Although no randomised trials using targeted radiotherapy in HSCT have been published, phase I and II trials have shown very encouraging results stimulating further clinical research in this field. After more than a decade of translational research the optimal combination of therapeutic radioisotope and vector has not been determined. This review summarises the clinical experience of targeted radiotherapy in HSCT and discusses the problems that still need to be solved to maximise the potential of this new treatment modality in HSCT

Human umbilical cord blood-derived stem cells and brain-derived neurotrophic factor protect injured optic nerve: viscoelasticity characterization

Directory of Open Access Journals (Sweden)

Xue-man Lv

2016-01-01

Full Text Available The optic nerve is a viscoelastic solid-like biomaterial. Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury. We hypothesized that stress relaxation and creep properties of the optic nerve change after injury. More-over, human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal. To validate this hypothesis, a rabbit model of optic nerve injury was established using a clamp approach. At 7 days after injury, the vitreous body re-ceived a one-time injection of 50 µg human brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood-derived stem cells. At 30 days after injury, stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly, with patho-logical changes in the injured optic nerve also noticeably improved. These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves, and thereby contributes to nerve recovery.

[Skin biopsy in diagnosis of chronic graft-versus-host disease in patients after allogeneic haematopoietic stem cell transplantation: pathologist's point of view on quantitative scoring system].

Science.gov (United States)

Grzanka, Dariusz; Styczyński, Jan; Debski, Robert; Krenska, Anna; Pacholska, Małgorzata; Prokurat, Andrzej I; Wysocki, Mariusz; Marszałek, Andrzej

2008-01-01

Pathology diagnosis of chronic graft-versus-host-disease (GVHD) after allogeneic haematopoietic stem cell transplantation (allo-HSCT) is an important issue in clinical follow-up, in spite of frequent difficulties in interpretation., related to dynamic changes occurring in the skin during the disease, as well as to sequelae of basic disease and immunosuppressive therapy. Recently presented Consensus NIH (National Health Institute, Bethesda, USA) of histopathologic (HP) analysis is still complex and intrinsically divergent, thus clinically difficult to implement. Analysis of clinical value of histological evaluation results of skin biopsy in children after allo-HSCT and its correlation with clinical status. Ten skin biopsies were taken from 7 patients (4 boys, 3 girls, age 3-15 years) after allo-HSCT (6 MFD, 1 MMUD) and analyzed after hematoxylin/eosine and immunohistochemical (CD3, CD45T, CD20) staining. Pathology analysis was based on commonly accepted criteria enabling simple and unambiguous interpretation. Results were compared with clinical data and indications for immunosuppressive therapy. It was found that reliable and coherent interpretation can be made when following parameters were taken into account: 1. in epithelium: the presence of apoptosis, archetypical changes and vacuolar degeneration in the basilar layer, presence of CD3/CD45 in the epidermis; 2. in the dermis: the extent of collagenization, presence of melanophages and lymphocyte infiltrations; 3. in the eccrine glands epithelium: eccrine glands atrophy and presence of lymphocytes. A new scoring system of skin biopsy analysis in patients with chronic GVHD based on the modified NIH Consensus was proposed. The preliminary clinical value of histological results was assessed. Skin biopsy evaluation based on limited qualitative and quantitative analysis of lymphocyte infiltrates together with studies on intensity of apoptosis, collagenization and archetypical changes is a valuable diagnostic method

Defining a stem cell hierarchy in the intestine: markers, caveats and controversies

Science.gov (United States)

Smith, Nicholas R.; Gallagher, Alexandra C.

2016-01-01

Abstract The past decade has appreciated rapid advance in identifying the once elusive intestinal stem cell (ISC) populations that fuel the continual renewal of the epithelial layer. This advance was largely driven by identification of novel stem cell marker genes, revealing the existence of quiescent, slowly‐ and active‐cycling ISC populations. However, a critical barrier for translating this knowledge to human health and disease remains elucidating the functional interplay between diverse stem cell populations. Currently, the precise hierarchical and regulatory relationships between these ISC populations are under intense scrutiny. The classical theory of a linear hierarchy, where quiescent and slowly‐cycling stem cells self‐renew but replenish an active‐cycling population, is well established in other rapidly renewing tissues such as the haematopoietic system. Efforts to definitively establish a similar stem cell hierarchy within the intestinal epithelium have yielded conflicting results, been difficult to interpret, and suggest non‐conventional alternatives to a linear hierarchy. While these new and potentially paradigm‐shifting discoveries are intriguing, the field will require development of a number of critical tools, including highly specific stem cell marker genes along with more rigorous experimental methodologies, to delineate the complex cellular relationships within this dynamic organ system. PMID:26864260

Health related quality of life and emotional health in children with chronic granulomatous disease: a comparison of those managed conservatively with those that have undergone haematopoietic stem cell transplant.

Science.gov (United States)

Cole, Theresa; McKendrick, Fiona; Titman, Penny; Cant, Andrew J; Pearce, Mark S; Cale, Catherine M; Goldblatt, David; Gennery, Andrew R

2013-01-01

Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency that predisposes to life-threatening infections and inflammation. Haematopoietic stem cell transplant (HSCT) can cure CGD. Chronic illness reduces quality of life. Children with haematological malignancies report improved quality of life post-HSCT. There are no data for children with CGD. This study evaluated quality of life and emotional well-being in CGD children treated conventionally or transplanted. Parents and children completed the Pediatric Quality of Life Inventory v4.0 (PedsQL) and Strengths and Difficulties Questionnaires (SDQ). Mean scores were compared with published UK norms. Comparisons were made for those that had or had not undergone HSCT. Forty-seven parents completed PedsQL (children aged 3-15). Twenty-one were post-HSCT. Forty-two completed SDQ (children aged 3-15). Nineteen post-HSCT. Median age for non-HSCT group 9 years. Median age for post-HSCT group 10 years. The HSCT group were median 3 years post-HSCT (range 1-9 years). HSCT survival was 90 %-two died without completing questionnaires Parent and self-reported quality of life for non-transplanted children was significantly lower than healthy children. Parents reported increased emotional difficulties compared to published norms. PedsQL and SDQ scores for transplanted children were not significantly different from healthy norms. This study demonstrates the quality of life is reduced in CGD. Transplanted patients have quality of life comparable to levels reported in healthy children. This data will help inform families and clinicians when deciding about treatment and may have relevance for other immunodeficiencies treated with transplant.

Growth Kinetics, Characterization, and Plasticity of Human Menstrual Blood Stem Cells

Directory of Open Access Journals (Sweden)

Davood Mehrabani

2016-03-01

Full Text Available One of the readily available sources of mesenchymal stem cells (MSCs is menstrual blood-derived stem cells (Men-SCs, which exhibit characteristics similar to other types of MSCs. This study was performed to determine the growth kinetics, plasticity, and characterization of Men-SCs in women. During spring 2014 in the southern Iranian city of Shiraz, menstrual blood (5 mL was obtained from 10 women on their third day of menstruation in 2 age groups of 30 to 40 and 40 to 50 years old. Ficoll was used to separate the mononuclear cell fraction. After the Men-SCs were cultured, they were subcultured up to passage 4. Growth behavior and population doubling time were evaluated by seeding 5×104 cells into 12- and 24-well culture plates, and the colonies were enumerated. The expression of CD44, CD90, and CD34 was evaluated. The osteogenic potential was assessed by alizarin red staining. The Men-SCs were shown to be plastic adherent and spindle-shaped. Regarding the growth curves in the 12- and 24-well culture plates, it was demonstrated that in the women aged between 30 and 40 years, population doubling time was 55.5 and 62 hours, respectively, while these values in the women aged between 40 and 50 years were 70.4 and 72.4 hours, correspondingly. Positive expression of CD44 and CD90 and negative expression of CD34 were noted. In the osteogenic differentiation medium, the cells differentiated toward osteoblasts. As human Men-SCs are easily collectable without any invasive procedure and are a safe and rapid source of MSCs, they can be a good candidate for stem cell banking and cell transplantation in women.

Hematopoietic stem cell transplantation in Switzerland: a comprehensive quality control report on centre effect.

Science.gov (United States)

Passweg, Jakob; Baldomero, Helen; Stern, Martin; Bargetzi, Mario; Ghielmini, Michele; Leibundgut, Kurt; Duchosal, Michel; Hess, Urs; Seger, Reinhard; Buhrfeind, Eva; Schanz, Urs; Gratwohl, Alois

2010-06-12

Interest groups advocate centre-specific outcome data as a useful tool for patients in choosing a hospital for their treatment and for decision-making by politicians and the insurance industry. Haematopoietic stem cell transplantation (HSCT) requires significant infrastructure and represents a cost-intensive procedure. It therefore qualifies as a prime target for such a policy. We made use of the comprehensive database of the Swiss Blood Stem Cells Transplant Group (SBST) to evaluate potential use of mortality rates. Nine institutions reported a total of 4717 HSCT - 1427 allogeneic (30.3%), 3290 autologous (69.7%) - in 3808 patients between the years 1997 and 2008. Data were analysed for survival- and transplantation-related mortality (TRM) at day 100 and at 5 years. The data showed marked and significant differences between centres in unadjusted analyses. These differences were absent or marginal when the results were adjusted for disease, year of transplant and the EBMT risk score (a score incorporating patient age, disease stage, time interval between diagnosis and transplantation, and, for allogeneic transplants, donor type and donor-recipient gender combination) in a multivariable analysis. These data indicate comparable quality among centres in Switzerland. They show that comparison of crude centre-specific outcome data without adjustment for the patient mix may be misleading. Mandatory data collection and systematic review of all cases within a comprehensive quality management system might, in contrast, serve as a model to ascertain the quality of other cost-intensive therapies in Switzerland.

Frozen cord blood hematopoietic stem cells differentiate into higher numbers of functional natural killer cells in vitro than mobilized hematopoietic stem cells or freshly isolated cord blood hematopoietic stem cells.

Directory of Open Access Journals (Sweden)

Martha Luevano

Full Text Available Adoptive natural killer (NK cell therapy relies on the acquisition of large numbers of NK cells that are cytotoxic but not exhausted. NK cell differentiation from hematopoietic stem cells (HSC has become an alluring option for NK cell therapy, with umbilical cord blood (UCB and mobilized peripheral blood (PBCD34(+ being the most accessible HSC sources as collection procedures are less invasive. In this study we compared the capacity of frozen or freshly isolated UCB hematopoietic stem cells (CBCD34(+ and frozen PBCD34(+ to generate NK cells in vitro. By modifying a previously published protocol, we showed that frozen CBCD34(+ cultures generated higher NK cell numbers without loss of function compared to fresh CBCD34(+ cultures. NK cells generated from CBCD34(+ and PBCD34(+ expressed low levels of killer-cell immunoglobulin-like receptors but high levels of activating receptors and of the myeloid marker CD33. However, blocking studies showed that CD33 expression did not impact on the functions of the generated cells. CBCD34(+-NK cells exhibited increased capacity to secrete IFN-γ and kill K562 in vitro and in vivo as compared to PBCD34(+-NK cells. Moreover, K562 killing by the generated NK cells could be further enhanced by IL-12 stimulation. Our data indicate that the use of frozen CBCD34(+ for the production of NK cells in vitro results in higher cell numbers than PBCD34(+, without jeopardizing their functionality, rendering them suitable for NK cell immunotherapy. The results presented here provide an optimal strategy to generate NK cells in vitro for immunotherapy that exhibit enhanced effector function when compared to alternate sources of HSC.

[Human herpesvirus-6 pneumonitis following autologous peripheral blood stem cell transplantation].

Science.gov (United States)

Saitoh, Yuu; Gotoh, Moritaka; Yoshizawa, Seiichiro; Akahane, Daigo; Fujimoto, Hiroaki; Ito, Yoshikazu; Ohyashiki, Kazuma

2018-01-01

A-46-year-old man was diagnosed with peripheral T cell lymphoma, not otherwise specified. He achieved a complete remission after pirarubicin, cyclophosphamide, vincristine, and prednisolone (THP-COP) therapy and successful autologous peripheral blood stem-cell transplantation (AutoSCT). However, 6 months post AutoSCT, he complained of fever. Chest computed tomography of the patient displayed bilateral interstitial pneumonitis. Human herpesvirus-6 (HHV-6) DNA was detected in his bronchoalveolar lavage fluid. Therefore, the patient was confirmed for HHV-6 pneumonitis. The treatment with foscarnet was effective, and no relapse was noticed in the patient. Besides, we have experienced pneumonitis of unknown origin in some patients after autologous or allogeneic stem-cell transplantations. Moreover, most of the above patients were clinically diagnosed using serum or plasma markers. Therefore, examining respiratory symptoms after AutoSCT would enable a more accurate diagnosis as well as treatment of patients with HHV-6 pneumonitis.

Turnover of circulating hematopoietic stem cells

Energy Technology Data Exchange (ETDEWEB)

Dorie, M J; Maloney, M A; Patt, H M

1979-10-01

Short-term parabiosis of male and female CBA/CaJ mice was used to investigate the turnover of circulating hematopoietic stem cells. The change and subsequent disappearance of donor stem cells were monitored by spleen colony assay and chromosome analysis of individual colonies. The results revealed an exponential disappearance of pluripotent stem cells from blood with a characteristic half time of 1.7 h. Blood-borne stem cells were shown to be equilibrated with a subpopulation of marrow stem cells exhibiting a disappearance half time of 9.5 h. Splenectomy did not change the apparent rate of stem cell removal from the blood.

Comparison between human cord blood serum and platelet-rich plasma supplementation for Human Wharton's Jelly Stem Cells and dermal fibroblasts culture

Directory of Open Access Journals (Sweden)

Hashemi SS

2016-08-01

Full Text Available We carried out a side-by-side comparison of the effects of Human cord blood serum (HcbS versus embryonic PRP on Human Wharton's Jelly Stem Cells(hWMSCand dermal fibroblasts proliferation. Human umbilical cord blood was collected to prepare activated serum (HCS and platelet-rich plasma (CPRP.Wharton's Jelly Stem Cells and dermal fibroblasts were cultured in complete medium with10% CPRP, 10%HCSor 10% fetal bovine serumand control (serum-free media.The efficiency of the protocols was evaluated in terms of the number of adherent cells and their expansion and Cell proliferation. We showed that proliferation of fibroblasts and mesenchymal stem cells in the presence of cord blood serum and platelet-rich plasma significantly more than the control group (p≤0/05. As an alternative to FBS, cord blood serum has been proved as an effective component in cell tissue culture applications and embraced a vast future in clinical applications of regenerative medicine. However, there is still a need to explore the potential of HCS and its safe applications in humanized cell therapy or tissue engineering.

[Absolute numbers of peripheral blood CD34+ hematopoietic stem cells prior to a leukapheresis procedure as a parameter predicting the efficiency of stem cell collection].

Science.gov (United States)

Galtseva, I V; Davydova, Yu O; Gaponova, T V; Kapranov, N M; Kuzmina, L A; Troitskaya, V V; Gribanova, E O; Kravchenko, S K; Mangasarova, Ya K; Zvonkov, E E; Parovichnikova, E N; Mendeleeva, L P; Savchenko, V G

To identify a parameter predicting a collection of at least 2·106 CD34+ hematopoietic stem cells (HSC)/kg body weight per leukapheresis (LA) procedure. The investigation included 189 patients with hematological malignancies and 3 HSC donors, who underwent mobilization of stem cells with their subsequent collection by LA. Absolute numbers of peripheral blood leukocytes and CD34+ cells before a LA procedure, as well as a number of CD34+ cells/kg body weight (BW) in the LA product stored on the same day were determined in each patient (donor). There was no correlation between the number of leukocytes and that of stored CD34+ cells/kg BW. There was a close correlation between the count of peripheral blood CD34+ cells prior to LA and that of collected CD34+ cells calculated with reference to kg BW. The optimal absolute blood CD34+ cell count was estimated to 20 per µl, at which a LA procedure makes it possible to collect 2·106 or more CD34+ cells/kg BW.

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.

Manganese effects on haematopoietic cells and circulating coelomocytes of Asterias rubens (Linnaeus)

International Nuclear Information System (INIS)

Oweson, Carolina; Skoeld, Helen; Pinsino, Annalisa; Matranga, Valeria; Hernroth, Bodil

2008-01-01

Manganese (Mn) is a naturally abundant metal in marine sediments where it mainly occurs as MnO 2 . During hypoxic conditions it is converted into a bioavailable state, Mn 2+ , and can reach levels that previously have shown effects on immune competent cells of the crustacean, Nephrops norvegicus. Here we investigated if Mn also affects circulating coelomocytes and their renewal in the common sea star, Asterias rubens, when exposed to concentrations of Mn that can be found in nature. When the sea stars were exposed to Mn it accumulated in the coelomic fluid and the number of circulating coelomocytes, in contrast to what was recorded in Nephrops, increased significantly. By using the substitute nucleotide, 5-bromo-2'-deoxyuridine, BrdU, for tracing cell division and by recording mitotic index by nuclei staining, we found that Mn induced proliferation of cells from a putative haematopoietic tissue, the coelomic epithelium. In addition, the haematopoietic tissue and coelomocytes showed stress response in terms of changes in HSP70 levels and protein carbonyls, as judged by immunohistochemistry and Western blotting. Measurement of dehydrogenase activity, using MTS/PMS, revealed that Mn showed cytotoxic properties. We also found that the phagocytotic capacity of coelomocytes was significantly inhibited by Mn. It was concluded that the exposure of A. rubens to Mn induced renewal of coelomocytes and impaired their immune response

Generation of human induced pluripotent stem cells from a Bombay individual: Moving towards 'universal-donor' red blood cells

Energy Technology Data Exchange (ETDEWEB)

Seifinejad, Ali; Taei, Adeleh [Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, P.O. Box 19395-4644, ACECR, Tehran (Iran, Islamic Republic of); Totonchi, Mehdi; Vazirinasab, Hamed [Department of Genetics, Royan Institute for Reproductive Biomedicine, ACECR, Tehran (Iran, Islamic Republic of); Hassani, Seideh Nafiseh [Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, P.O. Box 19395-4644, ACECR, Tehran (Iran, Islamic Republic of); Aghdami, Nasser [Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, P.O. Box 19395-4644, ACECR, Tehran (Iran, Islamic Republic of); Department of Regenerative Biomedicine, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Shahbazi, Ebrahim [Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, P.O. Box 19395-4644, ACECR, Tehran (Iran, Islamic Republic of); Yazdi, Reza Salman [Department of Genetics, Royan Institute for Reproductive Biomedicine, ACECR, Tehran (Iran, Islamic Republic of); Salekdeh, Ghasem Hosseini, E-mail: Salekdeh@royaninstitute.org [Department of Molecular Systems Biology, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Department of Systems Biology, Agricultural Biotechnology Research Institute of Iran, Karaj (Iran, Islamic Republic of); Baharvand, Hossein, E-mail: Baharvand@royaninstitute.org [Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, P.O. Box 19395-4644, ACECR, Tehran (Iran, Islamic Republic of); Department of Regenerative Biomedicine, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Department of Developmental Biology, University of Science and Culture, ACECR, Tehran (Iran, Islamic Republic of)

2010-01-01

Bombay phenotype is one of the rare phenotypes in the ABO blood group system that fails to express ABH antigens on red blood cells. Nonsense or missense mutations in fucosyltransfrase1 (FUT1) and fucosyltransfrase2 (FUT2) genes are known to create this phenotype. This blood group is compatible with all other blood groups as a donor, as it does not express the H antigen on the red blood cells. In this study, we describe the establishment of human induced pluripotent stem cells (iPSCs) from the dermal fibroblasts of a Bombay blood-type individual by the ectopic expression of established transcription factors Klf4, Oct4, Sox2, and c-Myc. Sequence analyses of fibroblasts and iPSCs revealed a nonsense mutation 826C to T (276 Gln to Ter) in the FUT1 gene and a missense mutation 739G to A (247 Gly to Ser) in the FUT2 gene in the Bombay phenotype under study. The established iPSCs resemble human embryonic stem cells in morphology, passaging, surface and pluripotency markers, normal karyotype, gene expression, DNA methylation of critical pluripotency genes, and in-vitro differentiation. The directed differentiation of the iPSCs into hematopoietic lineage cells displayed increased expression of the hematopoietic lineage markers such as CD34, CD133, RUNX1, KDR, {alpha}-globulin, and {gamma}-globulin. Such specific stem cells provide an unprecedented opportunity to produce a universal blood group donor, in-vitro, thus enabling cellular replacement therapies, once the safety issue is resolved.

[Allogenic hematopoietic stem cell transplantation with unrelated cord blood: report of three cases from the Chilean cord blood bank].

Science.gov (United States)

Barriga, Francisco; Wietstruck, Angélica; Rojas, Nicolás; Bertin, Pablo; Pizarro, Isabel; Carmona, Amanda; Guilof, Alejandro; Rojas, Iván; Oyarzún, Enrique

2013-08-01

Public cord blood banks are a source of hematopoietic stem cells for patients with hematological diseases who lack a family donor and need allogeneic transplantation. In June 2007 we started a cord blood bank with units donated in three maternity wards in Santiago, Chile. We report the first three transplants done with cord blood units form this bank. Cord blood units were obtained by intrauterine collection at delivery. They were depleted of plasma and red cells and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six hundred cord blood units were stored by March 2012. Three patients received allogeneic transplant with cord blood from our bank, two with high risk lymphoblastic leukemia and one with severe congenital anemia. They received conditioning regimens according to their disease and usual supportive care for unrelated donor transplantation until full hematopoietic and immune reconstitution was achieved. The three patients had early engraftment of neutrophils and platelets. The child corrected his anemia and the leukemia patients remain in complete remission. The post-transplant course was complicated with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are fully functional 24 and 33 months after transplant, the third is still receiving immunosuppression.

A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells.

Directory of Open Access Journals (Sweden)

Romeo Cecchelli

Full Text Available The human blood brain barrier (BBB is a selective barrier formed by human brain endothelial cells (hBECs, which is important to ensure adequate neuronal function and protect the central nervous system (CNS from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.

Stem Cell Heterogeneity of Mononucleated Cells from Murine Peripheral Blood: Molecular Analysis

Directory of Open Access Journals (Sweden)

Muhammad Dain Yazid

2011-01-01

Full Text Available The main purpose of this paper was to determine the heterogeneity of primary isolated mononucleated cells that originated from the peripheral blood system by observing molecular markers. The isolated cells were cultured in complete medium for 4 to 7 days prior to the separation of different cell types, that is, adherent and suspension. Following a total culture time of 14 days, adherent cells activated the Cd105 gene while suspension cells activated the Sca-1 gene. Both progenitor markers, Cbfa-1 and Ostf-1, were inactivated in both suspension and adherent cells after 14-day culture compared to cells cultured 3 days in designated differentiation medium. In conclusion, molecular analyses showed that primary mononucleated cells are heterogeneous, consisting of hematopoietic stem cells (suspension and mesenchymal stem cells (adherent while both cells contained no progenitor cells.

Hemostatic Status of Pre and Post Intracoronary Injection of Peripheral Blood Stem Cells in Patients with Recent Myocardial Infarction

Directory of Open Access Journals (Sweden)

Cosphiadi Irawan

2014-01-01

Full Text Available Aim: to investigate hemostatic parameter changes, such as platelet aggregation, blood and plasma viscosity, prothrombin time, APTT, CRP and fibrinogen, before and after administration of stem cell therapy. Methods: a total of 24 patients were enrolled. Peripheral blood stem cells (PBSCs were harvested and injected into the infarct-related artery after 5 consecutive days of G-CSF administration. Recombinant human erythropoietin was administered at the time of intracoronary PBSCs injection. Results: we were able to evaluate 11 from 24 of patients regarding hemostatic status pre–post stem cell injection. There were no significant difference between baseline vs 3 months in spontaneous aggregation (p=0.350, PT (p=0.793, aPTT (p=0.255 and TT (p=0.254. There were also no significant difference between baseline vs 3 months in plasma viscosity (p=0.442 and blood viscosity (p=0.843. Nevertheless the patient who had their blood and plasma viscosity above or below normal laboratory range return to normal level after the treatment. Both PT and APTT also show normalization value. Both Fibrinogen and CRP level show significant decrease between baseline and 3 months after treatment (p=0.009 and (p=0.04 respectively. Conclusion: combined G-CSF and EPO based-intracoronary infusion of PBSCs may open new perspective in the treatment of hypercoagulable state post AMI.

Dengue Virus Transmission by Blood Stem Cell Donor after Travel to Sri Lanka; Germany, 2013

Centers for Disease Control (CDC) Podcasts

2014-09-22

Dr. Mike Miller reads an abridged version of the article, Dengue Virus Transmission by Blood Stem Cell Donor after Travel to Sri Lanka; Germany, 2013.  Created: 9/22/2014 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 10/8/2014.

Induced Pluripotent Stem Cell-Derived Red Blood Cells and Platelet Concentrates: From Bench to Bedside.

Science.gov (United States)

Focosi, Daniele; Amabile, Giovanni

2017-12-27

Red blood cells and platelets are anucleate blood components indispensable for oxygen delivery and hemostasis, respectively. Derivation of these blood elements from induced pluripotent stem (iPS) cells has the potential to develop blood donor-independent and genetic manipulation-prone products to complement or replace current transfusion banking, also minimizing the risk of alloimmunization. While the production of erythrocytes from iPS cells has challenges to overcome, such as differentiation into adult-type phenotype that functions properly after transfusion, platelet products are qualitatively and quantitatively approaching a clinically-applicable level owing to advances in expandable megakaryocyte (MK) lines, platelet-producing bioreactors, and novel reagents. Guidelines that assure the quality of iPS cells-derived blood products for clinical application represent a novel challenge for regulatory agencies. Considering the minimal risk of tumorigenicity and the expected significant demand of such products, ex vivo production of iPS-derived blood components can pave the way for iPS translation into the clinic.

Towards a global system of vigilance and surveillance in unrelated donors of haematopoietic progenitor cells for transplantation.

Science.gov (United States)

Shaw, B E; Chapman, J; Fechter, M; Foeken, L; Greinix, H; Hwang, W; Phillips-Johnson, L; Korhonen, M; Lindberg, B; Navarro, W H; Szer, J

2013-11-01

Safety of living donors is critical to the success of blood, tissue and organ transplantation. Structured and robust vigilance and surveillance systems exist as part of some national entities, but historically no global systems are in place to ensure conformity, harmonisation and the recognition of rare adverse events (AEs). The World Health Assembly has recently resolved to require AE/reaction (AE/R) reporting both nationally and globally. The World Marrow Donor Association (WMDA) is an international organisation promoting the safety of unrelated donors and progenitor cell products for use in haematopoietic progenitor cell (HPC) transplantation. To address this issue, we established a system for collecting, collating, analysing, distributing and reacting to serious adverse events and reactions (SAE/R) in unrelated HPC donors. The WMDA successfully instituted this reporting system with 203 SAE/R reported in 2011. The committee generated two rapid reports, reacting to specific SAE/R, resulting in practice changing policies. The system has a robust governance structure, formal feedback to the WMDA membership and transparent information flows to other agencies, specialist physicians and transplant programs and the general public.

Stem cells: sources and therapies

Directory of Open Access Journals (Sweden)

Manuela Monti

2012-01-01

Full Text Available The historical, lexical and conceptual issues embedded in stem cell biology are reviewed from technical, ethical, philosophical, judicial, clinical, economic and biopolitical perspectives. The mechanisms assigning the simultaneous capacity to self-renew and to differentiate to stem cells (immortal template DNA and asymmetric division are evaluated in the light of the niche hypothesis for the stemness state. The induction of cell pluripotency and the different stem cells sources are presented (embryonic, adult and cord blood. We highlight the embryonic and adult stem cell properties and possible therapies while we emphasize the particular scientific and social values of cord blood donation to set up cord blood banks. The current scientific and legal frameworks of cord blood banks are reviewed at an international level as well as allogenic, dedicated and autologous donations. The expectations and the challenges in relation to present-day targeted diseases like diabetes mellitus type I, Parkinson's disease and myocardial infarction are evaluated in the light of the cellular therapies for regenerative medicine.

Induced Pluripotent Stem Cell Generation from Blood Cells Using Sendai Virus and Centrifugation.

Science.gov (United States)

Rim, Yeri Alice; Nam, Yoojun; Ju, Ji Hyeon

2016-12-21

The recent development of human induced pluripotent stem cells (hiPSCs) proved that mature somatic cells can return to an undifferentiated, pluripotent state. Now, reprogramming is done with various types of adult somatic cells: keratinocytes, urine cells, fibroblasts, etc. Early experiments were usually done with dermal fibroblasts. However, this required an invasive surgical procedure to obtain fibroblasts from the patients. Therefore, suspension cells, such as blood and urine cells, were considered ideal for reprogramming because of the convenience of obtaining the primary cells. Here, we report an efficient protocol for iPSC generation from peripheral blood mononuclear cells (PBMCs). By plating the transduced PBMCs serially to a new, matrix-coated plate using centrifugation, this protocol can easily provide iPSC colonies. This method is also applicable to umbilical cord blood mononuclear cells (CBMCs). This study presents a simple and efficient protocol for the reprogramming of PBMCs and CBMCs.

Treatment of aggressive multiple myeloma by high-dose chemotherapy and total body irradiation followed by blood stem cells autologous graft

International Nuclear Information System (INIS)

Fermand, J.P.; Levy, Y.; Gerota, J.; Benbunan, M.; Cosset, J.M.; Castaigne, S.; Seligmann, M.; Brouet, J.C.

1989-01-01

Eight patients with stage III aggressive multiple myeloma, refractory to current chemotherapy in six cases, were treated by high-dose chemotherapy (nitrosourea, etoposide, and melphalan) (HDC) and total body irradiation (TBI), followed by autografting with blood stem cells. These cells were previously collected by leukapheresis performed during hematologic recovery following cytotoxic drug-induced bone marrow aplasia. Seven patients were alive 9 to 17 months after HDC-TBI and graft. One died at day 40 from cerebral bleeding. All living patients achieved a 90% or greater reduction in tumor mass. In two cases, a complete remission (CR) has persisted at a follow-up of 15 and 16 months. Three patients have been well and off therapy with stable minimal residual disease (RD) since 10, 11, and 17 months, respectively. A patient in apparent CR and another with RD have relapsed 9 to 12 months posttreatment. Autologous blood-derived hematopoietic stem cells induced successful and sustained engraftment in all living patients. These results, although still preliminary, indicate that HDC and TBI, followed by blood stem cells autograft, which has both practical and theoretical interest over allogeneic or autologous bone marrow transplantation, deserve consideration in selected patients with multiple myeloma

Aerobic exercise capacity at long-term follow-up after paediatric allogeneic haematopoietic SCT

DEFF Research Database (Denmark)

Mathiesen, S; Uhlving, H H; Buchvald, F

2014-01-01

Peak oxygen uptake (VO2peak), a measure of aerobic exercise capacity, predicts mortality and morbidity in healthy and diseased individuals. Our aim was to determine VO2peak years after paediatric allogeneic haematopoietic SCT (HSCT) and to identify associations with baseline patient and donor...... type or GvHD were found. Although causes for reduced VO2peak may be multiple, our findings stress the need to focus on physical activity post HSCT to prevent lifestyle diseases and improve quality of life....

Early loss of Crebbp confers malignant stem cell properties on lymphoid progenitors.

Science.gov (United States)

Horton, Sarah J; Giotopoulos, George; Yun, Haiyang; Vohra, Shabana; Sheppard, Olivia; Bashford-Rogers, Rachael; Rashid, Mamunur; Clipson, Alexandra; Chan, Wai-In; Sasca, Daniel; Yiangou, Loukia; Osaki, Hikari; Basheer, Faisal; Gallipoli, Paolo; Burrows, Natalie; Erdem, Ayşegül; Sybirna, Anastasiya; Foerster, Sarah; Zhao, Wanfeng; Sustic, Tonci; Petrunkina Harrison, Anna; Laurenti, Elisa; Okosun, Jessica; Hodson, Daniel; Wright, Penny; Smith, Ken G; Maxwell, Patrick; Fitzgibbon, Jude; Du, Ming Q; Adams, David J; Huntly, Brian J P

2017-09-01

Loss-of-function mutations of cyclic-AMP response element binding protein, binding protein (CREBBP) are prevalent in lymphoid malignancies. However, the tumour suppressor functions of CREBBP remain unclear. We demonstrate that loss of Crebbp in murine haematopoietic stem and progenitor cells (HSPCs) leads to increased development of B-cell lymphomas. This is preceded by accumulation of hyperproliferative lymphoid progenitors with a defective DNA damage response (DDR) due to a failure to acetylate p53. We identify a premalignant lymphoma stem cell population with decreased H3K27ac, which undergoes transcriptional and genetic evolution due to the altered DDR, resulting in lymphomagenesis. Importantly, when Crebbp is lost later in lymphopoiesis, cellular abnormalities are lost and tumour generation is attenuated. We also document that CREBBP mutations may occur in HSPCs from patients with CREBBP-mutated lymphoma. These data suggest that earlier loss of Crebbp is advantageous for lymphoid transformation and inform the cellular origins and subsequent evolution of lymphoid malignancies.

Improving engraftment and immune reconstitution in umbilical cord blood transplantation

Directory of Open Access Journals (Sweden)

Robert eDanby

2014-02-01

Full Text Available Umbilical cord blood (UCB is an important source of haematopoietic stem cells (HSC for allogeneic transplantation when HLA-matched sibling and unrelated donors (MUD are unavailable. Although the overall survival rates of UCB transplantation are comparable to the results with MUD, UCB transplants are associated with slow engraftment, delayed immune reconstitution, and increased opportunistic infections. While this may be a consequence of the lower cell dose in UCB grafts, it also reflects the relative immaturity of cellular immunity within cord blood. Furthermore, the limited number of cells and the non-availability of donor lymphocyte infusions (DLI currently prevent the use of post-transplant cellular immunotherapy to boost donor-derived immunity to treat infection, mixed chimerism and disease relapse. Therefore, to further develop UCB transplantation, many strategies to enhance engraftment and immune reconstitution are currently under investigation. This review summarises our current understanding of engraftment and immune recovery following UCB transplantation and why this differs from allogeneic transplants using other sources of HSC. It also provides an comprehensive overview of the promising techniques being used to improve myeloid and lymphoid recovery, including expansion, homing, and delivery of UCB HSC; combined use of UCB with third party donors; isolation and expansion of NK cells, pathogen specific T cells, and regulatory T cells; methods to protect and/or improve thymopoiesis. As many of these strategies are now in clinical trials, it is anticipated that UCB transplantation will continue to advance, further expanding our understanding of UCB biology and HSC transplantation.

Facts about Stem Cells and Importance of Them

Directory of Open Access Journals (Sweden)

Masumeh Saeidi

2014-05-01

Full Text Available Stem cells are undifferentiated biological cells that can differentiate into specialized cells and can divide (through mitosis to produce more stem cells. They are found in multicellular organisms. In mammals, there are two broad types of stem cells: embryonic stem cells, which are isolated from the inner cell mass of blastocysts, and adult stem cells, which are found in various tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing adult tissues. In a developing embryo, stem cells can differentiate into all the specialized cells—ectoderm, endoderm and mesoderm (see induced pluripotent stem cells—but also maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues. There are three accessible sources of autologous adult stem cells in humans: Bone marrow, which requires extraction by harvesting, that is, drilling into bone (typically the femur or iliac crest, Adipose tissue (lipid cells, which requires extraction by liposuction, and Blood, which requires extraction through apheresis, wherein blood is drawn from the donor (similar to a blood donation, and passed through a machine that extracts the stem cells and returns other portions of the blood to the donor. Stem cells can also be taken from umbilical cord blood just after birth. Of all stem cell types, autologous harvesting involves the least risk. By definition, autologous cells are obtained from one's own body, just as one may bank his or her own blood for elective surgical procedures. Adult stem cells are frequently used in medical therapies, for example in bone marrow transplantation. Stem cells can now be artificially grown and transformed (differentiated into specialized cell types with characteristics consistent with cells of various tissues such as muscles or nerves. Embryonic cell lines and autologous embryonic stem cells generated through Somatic-cell nuclear transfer or dedifferentiation

Autoradiography at Cell and Chromosome Level in the Study of Multiplication and Cytodifferentiation of Haematopoietic Tissue

Energy Technology Data Exchange (ETDEWEB)

Gavosto, F. [Instituto di Clinica Medica, University of Turin (Italy)

1967-07-15

Haematopoietic tissue proliferates by the mitotic activity of the youngest cells. The first data on the proliferation of blood cells recorded by use of the stathmokinetic technique was followed by more detailed information obtained with autoradiographic studies and by using special precursors of DNA such as thymidine. It has been observed that in the bone marrow in progressive myeloid and erythroid maturation, proliferative capacity decreases progressively until it stops altogether at the myelocytic and polychromatic erythroblastic stage. For chronic myeloid leukaemia the labelling index of each proliferating cell type is similar to the values of the corresponding normal cells. In 1958 we used tritiated thymidine to study many cases of acute leukaemia, that is those with a complete differentiation block and a very high blast content, and we found a clear fall in proliferative capacity of these blast cells. The same results have been obtained in other laboratories and now, quite the contrary to what was thought a few years ago, namely that leukaemic cells grew faster than normal cells, we know that the rate of growth of these cells is often much slower than the corresponding normal cells.

Barium-cross-linked alginate-gelatine microcapsule as a potential platform for stem cell production and modular tissue formation.

Science.gov (United States)

Alizadeh Sardroud, Hamed; Nemati, Sorour; Baradar Khoshfetrat, Ali; Nabavinia, Mahbobeh; Beygi Khosrowshahi, Younes

2017-08-01

Influence of gelatine concentration and cross-linker ions of Ca 2+ and Ba 2+ was evaluated on characteristics of alginate hydrogels and proliferation behaviours of model adherent and suspendable stem cells of fibroblast and U937 embedded in alginate microcapsules. Increasing gelatine concentration to 2.5% increased extent of swelling to 15% and 25% for barium- and calcium-cross-linked hydrogels, respectively. Mechanical properties also decreased with increasing swelling of hydrogels. Both by increasing gelatine concentration and using barium ions increased considerably the proliferation of encapsulated model stem cells. Barium-cross-linked alginate-gelatine microcapsule tested for bone building block showed a 13.5 ± 1.5-fold expansion for osteoblast cells after 21 days with deposition of bone matrix. The haematopoietic stem cells cultured in the microcapsule after 7 days also showed up to 2-fold increase without adding any growth factor. The study demonstrates that barium-cross-linked alginate-gelatine microcapsule has potential for use as a simple and efficient 3D platform for stem cell production and modular tissue formation.

Advanced feeder-free generation of induced pluripotent stem cells directly from blood cells.

Science.gov (United States)

Trokovic, Ras; Weltner, Jere; Nishimura, Ken; Ohtaka, Manami; Nakanishi, Mahito; Salomaa, Veikko; Jalanko, Anu; Otonkoski, Timo; Kyttälä, Aija

2014-12-01

Generation of validated human induced pluripotent stem cells (iPSCs) for biobanking is essential for exploring the full potential of iPSCs in disease modeling and drug discovery. Peripheral blood mononuclear cells (PBMCs) are attractive targets for reprogramming, because blood is collected by a routine clinical procedure and is a commonly stored material in biobanks. Generation of iPSCs from blood cells has previously been reported using integrative retroviruses, episomal Sendai viruses, and DNA plasmids. However, most of the published protocols require expansion and/or activation of a specific cell population from PBMCs. We have recently collected a PBMC cohort from the Finnish population containing more than 2,000 subjects. Here we report efficient generation of iPSCs directly from PBMCs in feeder-free conditions in approximately 2 weeks. The produced iPSC clones are pluripotent and transgene-free. Together, these properties make this novel method a powerful tool for large-scale reprogramming of PBMCs and for iPSC biobanking. ©AlphaMed Press.

Low-frequency electrical stimulation induces the proliferation and differentiation of peripheral blood stem cells into Schwann cells.

Science.gov (United States)

Gu, Xudong; Fu, Jianming; Bai, Jing; Zhang, Chengwen; Wang, Jing; Pan, Wenping

2015-02-01

Functional recovery after peripheral nerve injury remains a tough problem at present. Specifically, a type of glial cell exists in peripheral nerves that promotes axonal growth and myelin formation and secretes various active substances, such as neurotrophic factors, extracellular matrix and adherence factors. These substances have important significance for the survival, growth and regeneration of nerve fibers. Numerous recent studies have shown that electrical stimulation can increase the number of myelinated nerve fibers. However, whether electrical stimulation acts on neurons or Schwann cells has not been verified in vivo. This study investigates low-frequency electrical stimulation-induced proliferation and differentiation of peripheral blood stem cells into Schwann cells and explores possible mechanisms. Peripheral blood stem cells from Sprague-Dawley rats were primarily cultured. Cells in passage 3 were divided into 4 groups: a low-frequency electrical stimulation group (20 Hz, 100 μs, 3 V), a low-frequency electrical stimulation+PD98059 (blocking the extracellular signal-regulated kinase [ERK] signaling pathway) group, a PD98059 group and a control group (no treatment). After induction, the cells were characterized. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide assay was employed to measure the absorbance values at 570 nm in the 4 groups. A Western blot assay was used to detect the expression of cyclin D1 and cyclin-dependent kinase 4 (CDK4) in each group. No significant difference in cell viability was detected before induction. Peripheral blood stem cells from the 4 groups differentiated into Schwann cells. Phosphorylated ERK 1/2, cyclin D1 and CDK4 protein levels were highest in the low-frequency electrical stimulation group and lowest in the ERK blockage group. Phosphorylated ERK 1/2, cyclin D1 and CDK4 protein levels in the low-frequency electrical stimulation+ERK blockage group were lower than those in the low-frequency electrical

Mobilized peripheral blood stem cells compared with bone marrow from HLA-identical siblings for reduced-intensity conditioning transplantation in acute myeloid leukemia in complete remission

DEFF Research Database (Denmark)

Nagler, Arnon; Labopin, Myriam; Shimoni, Avichai

2012-01-01

Reduced-intensity conditioning (RIC)-alloSCT is increasingly used for acute myelogenous leukemia. Limited data are available for the comparison of peripheral blood stem cells with bone marrow for RIC-alloSCT. We used the European Group for Blood and Marrow Transplantation (EBMT) ALWP data...... to compare the outcome of mobilized peripheral blood stem cells (PBSC) (n = 1430) vs. bone marrow (BM) (n = 107) for acute myelogenous leukemia (AML) patients with complete remission that underwent RIC-alloSCT from compatible sibling donors. The leukemia features, the disease status, and the time from...

Seventy-five genetic loci influencing the human red blood cell.

Science.gov (United States)

van der Harst, Pim; Zhang, Weihua; Mateo Leach, Irene; Rendon, Augusto; Verweij, Niek; Sehmi, Joban; Paul, Dirk S; Elling, Ulrich; Allayee, Hooman; Li, Xinzhong; Radhakrishnan, Aparna; Tan, Sian-Tsung; Voss, Katrin; Weichenberger, Christian X; Albers, Cornelis A; Al-Hussani, Abtehale; Asselbergs, Folkert W; Ciullo, Marina; Danjou, Fabrice; Dina, Christian; Esko, Tõnu; Evans, David M; Franke, Lude; Gögele, Martin; Hartiala, Jaana; Hersch, Micha; Holm, Hilma; Hottenga, Jouke-Jan; Kanoni, Stavroula; Kleber, Marcus E; Lagou, Vasiliki; Langenberg, Claudia; Lopez, Lorna M; Lyytikäinen, Leo-Pekka; Melander, Olle; Murgia, Federico; Nolte, Ilja M; O'Reilly, Paul F; Padmanabhan, Sandosh; Parsa, Afshin; Pirastu, Nicola; Porcu, Eleonora; Portas, Laura; Prokopenko, Inga; Ried, Janina S; Shin, So-Youn; Tang, Clara S; Teumer, Alexander; Traglia, Michela; Ulivi, Sheila; Westra, Harm-Jan; Yang, Jian; Zhao, Jing Hua; Anni, Franco; Abdellaoui, Abdel; Attwood, Antony; Balkau, Beverley; Bandinelli, Stefania; Bastardot, François; Benyamin, Beben; Boehm, Bernhard O; Cookson, William O; Das, Debashish; de Bakker, Paul I W; de Boer, Rudolf A; de Geus, Eco J C; de Moor, Marleen H; Dimitriou, Maria; Domingues, Francisco S; Döring, Angela; Engström, Gunnar; Eyjolfsson, Gudmundur Ingi; Ferrucci, Luigi; Fischer, Krista; Galanello, Renzo; Garner, Stephen F; Genser, Bernd; Gibson, Quince D; Girotto, Giorgia; Gudbjartsson, Daniel Fannar; Harris, Sarah E; Hartikainen, Anna-Liisa; Hastie, Claire E; Hedblad, Bo; Illig, Thomas; Jolley, Jennifer; Kähönen, Mika; Kema, Ido P; Kemp, John P; Liang, Liming; Lloyd-Jones, Heather; Loos, Ruth J F; Meacham, Stuart; Medland, Sarah E; Meisinger, Christa; Memari, Yasin; Mihailov, Evelin; Miller, Kathy; Moffatt, Miriam F; Nauck, Matthias; Novatchkova, Maria; Nutile, Teresa; Olafsson, Isleifur; Onundarson, Pall T; Parracciani, Debora; Penninx, Brenda W; Perseu, Lucia; Piga, Antonio; Pistis, Giorgio; Pouta, Anneli; Puc, Ursula; Raitakari, Olli; Ring, Susan M; Robino, Antonietta; Ruggiero, Daniela; Ruokonen, Aimo; Saint-Pierre, Aude; Sala, Cinzia; Salumets, Andres; Sambrook, Jennifer; Schepers, Hein; Schmidt, Carsten Oliver; Silljé, Herman H W; Sladek, Rob; Smit, Johannes H; Starr, John M; Stephens, Jonathan; Sulem, Patrick; Tanaka, Toshiko; Thorsteinsdottir, Unnur; Tragante, Vinicius; van Gilst, Wiek H; van Pelt, L Joost; van Veldhuisen, Dirk J; Völker, Uwe; Whitfield, John B; Willemsen, Gonneke; Winkelmann, Bernhard R; Wirnsberger, Gerald; Algra, Ale; Cucca, Francesco; d'Adamo, Adamo Pio; Danesh, John; Deary, Ian J; Dominiczak, Anna F; Elliott, Paul; Fortina, Paolo; Froguel, Philippe; Gasparini, Paolo; Greinacher, Andreas; Hazen, Stanley L; Jarvelin, Marjo-Riitta; Khaw, Kay Tee; Lehtimäki, Terho; Maerz, Winfried; Martin, Nicholas G; Metspalu, Andres; Mitchell, Braxton D; Montgomery, Grant W; Moore, Carmel; Navis, Gerjan; Pirastu, Mario; Pramstaller, Peter P; Ramirez-Solis, Ramiro; Schadt, Eric; Scott, James; Shuldiner, Alan R; Smith, George Davey; Smith, J Gustav; Snieder, Harold; Sorice, Rossella; Spector, Tim D; Stefansson, Kari; Stumvoll, Michael; Tang, W H Wilson; Toniolo, Daniela; Tönjes, Anke; Visscher, Peter M; Vollenweider, Peter; Wareham, Nicholas J; Wolffenbuttel, Bruce H R; Boomsma, Dorret I; Beckmann, Jacques S; Dedoussis, George V; Deloukas, Panos; Ferreira, Manuel A; Sanna, Serena; Uda, Manuela; Hicks, Andrew A; Penninger, Josef Martin; Gieger, Christian; Kooner, Jaspal S; Ouwehand, Willem H; Soranzo, Nicole; Chambers, John C

2012-12-20

Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.

Improvement of Blood Pressure, Glucose Metabolism, and Lipid Profile by the Intake of Powdered Asparagus (蘆筍 Lú Sǔn Bottom-stems and Cladophylls

Directory of Open Access Journals (Sweden)

Mie Nishimura

2013-10-01

Full Text Available Asparagus (蘆筍 Lú Sǔn; Asparagus officinalis L. is a common vegetable, long used as an herbal medicine. The cladophylls and bottom-stems of asparagus have various pharmacological effects, but they are generally discarded at harvesting. The present open clinical trial was performed to examine the effects of the intake of cladophylls and bottom-stems on the improvement of metabolic syndrome characterized by hypertension, hyperglycemia, and dyslipidemia. Twenty-eight healthy volunteers ingested either cladophyll or bottom-stem powder (6 g/day daily for 10 weeks. The cladophyll intake resulted in significant reduction in the subjects’ diastolic blood pressure and fasting plasma glucose (FPG, and decreased both the left cardio-ankle vascular index score and the total cholesterol level (T-CHO. The bottom-stem intake significantly reduced the subjects’ systolic and diastolic blood pressure and FPG as well as T-CHO. These results suggest the possibility that asparagus cladophylls and bottom-stems differentially improve hypertension, hyperglycemia, and dyslipidemia.

Mesenchymal stem cells from the Wharton's jelly of umbilical cord segments provide stromal support for the maintenance of cord blood hematopoietic stem cells during long-term ex vivo culture.

Science.gov (United States)

Bakhshi, Tiki; Zabriskie, Ryan C; Bodie, Shamanique; Kidd, Shannon; Ramin, Susan; Paganessi, Laura A; Gregory, Stephanie A; Fung, Henry C; Christopherson, Kent W

2008-12-01

Hematopoietic stem cells (HSCs) are routinely obtained from marrow, mobilized peripheral blood, and umbilical cord blood. Mesenchymal stem cells (MSCs) are traditionally isolated from marrow. Bone marrow-derived MSCs (BM-MSCs) have previously demonstrated their ability to act as a feeder layer in support of ex vivo cord blood expansion. However, the use of BM-MSCs to support the growth, differentiation, and engraftment of cord blood may not be ideal for transplant purposes. Therefore, the potential of MSCs from a novel source, the Wharton's jelly of umbilical cords, to act as stromal support for the long-term culture of cord blood HSC was evaluated. Umbilical cord-derived MSCs (UC-MSCs) were cultured from the Wharton's jelly of umbilical cord segments. The UC-MSCs were then profiled for expression of 12 cell surface receptors and tested for their ability to support cord blood HSCs in a long-term culture-initiating cell (LTC-IC) assay. Upon culture, UC-MSCs express a defined set of cell surface markers (CD29, CD44, CD73, CD90, CD105, CD166, and HLA-A) and lack other markers (CD45, CD34, CD38, CD117, and HLA-DR) similar to BM-MSCs. Like BM-MSCs, UC-MSCs effectively support the growth of CD34+ cord blood cells in LTC-IC assays. These data suggest the potential therapeutic application of Wharton's jelly-derived UC-MSCs to provide stromal support structure for the long-term culture of cord blood HSCs as well as the possibility of cotransplantation of genetically identical, HLA-matched, or unmatched cord blood HSCs and UC-MSCs in the setting of HSC transplantation.

Molecular epidemiology of Epizootic haematopoietic necrosis virus (EHNV).

Science.gov (United States)

Hick, Paul M; Subramaniam, Kuttichantran; Thompson, Patrick M; Waltzek, Thomas B; Becker, Joy A; Whittington, Richard J

2017-11-01

Low genetic diversity of Epizootic haematopoietic necrosis virus (EHNV) was determined for the complete genome of 16 isolates spanning the natural range of hosts, geography and time since the first outbreaks of disease. Genomes ranged from 125,591-127,487 nucleotides with 97.47% pairwise identity and 106-109 genes. All isolates shared 101 core genes with 121 potential genes predicted within the pan-genome of this collection. There was high conservation within 90,181 nucleotides of the core genes with isolates separated by average genetic distance of 3.43 × 10 -4 substitutions per site. Evolutionary analysis of the core genome strongly supported historical epidemiological evidence of iatrogenic spread of EHNV to naïve hosts and establishment of endemic status in discrete ecological niches. There was no evidence of structural genome reorganization, however, the complement of non-core genes and variation in repeat elements enabled fine scale molecular epidemiological investigation of this unpredictable pathogen of fish. Copyright © 2017 Elsevier Inc. All rights reserved.

Endurance Exercise Mobilizes Developmentally Early Stem Cells into Peripheral Blood and Increases Their Number in Bone Marrow: Implications for Tissue Regeneration

Directory of Open Access Journals (Sweden)

Krzysztof Marycz

2016-01-01

Full Text Available Endurance exercise has been reported to increase the number of circulating hematopoietic stem/progenitor cells (HSPCs in peripheral blood (PB as well as in bone marrow (BM. We therefore became interested in whether endurance exercise has the same effect on very small embryonic-like stem cells (VSELs, which have been described as a population of developmentally early stem cells residing in BM. Mice were run daily for 1 hour on a treadmill for periods of 5 days or 5 weeks. Human volunteers had trained in long-distance running for one year, six times per week. FACS-based analyses and RT-PCR of murine and human VSELs and HSPCs from collected bone marrow and peripheral blood were performed. We observed that endurance exercise increased the number of VSELs circulating in PB and residing in BM. In parallel, we observed an increase in the number of HSPCs. These observations were subsequently confirmed in young athletes, who showed an increase in circulating VSELs and HSPCs after intensive running exercise. We provide for the first time evidence that endurance exercise may have beneficial effects on the expansion of developmentally early stem cells. We hypothesize that these circulating stem cells are involved in repairing minor exercise-related tissue and organ injuries.

Lichen striatus occurring after allogenic peripheral blood stem cell transplantation in an adult with aplastic anemia.

Science.gov (United States)

Mun, Je-Ho; Park, Hyun-Je; Kim, Hoon-Soo; Kim, Su-Han; Ko, Hyun-Chang; Kim, Byung-Soo; Kim, Moon-Bum

2012-02-01

Lichens striatus (LS) is an acquired, self-limiting inflammatory dermatosis that follows the lines of Blaschko. The etiology of the eruption is unknown, but several theories have been proposed with focus on environmental factors, viral infection, cutaneous injury, hypersensitivity, and genetic predisposition. We describe a 19-year-old woman who developed a unilateral linear eruption 17 months after allogenic peripheral blood stem cell transplantation. Histopathology revealed features, which were consistent with LS. To the best of our knowledge, our patient is the first case describing the appearance of LS occurring after allogenic stem cell transplantation. We speculate that this condition represents an unusual form of localized, chronic graft-versus-host disease.

[Immunology in the medical practice.XXXII. Transplantation of autologous hematopoietic stem cells for treatment of refractory auto-immune diseases; preliminary favorable results with 35 patients].

Science.gov (United States)

Vlieger, A M; van den Hoogen, F H; Brinkman, D M; van Laar, J M; Schipperus, M; Kruize, A A; Wulffraat, N M

2000-08-12

The objective of this study was to document the experiences in the first Dutch pilot studies of the effect of transplantation of autologous haematopoietic stem cells in patients with therapy-resistant autoimmune disease. The first results in 21 adults and 14 children are promising: remission of the disease was achieved in 13 patients, while in the others a significant reduction of disease activity was seen with a corresponding improvement of the quality of life. Infectious complications were frequently observed. Two children with systemic juvenile idiopathic arthritis developed a fatal infection-associated macrophage activation syndrome. Multicentre randomised studies are necessary to study the effects of autologous stem cell transplantation and modifications such as T-cell depletion.

The meanings of consent to the donation of cord blood stem cells: perspectives from an interview-based study of a public cord blood bank in England.

Science.gov (United States)

Busby, Helen

2010-03-01

This paper explores the perspectives of women who have agreed that their umbilical cord blood may be collected for a public 'cord blood bank', for use in transplant medicine or research. Drawing on interview data from 27 mothers who agreed to the collection and use of their umbilical cord blood, these choices and the informed consent process are explored. It is shown that the needs of sick children requiring transplants are prominent in narrative accounts of cord blood banking, together with high expectations for future applications of stem cells. Given this dynamic, a concern arises that the complex and multiple uses of tissues and related data might be oversimplified in the consent process. In conclusion, the positive finding of a commitment to mutuality in cord blood banking among these women is underlined, and its implications for the wider debate on cord blood banking are discussed.

Stem Cell Transplant

Science.gov (United States)

... Graft-versus-host disease: A potential risk when stem cells come from donors If you receive a transplant ... medications and blood products into your body. Collecting stem cells for transplant If a transplant using your own ...

Single-cell analyses identify bioengineered niches for enhanced maintenance of hematopoietic stem cells.

Science.gov (United States)

Roch, Aline; Giger, Sonja; Girotra, Mukul; Campos, Vasco; Vannini, Nicola; Naveiras, Olaia; Gobaa, Samy; Lutolf, Matthias P

2017-08-09

The in vitro expansion of long-term hematopoietic stem cells (HSCs) remains a substantial challenge, largely because of our limited understanding of the mechanisms that control HSC fate choices. Using single-cell multigene expression analysis and time-lapse microscopy, here we define gene expression signatures and cell cycle hallmarks of murine HSCs and the earliest multipotent progenitors (MPPs), and analyze systematically single HSC fate choices in culture. Our analysis revealed twelve differentially expressed genes marking the quiescent HSC state, including four genes encoding cell-cell interaction signals in the niche. Under basal culture conditions, most HSCs rapidly commit to become early MPPs. In contrast, when we present ligands of the identified niche components such as JamC or Esam within artificial niches, HSC cycling is reduced and long-term multipotency in vivo is maintained. Our approach to bioengineer artificial niches should be useful in other stem cell systems.Haematopoietic stem cell (HSC) self-renewal is not sufficiently understood to recapitulate in vitro. Here, the authors generate gene signature and cell cycle hallmarks of single murine HSCs, and use identified endothelial receptors Esam and JamC as substrates to enhance HSC growth in engineered niches.

Clinical trials for stem cell therapies

Directory of Open Access Journals (Sweden)

Lomax Geoff

2011-05-01

Full Text Available Abstract In recent years, clinical trials with stem cells have taken the emerging field in many new directions. While numerous teams continue to refine and expand the role of bone marrow and cord blood stem cells for their vanguard uses in blood and immune disorders, many others are looking to expand the uses of the various types of stem cells found in bone marrow and cord blood, in particular mesenchymal stem cells, to uses beyond those that could be corrected by replacing cells in their own lineage. Early results from these trials have produced mixed results often showing minor or transitory improvements that may be attributed to extracellular factors. More research teams are accelerating the use of other types of adult stem cells, in particular neural stem cells for diseases where beneficial outcome could result from either in-lineage cell replacement or extracellular factors. At the same time, the first three trials using cells derived from pluripotent cells have begun.

Umbilical cord bloods hematopoietic stem cells ex vivo expansion (the literature review

Directory of Open Access Journals (Sweden)

T. V. Shamanskaya

2012-01-01

Full Text Available Umbilical cord blood (CB is now an attractive source of hematopoietic stem cells (HSCs for transplantation in pediatric and adult patients with various malignant and non-malignant diseases. However, its clinical application is limited by low cells numbers in graft, which correlates with delayed engraftment, an extension of time to platelets and neutrophils recovery and increasing risk of infectious complications. Several strategies have been suggested to overcome this limitation, one of which is obtaining a sufficient number of hematopoietic progenitor cells by ex vivo expansion. Literature review about CB HSCs expansion in given article is presented.

Bone marrow adipocytes promote the regeneration of stem cells and hematopoiesis by secreting SCF

Science.gov (United States)

Zhou, Bo O.; Yu, Hua; Yue, Rui; Zhao, Zhiyu; Rios, Jonathan J.; Naveiras, Olaia; Morrison, Sean J.

2017-01-01

Endothelial cells and Leptin Receptor+ (LepR+) stromal cells are critical sources of haematopoietic stem cell (HSC) niche factors, including Stem Cell Factor (SCF), in bone marrow. After irradiation or chemotherapy, these cells are depleted while adipocytes become abundant. We discovered that bone marrow adipocytes synthesize SCF. They arise from Adipoq-Cre/ER+ progenitors, which represent ~5% of LepR+ cells, and proliferate after irradiation. Scf deletion using Adipoq-Cre/ER inhibited hematopoietic regeneration after irradiation or 5-fluorouracil treatment, depleting HSCs and reducing mouse survival. Scf from LepR+ cells, but not endothelial, hematopoietic, or osteoblastic cells, also promoted regeneration. In non-irradiated mice, Scf deletion using Adipoq-Cre/ER did not affect HSC frequency in long bones, which have few adipocytes, but depleted HSCs in tail vertebrae, which have abundant adipocytes. A-ZIP/F1 ‘fatless” mice exhibited delayed hematopoietic regeneration in long bones but not in tail vertebrae, where adipocytes inhibited vascularization. Adipocytes are a niche component that promotes hematopoietic regeneration. PMID:28714970

Optimizing the method for generation of integration-free induced pluripotent stem cells from human peripheral blood.

Science.gov (United States)

Gu, Haihui; Huang, Xia; Xu, Jing; Song, Lili; Liu, Shuping; Zhang, Xiao-Bing; Yuan, Weiping; Li, Yanxin

2018-06-15

Generation of induced pluripotent stem cells (iPSCs) from human peripheral blood provides a convenient and low-invasive way to obtain patient-specific iPSCs. The episomal vector is one of the best approaches for reprogramming somatic cells to pluripotent status because of its simplicity and affordability. However, the efficiency of episomal vector reprogramming of adult peripheral blood cells is relatively low compared with cord blood and bone marrow cells. In the present study, integration-free human iPSCs derived from peripheral blood were established via episomal technology. We optimized mononuclear cell isolation and cultivation, episomal vector promoters, and a combination of transcriptional factors to improve reprogramming efficiency. Here, we improved the generation efficiency of integration-free iPSCs from human peripheral blood mononuclear cells by optimizing the method of isolating mononuclear cells from peripheral blood, by modifying the integration of culture medium, and by adjusting the duration of culture time and the combination of different episomal vectors. With this optimized protocol, a valuable asset for banking patient-specific iPSCs has been established.

Isolation of highly suppressive CD25+FoxP3+ T regulatory cells from G-CSF-mobilized donors with retention of cytotoxic anti-viral CTLs: application for multi-functional immunotherapy post stem cell transplantation.

Directory of Open Access Journals (Sweden)

Edward R Samuel

Full Text Available Previous studies have demonstrated the effective control of cytomegalovirus (CMV infections post haematopoietic stem cell transplant through the adoptive transfer of donor derived CMV-specific T cells (CMV-T. Strategies for manufacturing CMV immunotherapies has involved a second leukapheresis or blood draw from the donor, which in the unrelated donor setting is not always possible. We have investigated the feasibility of using an aliquot of the original G-CSF-mobilized graft as a starting material for manufacture of CMV-T and examined the activation marker CD25 as a targeted approach for identification and isolation following CMVpp65 peptide stimulation. CD25+ cells isolated from G-CSF-mobilized apheresis revealed a significant increase in the proportion of FoxP3 expression when compared with conventional non-mobilized CD25+ cells and showed a superior suppressive capacity in a T cell proliferation assay, demonstrating the emergence of a population of Tregs not present in non-mobilized apheresis collections. The expansion of CD25+ CMV-T in short-term culture resulted in a mixed population of CD4+ and CD8+ T cells with CMV-specificity that secreted cytotoxic effector molecules and lysed CMVpp65 peptide-loaded phytohaemagglutinin-stimulated blasts. Furthermore CD25 expanded cells retained their suppressive capacity but did not maintain FoxP3 expression or secrete IL-10. In summary our data indicates that CD25 enrichment post CMV stimulation in G-CSF-mobilized PBMCs results in the simultaneous generation of both a functional population of anti-viral T cells and Tregs thus illustrating a potential single therapeutic strategy for the treatment of both GvHD and CMV reactivation following allogeneic haematopoietic stem cell transplantation. The use of G-CSF-mobilized cells as a starting material for cell therapy manufacture represents a feasible approach to alleviating the many problems incurred with successive donations and procurement of cells from

Ex-Vivo Gene Therapy Using Lentiviral Mediated Gene Transfer Into Umbilical Cord Blood Derived Stem Cells

Directory of Open Access Journals (Sweden)

Hanieh Jalali

2016-02-01

Full Text Available Background Introduction of therapeutic genes into the injured site of nervous system can be achieved using transplantation of cellular vehicles containing desired gene. To transfer exogenous genes into the cellular vehicles, lentiviral vectors are one of interested vectors because of advantages such high transduction efficiency of dividing and non-dividing cells. Unrestricted somatic stem cells are subclasses of umbilical cord blood derived stem cells which are appreciate candidates to use as cellular vehicles for ex vivo gene therapy of nervous system. Objectives In current study we investigated the effect of lentiviral vector transduction on the neuronal related features of unrestricted somatic stem cells to indicate the probable and unwanted changes related to transduction procedure. Materials and Methods In this experimental study, lentiviral vector containing green fluorescent protein (GFP were transduced into unrestricted somatic stem cells and its effect was investigated with using MTT assay, qPCR and immunohistochemistry techniques. For statistical comparison of real time PCR results, REST software (2009, Qiagen was used. Results Obtained results showed lentiviral vector transduction did not have cytotoxic effects on unrestricted somatic stem cells and did not change neuronal differentiation capacity of them as well the expression of some neuronal related genes and preserved them in multilineage situation. Conclusions In conclusion, we suggested that lentiviral vectors could be proper vectors to transfer therapeutic gene into unrestricted somatic stem cells to provide a cellular vehicle for ex vivo gene therapy of nervous system disorders.

Productivity loss due to premature mortality caused by blood cancer: a study based on patients undergoing stem cell transplantation.

Science.gov (United States)

Ortega-Ortega, Marta; Oliva-Moreno, Juan; Jiménez-Aguilera, Juan de Dios; Romero-Aguilar, Antonio; Espigado-Tocino, Ildefonso

2015-01-01

Stem cell transplantation has been used for many years to treat haematological malignancies that could not be cured by other treatments. Despite this medical breakthrough, mortality rates remain high. Our purpose was to evaluate labour productivity losses associated with premature mortality due to blood cancer in recipients of stem cell transplantations. We collected primary data from the clinical histories of blood cancer patients who had undergone stem cell transplantation between 2006 and 2011 in two Spanish hospitals. We carried out a descriptive analysis and calculated the years of potential life lost and years of potential productive life lost. Labour productivity losses due to premature mortality were estimated using the Human Capital method. An alternative approach, the Friction Cost method, was used as part of the sensitivity analysis. Our findings suggest that, in a population of 179 transplanted and deceased patients, males and people who die between the ages of 30 and 49 years generate higher labour productivity losses. The estimated loss amounts to over €31.4 million using the Human Capital method (€480,152 using the Friction Cost method), which means an average of €185,855 per death. The highest labour productivity losses are produced by leukaemia. However, lymphoma generates the highest loss per death. Further efforts are needed to reduce premature mortality in blood cancer patients undergoing transplantations and reduce economic losses. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

Hematopoietic Stem Cell Transplantation and History

Directory of Open Access Journals (Sweden)

Atila Tanyeli

2014-02-01

Full Text Available Attemps to employ marrow stem cell for therapeutic purpose began in 1940’s. Marrow transplantation might be of use not only in irradiation protection, but also with therapeutic aim to marrow aplasia, leukemia and other diseases. The use and defining tissue antigens in humans were crucial to the improving of transplantation. The administration of methotrexate for GVHD improved the long term survival. Conditioning regimens for myeloablation designed according to diseases. Cord blood and peripheral blood stem cells were used for transplantion after 1980’s. Cord blood and bone marrow stem cell banks established to find HLA matched donor.

Targeting insulin resistance in type 2 diabetes via immune modulation of cord blood-derived multipotent stem cells (CB-SCs) in stem cell educator therapy: phase I/II clinical trial.

Science.gov (United States)

Zhao, Yong; Jiang, Zhaoshun; Zhao, Tingbao; Ye, Mingliang; Hu, Chengjin; Zhou, Huimin; Yin, Zhaohui; Chen, Yana; Zhang, Ye; Wang, Shanfeng; Shen, Jie; Thaker, Hatim; Jain, Summit; Li, Yunxiang; Diao, Yalin; Chen, Yingjian; Sun, Xiaoming; Fisk, Mary Beth; Li, Heng

2013-07-09

The prevalence of type 2 diabetes (T2D) is increasing worldwide and creating a significant burden on health systems, highlighting the need for the development of innovative therapeutic approaches to overcome immune dysfunction, which is likely a key factor in the development of insulin resistance in T2D. It suggests that immune modulation may be a useful tool in treating the disease. In an open-label, phase 1/phase 2 study, patients (N=36) with long-standing T2D were divided into three groups (Group A, oral medications, n=18; Group B, oral medications+insulin injections, n=11; Group C having impaired β-cell function with oral medications+insulin injections, n=7). All patients received one treatment with the Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separates mononuclear cells from the whole blood, briefly co-cultures them with adherent cord blood-derived multipotent stem cells (CB-SCs), and returns the educated autologous cells to the patient's circulation. Clinical findings indicate that T2D patients achieve improved metabolic control and reduced inflammation markers after receiving Stem Cell Educator therapy. Median glycated hemoglobin (HbA1C) in Group A and B was significantly reduced from 8.61%±1.12 at baseline to 7.25%±0.58 at 12 weeks (P=2.62E-06), and 7.33%±1.02 at one year post-treatment (P=0.0002). Homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) demonstrated that insulin sensitivity was improved post-treatment. Notably, the islet beta-cell function in Group C subjects was markedly recovered, as demonstrated by the restoration of C-peptide levels. Mechanistic studies revealed that Stem Cell Educator therapy reverses immune dysfunctions through immune modulation on monocytes and balancing Th1/Th2/Th3 cytokine production. Clinical data from the current phase 1/phase 2 study demonstrate that Stem Cell Educator therapy is a safe approach that produces lasting improvement in

Mesenchymal stem cells from the Wharton’s jelly of umbilical cord segments provide stromal support for the maintenance of cord blood hematopoietic stem cells during long-term ex vivo culture

Science.gov (United States)

Bakhshi, Tiki; Zabriskie, Ryan C.; Bodie, Shamanique; Kidd, Shannon; Ramin, Susan; Paganessi, Laura A.; Gregory, Stephanie A.; Fung, Henry C.; Christopherson, Kent W.

2012-01-01

BACKGROUND Hematopoietic stem cells (HSCs) are routinely obtained from marrow, mobilized peripheral blood, and umbilical cord blood. Mesenchymal stem cells (MSCs) are traditionally isolated from marrow. Bone marrow–derived MSCs (BM-MSCs) have previously demonstrated their ability to act as a feeder layer in support of ex vivo cord blood expansion. However, the use of BM-MSCs to support the growth, differentiation, and engraftment of cord blood may not be ideal for transplant purposes. Therefore, the potential of MSCs from a novel source, the Wharton’s jelly of umbilical cords, to act as stromal support for the long-term culture of cord blood HSC was evaluated. STUDY DESIGN AND METHODS Umbilical cord–derived MSCs (UC-MSCs) were cultured from the Wharton’s jelly of umbilical cord segments. The UC-MSCs were then profiled for expression of 12 cell surface receptors and tested for their ability to support cord blood HSCs in a long-term culture-initiating cell (LTC-IC) assay. RESULTS Upon culture, UC-MSCs express a defined set of cell surface markers (CD29, CD44, CD73, CD90, CD105, CD166, and HLA-A) and lack other markers (CD45, CD34, CD38, CD117, and HLA-DR) similar to BM-MSCs. Like BM-MSCs, UC-MSCs effectively support the growth of CD34+ cord blood cells in LTC-IC assays. CONCLUSION These data suggest the potential therapeutic application of Wharton’s jelly–derived UC-MSCs to provide stromal support structure for the long-term culture of cord blood HSCs as well as the possibility of cotransplantation of genetically identical, HLA-matched, or unmatched cord blood HSCs and UC-MSCs in the setting of HSC transplantation. PMID:18798803

Development of hematopoietic stem and progenitor cells from human pluripotent stem cells.

Science.gov (United States)

Chen, Tong; Wang, Fen; Wu, Mengyao; Wang, Zack Z

2015-07-01

Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), provide a new cell source for regenerative medicine, disease modeling, drug discovery, and preclinical toxicity screening. Understanding of the onset and the sequential process of hematopoietic cells from differentiated hPSCs will enable the achievement of personalized medicine and provide an in vitro platform for studying of human hematopoietic development and disease. During embryogenesis, hemogenic endothelial cells, a specified subset of endothelial cells in embryonic endothelium, are the primary source of multipotent hematopoietic stem cells. In this review, we discuss current status in the generation of multipotent hematopoietic stem and progenitor cells from hPSCs via hemogenic endothelial cells. We also review the achievements in direct reprogramming from non-hematopoietic cells to hematopoietic stem and progenitor cells. Further characterization of hematopoietic differentiation in hPSCs will improve our understanding of blood development and expedite the development of hPSC-derived blood products for therapeutic purpose. © 2015 Wiley Periodicals, Inc.

Stretching the limits: from homeostasis to stem cell plasticity in wound healing and cancer.

Science.gov (United States)

Ge, Yejing; Fuchs, Elaine

2018-05-01

Stem cells (SCs) govern tissue homeostasis and wound repair. They reside within niches, the special microenvironments within tissues that control SC lineage outputs. Upon injury or stress, new signals emanating from damaged tissue can divert nearby cells into adopting behaviours that are not part of their homeostatic repertoire. This behaviour, known as SC plasticity, typically resolves as wounds heal. However, in cancer, it can endure. Recent studies have yielded insights into the orchestrators of maintenance and lineage commitment for SCs belonging to three mammalian tissues: the haematopoietic system, the skin epithelium and the intestinal epithelium. We delineate the multifactorial determinants and general principles underlying the remarkable facets of SC plasticity, which lend promise for regenerative medicine and cancer therapeutics.

Impact of age and diagnosis on viability during centrifugation and cryopreservation of peripheral blood stem cell products.

Science.gov (United States)

Civriz Bozdag, S; Bay, M; Ayyıldız, E; Topcuoglu, P; Ilhan, O

2012-08-01

The viability of the hematopoietic stem cells infused to the patient is important for transplant outcome. We evaluated 31 peripheral blood stem cell product collected from 15 patients. We aimed to check the viabilities of the cells from patients with different age and diagnosis, in different stages of the cryopreservation procedure. We showed a markedly decreased viability rate after centrifugation and addition of DMSO. Percentages of viabilities were similar between young and old patients in each step. Type of hematological malignancy did not make a significant influence on the viability. High speed centrifugation has a negative impact on the viability. Copyright © 2012 Elsevier Ltd. All rights reserved.

Endometrial aspiration biopsy: a non-invasive method of obtaining functional lymphoid progenitor cells and mature natural killer cells.

LENUS (Irish Health Repository)

McMenamin, Moya

2012-09-01

The aim of this study was to compare the efficacy of endometrial aspiration biopsy (EAB) with the more traditional dilatation and curettage (D&C) for the procurement of lymphoid progenitor cells and uterine natural killer (NK) populations in endometrial tissue. This prospective observational study conducted in a tertiary referral university hospital examined endometrium obtained from 32 women admitted for laparoscopic gynaecological procedures. Each participant had endometrium sampled using both EAB and D&C. Both methods were assessed as a source of uterine NK and lymphoid progenitor cells. Similar proportions of mature CD45+CD56+ NK cells (range 25.4-36.2%) and CD45+CD34+ lymphoid progenitors (range 1.2-2.0%) were found in tissue obtained using both EAB and D&C. These cells were adequate for flow cytometric analysis, magnetic bead separation and culture. Colony formation by the CD34+ population demonstrated maturational potential. Tissues obtained via endometrial biopsy and D&C are equivalent, by analysis of uterine NK and lymphoid progenitor cells. The aim of this study was to compare two methods of endometrial sampling - endometrial aspiration biopsy and traditional dilatation and curettage - for the procurement of haematopoietic stem cells and uterine natural killer (NK) populations in endometrial tissue. Thirty-two women who had gynaecological procedures in a tertiary referral hospital participated in this study and had endometrial tissue collected via both methods. Similar populations of mature NK cells and haematopoietic stem cells were found in tissue obtained using both endometrial aspiration biopsy and dilatation and curettage. Tissue obtained via endometrial aspiration biopsy was adequate for the culture and growth of haematopoietic stem cells. We conclude that tissue obtained via endometrial biopsy and dilatation and curettage is equivalent, by analysis of uterine NK and haematopoietic stem cells using flow cytometry. This has implications for further

Peripheral Blood stem cell transplantation in children with Beta-thalassemia major

International Nuclear Information System (INIS)

Farzana, T.; Shamsi, T.S.; Irfan, M.; Ansari, S.H.; Baig, M.I.; Shakoor, N.

2003-01-01

Objective: To share the preliminary data on stem cell transplantation in Pakistan. Results: Engraftment was achieved in all patients except one who required a second dose of bone marrow graft on day +21. Median time to achieve absolute neutrophil count of > 0.5 x 10/sup 9/ /l was 9.0 days (range 8 - 31 days) and platelet count of > 20 x 10/sup 9/ /l was 14 days (12 - 35 days). Acute GVHD was seen in 3 patients, one patient had grade IV gut GVHD; another patient had grade III gut GVHD while third patient had grade II skin GVHD. Median hospital stay was 29 days. Six patients were well and transfusion independent 3 to 36 months post transplant. One episode of primary graft failure required a second dose of bone marrow harvest. Another episode of graft rejection received two doses of donor lymphocytes infusion. There were 4 deaths due to grade IV gut GVHD because of uncontrolled systemic Candida infection and one due to hepatic veno-occlusive (VOD) disease. Conclusion: Allogeneic peripheral blood stem cell transplantation can be safely and economically carried out in Pakistan. Although there had been 4 deaths during 36 months follow-up, with increasing understanding and experience the outcome is expected to improve. (author)

Biomechanical forces promote embryonic haematopoiesis

Science.gov (United States)

Adamo, Luigi; Naveiras, Olaia; Wenzel, Pamela L.; McKinney-Freeman, Shannon; Mack, Peter J.; Gracia-Sancho, Jorge; Suchy-Dicey, Astrid; Yoshimoto, Momoko; Lensch, M. William; Yoder, Mervin C.; García-Cardeña, Guillermo; Daley, George Q.

2009-01-01

Biomechanical forces are emerging as critical regulators of embryogenesis, particularly in the developing cardiovascular system1,2. After initiation of the heartbeat in vertebrates, cells lining the ventral aspect of the dorsal aorta, the placental vessels, and the umbilical and vitelline arteries initiate expression of the transcription factor Runx1 (refs 3–5), a master regulator of haematopoiesis, and give rise to haematopoietic cells4. It remains unknown whether the biomechanical forces imposed on the vascular wall at this developmental stage act as a determinant of haematopoietic potential6. Here, using mouse embryonic stem cells differentiated in vitro, we show that fluid shear stress increases the expression of Runx1 in CD41+c-Kit+ haematopoietic progenitor cells7,concomitantly augmenting their haematopoietic colony-forming potential. Moreover, we find that shear stress increases haematopoietic colony-forming potential and expression of haematopoietic markers in the paraaortic splanchnopleura/aorta–gonads–mesonephros of mouse embryos and that abrogation of nitric oxide, a mediator of shear-stress-induced signalling8, compromises haematopoietic potential in vitro and in vivo. Collectively, these data reveal a critical role for biomechanical forces in haematopoietic development. PMID:19440194

Prognostic Significance of Blood Transfusion in Newly Diagnosed Multiple Myeloma Patients without Autologous Hematopoietic Stem Cell Transplantation

Science.gov (United States)

Fan, Liping; Fu, Danhui; Zhang, Jinping; Wang, Qingqing; Ye, Yamei; Xie, Qianling

2017-01-01

The aim of this study was to evaluate whether blood transfusions affect overall survival (OS) and progression-free survival (PFS) in newly diagnosed multiple myeloma (MM) patients without hematopoietic stem cell transplantation. A total of 181 patients were enrolled and divided into two groups: 68 patients in the transfused group and 113 patients in the nontransfused group. Statistical analyses showed that there were significant differences in ECOG scoring, Ig isotype, platelet (Plt) counts, hemoglobin (Hb) level, serum creatinine (Scr) level, and β2-microglobulin (β2-MG) level between the two groups. Univariate analyses showed that higher International Staging System staging, Plt counts blood transfusion was associated with PFS but not OS in MM patients. Multivariate analyses showed that blood transfusion was not an independent factor for PFS in MM patients. Our preliminary results suggested that newly diagnosed MM patients may benefit from a liberal blood transfusion strategy, since blood transfusion is not an independent impact factor for survival. PMID:28567420

Genetic and serological typing of European infectious haematopoietic necrosis virus (IHNV) isolates

Science.gov (United States)

Johansson, T.; Einer-Jensen, K.; Batts, W.; Ahrens, P.; Bjorkblom, C.; Kurath, G.; Bjorklund, H.; Lorenzen, N.

2009-01-01

Infectious haematopoietic necrosis virus (IHNV) causes the lethal disease infectious haematopoietic necrosis (IHN) in juvenile salmon and trout. The nucleocapsid (N) protein gene and partial glycoprotein (G) gene (nucleotides 457 to 1061) of the European isolates IT-217A, FR-32/87, DE-DF 13/98 11621, DE-DF 4/99-8/99, AU-9695338 and RU-FR1 were sequenced and compared with IHNV isolates from the North American genogroups U, M and L. In phylogenetic studies the N gene of the Italian, French, German and Austrian isolates clustered in the M genogroup, though in a different subgroup than the isolates from the USA. Analyses of the partial G gene of these European isolates clustered them in the M genogroup close to the root while the Russian isolate clustered in the U genogroup. The European isolates together with US-WRAC and US-Col-80 were also tested in an enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies (MAbs) against the N protein. MAbs 136-1 and 136-3 reacted equally at all concentrations with the isolates tested, indicating that these antibodies identify a common epitope. MAb 34D3 separated the M and L genogroup isolates from the U genogroup isolate. MAb 1DW14D divided the European isolates into 2 groups. MAb 1DW14D reacted more strongly with DE-DF 13/98 11621 and RU-FR1 than with IT-217A, FR- 32/87, DE-DF 4/99-8/99 and AU-9695338. In the phylogenetic studies, the Italian, French, German and Austrian isolates clustered in the M genogroup, whereas in the serological studies using MAbs, the European M genogroup isolates could not be placed in the same specific group. These results indicate that genotypic and serotypic classification do not correlate. ?? 2009 Inter-Research.

Retinoic acid postconsolidation therapy for high-risk neuroblastoma patients treated with autologous haematopoietic stem cell transplantation.

Science.gov (United States)

Peinemann, Frank; van Dalen, Elvira C; Enk, Heike; Berthold, Frank

2017-08-25

Neuroblastoma is a rare malignant disease and mainly affects infants and very young children. The tumours mainly develop in the adrenal medullary tissue, with an abdominal mass as the most common presentation. About 50% of patients have metastatic disease at diagnosis. The high-risk group is characterised by metastasis and other features that increase the risk of an adverse outcome. High-risk patients have a five-year event-free survival of less than 50%. Retinoic acid has been shown to inhibit growth of human neuroblastoma cells and has been considered as a potential candidate for improving the outcome of patients with high-risk neuroblastoma. This review is an update of a previously published Cochrane Review. To evaluate the efficacy and safety of additional retinoic acid as part of a postconsolidation therapy after high-dose chemotherapy (HDCT) followed by autologous haematopoietic stem cell transplantation (HSCT), compared to placebo retinoic acid or to no additional retinoic acid in people with high-risk neuroblastoma (as defined by the International Neuroblastoma Risk Group (INRG) classification system). We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (2016, Issue 11), MEDLINE in PubMed (1946 to 24 November 2016), and Embase in Ovid (1947 to 24 November 2016). Further searches included trial registries (on 22 December 2016), conference proceedings (on 23 March 2017) and reference lists of recent reviews and relevant studies. We did not apply limits by publication year or languages. Randomised controlled trials (RCTs) evaluating additional retinoic acid after HDCT followed by HSCT for people with high-risk neuroblastoma compared to placebo retinoic acid or to no additional retinoic acid. Primary outcomes were overall survival and treatment-related mortality. Secondary outcomes were progression-free survival, event-free survival, early toxicity, late toxicity, and health-related quality of life. We used standard

Comparative transcriptomic analysis of endothelial progenitor cells derived from umbilical cord blood and adult peripheral blood: Implications for the generation of induced pluripotent stem cells

Directory of Open Access Journals (Sweden)

Xiugong Gao

2017-12-01

Full Text Available Induced pluripotent stem cells (iPSCs offer the potential to generate tissues with ethnic diversity enabling toxicity testing on selected populations. Recently, it has been reported that endothelial progenitor cells (EPCs derived from umbilical cord blood (CB or adult peripheral blood (PB afford a practical and efficient cellular substrate for iPSC generation. However, differences between EPCs from different blood sources have rarely been studied. In the current study, we derived EPCs from blood mononuclear cells (MNCs and reprogrammed EPCs into iPSCs. We also explored differences between CB-EPCs and PB-EPCs at the molecular and cellular levels through a combination of transcriptomic analysis and cell biology techniques. EPC colonies in CB-MNCs emerged 5–7 days earlier, were 3-fold higher in number, and consistently larger in size than in PB-MNCs. Similarly, iPSC colonies generated from CB-EPCs was 2.5-fold higher in number than from PB-EPCs, indicating CB-EPCs have a higher reprogramming efficiency than PB-EPCs. Transcriptomic analysis using microarrays found a total of 1133 genes differentially expressed in CB-EPCs compared with PB-EPCs, with 675 genes upregulated and 458 downregulated. Several canonical pathways were impacted, among which the human embryonic stem cell pluripotency pathway was of particular interest. The differences in the gene expression pattern between CB-EPCs and PB-EPCs provide a molecular basis for the discrepancies seen in their derivation and reprogramming efficiencies, and highlight the advantages of using CB as the cellular source for the generation of iPSCs and their derivative tissues for ethnic-related toxicological applications.

Comparative transcriptomic analysis of endothelial progenitor cells derived from umbilical cord blood and adult peripheral blood: Implications for the generation of induced pluripotent stem cells.

Science.gov (United States)

Gao, Xiugong; Yourick, Jeffrey J; Sprando, Robert L

2017-12-01

Induced pluripotent stem cells (iPSCs) offer the potential to generate tissues with ethnic diversity enabling toxicity testing on selected populations. Recently, it has been reported that endothelial progenitor cells (EPCs) derived from umbilical cord blood (CB) or adult peripheral blood (PB) afford a practical and efficient cellular substrate for iPSC generation. However, differences between EPCs from different blood sources have rarely been studied. In the current study, we derived EPCs from blood mononuclear cells (MNCs) and reprogrammed EPCs into iPSCs. We also explored differences between CB-EPCs and PB-EPCs at the molecular and cellular levels through a combination of transcriptomic analysis and cell biology techniques. EPC colonies in CB-MNCs emerged 5-7days earlier, were 3-fold higher in number, and consistently larger in size than in PB-MNCs. Similarly, iPSC colonies generated from CB-EPCs was 2.5-fold higher in number than from PB-EPCs, indicating CB-EPCs have a higher reprogramming efficiency than PB-EPCs. Transcriptomic analysis using microarrays found a total of 1133 genes differentially expressed in CB-EPCs compared with PB-EPCs, with 675 genes upregulated and 458 downregulated. Several canonical pathways were impacted, among which the human embryonic stem cell pluripotency pathway was of particular interest. The differences in the gene expression pattern between CB-EPCs and PB-EPCs provide a molecular basis for the discrepancies seen in their derivation and reprogramming efficiencies, and highlight the advantages of using CB as the cellular source for the generation of iPSCs and their derivative tissues for ethnic-related toxicological applications. Published by Elsevier B.V.

Long-term leukocyte reconstitution in NSG mice transplanted with human cord blood hematopoietic stem and progenitor cells.

Science.gov (United States)

Audigé, Annette; Rochat, Mary-Aude; Li, Duo; Ivic, Sandra; Fahrny, Audrey; Muller, Christina K S; Gers-Huber, Gustavo; Myburgh, Renier; Bredl, Simon; Schlaepfer, Erika; Scherrer, Alexandra U; Kuster, Stefan P; Speck, Roberto F

2017-05-30

Humanized mice (hu mice) are based on the transplantation of hematopoietic stem and progenitor cells into immunodeficient mice and have become important pre-clinical models for biomedical research. However, data about their hematopoiesis over time are scarce. We therefore characterized leukocyte reconstitution in NSG mice, which were sublethally irradiated and transplanted with human cord blood-derived CD34+ cells at newborn age, longitudinally in peripheral blood and, for more detailed analyses, cross-sectionally in peripheral blood, spleen and bone marrow at different time points. Human cell chimerism and absolute human cell count decreased between week 16 and 24 in the peripheral blood of hu mice, but were stable thereafter as assessed up to 32 weeks. Human cell chimerism in spleen and bone marrow was maintained over time. Notably, human cell chimerism in peripheral blood and spleen as well as bone marrow positively correlated with each other. Percentage of B cells decreased between week 16 and 24, whereas percentage of T cells increased; subsequently, they levelled off with T cells clearly predominating at week 32. Natural killer cells, monocytes and plasmacytoid dendritic cells (DCs) as well as CD1c + and CD141+ myeloid DCs were all present in hu mice. Proliferative responses of splenic T cells to stimulation were preserved over time. Importantly, the percentage of more primitive hematopoietic stem cells (HSCs) in bone marrow was maintained over time. Overall, leukocyte reconstitution was maintained up to 32 weeks post-transplantation in our hu NSG model, possibly explained by the maintenance of HSCs in the bone marrow. Notably, we observed great variation in multi-lineage hematopoietic reconstitution in hu mice that needs to be taken into account for the experimental design with hu mice.

Initial Attempts of Development and Characterization of an In Vitro Blood Brain Barrier Model Derived from Human Pluripotent Stem Cells

DEFF Research Database (Denmark)

Goldeman, Charlotte; Saaby, Lasse; Hall, Vanessa Jane

The human blood brain barrier has yet to be successfully replicated as an in vitro model. One of the more promising approaches has been to develop an in vitro model derived from human pluripotent stem cells. However, as promising as this model may be, a successful replication of the differentiation...... method on different kinds of pluripotent stem cell lines have yet to be accomplished. We try to approach the promising method as described by Stebbins et al. (2015) to differentiate human pluripotent stem cells into brain like endothelial cells (BECs). Five different human pluripotent stem cell lines...... configurations (mono culture, non-contact co-culture and contact co-culture) with primary rat astrocytes to induce barrier-like properties. Endothelial cell media supplemented with retinoic acid were then applied to the cells to ensure selective expansion of BECs. The different culture configurations were...

Generation and Characterization of Erythroid Cells from Human Embryonic Stem Cells and Induced Pluripotent Stem Cells: An Overview

Directory of Open Access Journals (Sweden)

Kai-Hsin Chang

2011-01-01

Full Text Available Because of the imbalance in the supply and demand of red blood cells (RBCs, especially for alloimmunized patients or patients with rare blood phenotypes, extensive research has been done to generate therapeutic quantities of mature RBCs from hematopoietic stem cells of various sources, such as bone marrow, peripheral blood, and cord blood. Since human embryonic stem cells (hESCs and induced pluripotent stem cells (iPSCs can be maintained indefinitely in vitro, they represent potentially inexhaustible sources of donor-free RBCs. In contrast to other ex vivo stem-cell-derived cellular therapeutics, tumorigenesis is not a concern, as RBCs can be irradiated without marked adverse effects on in vivo function. Here, we provide a comprehensive review of the recent publications relevant to the generation and characterization of hESC- and iPSC-derived erythroid cells and discuss challenges to be met before the eventual realization of clinical usage of these cells.

Lichen Striatus Occurring after Allogenic Peripheral Blood Stem Cell Transplantation in an Adult with Aplastic Anemia

OpenAIRE

Mun, Je-Ho; Park, Hyun-Je; Kim, Hoon-Soo; Kim, Su-Han; Ko, Hyun-Chang; Kim, Byung-Soo; Kim, Moon-Bum

2012-01-01

Lichens striatus (LS) is an acquired, self-limiting inflammatory dermatosis that follows the lines of Blaschko. The etiology of the eruption is unknown, but several theories have been proposed with focus on environmental factors, viral infection, cutaneous injury, hypersensitivity, and genetic predisposition. We describe a 19-year-old woman who developed a unilateral linear eruption 17 months after allogenic peripheral blood stem cell transplantation. Histopathology revealed features, which w...

Haematopoietic stem cell transplantation as first-line treatment in myeloma: a global perspective of current concepts and future possibilities

Directory of Open Access Journals (Sweden)

Catriona Elizabeth Mactier

2012-10-01

Full Text Available Stem cell transplantation forms an integral part of the treatment for multiple myeloma. This paper reviews the current role of transplantation and the progress that has been made in order to optimize the success of this therapy. Effective induction chemotherapy is important and a combination regimen incorporating the novel agent bortezomib is now favorable. Adequate induction is a crucial adjunct to stem cell transplantation and in some cases may potentially postpone the need for transplant. Different conditioning agents prior to transplantation have been explored: high-dose melphalan is most commonly used and bortezomib is a promising additional agent. There is no well-defined superior transplantation protocol but single or tandem autologous stem cell transplantations are those most commonly used, with allogeneic transplantation only used in clinical trials. The appropriate timing of transplantation in the treatment plan is a matter of debate. Consolidation and maintenance chemotherapies, particularly thalidomide and bortezomib, aim to improve and prolong disease response to transplantation and delay recurrence. Prognostic factors for the outcome of stem cell transplant in myeloma have been highlighted. Despite good responses to chemotherapy and transplantation, the problem of disease recurrence persists. Thus, there is still much room for improvement. Treatments which harness the graft-versus-myeloma effect may offer a potential cure for this disease. Trials of novel agents are underway, including targeted therapies for specific antigens such as vaccines and monoclonal antibodies.

Low-molecular-weight carbohydrate Pentaisomaltose may replace dimethyl sulfoxide as a safer cryoprotectant for cryopreservation of peripheral blood stem cells

DEFF Research Database (Denmark)

Svalgaard, Jesper Dyrendom; Haastrup, Eva Kannik; Reckzeh, Kristian

2016-01-01

-related side effects, there is an increasing demand for DMSO-free alternatives. We therefore investigated whether Pentaisomaltose (PIM), a low-molecular-weight carbohydrate (1 kDa), can be used for cryopreservation of peripheral blood stem cells, more specifically hematopoietic progenitor cell apheresis (HPC...

A non-fatal case of invasive zygomycete (Lichtheimia corymbifera) infection in an allogeneic haematopoietic cell transplant recipient

DEFF Research Database (Denmark)

Eickhardt, Steffen; Braendstrup, Peter; Clasen-Linde, Erik

2013-01-01

Post-transplant infections in allogeneic haematopoietic cell transplant (allo-HCT) recipients often have severe consequences. This is especially the case when dealing with zygomycete infections where the result is often fatal. A major problem when dealing with zygomycete infections is the need...... for an accurate and fast diagnosis as the phylum is highly resistant towards the conventional antifungals. We herein describe a non-fatal case of Lichtheimia corymbifera infection in an allo-HCT recipient....

Blood and Bone Marrow Donation

Science.gov (United States)

... for a stem cell transplant. Risks Bone marrow donation The most serious risk associated with donating bone ... you feel fully recovered. Peripheral blood stem cell donation The risks of this type of stem cell ...

Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level

Science.gov (United States)

Swiers, Gemma; Baumann, Claudia; O'Rourke, John; Giannoulatou, Eleni; Taylor, Stephen; Joshi, Anagha; Moignard, Victoria; Pina, Cristina; Bee, Thomas; Kokkaliaris, Konstantinos D.; Yoshimoto, Momoko; Yoder, Mervin C.; Frampton, Jon; Schroeder, Timm; Enver, Tariq; Göttgens, Berthold; de Bruijn, Marella F. T. R.

2013-12-01

Haematopoietic stem cells (HSCs) are the founding cells of the adult haematopoietic system, born during ontogeny from a specialized subset of endothelium, the haemogenic endothelium (HE) via an endothelial-to-haematopoietic transition (EHT). Although recently imaged in real time, the underlying mechanism of EHT is still poorly understood. We have generated a Runx1 +23 enhancer-reporter transgenic mouse (23GFP) for the prospective isolation of HE throughout embryonic development. Here we perform functional analysis of over 1,800 and transcriptional analysis of 268 single 23GFP+ HE cells to explore the onset of EHT at the single-cell level. We show that initiation of the haematopoietic programme occurs in cells still embedded in the endothelial layer, and is accompanied by a previously unrecognized early loss of endothelial potential before HSCs emerge. Our data therefore provide important insights on the timeline of early haematopoietic commitment.

Haematopoietic depletion in vaccine-induced neonatal pancytopenia depends on both the titre and specificity of alloantibody and levels of MHC I expression.

Science.gov (United States)

Bell, Charlotte R; MacHugh, Niall D; Connelley, Timothy K; Degnan, Kathryn; Morrison, W Ivan

2015-07-09

Bovine Neonatal Pancytopenia (BNP) is a disease of calves characterised by haematopoietic depletion, mediated by ingestion of alloantibodies in colostrum. It has been linked epidemiologically to vaccination of the dams of affected calves with a particular vaccine (Pregsure) containing a novel adjuvant. Evidence suggests that BNP-alloantibodies are directed against MHC I molecules, induced by contaminant bovine cellular material from Madin-Darby Bovine Kidney (MDBK) cells used in the vaccine's production. We aimed to investigate the specificity of BNP-alloantibody for bovine MHC I alleles, particularly those expressed by MDBK cells, and whether depletion of particular cell types is due to differential MHC I expression levels. A complement-mediated cytotoxicity assay was used to assess functional serum alloantibody titres in BNP-dams, Pregsure-vaccinated dams with healthy calves, cows vaccinated with an alternative product and unvaccinated controls. Alloantibody specificity was investigated using transfected mouse lines expressing the individual MHC I alleles identified from MDBK cells and MHC I-defined bovine leukocyte lines. All BNP-dams and 50% of Pregsure-vaccinated cows were shown to have MDBK-MHC I specific alloantibodies, which cross-reacted to varying degrees with other MHC I genotypes. MHC I expression levels on different blood cell types, assessed by flow cytometry, were found to correlate with levels of alloantibody-mediated damage in vitro and in vivo. Alloantibody-killed bone marrow cells were shown to express higher levels of MHC I than undamaged cells. The results provide evidence that MHC I-specific alloantibodies play a dominant role in the pathogenesis of BNP. Haematopoietic depletion was shown to be dependent on the titre and specificity of alloantibody produced by individual cows and the density of surface MHC I expression by different cell types. Collectively, the results support the hypothesis that MHC I molecules originating from MDBK cells

Caregiver burden among primary caregivers of patients undergoing peripheral blood stem cell transplantation: a cross sectional study.

Science.gov (United States)

Akgul, Nur; Ozdemir, Leyla

2014-08-01

This study aimed to identify caregiver burden and influencing factors on the burden in primary caregivers of peripheral blood stem cell transplantation patients within 2-12 months following transplant, indicating early recovery period after discharge. This descriptive cross sectional study was carried out at hematopoietic stem cell transplantation outpatient units of three university hospitals in Turkey. A total of 55 patient and caregiver dyads were recruited and interviewed. The data were collected using questionnaires developed by the researchers and caregiver burden was measured with the Zarit Burden Interview. The mean score of Zarit Burden Interview was 28.41 (SD = 13.90). Patients' symptoms including nausea and self depreciation feeling were related to greater caregiver burden. Self-depreciation was referred to feeling undervalued. The mean score of the tool was significantly higher in caregivers who have not been educated beyond primary school and also caregivers who had lower income. Caregivers who supported their patients to fulfill physical needs and who did not receive help for meeting patients' psychological needs had statistically more elevated levels of burden. Moreover, the extent of care giving activities undertaken was positively correlated with caregiver burden scores. While positive impact of the care giving process on family relations decreased caregiver burden; negative effect increased the burden. This study suggests that caregiver burden of primary caregivers caring for peripheral blood stem cell transplantation patients varies by education, income status, and the extent of care giving activities undertaken. Changes in family ties and relations due to care giving effected caregiver burden. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cord-Blood Banking

Science.gov (United States)

... cord blood mainly because of the promise that stem cell research holds for the future. Most of us would have little use for stem cells now, but research into using them to treat diseases is ongoing — ...

Generation of Patient-Specific induced Pluripotent Stem Cell from Peripheral Blood Mononuclear Cells by Sendai Reprogramming Vectors.

Science.gov (United States)

Quintana-Bustamante, Oscar; Segovia, Jose C

2016-01-01

Induced pluripotent stem cells (iPSC) technology has changed preclinical research since their generation was described by Shinya Yamanaka in 2006. iPSCs are derived from somatic cells after being reprogrammed back to an embryonic state by specific combination of reprogramming factors. These reprogrammed cells resemble all the characteristic of embryonic stem cells (ESC). The reprogramming technology is even more valuable to research diseases biology and treatment by opening gene and cell therapies in own patient's iPSC. Patient-specific iPSC can be generated from a large variety of patient cells by any of the myriad of reprogramming platforms described. Here, we describe the generation of patient-specific iPSC from patient peripheral blood mononuclear cells by Sendai Reprogramming vectors.

Proteomic profiling of tissue-engineered blood vessel walls constructed by adipose-derived stem cells.

Science.gov (United States)

Wang, Chen; Guo, Fangfang; Zhou, Heng; Zhang, Yun; Xiao, Zhigang; Cui, Lei

2013-02-01

Adipose-derived stem cells (ASCs) can differentiate into smooth muscle cells and have been engineered into elastic small diameter blood vessel walls in vitro. However, the mechanisms involved in the development of three-dimensional (3D) vascular tissue remain poorly understood. The present study analyzed protein expression profiles of engineered blood vessel walls constructed by human ASCs using methods of two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS). These results were compared to normal arterial walls. A total of 1701±15 and 1265±26 protein spots from normal and engineered blood vessel wall extractions were detected by 2DE, respectively. A total of 20 spots with at least 2.0-fold changes in expression were identified, and 38 differently expressed proteins were identified by 2D electrophoresis and ion trap MS. These proteins were classified into seven functional categories: cellular organization, energy, signaling pathway, enzyme, anchored protein, cell apoptosis/defense, and others. These results demonstrated that 2DE, followed by ion trap MS, could be successfully utilized to characterize the proteome of vascular tissue, including tissue-engineered vessels. The method could also be employed to achieve a better understanding of differentiated smooth muscle protein expression in vitro. These results provide a basis for comparative studies of protein expression in vascular smooth muscles of different origin and could provide a better understanding of the mechanisms of action needed for constructing blood vessels that exhibit properties consistent with normal blood vessels.

Superior Red Blood Cell Generation from Human Pluripotent Stem Cells Through a Novel Microcarrier-Based Embryoid Body Platform.

Science.gov (United States)

Sivalingam, Jaichandran; Lam, Alan Tin-Lun; Chen, Hong Yu; Yang, Bin Xia; Chen, Allen Kuan-Liang; Reuveny, Shaul; Loh, Yuin-Han; Oh, Steve Kah-Weng

2016-08-01

In vitro generation of red blood cells (RBCs) from human embryonic stem cells and human induced pluripotent stem cells appears to be a promising alternate approach to circumvent shortages in donor-derived blood supplies for clinical applications. Conventional methods for hematopoietic differentiation of human pluripotent stem cells (hPSC) rely on embryoid body (EB) formation and/or coculture with xenogeneic cell lines. However, most current methods for hPSC expansion and EB formation are not amenable for scale-up to levels required for large-scale RBC generation. Moreover, differentiation methods that rely on xenogenic cell lines would face obstacles for future clinical translation. In this study, we report the development of a serum-free and chemically defined microcarrier-based suspension culture platform for scalable hPSC expansion and EB formation. Improved survival and better quality EBs generated with the microcarrier-based method resulted in significantly improved mesoderm induction and, when combined with hematopoietic differentiation, resulted in at least a 6-fold improvement in hematopoietic precursor expansion, potentially culminating in a 80-fold improvement in the yield of RBC generation compared to a conventional EB-based differentiation method. In addition, we report efficient terminal maturation and generation of mature enucleated RBCs using a coculture system that comprised primary human mesenchymal stromal cells. The microcarrier-based platform could prove to be an appealing strategy for future scale-up of hPSC culture, EB generation, and large-scale generation of RBCs under defined and xeno-free conditions.

Cost-effectiveness of private umbilical cord blood banking.

Science.gov (United States)

Kaimal, Anjali J; Smith, Catherine C; Laros, Russell K; Caughey, Aaron B; Cheng, Yvonne W

2009-10-01

To investigate the cost-effectiveness of private umbilical cord blood banking. A decision-analytic model was designed comparing private umbilical cord blood banking with no umbilical cord blood banking. Baseline assumptions included a cost of $3,620 for umbilical cord blood banking and storage for 20 years, a 0.04% chance of requiring an autologous stem cell transplant, a 0.07% chance of a sibling requiring an allogenic stem cell transplant, and a 50% reduction in risk of graft-versus-host disease if a sibling uses banked umbilical cord blood. Private cord blood banking is not cost-effective because it cost an additional $1,374,246 per life-year gained. In sensitivity analysis, if the cost of umbilical cord blood banking is less than $262 or the likelihood of a child needing a stem cell transplant is greater than 1 in 110, private umbilical cord blood banking becomes cost-effective. Currently, private umbilical cord blood banking is cost-effective only for children with a very high likelihood of needing a stem cell transplant. Patients considering private blood banking should be informed of the remote likelihood that a unit will be used for a child or another family member. III.

Severe acute radiation syndrome. Treatment of a lethally 60Co-source irradiated accident victim in China with HLA-mismatched peripheral blood stem cell transplantation and mesenchymal stem cells

International Nuclear Information System (INIS)

Guo Mei; Dong Zheng; Qiao Jianhui

2014-01-01

This is a case report of a 32-year-old man exposed to a total body dose of 14.5 Gy γ-radiation in a lethal 60 Co-source irradiation accident in 2008 in China. Frequent nausea, vomiting and marked neutropenia and lymphopenia were observed from 30 min to 45 h after exposure. HLA-mismatched peripheral blood stem cell transplantation combined with infusion of mesenchymal stem cells was used at Day 7. Rapid hematopoietic recovery, stable donor engraftment and healing of radioactive skin ulceration were achieved during Days 18-36. The patient finally developed intestinal obstruction and died of multi-organ failure on Day 62, although intestinal obstruction was successfully released by emergency bowel resection. (author)

Restrictive versus liberal red blood cell transfusion strategies for people with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without haematopoietic stem cell support

Science.gov (United States)

Estcourt, Lise J; Malouf, Reem; Trivella, Marialena; Fergusson, Dean A; Hopewell, Sally; Murphy, Michael F

2017-01-01

Background Many people diagnosed with haematological malignancies experience anaemia, and red blood cell (RBC) transfusion plays an essential supportive role in their management. Different strategies have been developed for RBC transfusions. A restrictive transfusion strategy seeks to maintain a lower haemoglobin level (usually between 70 g/L to 90 g/L) with a trigger for transfusion when the haemoglobin drops below 70 g/L), whereas a liberal transfusion strategy aims to maintain a higher haemoglobin (usually between 100 g/L to 120 g/L, with a threshold for transfusion when haemoglobin drops below 100 g/L). In people undergoing surgery or who have been admitted to intensive care a restrictive transfusion strategy has been shown to be safe and in some cases safer than a liberal transfusion strategy. However, it is not known whether it is safe in people with haematological malignancies. Objectives To determine the efficacy and safety of restrictive versus liberal RBC transfusion strategies for people diagnosed with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without a haematopoietic stem cell transplant (HSCT). Search methods We searched for randomised controlled trials (RCTs) and non-randomised trials (NRS) in MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1982), Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 6), and 10 other databases (including four trial registries) to 15 June 2016. We also searched grey literature and contacted experts in transfusion for additional trials. There was no restriction on language, date or publication status. Selection criteria We included RCTs and prospective NRS that evaluated a restrictive compared with a liberal RBC transfusion strategy in children or adults with malignant haematological disorders or undergoing HSCT. Data collection and analysis We used the standard methodological procedures expected by Cochrane. Main results

Seeding of single hemopoietic stem cells and self renewal of committed stem cells

International Nuclear Information System (INIS)

Brecher, G.

1986-01-01

Single cells and two to five proliferating cells were transfused into mice whose own stem cells had been killed by irradiation. When a small inoculum of 50,000 AB marrow cells was given only 4 of 20 recipients survived, but all 4 had only PGK A enzyme in their peripheral blood cells. The results indicate that the survivors received a single pluripotential stem cell capable of proliferating. Survivors showed no deterioration in their blood picture after many months. It was concluded that there is no clonal succession in the marrow cells. Further studies with transfusions of 100,000 and 10,000,000 marrow cells after lethal irradiation suggest that there is production of committed stem cells with significant self-renewal

Angiopoietin-like protein 3 promotes preservation of stemness during Ex Vivo expansion of murine hematopoietic stem cells

NARCIS (Netherlands)

E. Farahbakhshian (Elnaz); M.M.A. Verstegen (Monique); T.P. Visser (Trudi); S. Kheradmandkia (Sima); D. Geerts (Dirk); S. Arshad (Shazia); N. Riaz (Noveen); F.G. Grosveld (Frank); N.P. van Til (Niek); J.P.P. Meijerink (Jules)

2014-01-01

textabstractAllogeneic hematopoietic stem cell (HSC) transplantations from umbilical cord blood or autologous HSCs for gene therapy purposes are hampered by limited number of stem cells. To test the ability to expand HSCs in vitro prior to transplantation, two growth factor cocktails containing stem

Effect of colorectal cancer on the number of normal stem cells circulating in peripheral blood.

Science.gov (United States)

Marlicz, Wojciech; Sielatycka, Katarzyna; Serwin, Karol; Kubis, Ewa; Tkacz, Marta; Głuszko, Rafał; Białek, Andrzej; Starzyńska, Teresa; Ratajczak, Mariusz Z

2016-12-01

Bone marrow (BM) residing stem cells are mobilized from their BM niches into peripheral blood (PB) in several pathological situations including tissue organ injury and systemic inflammation. We recently reported that the number of BM-derived stem cells (SCs) increases in patients with pancreatic and stomach cancer. Accordingly, we observed higher numbers of circulating very small embryonic/epiblast‑like stem cells (VSELs) and mesenchymal stem cells (MSCs) that were associated with the activation of pro-mobilizing complement cascade and an elevated level of sphingosine-1 phosphate (S1P) in PB plasma. We wondered if a similar correlation occurs in patients with colorectal cancer (CRC). A total of 46 patients were enrolled in this study: 17 with CRC, 18 with benign colonic adenomas (BCA) and 11 healthy individuals. By employing fluorescence-activated cell sorting (FACS) we evaluated the number of BM-derived SCs circulating in PB: i) CD34+/Lin-/CD45- and CD133-/Lin-/CD45- VSELs; ii) CD45-/CD105+/CD90+/CD29+ MSCs; iii) CD45-/CD34+/CD133+/KDR+ endothelial progenitor cells (EPCs); and iv) CD133+/Lin-/CD45+ or CD34+/Lin-/CD45+ cells enriched for hematopoietic stem/progenitor cells (HSPCs). In parallel, we measured in the PB parameters regulating the egress of SCs from BM into PB. In contrast to pancreatic and gastric cancer patients, CRC subjects presented neither an increase in the number of circulating SCs nor the activation of pro-mobilizing factors such as complement, coagulation and fibrinolytic cascade, circulating stromal derived factor 1 (SDF‑1), vascular endothelial growth factor (VEGF) and intestinal permeability marker (zonulin). In conclusion, mobilization of SCs in cancer patients depends on the type of malignancy and its ability to activate pro-mobilization cascades.

Banking cord blood stem cells: attitude and knowledge of pregnant women in five European countries.

Science.gov (United States)

Katz, Gregory; Mills, Antonia; Garcia, Joan; Hooper, Karen; McGuckin, Colin; Platz, Alexander; Rebulla, Paolo; Salvaterra, Elena; Schmidt, Alexander H; Torrabadella, Marta

2011-03-01

This study explores pregnant women's awareness of cord blood stem cells and their attitude regarding banking options in France, Germany, Italy, Spain, and the UK. Questionnaires were distributed in six maternities. This anonymous and self-completed questionnaire included 29 multiple-choice questions based on: 1) sociodemographic factors, 2) awareness and access to information about cord blood banking, 3) banking option preferences, and 4) donating cord blood units (CBUs) to research. A total of 79% of pregnant women had little awareness of cord blood banking (n = 1620). A total of 58% of women had heard of the therapeutic benefits of cord blood, of which 21% received information from midwives and obstetricians. A total of 89% of respondents would opt to store CBUs. Among them, 76% would choose to donate CBUs to a public bank to benefit any patient in need of a cord blood transplant. Twelve percent would choose a mixed bank, and 12%, a private bank. A total of 92% would donate their child's CBU to research when it is not suitable for transplantation. The study reveals a strong preference for public banking in all five countries, based on converging values such as solidarity. Attitudes of pregnant women are not an obstacle to the rapid expansion of allogeneic banking in these EU countries. Banking choices do not appear to be correlated with household income. The extent of commercial marketing of cord blood banks in mass media highlights the importance for obstetric providers to play a central role in raising women's awareness early during their pregnancy with evidence-based medical information about banking options. © 2010 American Association of Blood Banks.

Blood Stem Cell Activity Is Arrested by Th1-Mediated Injury Preventing Engraftment following Nonmyeloablative Conditioning

Science.gov (United States)

Florek, Mareike; Kohrt, Holbrook E. K.; Küpper, Natascha J.; Filatenkov, Alexander; Linderman, Jessica A.; Hadeiba, Husein; Negrin, Robert S.

2016-01-01

T cells are widely used to promote engraftment of hematopoietic stem cells (HSCs) during an allogeneic hematopoietic cell transplantation. Their role in overcoming barriers to HSC engraftment is thought to be particularly critical when patients receive reduced doses of preparative chemotherapy and/or radiation compared with standard transplantations. In this study, we sought to delineate the effects CD4+ cells on engraftment and blood formation in a model that simulates clinical hematopoietic cell transplantation by transplanting MHC-matched, minor histocompatibility–mismatched grafts composed of purified HSCs, HSCs plus bulk T cells, or HSCs plus T cell subsets into mice conditioned with low-dose irradiation. Grafts containing conventional CD4+ T cells caused marrow inflammation and inhibited HSC engraftment and blood formation. Posttransplantation, the marrows of HSCs plus CD4+ cell recipients contained IL-12–secreting CD11c+ cells and IFN-γ–expressing donor Th1 cells. In this setting, host HSCs arrested at the short-term stem cell stage and remained in the marrow in a quiescent cell cycling state (G0). As a consequence, donor HSCs failed to engraft and hematopoiesis was suppressed. Our data show that Th1 cells included in a hematopoietic allograft can negatively impact HSC activity, blood reconstitution, and engraftment of donor HSCs. This potential negative effect of donor T cells is not considered in clinical transplantation in which bulk T cells are transplanted. Our findings shed new light on the effects of CD4+ T cells on HSC biology and are applicable to other pathogenic states in which immune activation in the bone marrow occurs such as aplastic anemia and certain infectious conditions. PMID:27815446

Comparable results of autologous and allogeneic haematopoietic stem cell transplantation for adults with Philadelphia-positive acute lymphoblastic leukaemia in first complete molecular remission: An analysis by the Acute Leukemia Working Party of the EBMT.

Science.gov (United States)

Giebel, Sebastian; Labopin, Myriam; Potter, Michael; Poiré, Xavier; Sengeloev, Henrik; Socié, Gerard; Huynh, Anne; Afanasyev, Boris V; Schanz, Urs; Ringden, Olle; Kalhs, Peter; Beelen, Dietrich W; Campos, Antonio M; Masszi, Tamás; Canaani, Jonathan; Mohty, Mohamad; Nagler, Arnon

2018-06-01

Allogeneic haematopoietic stem cell transplantation (alloHSCT) is considered a standard treatment for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) achieving complete remission after induction containing tyrosine kinase inhibitors (TKIs). We retrospectively compared results of myeloablative alloHSCT from either matched sibling donor (MSD) or unrelated donor (URD) with autologous (auto) HSCT for adults with Ph+ ALL in molecular remission, treated between 2007 and 2014. In univariate analysis, the incidence of relapse at 2 years was 47% after autoHSCT, 28% after MSD-HSCT and 19% after URD-HSCT (P = 0.0002). Respective rates of non-relapse mortality were 2%, 18%, and 22% (P = 0.001). The probabilities of leukaemia-free survival were 52%, 55% and 60% (P = 0.69), while overall survival rates were 70%, 70% and 69% (P = 0.58), respectively. In multivariate analysis, there was a trend towards increased risk of overall mortality after MSD-HSCT (hazard ratio [HR], 1.5, P = 0.12) and URD-HSCT (HR, 1.6, P = 0.08) when referred to autoHSCT. The use of total body irradiation (TBI)-based regimens was associated with reduced risk of relapse (HR, 0.65, P = 0.02) and overall mortality (HR, 0.67, P = 0.01). In the era of TKIs, outcomes of myeloablative autoHSCT and alloHSCT for patients with Ph+ ALL in first molecular remission are comparable. Therefore, autoHSCT appears to be an attractive treatment option potentially allowing for circumvention of alloHSCT sequelae. Irrespective of the type of donor, TBI-based regimens should be considered the preferable type of conditioning for Ph+ ALL. Copyright © 2018 Elsevier Ltd. All rights reserved.

Motivations, experiences, and perspectives of bone marrow and peripheral blood stem cell donors: thematic synthesis of qualitative studies.

Science.gov (United States)

Garcia, Maria C; Chapman, Jeremy R; Shaw, Peter J; Gottlieb, David J; Ralph, Angelique; Craig, Jonathan C; Tong, Allison

2013-07-01

Hematopoietic stem cell (HSC) transplantation using bone marrow and peripheral blood stem cells is a lifesaving treatment for patients with leukemia or other blood disorders. However, donors face the risk of physical and psychosocial complications. We aimed to synthesize qualitative studies on the experiences and perspectives of HSC donors. We searched MEDLINE, Embase, PsycINFO, CINAHL, Google Scholar, and reference lists of relevant articles to November 13, 2012. Thematic synthesis was used to analyze the findings. Thirty studies involving 1552 donors were included. The decision to donate included themes of saving life, family loyalty, building a positive identity, religious conviction, fear of invasive procedures, and social pressure and obligation. Five themes about the donation experience were identified: mental preparedness (pervasive pain, intense disappointment over recipient death, exceeding expectations, and valuing positive recipient gains), burden of responsibility (striving to be a quality donor, unresolved guilt, and exacerbated grief), feeling neglected (medical dismissiveness and family inattention), strengthened relationships (stronger family ties, establishing blood bonds), and personal sense of achievement (satisfaction and pride, personal development, hero status, and social recognition). Although HSC donation was appreciated as an opportunity to save life, some donors felt anxious and unduly compelled to donate. HSC donors became emotionally invested and felt responsible for their recipient's outcomes and were profoundly grieved and disappointed if the transplantation was unsuccessful. To maximize donor satisfaction and mitigate the psychosocial risks for HSC donors, strategies to address the emotional challenges of anxiety, sense of coercion, guilt, and grief in donors are warranted. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Stem Cells and Blood: Where have we come from... and where are we going?; Celulas Madre y sangre: De donde venimos y... donde vamos a parar

Energy Technology Data Exchange (ETDEWEB)

Bueren, J. A.

2011-07-01

Since 1961, they year when the first trial that characterized the behaviour of a stem cell in mice exposed to high doses of radiation was described, research in this field has proceeded at an unpredictable place. Knowledge of the function of hematopoietic stem cells which are responsible for forming blood cells facilitated the development of therapies based on the transplant of bone marrow and other cell source, e. g. blood from the umbilical cord. These breakthroughs, together with the progress of molecular biology and virology, made it possible to manipulate the genome of hematopoietic stem cells so effectively and safely that the transplant of genetically modified cells has become a variable therapeutic alternative for the treatment of certain genetic diseases and also cancer. This brief article describes some of the contributions that our Hematopoiesis and Gene Therapy Division of the CIEMAT and the CIBER for Rare Diseases has been developing in this fascinating field of stem cells and gene therapy, in the context of the international research being carried out in this area. (Author) 34 refs.

High-activity samarium-153-EDTMP therapy followed by autologous peripheral blood stem cell support in unresectable osteosarcoma

International Nuclear Information System (INIS)

Franzius, Ch.; Eckardt, J.; Sciuk, J.; Schober, O.; Bielack, S.; Flege, S.; Juergens, H.

2001-01-01

Purpose: Despite highly efficacious chemotherapy, patients with osteosarcomas still have a poor prognosis if adequate surgical control cannot be obtained. These patients may benefit from therapy with radiolabeled phosphonates. Patients and Methods: Six patients (three male, three female; seven to 41 years) with unresectable primary osteosarcoma (n = 3) or unresectable recurrent sites of osteosarcomas (n = 3) were treated with high-activity of Sm-153-EDTMP (150 MBq/kg BW). In all patients autologous peripheral blood stem cells had been collected before Sm-153-EDTMP therapy. Results: No immediate adverse reactions were observed in the patients. In one patient bone pain increased during the first 48 hrs after therapy. Three patients received pain relief. Autologous peripheral blood stem cell reinfusion was performed on day +12 to +27 in all patients to overcome potentially irreversible damage to the hematopoietic stem cells. In three patient external radiotherapy of the primary tumor site was performed after Sm-153-EDTMP therapy and in two of them polychemotherapy was continued. Thirty-six months later one of these patients is still free of progression. Two further patients are still alive. However, they have developed new metastases. The three patients who had no accompanying external radiotherapy, all died of disease progression five to 20 months after therapy. Conclusion: These preliminary results show that high-dose Sm-153-EDTMP therapy is feasible and warrants further evaluation of efficacy. The combination with external radiation and polychemotherapy seems to be most promising. Although osteosarcoma is believed to be relatively radioresistant, the total focal dose achieved may delay local progression or even achieve permanent local tumor control in patients with surgically inaccessible primary or relapsing tumors. (orig.)

A non-fatal case of invasive zygomycete (Lichtheimia corymbifera) infection in an allogeneic haematopoietic cell transplant recipient.

Science.gov (United States)

Eickhardt, Steffen; Braendstrup, Peter; Clasen-Linde, Erik; Jensen, Karl E; Alhede, Morten; Bjarnsholt, Thomas; Høiby, Niels; Vindeløv, Lars; Moser, Claus

2013-05-01

Post-transplant infections in allogeneic haematopoietic cell transplant (allo-HCT) recipients often have severe consequences. This is especially the case when dealing with zygomycete infections where the result is often fatal. A major problem when dealing with zygomycete infections is the need for an accurate and fast diagnosis as the phylum is highly resistant towards the conventional antifungals. We herein describe a non-fatal case of Lichtheimia corymbifera infection in an allo-HCT recipient. © 2012 The Authors APMIS © 2012 APMIS.

Transient spontaneous engraftment of CD34 hematopoietic cord blood stem cells as seen in peripheral blood: treatment of leprosy patients with anemia by placental umbilical cord whole blood transfusion.

Science.gov (United States)

Bhattacharya, N

2006-01-01

Cord blood, because of its rich mix of fetal and adult hemoglobin, high platelet and white blood cell (WBC) counts, and a plasma filled with cytokine and growth factors, as well as its hypoantigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood transfusion. Our experience of 74 units (50 ml-146 ml mean, 86 ml +/- 7.6 ml SD, median 80 ml, mean packed cell volume 48 +/- 4.1 SD, mean percent hemoglobin concentration 16.2 g/dl +/- 1.8 g/dl of placental umbilical cord whole blood collection (from 1 April 1999) after lower uterine cesarean section (LUCS) from consenting mothers and transfusion of the same to 16 informed, consenting patients with percent plasma hemoglobin 8 g/dl or less, is presented here. After collection the blood was immediately preserved in the refrigerator and transfused within 72 hours of collection. Fifteen males and one female, aged 12-72 yrs (mean 48.4 yrs) participated: five cases were pausibacillary type (PB) and 11 cases were multibacillary type (MB). The clinical spectrum of the cases varied widely from the tuberculoid to the lepromatous type and one patient presented with gangrene of the leg preceding an auto amputation which was infested with maggots. Each case was approved by the institutional ethical committee and received two to eight units of freshly collected placental umbilical cord blood in one transfusion without encountering any clinical, immunological or non-immunological reaction. Seven days after completion of the placental umbilical cord blood transfusion, the peripheral blood hematopoietic stem cell (CD34) estimation revealed a rise from the pretransfusion base level (.09%), varying from 3.6% to 16.2%, in 75% of the cases, without provoking any clinical graft vs host reaction in any of the leprosy victims. This value returned to normal within three months in most cases.

Cord blood full blood count parameters in Lagos, Nigeria | Adewumi ...

African Journals Online (AJOL)

Due to its usefulness in the assessment of health status of individuals, its parameters in cord blood, a major source of haemopoietic stem cell transplantation and an ideal source for laboratory investigations for newborns were determined to provide a useful guide to local neonatologists and stem cell transplant physicians.

Scotblood 2007: Tackling local and global issues in transfusion medicine - donor recruitment, effective use of blood, stem cell plasticity, and vCJD.

Science.gov (United States)

Bessos, Hagop; Fraser, Robin; Seghatchian, Jerard

2008-02-01

This commentary briefly highlights some of the local and the global contemporary issues affecting transfusion medicine worldwide. The main areas of focus addressed this year were: donor recruitment, stem cell plasticity, the effective use of blood, and vCJD.

A comparison of the observed and the expected cancers of the haematopoietic and lymphatic systems among workers at Windscale

International Nuclear Information System (INIS)

Dolphin, G.W.

1976-12-01

Data are given about the cases of cancers of the haematopoietic and lymphatic systems among workers at Windscale Works, BNFL during the period 1950 to 1974. The number of cancers of these types expected to occur in the working population at Windscale has been estimated for the same period. For none of these types is the observed number of cancers significantly different at the 95% confidence level from that expected. (author)

A Comparative Study to Evaluate Myogenic Differentiation Potential of Human Chorion versus Umbilical Cord Blood-derived Mesenchymal Stem Cells.

Science.gov (United States)

Bana, Nikoo; Sanooghi, Davood; Soleimani, Mansoureh; Hayati Roodbari, Nasim; Alavi Moghaddam, Sepideh; Joghataei, Mohammad Taghi; Sayahpour, Forough Azam; Faghihi, Faezeh

2017-08-01

Musculodegenerative diseases threaten the life of many patients in the world. Since drug administration is not efficient in regeneration of damaged tissues, stem cell therapy is considered as a good strategy to restore the lost cells. Since the efficiency of myogenic differentiation potential of human Chorion- derived Mesenchymal Stem Cells (C-MSCs) has not been addressed so far; we set out to evaluate myogenic differentiation property of these cells in comparison with Umbilical Cord Blood- derived Mesenchymal Stem Cells (UCB-MSCs) in the presence of 5-azacytidine. To do that, neonate placenta Umbilical Cord Blood were transferred to the lab. After characterization of the isolated cells using flowcytometry and multilineage differentiation capacity, the obtained Mesenchymal Stem Cells were cultured in DMEM/F12 supplemented with 2% FBS and 10μM of 5-azacytidine to induce myogenic differentiation. Real-time PCR and immunocytochemistry were used to assess the myogenic properties of the cells. Our data showed that C-MSCs and UCB-MSCs were spindle shape in morphology. They were positive for CD90, CD73 and CD44 antigens, and negative for hematopoietic markers. They also differentiated into osteoblast and adipoblast lineages. Real-time PCR results showed that the cells could express MyoD, desmin and α-MHC at the end of the first week (P<0.05). No significant upregulation was detected in the expression of GATA-4 in both groups. Immunocytochemical staining revealed the expression of Desmin, cTnT and α-MHC. Results showed that these cells are potent to differentiate into myoblast- like cells. An upregulation in the expression of some myogenic markers (desmin, α- MHC) was observed in C-MSCs in comparison with UCB-MSCs. Copyright © 2017. Published by Elsevier Ltd.

Stem cells from umbilical cord blood do have myogenic potential, with and without differentiation induction in vitro

Directory of Open Access Journals (Sweden)

Gollop Thomaz R

2009-01-01

Full Text Available Abstract The dystrophin gene, located at Xp21, codifies dystrophin, which is part of a protein complex responsible for the membrane stability of muscle cells. Its absence on muscle causes Duchenne Muscular Dystrophy (DMD, a severe disorder, while a defect of muscle dystrophin causes Becker Muscular Dystrophy (DMB, a milder disease. The replacement of the defective muscle through stem cells transplantation is a possible future treatment for these patients. Our objective was to analyze the potential of CD34+ stem cells from umbilical cord blood to differentiate in muscle cells and express dystrophin, in vitro. Protein expression was analyzed by Immunofluorescence, Western Blotting (WB and Reverse Transcriptase – Polymerase Chain Reaction (RT-PCR. CD34+ stem cells and myoblasts from a DMD affected patient started to fuse with muscle cells immediately after co-cultures establishment. Differentiation in mature myotubes was observed after 15 days and dystrophin-positive regions were detected through Immunofluorescence analysis. However, WB or RT-PCR analysis did not detect the presence of normal dystrophin in co-cultures of CD34+ and DMD or DMB affected patients' muscle cells. In contrast, some CD34+ stem cells differentiated in dystrophin producers' muscle cells, what was observed by WB, reinforcing that this progenitor cell has the potential to originate muscle dystrophin in vitro, and not just in vivo like reported before.

Alternative Blood Products and Clinical Needs in Transfusion Medicine

OpenAIRE

Whitsett, Carolyn; Vaglio, Stefania; Grazzini, Giuliano

2012-01-01

The primary focus of national blood programs is the provision of a safe and adequate blood supply. This goal is dependent on regular voluntary donations and a regulatory infrastructure that establishes and enforces standards for blood safety. Progress in ex vivo expansion of blood cells from cell sources including peripheral blood, cord blood, induced pluripotent stem cells, and human embryonic stem cell lines will likely make alternative transfusion products available for clinical use in the...

Engraftment Outcomes after HPC Co-Culture with Mesenchymal Stromal Cells and Osteoblasts

Directory of Open Access Journals (Sweden)

Matthew M. Cook

2013-09-01

Full Text Available Haematopoietic stem cell (HSC transplantation is an established cell-based therapy for a number of haematological diseases. To enhance this therapy, there is considerable interest in expanding HSCs in artificial niches prior to transplantation. This study compared murine HSC expansion supported through co-culture on monolayers of either undifferentiated mesenchymal stromal cells (MSCs or osteoblasts. Sorted Lineage− Sca-1+ c-kit+ (LSK haematopoietic stem/progenitor cells (HPC demonstrated proliferative capacity on both stromal monolayers with the greatest expansion of LSK shown in cultures supported by osteoblast monolayers. After transplantation, both types of bulk-expanded cultures were capable of engrafting and repopulating lethally irradiated primary and secondary murine recipients. LSKs co-cultured on MSCs showed comparable, but not superior, reconstitution ability to that of freshly isolated LSKs. Surprisingly, however, osteoblast co-cultured LSKs showed significantly poorer haematopoietic reconstitution compared to LSKs co-cultured on MSCs, likely due to a delay in short-term reconstitution. We demonstrated that stromal monolayers can be used to maintain, but not expand, functional HSCs without a need for additional haematopoietic growth factors. We also demonstrated that despite apparently superior in vitro performance, co-injection of bulk cultures of osteoblasts and LSKs in vivo was detrimental to recipient survival and should be avoided in translation to clinical practice.

The effect of amniotic membrane extract on umbilical cord blood mesenchymal stem cell expansion: is there any need to save the amniotic membrane besides the umbilical cord blood?

Directory of Open Access Journals (Sweden)

Zahra Vojdani

2016-01-01

Full Text Available Objective(s: Umbilical cord blood is a good source of the mesenchymal stem cells that can be banked, expanded and used in regenerative medicine.  The objective of this study was to test whether amniotic membrane extract, as a rich source of growth factors such as basic-fibroblast growth factor, can promote the proliferation potential of the umbilical cord mesenchymal stem cells. Materials and Methods: The study design was interventional. Umbilical cord mesenchymal stem cells were isolated from voluntary healthy infants from hospitals in Shiraz, Iran, cultured in the presence of basic-fibroblast growth factor and amniotic membrane extracts (from pooled - samples, and compared with control cultures. Proliferation assay was performed and duplication number and time were calculated. The expression of stem cell’s specific markers and the differentiation capacity toward osteogenic and adipogenic lineages were evaluated. Results: Amniotic membrane extract led to a significant increase in the proliferation rate and duplication number and a decrease in the duplication time without any change in the cell morphology. Both amniotic membrane extract and basic-fibroblast growth factor altered the expressing of CD44 and CD105 in cell population. Treating basic-fibroblast growth factor but not the amniotic membrane extract favored the differentiation potential of the stem cells toward osteogenic lineage. Conclusion: The amniotic membrane extract administration accelerated cell proliferation and modified the CD marker characteristics which may be due to the induction of differentiation toward a specific lineage.  Amniotic membrane extract may enhance the proliferation rate and duplication number of the stem cell through changing the duplication time.

Combination stem cell therapy for heart failure

Directory of Open Access Journals (Sweden)

Ichim Thomas E

2010-04-01

Full Text Available Abstract Patients with congestive heart failure (CHF that are not eligible for transplantation have limited therapeutic options. Stem cell therapy such as autologous bone marrow, mobilized peripheral blood, or purified cells thereof has been used clinically since 2001. To date over 1000 patients have received cellular therapy as part of randomized trials, with the general consensus being that a moderate but statistically significant benefit occurs. Therefore, one of the important next steps in the field is optimization. In this paper we discuss three ways to approach this issue: a increasing stem cell migration to the heart; b augmenting stem cell activity; and c combining existing stem cell therapies to recapitulate a "therapeutic niche". We conclude by describing a case report of a heart failure patient treated with a combination stem cell protocol in an attempt to augment beneficial aspects of cord blood CD34 cells and mesenchymal-like stem cells.

MiRNAs and piRNAs from bone marrow mesenchymal stem cell extracellular vesicles induce cell survival and inhibit cell differentiation of cord blood hematopoietic stem cells: a new insight in transplantation.

Science.gov (United States)

De Luca, Luciana; Trino, Stefania; Laurenzana, Ilaria; Simeon, Vittorio; Calice, Giovanni; Raimondo, Stefania; Podestà, Marina; Santodirocco, Michele; Di Mauro, Lazzaro; La Rocca, Francesco; Caivano, Antonella; Morano, Annalisa; Frassoni, Francesco; Cilloni, Daniela; Del Vecchio, Luigi; Musto, Pellegrino

2016-02-09

Hematopoietic stem cells (HSC), including umbilical cord blood CD34+ stem cells (UCB-CD34+), are used for the treatment of several diseases. Although different studies suggest that bone marrow mesenchymal stem cells (BM-MSC) support hematopoiesis, the exact mechanism remains unclear. Recently, extracellular vesicles (EVs) have been described as a novel avenue of cell communication, which may mediate BM-MSC effect on HSC. In this work, we studied the interaction between UCB-CD34+ cells and BM-MSC derived EVs. First, by sequencing EV derived miRNAs and piRNAs we found that EVs contain RNAs able to influence UCB-CD34+ cell fate. Accordingly, a gene expression profile of UCB-CD34+ cells treated with EVs, identified about 100 down-regulated genes among those targeted by EV-derived miRNAs and piRNAs (e.g. miR-27b/MPL, miR-21/ANXA1, miR-181/EGR2), indicating that EV content was able to modify gene expression profile of receiving cells. Moreover, we demonstrated that UCB-CD34+ cells, exposed to EVs, significantly changed different biological functions, becoming more viable and less differentiated. UCB-CD34+ gene expression profile also identified 103 up-regulated genes, most of them codifying for chemokines, cytokines and their receptors, involved in chemotaxis of different BM cells, an essential function of hematopoietic reconstitution. Finally, the exposure of UCB-CD34+ cells to EVs caused an increased expression CXCR4, paralleled by an in vivo augmented migration from peripheral blood to BM niche in NSG mice. This study demonstrates the existence of a powerful cross talk between BM-MSC and UCB-CD34+ cells, mediated by EVs, providing new insight in the biology of cord blood transplantation.

Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis.

Directory of Open Access Journals (Sweden)

Biaoru Li

Full Text Available Fetal stem cells isolated from umbilical cord blood (UCB possess a great capacity for proliferation and differentiation and serve as a valuable model system to study gene regulation. Expanded knowledge of the molecular control of hemoglobin synthesis will provide a basis for rational design of therapies for β-hemoglobinopathies. Transcriptome data are available for erythroid progenitors derived from adult stem cells, however studies to define molecular mechanisms controlling globin gene regulation during fetal erythropoiesis are limited. Here, we utilize UCB-CD34+ stem cells induced to undergo erythroid differentiation to characterize the transcriptome and transcription factor networks (TFNs associated with the γ/β-globin switch during fetal erythropoiesis. UCB-CD34+ stem cells grown in the one-phase liquid culture system displayed a higher proliferative capacity than adult CD34+ stem cells. The γ/β-globin switch was observed after day 42 during fetal erythropoiesis in contrast to adult progenitors where the switch occurred around day 21. To gain insights into transcription factors involved in globin gene regulation, microarray analysis was performed on RNA isolated from UCB-CD34+ cell-derived erythroid progenitors harvested on day 21, 42, 49 and 56 using the HumanHT-12 Expression BeadChip. After data normalization, Gene Set Enrichment Analysis identified transcription factors (TFs with significant changes in expression during the γ/β-globin switch. Forty-five TFs were silenced by day 56 (Profile-1 and 30 TFs were activated by day 56 (Profile-2. Both GSEA datasets were analyzed using the MIMI Cytoscape platform, which discovered TFNs centered on KLF4 and GATA2 (Profile-1 and KLF1 and GATA1 for Profile-2 genes. Subsequent shRNA studies in KU812 leukemia cells and human erythroid progenitors generated from UCB-CD34+ cells supported a negative role of MAFB in γ-globin regulation. The characteristics of erythroblasts derived from UCB-CD34

Transcriptional activity of telomerase complex in CD34- stem cells of cord blood in dependence of preparation time.

Directory of Open Access Journals (Sweden)

M Bojdys-Szyndlar

2009-12-01

Full Text Available The aim of the study was to determine whether the expression of telomerase subunits encoding genes changes during the process of cord blood preparation. It should establish if the commonly accepted 24 hours time interval in stem cells kriopreservation procedure significantly influences their immortalization and so decreases the "quality" of cord blood stem cells. Investigation includes 69 women. Spontaneous labour was the inclusion condition. The material was collected at birth after clamping of umbilical cord by direct vasopuncture. CD34- cells were extracted from cord blood (MACS, Miltenyi Biotec; Bisley, Surrey, UK. The expression profile of telomerase activators and inhibitors encoding genes was determined using HG_U133A oligonucleotide microarray (Affymetrix. We used a real-time quantitative RT-PCR assay to quantify the telomerase TERT, hTR and TP1 subunits mRNA copy numbers in CD34- cells in 0, 6, 12 and 24 hours after cord blood collection. We observed significant decrease of numbers of copies of TERTA+B mRNA within the successive hours of observation. Significant decrease of numbers of TERTA mRNA copies was confirmed after 24 hours. However, we observed significant increase of numbers of copies of TERTB mRNA after 6 hours of observation. Similar level was maintained during another 6h. The significantly lower number of copies of TERTB mRNA was observed after 24h. We also observed significant increase of number of copies of TERT mRNA after 6 hours. Number of copies of TERT mRNA significantly decreased after another 6h, remaining, however, on a higher then initial one. The significant lower number of copies of TERT mRNA was observed 24h after delivery. The possible explanation of those results is discussed in the paper.

Effect of CD34+ cord blood stem cell transfected by plasmid vector pIRES2-FL-IL-3 on the mice after irradiation

International Nuclear Information System (INIS)

Zhang Yong; Zhang Linsheng; Zhang Hongbing; Guo Chaohua; Tong Shiwu

2008-01-01

Objective: To observe the effect of CD34 cord blood stem cell transfected by plasmid vector plRES2-FL-IL-3 on the mouse after irradiation and to investigate its mechanisms. Methods: In the co-expressed group (12 mice), CD 34 + cord blood stem cells were transfected by plasmid vector pIRES2-FL-IL-3.5 x lO 5 cells were injected intravenously in the mouse. The hemogram changes in mice were detected 2, 4 and 6 weeks after radiation. At 6 weeks after irradiation, the expression of the CD 34 in spleen was detected by immumofluorescence method. The mRNA level and the activity of IL-3 and FL were detected by RT-PCR and Western blot. Other 3 groups were CD 34 + cell group (CD 34 group), pIRES2-IL-3 group(IL 3 group) and pIRES2-FL group(FL group), and there were 12 mice in each group. Results: The survival rate of CD 34 group, IL3 group and FL group at the 6th week were 25.0% (3/12), 50.0% (6/12) and 50.0% (6/12), respectively. It was 91.7% (11/12) in the co-expressed group, which was higher than those in the other groups. The expression of the CD 34 of spleen in the co-expressed group was higher than those of the other groups. The mRNA level and the activity of IL-3 and FL of spleen in the co-expressed group were higher than those in the other groups too. Conclusions: The CD 34 '+ cord blood stem cells transfected by plasmid vector pIRES2-FL-IL-3 have hemogenesis promotion effect on the mice after irradiation, which was related with the aggregation, proliferation of stem cells and the high expression of the interest proteins.. (authors)

Multi-isotope imaging mass spectrometry quantifies stem cell division and metabolism.

Science.gov (United States)

Steinhauser, Matthew L; Bailey, Andrew P; Senyo, Samuel E; Guillermier, Christelle; Perlstein, Todd S; Gould, Alex P; Lee, Richard T; Lechene, Claude P

2012-01-15

Mass spectrometry with stable isotope labels has been seminal in discovering the dynamic state of living matter, but is limited to bulk tissues or cells. We developed multi-isotope imaging mass spectrometry (MIMS) that allowed us to view and measure stable isotope incorporation with submicrometre resolution. Here we apply MIMS to diverse organisms, including Drosophila, mice and humans. We test the 'immortal strand hypothesis', which predicts that during asymmetric stem cell division chromosomes containing older template DNA are segregated to the daughter destined to remain a stem cell, thus insuring lifetime genetic stability. After labelling mice with (15)N-thymidine from gestation until post-natal week 8, we find no (15)N label retention by dividing small intestinal crypt cells after a four-week chase. In adult mice administered (15)N-thymidine pulse-chase, we find that proliferating crypt cells dilute the (15)N label, consistent with random strand segregation. We demonstrate the broad utility of MIMS with proof-of-principle studies of lipid turnover in Drosophila and translation to the human haematopoietic system. These studies show that MIMS provides high-resolution quantification of stable isotope labels that cannot be obtained using other techniques and that is broadly applicable to biological and medical research.

Stem Cell Therapy: An emerging science

International Nuclear Information System (INIS)

Khan, Muhammad M.

2007-01-01

The research on stem cells is advancing knowledge about the development of an organism from a single cell and to how healthy cells replace damaged cells in adult organisms. Stem cell therapy is emerging rapidly nowadays as a technical tool for tissue repair and replacement. The purpose of this review to provide a framework of understanding for the challenges behind translating fundamental stem cell biology and its potential use into clinical therapies, also to give an overview on stem cell research to the scientists of Saudi Arabia in general. English language MEDLINE publications from 1980 through January 2007 for experimental, observational and clinical studies having relation with stem cells with different diseases were reviewed. Approximately 85 publications were reviewed based on the relevance, strength and quality of design and methods, 36 publications were selected for inclusion. Stem cells reside in a specific area of each tissue where they may remain undivided for several years until they are activated by disease or tissue injury. The embryonic stem cells are typically derived from four or five days old embryos and they are pluripotent. The adult tissues reported to contain stem cells brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin and liver. The promise of stem cell therapies is an exciting one, but significant technical hurdles remain that will only be overcome through years of intensive research. (author)

Mortality from lymphatic and haematopoietic cancer in Scottish coastal towns

International Nuclear Information System (INIS)

Lloyd, O.Ll.; Macdonald, J.; Lloyd, M.M.

1984-01-01

Using annual Scottish registration data, the authors have been examining mortality from cancers including all leukaemias, classified within malignant neoplasm of lymphatic and haematopoietic tissue, from 1969/73. The results showed: (1) Coastal burghs had a higher standardised mortality than did inland burghs; (2) the SMRs in communities of the east coast as a whole were consistently higher than those in west-coast communities, whether small burghs, large burghs, or cities were considered; (3) all segments of the eastern coastline, other than the open coastline stretching from Aberdeenshire to Angus, showed relatively high SMRs; (4) on the west coast, the highest SMRs (of only 100) were in Ayrshire and Glasgow; (5) in terms of statistical significance at the level p<=0.5, mortality in inland burghs was significantly low, while in east-coast burghs, in Edinburgh, and in Aberdeen it was significantly high. The geographical distribution cannot be explained in terms of nuclear power stations, and differs importantly from that given by registration data for leukaemia alone (Heasman et al, May 26, p.1188). (U.K.)

Banking Umbilical Cord Blood (UCB) Stem Cells: Awareness, Attitude and Expectations of Potential Donors from One of the Largest Potential Repository (India).

Science.gov (United States)

Pandey, Deeksha; Kaur, Simar; Kamath, Asha

2016-01-01

The concept of Umbilical Cord blood (UCB) stem cells is emerging as a non-invasive, efficacious alternative source of hematopoietic stem cells to treat a variety of blood and bone marrow diseases, blood cancers, metabolic disorders and immune deficiencies. Aim of the present study was to determine the level of awareness about banking UCB among pregnant women in India. We also assessed patient perception for banking of UCB and explored the patient expectations of banking UCB in future. This is the first study to assess current attitudes, in a sample population of potential donors from one of the largest potential UCB repository (India). Obtaining this information may help optimize recruitment efforts and improve patient education. Present explorative questionnaire based survey included 254 pregnant women in the final analysis. We established only 26.5% pregnant women in our study population knew what exactly is meant by UCB. A large proportion (55.1%) was undecided on whether they want to bank UCB or not. Women were more aware of the more advertised private cord blood banking compared to public banking. More than half of the pregnant women expected their obstetrician to inform them regarding UCB. One-third of the women in our population had undue expectations from banking of the UCB. Obstetricians should play a more active role in explaining the patients regarding pros and cons of UCB banking.

Banking Umbilical Cord Blood (UCB Stem Cells: Awareness, Attitude and Expectations of Potential Donors from One of the Largest Potential Repository (India.

Directory of Open Access Journals (Sweden)

Deeksha Pandey

Full Text Available The concept of Umbilical Cord blood (UCB stem cells is emerging as a non-invasive, efficacious alternative source of hematopoietic stem cells to treat a variety of blood and bone marrow diseases, blood cancers, metabolic disorders and immune deficiencies. Aim of the present study was to determine the level of awareness about banking UCB among pregnant women in India. We also assessed patient perception for banking of UCB and explored the patient expectations of banking UCB in future. This is the first study to assess current attitudes, in a sample population of potential donors from one of the largest potential UCB repository (India. Obtaining this information may help optimize recruitment efforts and improve patient education.Present explorative questionnaire based survey included 254 pregnant women in the final analysis.We established only 26.5% pregnant women in our study population knew what exactly is meant by UCB. A large proportion (55.1% was undecided on whether they want to bank UCB or not. Women were more aware of the more advertised private cord blood banking compared to public banking. More than half of the pregnant women expected their obstetrician to inform them regarding UCB. One-third of the women in our population had undue expectations from banking of the UCB.Obstetricians should play a more active role in explaining the patients regarding pros and cons of UCB banking.

Stem Cell Transplants in Cancer Treatment

Science.gov (United States)

Stem cell transplants are procedures that restore blood-forming stem cells in cancer patients who have had theirs destroyed by very high doses of chemotherapy or radiation therapy. Learn about the types of transplants and side effects that may occur.

Red blood cell production

Science.gov (United States)

... bone marrow of bones. Stem cells in the red bone marrow called hemocytoblasts give rise to all of the formed elements in blood. If a hemocytoblast commits to becoming a cell called a proerythroblast, it will develop into a new red blood cell. The formation of a red blood ...

Blood and Bone Marrow Transplant?

Science.gov (United States)

... Topics / Blood and Bone Marrow Transplant Blood and Bone Marrow Transplant Also known as Hematopoietic Stem Cell Transplant , Hematopoietic ... person, called a donor, it is an allogeneic transplant. Blood or bone marrow transplants most commonly are used to treat ...

Generation of “Off-the-Shelf” Natural Killer Cells from Peripheral Blood Cell-Derived Induced Pluripotent Stem Cells

Directory of Open Access Journals (Sweden)

Jieming Zeng

2017-12-01

Full Text Available Summary: Current donor cell-dependent strategies can only produce limited “made-to-order” therapeutic natural killer (NK cells for limited patients. To provide unlimited “off-the-shelf” NK cells that serve many recipients, we designed and demonstrated a holistic manufacturing scheme to mass-produce NK cells from induced pluripotent stem cells (iPSCs. Starting with a highly accessible human cell source, peripheral blood cells (PBCs, we derived a good manufacturing practice-compatible iPSC source, PBC-derived iPSCs (PBC-iPSCs for this purpose. Through our original protocol that excludes CD34+ cell enrichment and spin embryoid body formation, high-purity functional and expandable NK cells were generated from PBC-iPSCs. Above all, most of these NK cells expressed no killer cell immunoglobulin-like receptors (KIRs, which renders them unrestricted by recipients' human leukocyte antigen genotypes. Hence, we have established a practical “from blood cell to stem cells and back with less (less KIRs” strategy to generate abundant “universal” NK cells from PBC-iPSCs for a wide range of patients. : To provide unlimited “off-the-shelf” NK cells that serve many recipients, Zeng and colleagues demonstrate a manufacturing scheme to mass-produce NK cells from peripheral blood cell-derived iPSCs (PBC-iPSCs. Through their original protocol, high-purity functional NK cells are generated from PBC-iPSCs. Most of these NK cells express no killer cell immunoglobulin-like receptors, which renders them unrestricted by recipients' HLA genotypes. Keywords: induced pluripotent stem cells, peripheral blood cells, natural killer cells, killer cell immunoglobulin-like receptors, cell therapy, immunotherapy, cancer, cytotoxicity

IMMUNE STATE IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES AT LATE TERMS AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION

Directory of Open Access Journals (Sweden)

N. V. Minaeva

2012-01-01

Full Text Available Abstract. Autologous hematopoietic stem cell transplantation (auto-HSCT is one of the most effective methods for treatment of patients with various forms of hemoblastoses, both in adults and children. However, high-dose chemotherapy protocols used in this procedure are characterized by pronounced myeloand immunotoxicity. Appropriate data concerning immune state at long terms after high-dose chemotherapy and auto-HSCT are sparse and controversial, and there is no consensus on time dynamics of immune system reconstitution. The aim of this study was a comprehensive evaluation of immunity in recipients of auto-HSCT at longer terms. Clinical and immunological testing was performed in ninety-eight patients with hematological malignancies before starting a high-dose chemotherapy, and at late post-transplant period. The state of cellular immunity was assessed as expression of surface CD3+, CD4+, CD8+, CD16+, CD19+ lymphocyte antigens. Humoral immunity was evaluated by serum IgG, IgA, and IgM levels. The studies have revealed disorders of cellular and humoral immunity, as well as nonspecific immune resistance factors in recipients of autologous hematopoietic stem cells at late terms post-transplant. Immune reconstitution in patients receiving highdose consolidation treatment followed by auto-HSCT takes longer time than in patients who did not receive autologous hematopoietic stem cells. Severity of these disturbances and immune reconstitution rates depend on the type of conditioning regimen, and the source of haematopoietic stem cells used for transplantation.

Syngeneic peripheral blood stem cell transplantation with immunosuppression for hepatitis-associated severe aplastic anemia

Directory of Open Access Journals (Sweden)

Aleksandar Savic

2010-12-01

Full Text Available Hepatitis-associated aplastic anemia occurs in up to 10% of all aplastic anemia cases. Syngeneic bone marrow transplantation is rare in patients with severe aplastic anemia and usually requires pre-transplant conditioning to provide engraftment. We report on a 29-year-old male patient with hepatitis-associated severe aplastic anemia who had a series of severe infectious conditions before transplantation, including tracheal inflammation. Life-threatening bleeding, which developed after bronchoscopy, was successfully treated with activated recombinant factor VII and platelet transfusions. Syngeneic peripheral blood stem cell transplantation using immunosuppressive treatment with antithymocyte globulin and cyclosporin A without high-dose pre-transplant conditioning was performed, followed by complete hematologic and hepatic recovery.

Cytokine-primed bone marrow stem cells vs. peripheral blood stem cells for autologous transplantation: a randomized comparison of GM-CSF vs. G-CSF.

Science.gov (United States)

Weisdorf, D; Miller, J; Verfaillie, C; Burns, L; Wagner, J; Blazar, B; Davies, S; Miller, W; Hannan, P; Steinbuch, M; Ramsay, N; McGlave, P

1997-10-01

Autologous transplantation for non-Hodgkins lymphoma and Hodgkin's disease is widely used as standard therapy for those with high-risk or relapsed tumor. Peripheral blood stem cell (PBSC) collections have nearly completely replaced bone marrow stem cell (BMSC) harvests because of the perceived advantages of more rapid engraftment, less tumor contamination in the inoculum, and better survival after therapy. The advantage of PBSC, however, may derive from the hematopoietic stimulating cytokines used for PBSC mobilization. Therefore, we tested a randomized comparison of GM-CSF vs. G-CSF used to prime either BMSC or PBSC before collection for use in autologous transplantation. Sixty-two patients receiving transplants (31 PBSC; 31 BMSC) for non-Hodgkin's lymphoma (n = 51) or Hodgkin's disease (n = 11) were treated. All patients received 6 days of randomly assigned cytokine. Those with cellular marrow in morphologic remission underwent BMSC harvest, while those with hypocellular marrow or microscopic marrow tumor involvement had PBSC collected. Neutrophil recovery was similarly rapid in all groups (median 14 days; range 10-23 days), though two patients had delayed neutrophil recovery using GM-CSF primed PBSC (p = 0.01). Red cell and platelet recovery were significantly quicker after BMSC mobilized with GM-CSF or PBSC mobilized with G-CSF. This speedier hematologic recovery resulted in earlier hospital discharge as well. However, in multivariate analysis, neither the stem cell source nor randomly assigned G-CSF vs. GM-CSF was independently associated with earlier multilineage hematologic recovery or shorter hospital stay. Relapse-free survival was not independently affected by either the assigned stem cell source or the randomly assigned priming cytokine, though malignant relapse was more frequent in those assigned to PBSC (RR of relapse 3.15, p = 0.03). These data document that BMSC, when collected following cytokine priming, can yield a similarly rapid hematologic

Potency of umbilical cord blood- and Wharton's jelly-derived mesenchymal stem cells for scarless wound healing.

Science.gov (United States)

Doi, Hanako; Kitajima, Yuriko; Luo, Lan; Yan, Chan; Tateishi, Seiko; Ono, Yusuke; Urata, Yoshishige; Goto, Shinji; Mori, Ryoichi; Masuzaki, Hideaki; Shimokawa, Isao; Hirano, Akiyoshi; Li, Tao-Sheng

2016-01-05

Postnatally, scars occur as a consequence of cutaneous wound healing. Scarless wound healing is highly desired for patients who have undergone surgery or trauma, especially to exposed areas. Based on the properties of mesenchymal stem cells (MSCs) for tissue repair and immunomodulation, we investigated the potential of MSCs for scarless wound healing. MSCs were expanded from umbilical cord blood (UCB-MSCs) and Wharton's jelly (WJ-MSCs) from healthy donors who underwent elective full-term pregnancy caesarean sections. UCB-MSCs expressed lower levels of the pre-inflammatory cytokines IL1A and IL1B, but higher levels of the extracellular matrix (ECM)-degradation enzymes MMP1 and PLAU compared with WJ-MSCs, suggesting that UCB-MSCs were more likely to favor scarless wound healing. However, we failed to find significant benefits for stem cell therapy in improving wound healing and reducing collagen deposition following the direct injection of 1.0 × 10(5) UCB-MSCs and WJ-MSCs into 5 mm full-thickness skin defect sites in nude mice. Interestingly, the implantation of UCB-MSCs tended to increase the expression of MMP2 and PLAU, two proteases involved in degradation of the extracellular matrix in the wound tissues. Based on our data, UCB-MSCs are more likely to be a favorable potential stem cell source for scarless wound healing, although a better experimental model is required for confirmation.

Autophagy as an ultrastructural marker of heavy metal toxicity in human cord blood hematopoietic stem cells

International Nuclear Information System (INIS)

Di Gioacchino, Mario; Petrarca, Claudia; Perrone, Angela; Farina, Massimo; Sabbioni, Enrico; Hartung, Thomas; Martino, Simone; Esposito, Diana L.; Lotti, Lavinia Vittoria; Mariani-Costantini, Renato

2008-01-01

Stem cells are a key target of environmental toxicants, but little is known about their toxicological responses. We aimed at developing an in-vitro model based on adult human stem cells to identify biomarkers of heavy metal exposure. To this end we investigated the responses of human CD34+ hematopoietic progenitor cells to hexavalent chromium (Cr[VI]) and cadmium (Cd). Parallel cultures of CD34+ cells isolated from umbilical cord blood were exposed for 48 h to 0.1 μM and 10 μM Cr(VI) or Cd. Cultures treated with 10 μM Cr(VI) or Cd showed marked cell loss. Ultrastructural analysis of surviving cells revealed prominent autophagosomes/autophagolysosomes, which is diagnostic of autophagy, associated with mitochondrial damage and replication, dilatation of the rough endoplasmic reticulum and Golgi complex, cytoplasmic lipid droplets and chromatin condensation. Treated cells did not show the morphologic hallmarks of apoptosis. Treatment with 0.1 μM Cr(VI) or Cd did not result in cell loss, but at the ultrastructural level cells showed dilated endoplasmic reticulum and evidence of mitochondrial damage. We conclude that autophagy is implicated in the response of human hematopoietic stem cells to toxic concentrations of Cr(VI) and Cd. Autophagy, which mediates cell survival and death under stress, deserves further evaluation to be established as biomarker of metal exposure

Autophagy as an ultrastructural marker of heavy metal toxicity in human cord blood hematopoietic stem cells

Energy Technology Data Exchange (ETDEWEB)

Di Gioacchino, Mario [Aging Research Center, ' G. d' Annunzio' University Foundation, Via Colle dell' Ara, 66100 Chieti (Italy); Medicine and Science of Ageing University of Chieti-Pescara, Via dei Vestini 1, 66100 Chieti (Italy)], E-mail: m.digioacchino@unich.it; Petrarca, Claudia; Perrone, Angela [Aging Research Center, ' G. d' Annunzio' University Foundation, Via Colle dell' Ara, 66100 Chieti (Italy); Medicine and Science of Ageing University of Chieti-Pescara, Via dei Vestini 1, 66100 Chieti (Italy); Farina, Massimo; Sabbioni, Enrico; Hartung, Thomas [Oncology and Neurosciences University of Chieti-Pescara, Via dei Vestini 1, 66100 Chieti (Italy); Martino, Simone [Department of Experimental Medicine, University La Sapienza, Viale Regina Elena 324, 00161 Rome (Italy); Esposito, Diana L. [Aging Research Center, ' G. d' Annunzio' University Foundation, Via Colle dell' Ara, 66100 Chieti (Italy); Oncology and Neurosciences University of Chieti-Pescara, Via dei Vestini 1, 66100 Chieti (Italy); Lotti, Lavinia Vittoria [Department of Experimental Medicine, University La Sapienza, Viale Regina Elena 324, 00161 Rome (Italy); Mariani-Costantini, Renato [Aging Research Center, ' G. d' Annunzio' University Foundation, Via Colle dell' Ara, 66100 Chieti (Italy); Oncology and Neurosciences University of Chieti-Pescara, Via dei Vestini 1, 66100 Chieti (Italy)

2008-03-15

Stem cells are a key target of environmental toxicants, but little is known about their toxicological responses. We aimed at developing an in-vitro model based on adult human stem cells to identify biomarkers of heavy metal exposure. To this end we investigated the responses of human CD34+ hematopoietic progenitor cells to hexavalent chromium (Cr[VI]) and cadmium (Cd). Parallel cultures of CD34+ cells isolated from umbilical cord blood were exposed for 48 h to 0.1 {mu}M and 10 {mu}M Cr(VI) or Cd. Cultures treated with 10 {mu}M Cr(VI) or Cd showed marked cell loss. Ultrastructural analysis of surviving cells revealed prominent autophagosomes/autophagolysosomes, which is diagnostic of autophagy, associated with mitochondrial damage and replication, dilatation of the rough endoplasmic reticulum and Golgi complex, cytoplasmic lipid droplets and chromatin condensation. Treated cells did not show the morphologic hallmarks of apoptosis. Treatment with 0.1 {mu}M Cr(VI) or Cd did not result in cell loss, but at the ultrastructural level cells showed dilated endoplasmic reticulum and evidence of mitochondrial damage. We conclude that autophagy is implicated in the response of human hematopoietic stem cells to toxic concentrations of Cr(VI) and Cd. Autophagy, which mediates cell survival and death under stress, deserves further evaluation to be established as biomarker of metal exposure.

Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned Rats

Science.gov (United States)

Calatrava-Ferreras, Lucía; Gonzalo-Gobernado, Rafael; Herranz, Antonio S.; Reimers, Diana; Montero Vega, Teresa; Jiménez-Escrig, Adriano; Richart López, Luis Alberto; Bazán, Eulalia

2012-01-01

Cerebellar ataxias include a heterogeneous group of infrequent diseases characterized by lack of motor coordination caused by disturbances in the cerebellum and its associated circuits. Current therapies are based on the use of drugs that correct some of the molecular processes involved in their pathogenesis. Although these treatments yielded promising results, there is not yet an effective therapy for these diseases. Cell replacement strategies using human umbilical cord blood mononuclear cells (HuUCBMCs) have emerged as a promising approach for restoration of function in neurodegenerative diseases. The aim of this work was to investigate the potential therapeutic activity of HuUCBMCs in the 3-acetylpyridine (3-AP) rat model of cerebellar ataxia. Intravenous administered HuUCBMCs reached the cerebellum and brain stem of 3-AP ataxic rats. Grafted cells reduced 3-AP-induced neuronal loss promoted the activation of microglia in the brain stem, and prevented the overexpression of GFAP elicited by 3-AP in the cerebellum. In addition, HuUCBMCs upregulated the expression of proteins that are critical for cell survival, such as phospho-Akt and Bcl-2, in the cerebellum and brain stem of 3-AP ataxic rats. As all these effects were accompanied by a temporal but significant improvement in motor coordination, HuUCBMCs grafts can be considered as an effective cell replacement therapy for cerebellar disorders. PMID:23150735

Proportional-Integral-Derivative (PID) Control of Secreted Factors for Blood Stem Cell Culture.

Science.gov (United States)

Caldwell, Julia; Wang, Weijia; Zandstra, Peter W

2015-01-01

Clinical use of umbilical cord blood has typically been limited by the need to expand hematopoietic stem and progenitor cells (HSPC) ex vivo. This expansion is challenging due to the accumulation of secreted signaling factors in the culture that have a negative regulatory effect on HSPC output. Strategies for global regulation of these factors through dilution have been developed, but do not accommodate the dynamic nature or inherent variability of hematopoietic cell culture. We have developed a mathematical model to simulate the impact of feedback control on in vitro hematopoiesis, and used it to design a proportional-integral-derivative (PID) control algorithm. This algorithm was implemented with a fed-batch bioreactor to regulate the concentrations of secreted factors. Controlling the concentration of a key target factor, TGF-β1, through dilution limited the negative effect it had on HSPCs, and allowed global control of other similarly-produced inhibitory endogenous factors. The PID control algorithm effectively maintained the target soluble factor at the target concentration. We show that feedback controlled dilution is predicted to be a more cost effective dilution strategy compared to other open-loop strategies, and can enhance HSPC expansion in short term culture. This study demonstrates the utility of secreted factor process control strategies to optimize stem cell culture systems, and motivates the development of multi-analyte protein sensors to automate the manufacturing of cell therapies.

Successful collection of peripheral blood stem cells upon VIDE chemomobilization in sarcoma patients.

Science.gov (United States)

Kriegsmann, Katharina; Heilig, Christoph; Cremer, Martin; Novotny, Philipp; Kriegsmann, Mark; Bruckner, Thomas; Müller-Tidow, Carsten; Egerer, Gerlinde; Wuchter, Patrick

2017-11-01

In patients with Ewing sarcoma and some distinct subgroups of soft tissue sarcoma (STS), a quantitatively sufficient autologous peripheral blood stem cell (PBSC) collection for stem cell support might facilitate treatment continuation, dose-intensification, and high-dose chemotherapy. Here, we provide a detailed evaluation of PBSC collection upon vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) chemomobilization. Mobilization and collection parameters of 42 sarcoma patients (Ewing sarcoma n = 35, other STS n = 7) were analyzed retrospectively. Data were evaluated with regard to the number of previous VIDE therapy cycles. All patients reached the collection goal of ≥2.0 × 10 6 CD34 + cells/kg body weight (bw) upon VIDE/G-CSF mobilization, in the majority of cases with one single leukapheresis (LP) session (n = 29, 69%). No significant differences were identified with regard to mobilization and collection variables or the number of previous induction VIDE therapy cycles. However, upon 5 cycles of VIDE, we found the highest relative proportion of patients who required two or three LP sessions. Our data demonstrate the feasibility of successful PBSC collection upon VIDE chemomobilization even after up to five cycles of induction therapy, while at the same time the increasing risk of bone marrow exhaustion with every consecutive cycle is outlined. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Challenges for heart disease stem cell therapy

Directory of Open Access Journals (Sweden)

Hoover-Plow J

2012-02-01

Full Text Available Jane Hoover-Plow, Yanqing GongDepartments of Cardiovascular Medicine and Molecular Cardiology, Joseph J Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USAAbstract: Cardiovascular diseases (CVDs are the leading cause of death worldwide. The use of stem cells to improve recovery of the injured heart after myocardial infarction (MI is an important emerging therapeutic strategy. However, recent reviews of clinical trials of stem cell therapy for MI and ischemic heart disease recovery report that less than half of the trials found only small improvements in cardiac function. In clinical trials, bone marrow, peripheral blood, or umbilical cord blood cells were used as the source of stem cells delivered by intracoronary infusion. Some trials administered only a stem cell mobilizing agent that recruits endogenous sources of stem cells. Important challenges to improve the effectiveness of stem cell therapy for CVD include: (1 improved identification, recruitment, and expansion of autologous stem cells; (2 identification of mobilizing and homing agents that increase recruitment; and (3 development of strategies to improve stem cell survival and engraftment of both endogenous and exogenous sources of stem cells. This review is an overview of stem cell therapy for CVD and discusses the challenges these three areas present for maximum optimization of the efficacy of stem cell therapy for heart disease, and new strategies in progress.Keywords: mobilization, expansion, homing, survival, engraftment

Critical appraisal of cerebral blood flow measured from brain stem and cerebellar regions after 133 Xe inhalation in humans

International Nuclear Information System (INIS)

Juge, O.; Meyer, J.S.; Sakai, F.; Yamaguchi, F.; Yamamoto, M.; Shaw, T.

1979-01-01

Validity of regional blood flow (rCBF) measurements recorded over the human posterior fossa after 133Xe inhalation was tested. Recording of counts from both brain stem and cerebellum (BSC) was reproducible and contamination by counts derived from surrounding anatomical structures was low and no greater than that found over hemispheres. BSC flow values showed significant correlation with the state of awareness as judged by clinical and EEG evaluation

Traumatic primary brain stem haemorrhage

International Nuclear Information System (INIS)

Andrioli, G.C.; Zuccarello, M.; Trincia, G.; Fiore, D.L.; De Caro, R.

1983-01-01

We report 36 cases of post-traumatic 'primary brain stem haemorrhage' visualized by the CT scan and confirmed at autopsy. Clinical experience shows that many technical factors influence the inability to visualize brain stem haemorrhages. Experimental injection of fresh blood into the pons and midbrain of cadavers shows that lesions as small as 0.25 ml in volume may be visualized. The volume and the anatomical configuration of traumatic lesions of the brain stem extended over a rostro-caudal direction, and their proximity to bony structures at the base of the skull are obstacles to the visualization of brain stem haemorrhages. (Author)

Comparison of the chromosomal radiosensitivity of blood lymphocytes and stem-cell spermatogonia in the rhesus monkey and the mouse

International Nuclear Information System (INIS)

Buul, P.P.W. van; Richardson, J.F.; Boer, P. de; Zwanenburg, S.

1980-01-01

By experiments similar to those with the mouse we studied, in the rhesus monkey (Macaca mulatta), the induction by X-rays of reciprocal translocations in steam-cell spermatogonia and of dicentric chromosomes in blood lymphocytes. Human blood lymphocytes and rhesus monkey lymphocytes showed about equal sensitivity to dicentric induction. This equal radiosensitivity of somatic cells, however, provides no clue to the quantitative extrapolation to the human situation of the data obtained on translocation induction in stem-cell spermatogonia of the rhesus monkey. In our opinion, only direct observations on induced chromosomal aberrations in germ cells of higher primates and man can play a decisive role in estimating human genetic radiation risks arising from chromosomal aberrations. (orig./AJ)

Proteomic validation of multifunctional molecules in mesenchymal stem cells derived from human bone marrow, umbilical cord blood and peripheral blood.

Directory of Open Access Journals (Sweden)

Jumi Kim

Full Text Available Mesenchymal stem cells (MSCs are one of the most attractive therapeutic resources in clinical application owing to their multipotent capability, which means that cells can differentiate into various mesenchymal tissues such as bone, cartilage, fat, tendon, muscle and marrow stroma. Depending on the cellular source, MSCs exhibit different application potentials according to their different in vivo functions, despite similar phenotypic and cytological characteristics. To understand the different molecular conditions that govern the different application or differentiation potential of each MSC according to cellular source, we generated a proteome reference map of MSCs obtained from bone marrow (BM, umbilical cord blood (CB and peripheral blood (PB. We identified approximately 30 differentially regulated (or expressed proteins. Most up-regulated proteins show a cytoskeletal and antioxidant or detoxification role according to their functional involvement. Additionally, these proteins are involved in the increase of cell viability, engraftment and migration in pathological conditions in vivo. In summary, we examined differentially expressed key regulatory factors of MSCs obtained from several cellular sources, demonstrated their differentially expressed proteome profiles and discussed their functional role in specific pathological conditions. With respect to the field of cell therapy, it may be particularly crucial to determine the most suitable cell sources according to target disease.

[Perinatal sources of stem cells].

Science.gov (United States)

Piskorska-Jasiulewicz, Magdalena Maria; Witkowska-Zimny, Małgorzata

2015-03-08

Recently, stem cell biology has become an interesting topic. Several varieties of human stem cells have been isolated and identified in vivo and in vitro. Successful application of hematopoietic stem cells in hematology has led to the search for other sources of stem cells and expanding the scale of their application. Perinatal stem cells are a versatile cell population, and they are interesting for both scientific and practical objectives. Stem cells from perinatal tissue may be particularly useful in the clinic for autologous transplantation for fetuses and newborns, and after banking in later stages of life, as well as for in utero transplantation in the case of genetic disorders. In this review paper we focus on the extraction and therapeutic potential of stem cells derived from perinatal tissues such as the placenta, the amnion, amniotic fluid, umbilical cord blood and Wharton's jelly.

Treatment of radiation syndrome with emphasis on stem cell implantation

International Nuclear Information System (INIS)

Ashry, O.M.

2010-01-01

Within few years, the possibility that the human body contains cells that can repair and regenerate damaged and diseased tissue has gone from an unlikely proposition to a virtual certainty. Patients who have received doses of radiation in the potentially low to mid-lethal range (2-6 Gy) will have depression in bone-marrow function with cessation of blood-cell production leading to pancytopenia. Selection of cases for stem cell transplantation is based upon clinical signs and symptoms. Hematopoietic stem cell which produces blood cell progeny provides support for hematopoietic and other cells within the marrow, and has also been a focus for possible tissue repair. Another cell type termed mesenchymal or stromal also exists in the marrow. This cell provides support for hematopoietic and other cells within the marrow, and has also been a focus for possible tissue repair. Stem cells are obtained from bone marrow, peripheral blood, placental and umbilical cord blood, embryonic stem cells and embryonic germ cells. These cells have great potential for clinical research due to their potential to regenerate tissue. As well known, the cryo preservation process can store any cell type, particularly blood cells, for an indeterminate time. (author)

Evaluation of motor neuron differentiation potential of human umbilical cord blood- derived mesenchymal stem cells, in vitro.

Science.gov (United States)

Yousefi, Behnam; Sanooghi, Davood; Faghihi, Faezeh; Joghataei, Mohammad Taghi; Latifi, Nourahmad

2017-04-01

Many people suffer from spinal cord injuries annually. These deficits usually threaten the quality of life of patients. As a postpartum medically waste product, human Umbilical Cord Blood (UCB) is a rich source of stem cells with self- renewal properties and neural differentiation capacity which made it useful in regenerative medicine. Since there is no report on potential of human umbilical cord blood-derived mesenchymal stem cells into motor neurons, we set out to evaluate the differentiation properties of these cells into motor neuron-like cells through administration of Retinoic Acid(RA), Sonic Hedgehog(Shh) and BDNF using a three- step in vitro procedure. The results were evaluated using Real-time PCR, Flowcytometry and Immunocytochemistry for two weeks. Our data showed that the cells changed into bipolar morphology and could express markers related to motor neuron; including Hb-9, Pax-6, Islet-1, NF-H, ChAT at the level of mRNA and protein. We could also quantitatively evaluate the expression of Islet-1, ChAT and NF-H at 7 and 14days post- induction using flowcytometry. It is concluded that human UCB-MSCs is potent to express motor neuron- related markers in the presence of RA, Shh and BDNF through a three- step protocol; thus it could be a suitable cell candidate for regeneration of motor neurons in spinal cord injuries. Copyright © 2017. Published by Elsevier B.V.

Concepts, Utility and Limitations of Cord Blood Banking: What Clinicians Need to Know.

Science.gov (United States)

Narayanan, Dhanya Lakshmi; Phadke, Shubha R

2018-03-20

Stem cell transplantation and cord blood banking have received much popularity among general public and medical professionals in the recent past. But information about the scientific aspects, its utility and limitations is incomplete amongst laypersons as well as many medical practitioners. Stem cells differ from all other types of cells in the human body because of their ability to multiply in order to self perpetuate and differentiate into specialized cells. Stems cells could be totipotent, multipotent, pluripotent, oligopotent or unipotent depending on the type of cells that can arise or differentiate from them. Umbilical cord blood serves as a potent source of hematopoeitic stem cells and is being used to treat various disorders like blood cancers, hemoglobinopathies and immunodeficiency disorders for which hematological stem cell transplantation is the standard of care. Cord blood can be collected at ease, without any major complications and has a lower incidence of graft vs. host reaction compared to bone marrow cells or peripheral blood cells. Both public and private banks have been established for collection and storage of umbilical cord blood. However, false claims and misleading commercial advertisements about the use of umbilical cord blood stem cells for the treatment of a variety of conditions ranging from neuromuscular disorders to cosmetic benefits are widespread and create unrealistic expectations in laypersons and clinicians. Many clinicians and laypersons are unaware of the limitations of cord blood banking, as in treating a genetic disorder by autologous cord blood transplant. Knowledge and awareness about the scientific indications of cord blood stem cell transplantation and realistic expectations about the utility of cord blood among medical practitioners are essential for providing accurate information to laypersons before they decide to preserve umbilical cord blood in private banks and thus prevent malpractice.

Fundamental Principles of Stem Cell Banking.

Science.gov (United States)

Sun, Changbin; Yue, Jianhui; He, Na; Liu, Yaqiong; Zhang, Xi; Zhang, Yong

2016-01-01

Stem cells are highly promising resources for application in cell therapy, regenerative medicine, drug discovery, toxicology and developmental biology research. Stem cell banks have been increasingly established all over the world in order to preserve their cellular characteristics, prevent contamination and deterioration, and facilitate their effective use in basic and translational research, as well as current and future clinical application. Standardization and quality control during banking procedures are essential to allow researchers from different labs to compare their results and to develop safe and effective new therapies. Furthermore, many stem cells come from once-in-a-life time tissues. Cord blood for example, thrown away in the past, can be used to treat many diseases such as blood cancers nowadays. Meanwhile, these cells stored and often banked for long periods can be immediately available for treatment when needed and early treatment can minimize disease progression. This paper provides an overview of the fundamental principles of stem cell banking, including: (i) a general introduction of the construction and architecture commonly used for stem cell banks; (ii) a detailed section on current quality management practices; (iii) a summary of questions we should consider for long-term storage, such as how long stem cells can be stored stably, how to prevent contamination during long term storage, etc.; (iv) the prospects for stem cell banking.

Discovery of the rare HLA-B*39:77 allele in an unrelated Taiwanese bone marrow stem cell donor using the sequence-based typing method.

Science.gov (United States)

Yang, K L; Lee, S K; Lin, P Y

2013-08-01

We detected a rare HLA-B locus allele, B*39:77, in a Taiwanese unrelated marrow stem cell donor in our routine HLA sequence-based typing (SBT) exercise for a possible haematopoietic stem cell donation. In exons 2, 3 and 4, the DNA sequence of B*39:77 is identical to the sequence of B*39:01:01:01 except one nucleotide at nucleotide position 733 (G->A) in exon 4. The nucleotide variation caused one amino acid alteration at residue 221 (Gly->Ser). B*39:77 was probably derived from a nucleotide substitution event involving B*39:01:01:01. The probable HLA-A, -B, -C, -DRB1 and -DQB1 haplotype in association with B*39:77 may be deduced as A*02:01-B*39:77-C*07:02-DRB1*08:03-DQB1*06:01. Our discovery of B*39:77 in Taiwanese adds further polymorphism of B*39 variants in Taiwanese population. © 2013 John Wiley & Sons Ltd.

The effects of equine peripheral blood stem cells on cutaneous wound healing: a clinical evaluation in four horses.

Science.gov (United States)

Spaas, J H; Broeckx, S; Van de Walle, G R; Polettini, M

2013-04-01

Stem-cell therapy represents a promising strategy for the treatment of challenging pathologies, such as large, infected wounds that are unresponsive to conventional therapies. The present study describes the clinical application of peripheral blood stem cells (PBSCs) for the treatment of four adult Warmblood horses with naturally occurring wounds, which were unresponsive to conventional therapies for at least 3 months. A visual assessment was performed, and a number of wound-healing parameters (granulation tissue, crust formation and scar formation) were evaluated. In all cases, tissue overgrowth was visible within 4 weeks after PBSC injection, followed by the formation of crusts and small scars in the centre of the wound, with hair regeneration at the edges. In conclusion, this is the first report of PBSC therapy of skin wounds in horses, and it produced a positive visual and clinical outcome. © The Author(s) CED © 2013 British Association of Dermatologists.

Perinatal sources of stem cells

Directory of Open Access Journals (Sweden)

Magdalena Maria Piskorska-Jasiulewicz

2015-03-01

Full Text Available Recently, stem cell biology has become an interesting topic. Several varieties of human stem cells have been isolated and identified in vivo and in vitro. Successful application of hematopoietic stem cells in hematology has led to the search for other sources of stem cells and expanding the scale of their application. Perinatal stem cells are a versatile cell population, and they are interesting for both scientific and practical objectives. Stem cells from perinatal tissue may be particularly useful in the clinic for autologous transplantation for fetuses and newborns, and after banking in later stages of life, as well as for in utero transplantation in the case of genetic disorders. In this review paper we focus on the extraction and therapeutic potential of stem cells derived from perinatal tissues such as the placenta, the amnion, amniotic fluid, umbilical cord blood and Wharton’s jelly.

Stem Cell Treatment for Type 1 Diabetes

Directory of Open Access Journals (Sweden)

Ming eLi

2014-03-01

Full Text Available Type 1 diabetes mellitus (T1DM is a common chronic disease in children, characterized by a loss of  cells, which results in defects in insulin secretion and hyperglycemia. Chronic hyperglycemia causes diabetic complications, including diabetic nephropathy, neuropathy and retinopathy. Curative therapies mainly include diet and insulin administration. Although hyperglycemia can be improved by insulin administration, exogenous insulin injection cannot successfully mimic the insulin secretion from normal  cells, which keeps blood glucose levels within the normal range all the time. Islet and pancreas transplantation achieves better glucose control, but there is a lack of organ donors. Cell based therapies have also been attempted to treat T1DM. Stem cells such as embryonic stem cells, induced pluripotent stem cells and tissue stem cells (TSCs such as bone marrow-, adipose tissue- and cord blood-derived stem cells, have been shown to generate insulin-producing cells. In this review, we summarize the most-recently available information about T1DM and the use of TSCs to treat T1DM.

Characterization of the Stem-Cell Population of Phenylhydrazine-Treated Rodents

Energy Technology Data Exchange (ETDEWEB)

Hodgson, G.; Guzman, E.; Herrera, C. [Department of Biology, Vacuity Of Sciences University of Chile, Santiago (Chile)

1968-08-15

A study was made of the content of stem cells in the spleen, blood and bone marrow of mice treated with phenylhydrazine; the experimental method used was transplantation in lethally-irradiated mice. There was a marked increase in the content of stem cells in liver and blood and a small increase in bone marrow in the case of animals treated with phenylhydrazine. Judging by the effects of vinblastine, about 80% of the stem cells of spleen pass through mitosis within 24 hours, while only 20% of the marrow cells and none of the blood stem cells pass through mitosis within this period. To obtain information on the average residence time of stem cells in blood, bone marrow was injected intravenously into normal rats and the blood content was determined at intervals, A disappearance half-life of 6 minutes was found. To estimate the increase in the number of stem cells in the spleen of animals treated with phenylhydrazine, rats with and without spleen were irradiated with 500 rad ({sup 137}Cs gamma) after being given five phenylhydrazine injections. The rats without spleen developed severe anaemia with high mortality (70%), compared with the rats with spleen. Among the survivors, erythropoiesis started to recover later and proceeded more slowly in rats that had undergone splenectomy than in those with spleen. Transfusion corrected the anaemia in the rats without spleen and reduced the high mortality, but did not alter the rate of erythropoiesis recovery. The spleen plays an important part in erythropoiesis and the bone-marrow function recovers sooner in rats with spleen than in those without. Although the spleen is important for erythropoiesis recovery after irradiation preceded by treatment with phenylhydrazine, it has no effect on recovery after irradiation alone. It seems as though the spleen is required when proliferation of stem cells at the maximum rate is essential for survival. It is possible that the spleen constitutes a favourable local environment for the

Human mesenchymal stem cells suppress donor CD4(+) T cell proliferation and reduce pathology in a humanized mouse model of acute graft-versus-host disease.

Science.gov (United States)

Tobin, L M; Healy, M E; English, K; Mahon, B P

2013-05-01

Acute graft-versus-host disease (aGVHD) is a life-threatening complication following allogeneic haematopoietic stem cell transplantation (HSCT), occurring in up to 30-50% of patients who receive human leucocyte antigen (HLA)-matched sibling transplants. Current therapies for steroid refractory aGVHD are limited, with the prognosis of patients suboptimal. Mesenchymal stem or stromal cells (MSC), a heterogeneous cell population present in many tissues, display potent immunomodulatory abilities. Autologous and allogeneic ex-vivo expanded human MSC have been utilized to treat aGVHD with promising results, but the mechanisms of therapeutic action remain unclear. Here a robust humanized mouse model of aGVHD based on delivery of human peripheral blood mononuclear cells (PBMC) to non-obese diabetic (NOD)-severe combined immunodeficient (SCID) interleukin (IL)-2rγ(null) (NSG) mice was developed that allowed the exploration of the role of MSC in cell therapy. MSC therapy resulted in the reduction of liver and gut pathology and significantly increased survival. Protection was dependent upon the timing of MSC therapy, with conventional MSC proving effective only after delayed administration. In contrast, interferon (IFN)-γ-stimulated MSC were effective when delivered with PBMC. The beneficial effect of MSC therapy in this model was not due to the inhibition of donor PBMC chimerism, as CD45(+) and T cells engrafted successfully in this model. MSC therapy did not induce donor T cell anergy, FoxP3(+) T regulatory cells or cause PBMC apoptosis in this model; however, it was associated with the direct inhibition of donor CD4(+) T cell proliferation and reduction of human tumour necrosis factor-α in serum. © 2012 British Society for Immunology.

Clinical Use and Patentability of Cord Blood

Science.gov (United States)

Cavusoglu, Turker; Kilic, Kubilay Dogan; Yigitturk, Gurkan; Tomruk, Canberk; Turgut, Mehmet; Uyanikgil, Yigit

2018-03-14

The blood in the umbilical cord that provides the connection between mother and fetus during pregnancy is called cord blood. The blood of umbilical cord which is usually got rid of following birth, is a very rich stem cell source. Cord blood collection gives no harm to the mother and baby. Besides, its allogeneic and au-tologous usage, the most important disadvantage is that the number of cells is insufficient in adults. Today, it is predominantly used for therapeutic purposes for many diseases. The aim of this review is giving a detailed information about groups of stem cells in cord blood and determining the point of clinical use. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The small GTPase RhoH is an atypical regulator of haematopoietic cells

Directory of Open Access Journals (Sweden)

Kubatzky Katharina F

2008-09-01

Full Text Available Abstract Rho GTPases are a distinct subfamily of the superfamily of Ras GTPases. The best-characterised members are RhoA, Rac and Cdc42 that regulate many diverse actions such as actin cytoskeleton reorganisation, adhesion, motility as well as cell proliferation, differentiation and gene transcription. Among the 20 members of that family, only Rac2 and RhoH show an expression restricted to the haematopoietic lineage. RhoH was first discovered in 1995 as a fusion transcript with the transcriptional repressor LAZ3/BCL6. It was therefore initially named translation three four (TTF but later on renamed RhoH due to its close relationship to the Ras/Rho family of GTPases. Since then, RhoH has been implicated in human cancer as the gene is subject to somatic hypermutation and by the detection of RHOH as a translocation partner for LAZ3/BCL6 or other genes in human lymphomas. Underexpression of RhoH is found in hairy cell leukaemia and acute myeloid leukaemia. Some of the amino acids that are crucial for GTPase activity are mutated in RhoH so that the protein is a GTPase-deficient, so-called atypical Rho GTPase. Therefore other mechanisms of regulating RhoH activity have been described. These include regulation at the mRNA level and tyrosine phosphorylation of the protein's unique ITAM-like motif. The C-terminal CaaX box of RhoH is mainly a target for farnesyl-transferase but can also be modified by geranylgeranyl-transferase. Isoprenylation of RhoH and changes in subcellular localisation may be an additional factor to fine-tune signalling. Little is currently known about its signalling, regulation or interaction partners. Recent studies have shown that RhoH negatively influences the proliferation and homing of murine haematopoietic progenitor cells, presumably by acting as an antagonist for Rac1. In leukocytes, RhoH is needed to keep the cells in a resting, non-adhesive state, but the exact mechanism has yet to be elucidated. RhoH has also been

Stem cell therapy. Use of differentiated pluripotent stem cells as replacement therapy for treating disease

DEFF Research Database (Denmark)

Fox, Ira J; Daley, George Q; Goldman, Steven A

2014-01-01

Pluripotent stem cells (PSCs) directed to various cell fates holds promise as source material for treating numerous disorders. The availability of precisely differentiated PSC-derived cells will dramatically affect blood component and hematopoietic stem cell therapies and should facilitate......, and industry is critical for generating new stem cell-based therapies....... treatment of diabetes, some forms of liver disease and neurologic disorders, retinal diseases, and possibly heart disease. Although an unlimited supply of specific cell types is needed, other barriers must be overcome. This review of the state of cell therapies highlights important challenges. Successful...

Cotransplantation of Mesenchymal Stem Cells and Immature Dendritic Cells Potentiates the Blood Glucose Control of Islet Allografts

Directory of Open Access Journals (Sweden)

Guanghui Long

2017-01-01

Full Text Available Background. Transplantation of islets is a promising alternative to treat type 1 diabetes (T1D, but graft rejection is the major obstacle to its application in clinical practice. We evaluated the effects of mesenchymal stem cells (MSCs and immature dendritic cells (imDCs on islet transplantation in diabetic model. Methods. The streptozotocin T1D model was established in BABL/c mice. Rat islets were isolated and identified with dithizone (DTZ staining. MSCs and imDCs were isolated from bone marrow of syngenic mice. Islets, alone or along with MSCs and/or imDCs, were transplanted to the left kidney capsule of diabetic mice. The blood glucose levels and glycosylated hemoglobin levels after transplantation were monitored. Results. Cotransplantation significantly decreased blood glucose and glycosylated hemoglobin levels in the diabetes mice. Transplantation of 200 islets + 2 × 105 MSCs + 2 × 105 imDCs could not only restore normal blood glucose levels, but also significantly prolong graft survival for 12.6±3.48 days. Conclusions. Cotransplantation of allogenic islets with imDCs and/or MSCs can significantly promote graft survival, reverse hyperglycemia, and effectively control the glycosylated hemoglobin levels.

N-Cadherin Upregulation Promotes the Neurogenic Differentiation of Menstrual Blood-Derived Endometrial Stem Cells.

Science.gov (United States)

Liu, Yanli; Yang, Fen; Liang, Shengying; Liu, Qing; Fu, Sulei; Wang, Zhenyu; Yang, Ciqing; Lin, Juntang

2018-01-01

Peripheral nerve injuries are typically caused by either trauma or medical disorders, and recently, stem cell-based therapies have provided a promising treatment approach. Menstrual blood-derived endometrial stem cells (MenSCs) are considered an ideal therapeutic option for peripheral nerve repair due to a noninvasive collection procedure and their high proliferation rate and immunological tolerance. Here, we successfully isolated MenSCs and examined their biological characteristics including their morphology, multipotency, and immunophenotype. Subsequent in vitro studies demonstrated that MenSCs express high levels of neurotrophic factors, such as NT3, NT4, BDNF, and NGF, and are capable of transdifferentiating into glial-like cells under conventional induction conditions. Moreover, upregulation of N-cadherin (N-cad) mRNA and protein expression was observed after neurogenic differentiation. In vivo studies clearly showed that N-cad knockdown via in utero electroporation perturbed the migration and maturation of mouse neural precursor cells (NPCs). Finally, a further transfection assay also confirmed that N-cad upregulation in MenSCs results in the expression of S100. Collectively, our results confirmed the paracrine effect of MenSCs on neuroprotection as well as their potential for transdifferentiation into glial-like cells and demonstrated that N-cad upregulation promotes the neurogenic differentiation of MenSCs, thereby providing support for transgenic MenSC-based therapy for peripheral nerve injury.

Peripheral blood stem cell harvest in patients with limited stage small-cell lung cancer

Energy Technology Data Exchange (ETDEWEB)

Katakami, Nobuyuki; Takakura, Shunji; Fujii, Hiroshi; Nishimura, Takashi; Umeda, Bunichi [Kobe City General Hospital (Japan)

2000-06-01

Chemotherapy plus granulocyte colony-stimulating factor (G-CSF) induced mobilization of peripheral blood stem cells (PBSC) was performed in patients with limited stage small-cell lung cancer. Chemotherapy consisted of cisplatin/etoposide or cisplatin/adriamycin/etoposide. The amounts of CD34 positive cells and granulocyte-macrophage colony forming units (CFU-GM) collected during 2-3 courses of apheresis were 3.1{+-}2.9 x 10{sup 6}/kg (n=10) and 3.1{+-}1.5 x 10{sup 5}/kg (n=8) , respectively. Adequate amounts of PBSC were also harvested even in patients treated with concurrent chemoradiotherapy. Eight patients were successfully treated with high-dose chemotherapy consisting of ifosfamide, carboplatin and etoposide with PBSC transfusion. The patients'-bone marrow reconstruction was rapid and no treatment-related death was observed. (author)

Fanconi anaemia in South Africa: Past, present and future

African Journals Online (AJOL)

research and enhanced understanding of this disorder, the diagnosis of FA remains a .... inter-strand cross-link repair, nucleolytic incision and translesion. DNA synthesis. .... In developed nations, the availability of haematopoietic stem cell.

Timing of Peripheral Blood Stem Cell Yield: Comparison of Alternative Methods with the Classic Method for CD34+ Cell Determination

Directory of Open Access Journals (Sweden)

I. Fatorova

2014-01-01

Full Text Available Hematopoietic stem cells (HSCs, still represent a certain mystery in biology, have a unique property of dividing into equal cells and repopulating the hematopoietic tissue. This potential enables their use in transplantation treatments. The quality of the HSC grafts for transplantation is evaluated by flow cytometric determination of the CD34+ cells, which enables optimal timing of the first apheresis and the acquisition of maximal yield of the peripheral blood stem cells (PBSCs. To identify a more efficient method for evaluating CD34+ cells, we compared the following alternative methods with the reference method: hematopoietic progenitor cells (HPC enumeration (using the Sysmex XE-2100 analyser, detection of CD133+ cells, and quantification of aldehyde dehydrogenase activity in the PBSCs. 266 aphereses (84 patients were evaluated. In the preapheretic blood, the new methods produced data that were in agreement with the reference method. The ROC curves have shown that for the first-day apheresis target, the optimal predictive cut-off value was 0.032 cells/mL for the HPC method (sensitivity 73.4%, specificity 69.3%. HPC method exhibited a definite practical superiority as compared to other methods tested. HPC enumeration could serve as a supplementary method for the optimal timing of the first apheresis; it is simple, rapid, and cheap.

Umbilical Cord Blood Banking for Transplantation in Morocco: Problems and opportunities

Directory of Open Access Journals (Sweden)

Mazini L

2014-11-01

Full Text Available Since the success of the first umbilical cord blood (UCB transplantation in a child with Fanconi anaemia in 1989, great interests have emerged for this source of stem cells. UCB provides an unlimited source of ethnically diverse stem cells and is an alternative for bone marrow (BM and peripheral blood (PB heamatopoietic stem cell transplantation (HSCT. Thus, UCB and manipulated stem cells are now collected and banked according to international accreditation standards for listing on registries allowing rapid search and accessibility worldwide. This work aims to identify problems limiting the creation of a Moroccan cord blood bank and to highlight opportunities and issues of a new legislation promoting additional applications of cell therapy.

Evaluation of hollow fiber culture for large-scale production of mouse embryonic stem cell-derived hematopoietic stem cells.

Science.gov (United States)

Nakano, Yu; Iwanaga, Shinya; Mizumoto, Hiroshi; Kajiwara, Toshihisa

2018-03-03

Hematopoietic stem cells (HSCs) have the ability to differentiate into all types of blood cells and can be transplanted to treat blood disorders. However, it is difficult to obtain HSCs in large quantities because of the shortage of donors. Recent efforts have focused on acquiring HSCs by differentiation of pluripotent stem cells. As a conventional differentiation method of pluripotent stem cells, the formation of embryoid bodies (EBs) is often employed. However, the size of EBs is limited by depletion of oxygen and nutrients, which prevents them from being efficient for the production of HSCs. In this study, we developed a large-scale hematopoietic differentiation approach for mouse embryonic stem (ES) cells by applying a hollow fiber (HF)/organoid culture method. Cylindrical organoids, which had the potential for further spontaneous differentiation, were established inside of hollow fibers. Using this method, we improved the proliferation rate of mouse ES cells to produce an increased HSC population and achieved around a 40-fold higher production volume of HSCs in HF culture than in conventional EB culture. Therefore, the HF/organoid culture method may be a new mass culture method to acquire pluripotent stem cell-derived HSCs.

Generation of integration-free induced pluripotent stem cells (GZHMUi001-A by reprogramming peripheral blood mononuclear cells from a 47, XXX syndrome patient

Directory of Open Access Journals (Sweden)

Yuchang Chen

2017-08-01

Full Text Available 47, XXX syndrome is one of several sex-chromosomal aneuploidies, and it has an incidence of approximately 1/1000 in newborn females. Because of heterogeneity in X-inactivation, these patients may exhibit a variety of clinical symptoms. Here, we report the generation of an integration-free human induced pluripotent stem cell line (GZHMUi001-A by using Sendai virus to reprogram peripheral blood mononuclear cells from a 47, XXX syndrome patient with premature ovarian failure. This 47, XXX iPS cell line has characteristics of pluripotent stem cells and is a useful tool for the investigation of this X chromosome aneuploid disease.

Generation of integration-free induced pluripotent stem cells (GZHMUi001-A) by reprogramming peripheral blood mononuclear cells from a 47, XXX syndrome patient.

Science.gov (United States)

Chen, Yuchang; Ou, Zhanhui; Song, Bing; Xian, Yexing; Ouyang, Shuming; Xie, Yuhuan; Xue, Yanting; Sun, Xiaofang

2017-08-01

47, XXX syndrome is one of several sex-chromosomal aneuploidies, and it has an incidence of approximately 1/1000 in newborn females. Because of heterogeneity in X-inactivation, these patients may exhibit a variety of clinical symptoms. Here, we report the generation of an integration-free human induced pluripotent stem cell line (GZHMUi001-A) by using Sendai virus to reprogram peripheral blood mononuclear cells from a 47, XXX syndrome patient with premature ovarian failure. This 47, XXX iPS cell line has characteristics of pluripotent stem cells and is a useful tool for the investigation of this X chromosome aneuploid disease. Copyright © 2017. Published by Elsevier B.V.

Few single nucleotide variations in exomes of human cord blood induced pluripotent stem cells.

Directory of Open Access Journals (Sweden)

Rui-Jun Su

Full Text Available The effect of the cellular reprogramming process per se on mutation load remains unclear. To address this issue, we performed whole exome sequencing analysis of induced pluripotent stem cells (iPSCs reprogrammed from human cord blood (CB CD34(+ cells. Cells from a single donor and improved lentiviral vectors for high-efficiency (2-14% reprogramming were used to examine the effects of three different combinations of reprogramming factors: OCT4 and SOX2 (OS, OS and ZSCAN4 (OSZ, OS and MYC and KLF4 (OSMK. Five clones from each group were subject to whole exome sequencing analysis. We identified 14, 11, and 9 single nucleotide variations (SNVs, in exomes, including untranslated regions (UTR, in the five clones of OSMK, OS, and OSZ iPSC lines. Only 8, 7, and 4 of these, respectively, were protein-coding mutations. An average of 1.3 coding mutations per CB iPSC line is remarkably lower than previous studies using fibroblasts and low-efficiency reprogramming approaches. These data demonstrate that point nucleotide mutations during cord blood reprogramming are negligible and that the inclusion of genome stabilizers like ZSCAN4 during reprogramming may further decrease reprogramming-associated mutations. Our findings provide evidence that CB is a superior source of cells for iPSC banking.

Knowledge and attitudes of pregnant women with regard to collection, testing and banking of cord blood stem cells.

Science.gov (United States)

Fernandez, Conrad V; Gordon, Kevin; Van den Hof, Michiel; Taweel, Shaureen; Baylis, Françoise

2003-03-18

Umbilical cord blood is used as a source of hematopoietic stem cells for bone marrow transplantation in the treatment of malignant and nonmalignant disease. We sought to examine pregnant women's knowledge and attitudes regarding cord blood banking, as their support is crucial to the success of cord blood transplant programs. A questionnaire examining sociodemographic factors and women's attitudes to cord blood banking was developed on the basis of findings from 2 focus groups and a pilot study. The questionnaire was distributed to 650 women attending antenatal clinics at a regional women's hospital between April and July 2001. A total of 443 women (68%) responded. More than half of the women (307/438 or 70% [95% confidence interval, CI, 66% to 74%]) reported poor or very poor knowledge about cord blood banking. Many of the respondents (299/441 or 68% [95% CI 63% to 72%]) thought that physicians should talk to pregnant women about the collection of cord blood, and they wanted to receive information about this topic from health care professionals (290/441 or 66% [95% CI 61% to 70%]) or prenatal classes (308/441 or 70% [95% CI 65% to 74%]). Most of the women (379/442 or 86% [95% CI 82% to 89%]) would elect to store cord blood in a public bank, many citing altruism as the reason for this choice. A much smaller proportion (63/442 or 14% [95% CI 11% to 18%]) would elect private banking, indicating that this would be a good investment or that they would feel guilty if the blood had not been stored. Additional acceptable uses for cord blood included research (mentioned by 294/436 women or 67% [95% CI 63% to 72%]) and gene therapy (mentioned by 169/437 women or 39% [95% CI 34% to 43%]). Most of the women in this study supported the donation of cord blood to public cord blood banks for potential transplantation and research.

Stem cells and the evolving notion of cellular identity

OpenAIRE

Daley, George Q.

2015-01-01

Stem cells are but one class of the myriad types of cells within an organism. With potential to self-renew and capacity to differentiate, stem cells play essential roles at multiple stages of development. In the early embryo, pluripotent stem cells represent progenitors for all tissues while later in development, tissue-restricted stem cells give rise to cells with highly specialized functions. As best understood in the blood, skin and gut, stem cells are the seeds that sustain tissue homeost...

Chronic Myeloid Leukemia Blood Inflicted Injury in Cord Derived Wharton's Jelly Mesenchymal Stem Cells

International Nuclear Information System (INIS)

Wajid, N.; Ali, M.; Javed, S.; Ali, F.; Anwar, S. S.

2016-01-01

Objective: To determine the effects of blood from CML patients on human umbilical cord derived Wharton's jelly mesenchymal stem cells (WJMSCs) for evaluation of their therapeutic potential. Study Design: An experimental study. Place and Duration of Study: Centre for Research in Molecular Medicine, University of Lahore, from September 2013 to December 2014. Methodology: Possible behavior of WJMSCs in CML patients was assessed by culturing these cells in their plasma. WJMSCs at passage 3 were cultured in plasma isolated from 9 CML patients as well as 9 normal subjects. Effects on cell viability, proliferation, LDH release, paracrine factors (p38 and p53) and oxidative stress were evaluated. Result: WJMSCs cultured in plasma of CML patients showed decreased viability, slow proliferation, high LDH release, high expression of p38 and p53 and a high oxidative stress compared to normal subjects. Conclusion: Stressed environment of CML patients' blood/plasma induced injury to WJMSCs as well as reduced their viability. Effectiveness of these cells for therapeutics of CML is, therefore, likely to be reduced. (author)

Next-generation sequencing-based detection of circulating tumour DNA After allogeneic stem cell transplantation for lymphoma.

Science.gov (United States)

Herrera, Alex F; Kim, Haesook T; Kong, Katherine A; Faham, Malek; Sun, Heather; Sohani, Aliyah R; Alyea, Edwin P; Carlton, Victoria E; Chen, Yi-Bin; Cutler, Corey S; Ho, Vincent T; Koreth, John; Kotwaliwale, Chitra; Nikiforow, Sarah; Ritz, Jerome; Rodig, Scott J; Soiffer, Robert J; Antin, Joseph H; Armand, Philippe

2016-12-01

Next-generation sequencing (NGS)-based circulating tumour DNA (ctDNA) detection is a promising monitoring tool for lymphoid malignancies. We evaluated whether the presence of ctDNA was associated with outcome after allogeneic haematopoietic stem cell transplantation (HSCT) in lymphoma patients. We studied 88 patients drawn from a phase 3 clinical trial of reduced-intensity conditioning HSCT in lymphoma. Conventional restaging and collection of peripheral blood samples occurred at pre-specified time points before and after HSCT and were assayed for ctDNA by sequencing of the immunoglobulin or T-cell receptor genes. Tumour clonotypes were identified in 87% of patients with adequate tumour samples. Sixteen of 19 (84%) patients with disease progression after HSCT had detectable ctDNA prior to progression at a median of 3·7 months prior to relapse/progression. Patients with detectable ctDNA 3 months after HSCT had inferior progression-free survival (PFS) (2-year PFS 58% vs. 84% in ctDNA-negative patients, P = 0·033). In multivariate models, detectable ctDNA was associated with increased risk of progression/death (Hazard ratio 3·9, P = 0·003) and increased risk of relapse/progression (Hazard ratio 10·8, P = 0·0006). Detectable ctDNA is associated with an increased risk of relapse/progression, but further validation studies are necessary to confirm these findings and determine the clinical utility of NGS-based minimal residual disease monitoring in lymphoma patients after HSCT. © 2016 John Wiley & Sons Ltd.

Differentiation of embryonic stem cells towards hematopoietic cells: progress and pitfalls.

Science.gov (United States)

Tian, Xinghui; Kaufman, Dan S

2008-07-01

Hematopoietic development from embryonic stem cells has been one of the most productive areas of stem cell biology. Recent studies have progressed from work with mouse to human embryonic stem cells. Strategies to produce defined blood cell populations can be used to better understand normal and abnormal hematopoiesis, as well as potentially improve the generation of hematopoietic cells with therapeutic potential. Molecular profiling, phenotypic and functional analyses have all been utilized to demonstrate that hematopoietic cells derived from embryonic stem cells most closely represent a stage of hematopoiesis that occurs at embryonic/fetal developmental stages. Generation of hematopoietic stem/progenitor cells comparable to hematopoietic stem cells found in the adult sources, such as bone marrow and cord blood, still remains challenging. However, genetic manipulation of intrinsic factors during hematopoietic differentiation has proven a suitable approach to induce adult definitive hematopoiesis from embryonic stem cells. Concrete evidence has shown that embryonic stem cells provide a powerful approach to study the early stage of hematopoiesis. Multiple hematopoietic lineages can be generated from embryonic stem cells, although most of the evidence suggests that hematopoietic development from embryonic stem cells mimics an embryonic/fetal stage of hematopoiesis.

Ovarian tissue cryopreservation in girls undergoing haematopoietic stem cell transplant: experience of a single centre.

Science.gov (United States)

Biasin, E; Salvagno, F; Berger, M; Nesi, F; Quarello, P; Vassallo, E; Evangelista, F; Marchino, G L; Revelli, A; Benedetto, C; Fagioli, F

2015-09-01

Fertility after childhood haemopoietic stem cell transplant (HSCT) is a major concern. Conditioning regimens before HSCT present a high risk (>80%) of ovarian failure. Since 2000, we have proposed cryopreservation of ovarian tissue to female patients undergoing HSCT at our centre, to preserve future fertility. After clinical and haematological evaluation, the patients underwent ovarian tissue collection by laparoscopy. The tissue was analysed by histologic examination to detect any tumour contamination and then frozen following the slow freezing procedure and cryopreserved in liquid nitrogen. From August 2000 to September 2013, 47 patients planned to receive HSCT, underwent ovarian tissue cryopreservation. The median age at diagnosis was 11.1 years and at the time of procedure it was 13 years, respectively. Twenty-four patients were not pubertal at the time of storage, whereas 23 patients had already experienced menarche. The median time between laparoscopy and HSCT was 25 days. Twenty-six out of 28 evaluable patients (93%) developed hypergonadotropic hypogonadism at a median time of 23.3 months after HSCT. One patient required autologous orthotopic transplantation that resulted in one live birth. Results show a very high rate of iatrogenic hypergonadotropic hypogonadism, highlighting the need for fertility preservation in these patients.

Spatio-temporal Characterization of Ligand-Receptor Interactions in Blood Stem-Cell Rolling

KAUST Repository

Al Alwan, Bader

2017-08-16

One of the most important issues in the research on hematopoietic stem/progenitor cells (HSPCs) is to understand the mechanism of the homing process of these cells to the bone marrow after being transplanted into patients and establish the production of various blood cell types. The HSPCs first come in contact with the endothelial cells. This contact is known as adhesion and occurs through a multi-step paradigm ending with transmigration to the bone marrow niche. The initial step of the homing, tethering and rolling of HSPCs is mediated by P- and E-Selectins expressed on the endothelial cell surface through their interactions with the ligands expressed by HSPCs. Here we developed a novel experimental method to unravel the molecular mechanisms of the selectin-ligands interactions in vitro at the single molecule level by combining microfluidics and single-molecule fluorescence imaging. Our method enables direct visualization of the nanoscale spatiotemporal dynamics of the E-selectin-ligand (PSGL-1) interactions under conditions of shear stress acting on the cells at the molecular level in real time.

Studies on the regeneration of the CFU-C population in blood and bone marrow or lethally irradiated dogs after autologous transfusion of cryopreserved mononuclear blood cells

International Nuclear Information System (INIS)

Nothdurft, W.; Bruch, C.; Fliedner, T.M.; Rueber, E.

1977-01-01

In a group of 8 lethally irradiated (1200 R) dogs, that were transfused autologously with cryopreserved mononuclear cells (MNC) derived from the peripheral blood by leucapheresis the concentration of colony-forming units in agar (CFU-C) in bone marrow and peripheral blood was estimated at regular intervals after irradiation and transfusion of MNC. The numbers of MNC transfused per kg body weight ranged from 0.32 x 10 9 to 1.63 x 10 9 with an incidence of CFU-C between 0.02 x 10 5 and 1.38 x 10 5 . In 6 dogs the CFU-C levels in the bone marrow reached the normal preirradiation values between days 15 and 20. But in 2 dogs that had received the lowest CFU-C numbers the regeneration of the bone marrow CFU-C was markedly delayed. In general the time course of the bone marrow repopulation by CFU-C for single dogs was reflected by a corresponding regeneration pattern of the blood CFU-C. The time course of the curves for the blood CFU-C levels on the other hand was of the same kind as for the granulocyte values in the peripheral blood, that reached the normal levels mainly around day 30 and thereafter. Considerable fluctuations were seen in the blood CFU-C levels of single dogs before irradiation and after mononuclear leucocyte transfusion. Despite of such limitations the blood CFU-C content appeared to be a useful indicator of haematopoietic regeneration of the bone marrow. (author)

The influence of BDNF on human umbilical cord blood stem/progenitor cells: implications for stem cell-based therapy of neurodegenerative disorders.

Science.gov (United States)

Paczkowska, Edyta; Łuczkowska, Karolina; Piecyk, Katarzyna; Rogińska, Dorota; Pius-Sadowska, Ewa; Ustianowski, Przemysław; Cecerska, Elżbieta; Dołęgowska, Barbara; Celewicz, Zbigniew; Machaliński, Bogusław

2015-01-01

Umbilical cord blood (UCB)-derived stem/progenitor cells (SPCs) have demonstrated the potential to improve neurologic function in different experimental models. SPCs can survive after transplantation in the neural microenvironment and indu ce neuroprotection, endogenous neurogenesis by secreting a broad repertoire of trophic and immunomodulatory cytokines. In this study, the influence of brain-derived neurotrophic factor (BDNF) pre-treatment was comprehensively evaluated in a UCB-derived lineage-negative (Lin-) SPC population. UCB-derived Lin- cells were evaluated with respect to the expression of (i) neuronal markers using immunofluorescence staining and (ii) specific (TrkB) receptors for BDNF using flow cytometry. Next, after BDNF pre-treatment, Lin- cells were extensively assessed with respect to apoptosis using Western blotting and proliferation via BrdU incorporation. Furthermore, NT-3 expression levels in Lin- cells using RQ PCR and antioxidative enzyme activities were assessed. We demonstrated neuronal markers as well as TrkB expression in Lin- cells and the activation of the TrkB receptor by BDNF. BDNF pre-treatment diminished apoptosis in Lin- cells and influenced the proliferation of these cells. We observed significant changes in antioxidants as well as in the increased expression of NT-3 in Lin- cells following BDNF exposure. Complex global miRNA and mRNA profiling analyses using microarray technology and GSEA revealed the differential regulation of genes involved in the proliferation, gene expression, biosynthetic processes, translation, and protein targeting. Our results support the hypothesis that pre-treatment of stem/progenitor cells could be beneficial and may be used as an auxiliary strategy for improving the properties of SPCs.

Reduced Haematopoietic Output in Automobile Mechanics and Sprayers with Chronic Exposure to Petrochemicals: A Case-Control Study in Cape Coast, Ghana.

Science.gov (United States)

Adu, Patrick; Pobee, Richard; Awuah, Aaron; Asiamah, Paul B; Amoani, Festus; Gyabaa, Sampson

2018-01-01

Automobile mechanics and sprayers are at a higher risk of exposure to hazardous chemicals such as polycyclic aromatic hydrocarbons and heavy metals which may cause adverse health outcomes. This study aimed to use reticulocyte count as an indirect measure of the haematological output in automobile mechanics and sprayers in the Cape Coast Metropolis, Ghana. This cross-sectional study recruited 130 participants: 90 cases (57 automobile mechanics and 33 automobile sprayers) and 40 controls (nonautomobile workers). Venous blood samples were drawn from the participants and examined for full blood count and absolute reticulocyte count. Semi-structured questionnaire was used to collect demographic and occupational safety information from participants. 75.6% of cases had never received occupational safety training. Whereas 35.1% of automobile mechanics routinely siphoned fuel, 36.4% of automobile sprayers never used nose masks in the discharge of their duties. Controls had significantly higher WBC counts compared to mechanics ( p = 0.0001; 5.04 ± 1.7 versus 3.81 ± 1.1), or sprayers ( p = 0.0004; 5.04 ± 1.7 versus 3.74 ± 0.9). Lymphocyte, monocyte, and platelet counts were also significantly higher in controls compared to cases. Whereas RBC counts were significantly higher in controls compared to automobile mechanics (4.85 versus 4.66; p = 0.034), haemoglobin levels were significantly higher in automobile sprayers compared to controls (15.13 versus 14.1 g/dl; p = 0.0126). Absolute reticulocyte count was significantly higher in controls compared to cases [ p mechanics)]. Among the cases however, only RBC counts were significantly lower in automobile mechanics compared to automobile sprayers ( p = 0.0088; 4.66 ± 0.4 versus 4.85 ± 0.5). It was evident that both automobile mechanics and sprayers had significantly reduced haematopoietic output. Occupational safety training is not given priority and must be addressed.

Cell-based therapeutic strategies for multiple sclerosis

DEFF Research Database (Denmark)

Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C

2017-01-01

and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities......, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved...

Tooth Tissue Engineering: The Importance of Blood Products as a Supplement in Tissue Culture Medium for Human Pulp Dental Stem Cells.

Science.gov (United States)

Pisciolaro, Ricardo Luiz; Duailibi, Monica Talarico; Novo, Neil Ferreira; Juliano, Yara; Pallos, Debora; Yelick, Pamela Crotty; Vacanti, Joseph Phillip; Ferreira, Lydia Masako; Duailibi, Silvio Eduardo

2015-11-01

One of the goals in using cells for tissue engineering (TE) and cell therapy consists of optimizing the medium for cell culture. The present study compares three different blood product supplements for improved cell proliferation and protection against DNA damage in cultured human dental pulp stem cells for tooth TE applications. Human cells from dental pulp were first characterized as adult stem cells (ectomesenchymal mixed origin) by flow cytometry. Next, four different cell culture conditions were tested: I, supplement-free; II, supplemented with fetal bovine serum; III, allogeneic human serum; and IV, autologous human serum. Cultured cells were then characterized for cell proliferation, mineralized nodule formation, and colony-forming units (CFU) capability. After 28 days in culture, the comet assay was performed to assess possible damage in cellular DNA. Our results revealed that Protocol IV achieved higher cell proliferation than Protocol I (p = 0.0112). Protocols II and III resulted in higher cell proliferation than Protocol I, but no statistical differences were found relative to Protocol IV. The comet assay revealed less cell damage in cells cultured using Protocol IV as compared to Protocols II and III. The damage percentage observed on Protocol II was significantly higher than all other protocols. CFUs capability was highest using Protocol IV (p = 0.0018) and III, respectively, and the highest degree of mineralization was observed using Protocol IV as compared to Protocols II and III. Protocol IV resulted in significantly improved cell proliferation, and no cell damage was observed. These results demonstrate that human blood product supplements can be used as feasible supplements for culturing adult human dental stem cells.

Characterization of Regenerative Phenotype of Unrestricted Somatic Stem Cells (USSC) from Human Umbilical Cord Blood (hUCB) by Functional Secretome Analysis*

Science.gov (United States)

Schira, Jessica; Falkenberg, Heiner; Hendricks, Marion; Waldera-Lupa, Daniel M.; Kögler, Gesine; Meyer, Helmut E.; Müller, Hans Werner; Stühler, Kai

2015-01-01

Stem cell transplantation is a promising therapeutic strategy to enhance axonal regeneration after spinal cord injury. Unrestricted somatic stem cells (USSC) isolated from human umbilical cord blood is an attractive stem cell population available at GMP grade without any ethical concerns. It has been shown that USSC transplantation into acute injured rat spinal cords leads to axonal regrowth and significant locomotor recovery, yet lacking cell replacement. Instead, USSC secrete trophic factors enhancing neurite growth of primary cortical neurons in vitro. Here, we applied a functional secretome approach characterizing proteins secreted by USSC for the first time and validated candidate neurite growth promoting factors using primary cortical neurons in vitro. By mass spectrometric analysis and exhaustive bioinformatic interrogation we identified 1156 proteins representing the secretome of USSC. Using Gene Ontology we revealed that USSC secretome contains proteins involved in a number of relevant biological processes of nerve regeneration such as cell adhesion, cell motion, blood vessel formation, cytoskeleton organization and extracellular matrix organization. We found for instance that 31 well-known neurite growth promoting factors like, e.g. neuronal growth regulator 1, NDNF, SPARC, and PEDF span the whole abundance range of USSC secretome. By the means of primary cortical neurons in vitro assays we verified SPARC and PEDF as significantly involved in USSC mediated neurite growth and therewith underline their role in improved locomotor recovery after transplantation. From our data we are convinced that USSC are a valuable tool in regenerative medicine as USSC's secretome contains a comprehensive network of trophic factors supporting nerve regeneration not only by a single process but also maintained its regenerative phenotype by a multitude of relevant biological processes. PMID:26183719

Characterization of hemopoietic stem cell chimerism in antibody-facilitated bone marrow chimeras

International Nuclear Information System (INIS)

Francescutti, L.H.; Gambel, P.; Wegmann, T.G.

1985-01-01

The authors have previously described a model for bone marrow transplantation that involves preparation of the host with monoclonal antibody against class I or class II antigens instead of irradiation or cytotoxic drugs. This allows engraftment and subsequent repopulation of the host by donor tissue. They have previously reported on chimerism in the peripheral blood of P1----(P1 X P2)F1 animals. In this report, the authors describe the examination of the bone marrow and spleen stem cell chimerism of these antibody-facilitated (AF) chimeras, by determining, with an isozyme assay, the phenotype of methylcellulose colonies grown from stem cells. They have found a correlation between peripheral blood chimerism and the stem cell constitution of both spleen and bone marrow. The peripheral blood chimerism also correlates with the level of chimerism in macrophages derived from peritoneal exudate cells. These findings indicate that assaying the peripheral blood of such chimeras provides an excellent indication of the degree of chimerism at the stem cell level and stands in sharp contrast to the level of chimerism in certain lymphoid compartments

Cellular bases of radiation-induced residual insufficiency in the haematopoietic system

International Nuclear Information System (INIS)

Wangenheim, K.H. v.; Peterson, H.P.; Feinendegen, L.E.

1984-01-01

Following radiation exposure, man's survival and further well-being largely depends on the degree of damage to his heamatopietic system. Stem cells are particualarly sensitive to radiation. Over and beyond acute radiation damge, residual radiation damage is of significance since it reduces the performance of the haematopietic system and enhances the risk of leukaemia. Knowledge concerning cellular bases may be important for preventive and therapeutic measures. The measurement method presented is based on the fact that stem cells from transfused bone marrow will settle in the spleen of highly irradiated mice and be able to reconstruct the haematopietic system. Initally individual colonies can be observed which originate from a single stem cell and the proliferation of its descendants. Counting these colonies will give the number of stem cells. The reduction of the proliferation factor measured in the stem-cell quality test apparently is not due to a shift in the age structure of the stem cell compartment but to a damage which is located within a more or less substantial proportion of the stem cells themselves. This damage is the cause of stem cell descendant growth retarded on an average. It is probable that recovery observed after irradiation is brought about by less-damaged or undamaged stem cells replacing damaged ones. Initial results point to the fact that this replacement can be influenced by treatment after irradiation. (orig./MG) [de

Wnt signaling in the stem cell niche

NARCIS (Netherlands)

Rattis, Frédérique Marie; Voermans, Carlijn; Reya, Tannishtha

2004-01-01

All the cells present in the blood are derived from the hematopoietic stem cell (HSC). Because mature blood cells have a limited life span, HSCs must perpetuate themselves through self-renewal to maintain a functional hematopoietic compartment for the lifetime of an organism. This review focuses on

Gene Transfer Properties and Structural Modeling of Human Stem Cell-derived AAV

OpenAIRE

Smith, Laura J; Ul-Hasan, Taihra; Carvaines, Sarah K; Van Vliet, Kim; Yang, Ethel; Wong, Kamehameha K; Agbandje-McKenna, Mavis; Chatterjee, Saswati

2014-01-01

Adeno-associated virus (AAV) vectors are proving to be remarkably successful for in vivo gene delivery. Based upon reports of abundant AAV in the human marrow, we tested CD34+ hematopoietic stem cells for the presence of natural AAV. Here, we report for the first time, the presence of novel AAV variants in healthy CD34+ human peripheral blood stem cells. The majority of healthy peripheral blood stem cell donors were found to harbor AAV in their CD34+ cells. Every AAV isolated from CD34+ cells...

Fine-tuning Hematopoiesis: Microenvironmental factors regulating self-renewal and differentiation of hematopoietic stem cells

NARCIS (Netherlands)

T.C. Luis (Tiago)

2010-01-01

markdownabstract__Abstract__ Hematopoietic stem cells (HSCs) have the ability to self renew and generate all lineages of blood cells. Although it is currently well established that hematopoietic stem cells (HSCs) regenerate the blood compartment, it was only in the 1960s that was introduced the

Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Contribute to Chondrogenesis in Coculture with Chondrocytes.

Science.gov (United States)

Li, Xingfu; Duan, Li; Liang, Yujie; Zhu, Weimin; Xiong, Jianyi; Wang, Daping

2016-01-01

Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) have been shown as the most potential stem cell source for articular cartilage repair. In this study, we aimed to develop a method for long-term coculture of human articular chondrocytes (hACs) and hUCB-MSCs at low density in vitro to determine if the low density of hACs could enhance the hUCB-MSC chondrogenic differentiation as well as to determine the optimal ratio of the two cell types. Also, we compared the difference between direct coculture and indirect coculture at low density. Monolayer cultures of hUCB-MSCs and hACs were investigated at different ratios, at direct cell-cell contact groups for 21 days. Compared to direct coculture, hUCB-MSCs and hACs indirect contact culture significantly increased type II collagen (COL2) and decreased type I collagen (COL1) protein expression levels. SRY-box 9 (SOX9) mRNA levels and protein expression were highest in indirect coculture. Overall, these results indicate that low density direct coculture induces fibrocartilage. However, indirect coculture in conditioned chondrocyte cell culture medium can increase expression of chondrogenic markers and induce hUCB-MSCs differentiation into mature chondrocytes. This work demonstrates that it is possible to promote chondrogenesis of hUCB-MSCs in combination with hACs, further supporting the concept of novel coculture strategies for tissue engineering.

Hematopoietic Stem Cell Transplantation Activity in Pediatric Cancer between 2008 and 2014 in the United States: A Center for International Blood and Marrow Transplant Research Report.

Science.gov (United States)

Khandelwal, Pooja; Millard, Heather R; Thiel, Elizabeth; Abdel-Azim, Hisham; Abraham, Allistair A; Auletta, Jeffery J; Boulad, Farid; Brown, Valerie I; Camitta, Bruce M; Chan, Ka Wah; Chaudhury, Sonali; Cowan, Morton J; Angel-Diaz, Miguel; Gadalla, Shahinaz M; Gale, Robert Peter; Hale, Gregory; Kasow, Kimberly A; Keating, Amy K; Kitko, Carrie L; MacMillan, Margaret L; Olsson, Richard F; Page, Kristin M; Seber, Adriana; Smith, Angela R; Warwick, Anne B; Wirk, Baldeep; Mehta, Parinda A

2017-08-01

This Center for International Blood and Marrow Transplant Research report describes the use of hematopoietic stem cell transplantation (HSCT) in pediatric patients with cancer, 4408 undergoing allogeneic (allo) and3076 undergoing autologous (auto) HSCT in the United States between 2008 and 2014. In both settings, there was a greater proportion of boys (n = 4327; 57%), children reports of transplant practices in the United States. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Stem cells are units of natural selection for tissue formation, for germline development, and in cancer development.

Science.gov (United States)

Weissman, Irving L

2015-07-21

It is obvious that natural selection operates at the level of individuals and collections of individuals. Nearly two decades ago we showed that in multi-individual colonies of protochordate colonial tunicates sharing a blood circulation, there exists an exchange of somatic stem cells and germline stem cells, resulting in somatic chimeras and stem cell competitions for gonadal niches. Stem cells are unlike other cells in the body in that they alone self-renew, so that they form clones that are perpetuated for the life of the organism. Stem cell competitions have allowed the emergence of competitive somatic and germline stem cell clones. Highly successful germline stem cells usually outcompete less successful competitors both in the gonads of the genotype partner from which they arise and in the gonads of the natural parabiotic partners. Therefore, natural selection also operates at the level of germline stem cell clones. In the colonial tunicate Botryllus schlosseri the formation of natural parabionts is prevented by a single-locus highly polymorphic histocompatibility gene called Botryllus histocompatibility factor. This limits germline stem cell predation to kin, as the locus has hundreds of alleles. We show that in mice germline stem cells compete for gonad niches, and in mice and humans, blood-forming stem cells also compete for bone marrow niches. We show that the clonal progression from blood-forming stem cells to acute leukemias by successive genetic and epigenetic events in blood stem cells also involves competition and selection between clones and propose that this is a general theme in cancer.

Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

OpenAIRE

Kosan, Christian; Godmann, Maren

2015-01-01

All hematopoiesis cells develop from multipotent progenitor cells. Hematopoietic stem cells (HSC) have the ability to develop into all blood lineages but also maintain their stemness. Different molecular mechanisms have been identified that are crucial for regulating quiescence and self-renewal to maintain the stem cell pool and for inducing proliferation and lineage differentiation. The stem cell niche provides the microenvironment to keep HSC in a quiescent state. Furthermore, several trans...

Age, Sex, and Religious Beliefs Impact the Attitude towards Cord Blood Banking.

Science.gov (United States)

Sundell, Inger Birgitta; Setzer, Teddi J

2015-01-01

In this study, a self-administered questionnaire was used to assess opinions about stem cell research and cord blood banking. Three attitudes were examined: willingness to accept cord blood banking, willingness to accept embryonic stem cell research, and religious belief system. A total of 90 Wayne State University students enrolled in the study in response to an invitation posted on a web page for the university. Sex distribution among study participants was 79 females and eight males; three declined to state their sex. Support for cord blood banking was high (> 70%) among students. Students over the age of 25 years of age were more (85%) positive than students 18 to 24 years old (57%). They prefered a public cord blood bank over a private cord blood bank. Atheist/agnostic or spiritual/not religious students (> 90%), Catholic students (78%) and Christian students (58%) support cord blood banking. Age, sex and religion seems influence the student's attitude towards stem cell research and cord blood banking.

Feasibility analysis of treating severe intrauterine adhesions by transplanting menstrual blood-derived stem cells.

Science.gov (United States)

Zheng, Sheng-Xia; Wang, Jian; Wang, Xue-Li; Ali, Asim; Wu, Li-Min; Liu, Yu-Sheng

2018-04-01

Intrauterine adhesions (IUA) are associated with the loss of stem cells in the endometrium. Menstrual blood‑derived stem cells (MenSCs) can be isolated from the menstrual blood and differentiated into endometrial cells. To check the transplantation feasibility of MenSCs for the treatment of severe IUA, MenSCs were isolated from menstrual blood, cultured in Dulbecco's modified Eagle's medium (DMEM), identified by immunocytochemistry and flow cytometry, differentiated into endometrial cells in vitro, and finally transplanted into the axillary subcutaneous tissue of non‑obese diabetic/severe combined immunodeficiency (NOD‑SCID) mice to create endometrial tissue. Additionally, the cloning efficiency and POU domain class 5 transcription factor 1 (OCT‑4) positivity of MenSCs from patients with severe IUA were compared with those from healthy women. Immunocytochemistry and flow cytometry results showed that 95.1±0.8% cells were OCT‑4‑positive, 0.9±0.4% were cluster of differentiation (CD)45‑positive, 1.8±0.9% were STRO‑1‑positive and 1.0±0.4% were human leukocyte antigen‑antigen D related‑positive. Following differentiation in vitro, the results of immunocytochemistry, reverse transcription‑polymerase chain reaction and western blot analysis showed that the expression of cytokeratin (CK) and vimentin (VIM) was increased in MenSCs compared with that in control subjects. Subsequent to transplantation in mice administered with sequential 17β‑estradiol and progesterone, CK, VIM, estrogen receptor and progesterone receptor were expressed in the transplantation regions, suggesting that MenSCs could differentiate into endometrial tissues in vivo. The cloning efficiency and OCT‑4 positivity of MenSCs from patients with severe IUA was significantly decreased. In conclusion, to the best of our knowledge, this is the first study in which MenSCs could differentiate into endometrial cells in vitro and create endometrial tissue in NOD‑SCID mice

Current Technologies Based on the Knowledge of the Stem Cells Microenvironments.

Science.gov (United States)

Mawad, Damia; Figtree, Gemma; Gentile, Carmine

2017-01-01

The stem cell microenvironment or niche plays a critical role in the regulation of survival, differentiation and behavior of stem cells and their progenies. Recapitulating each aspect of the stem cell niche is therefore essential for their optimal use in in vitro studies and in vivo as future therapeutics in humans. Engineering of optimal conditions for three-dimensional stem cell culture includes multiple transient and dynamic physiological stimuli, such as blood flow and tissue stiffness. Bioprinting and microfluidics technologies, including organs-on-a-chip, are among the most recent approaches utilized to replicate the three-dimensional stem cell niche for human tissue fabrication that allow the integration of multiple levels of tissue complexity, including blood flow. This chapter focuses on the physico-chemical and genetic cues utilized to engineer the stem cell niche and provides an overview on how both bioprinting and microfluidics technologies are improving our knowledge in this field for both disease modeling and tissue regeneration, including drug discovery and toxicity high-throughput assays and stem cell-based therapies in humans.

Does the preference of peripheral versus central venous access in peripheral blood stem cell collection/yield change stem cell kinetics in autologous stem cell transplantation?

Science.gov (United States)

Dogu, Mehmet Hilmi; Kaya, Ali Hakan; Berber, Ilhami; Sari, İsmail; Tekgündüz, Emre; Erkurt, Mehmet Ali; Iskender, Dicle; Kayıkçı, Ömur; Kuku, Irfan; Kaya, Emin; Keskin, Ali; Altuntaş, Fevzi

2016-02-01

Central venous access is often used during apheresis procedure in stem cell collection. The aim of the present study was to evaluate whether central or peripheral venous access has an effect on stem cell yield and the kinetics of the procedure and the product in patients undergoing ASCT after high dose therapy. A total of 327 patients were retrospectively reviewed. The use of peripheral venous access for stem cell yield was significantly more frequent in males compared to females (p = 0.005). Total volume of the product was significantly lower in central venous access group (p = 0.046). As being a less invasive procedure, peripheral venous access can be used for stem cell yield in eligible selected patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Transplant of Hepatocytes, Undifferentiated Mesenchymal Stem Cells, and In Vitro Hepatocyte-Differentiated Mesenchymal Stem Cells in a Chronic Liver Failure Experimental Model: A Comparative Study.

Science.gov (United States)

El Baz, Hanan; Demerdash, Zeinab; Kamel, Manal; Atta, Shimaa; Salah, Faten; Hassan, Salwa; Hammam, Olfat; Khalil, Heba; Meshaal, Safa; Raafat, Inas

2018-02-01

Liver transplant is the cornerstone line of treatment for chronic liver diseases; however, the long list of complications and obstacles stand against this operation. Searching for new modalities for treatment of chronic liver illness is a must. In the present research, we aimed to compare the effects of transplant of undifferentiated human mesenchymal stem cells, in vitro differentiated mesenchymal stem cells, and adult hepatocytes in an experimental model of chronic liver failure. Undifferentiated human cord blood mesenchymal stem cells were isolated, pro-pagated, and characterized by morphology, gene expression analysis, and flow cytometry of surface markers and in vitro differentiated into hepatocyte-like cells. Rat hepatocytes were isolated by double perfusion technique. An animal model of chronic liver failure was developed, and undifferentiated human cord blood mesenchymal stem cells, in vitro hepato-genically differentiated mesenchymal stem cells, or freshly isolated rat hepatocytes were transplanted into a CCL4 cirrhotic experimental model. Animals were killed 3 months after transplant, and liver functions and histopathology were assessed. Compared with the cirrhotic control group, the 3 cell-treated groups showed improved alanine aminotransferase, aspartate aminotransferase, albumin, and bilirubin levels, with best results shown in the hepatocyte-treated group. Histopathologic examination of the treated groups showed improved fibrosis, with best results obtained in the undifferentiated mesenchymal stem cell-treated group. Both adult hepatocytes and cord blood mesenchymal stem cells proved to be promising candidates for cell-based therapy in liver regeneration on an experimental level. Improved liver function was evident in the hepatocyte-treated group, and fibrosis control was more evident in the undifferentiated mesenchymal stem cell-treated group.

Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia.

Science.gov (United States)

Cavazzana-Calvo, Marina; Payen, Emmanuel; Negre, Olivier; Wang, Gary; Hehir, Kathleen; Fusil, Floriane; Down, Julian; Denaro, Maria; Brady, Troy; Westerman, Karen; Cavallesco, Resy; Gillet-Legrand, Beatrix; Caccavelli, Laure; Sgarra, Riccardo; Maouche-Chrétien, Leila; Bernaudin, Françoise; Girot, Robert; Dorazio, Ronald; Mulder, Geert-Jan; Polack, Axel; Bank, Arthur; Soulier, Jean; Larghero, Jérôme; Kabbara, Nabil; Dalle, Bruno; Gourmel, Bernard; Socie, Gérard; Chrétien, Stany; Cartier, Nathalie; Aubourg, Patrick; Fischer, Alain; Cornetta, Kenneth; Galacteros, Frédéric; Beuzard, Yves; Gluckman, Eliane; Bushman, Frederick; Hacein-Bey-Abina, Salima; Leboulch, Philippe

2010-09-16

The β-haemoglobinopathies are the most prevalent inherited disorders worldwide. Gene therapy of β-thalassaemia is particularly challenging given the requirement for massive haemoglobin production in a lineage-specific manner and the lack of selective advantage for corrected haematopoietic stem cells. Compound β(E)/β(0)-thalassaemia is the most common form of severe thalassaemia in southeast Asian countries and their diasporas. The β(E)-globin allele bears a point mutation that causes alternative splicing. The abnormally spliced form is non-coding, whereas the correctly spliced messenger RNA expresses a mutated β(E)-globin with partial instability. When this is compounded with a non-functional β(0) allele, a profound decrease in β-globin synthesis results, and approximately half of β(E)/β(0)-thalassaemia patients are transfusion-dependent. The only available curative therapy is allogeneic haematopoietic stem cell transplantation, although most patients do not have a human-leukocyte-antigen-matched, geno-identical donor, and those who do still risk rejection or graft-versus-host disease. Here we show that, 33 months after lentiviral β-globin gene transfer, an adult patient with severe β(E)/β(0)-thalassaemia dependent on monthly transfusions since early childhood has become transfusion independent for the past 21 months. Blood haemoglobin is maintained between 9 and 10 g dl(-1), of which one-third contains vector-encoded β-globin. Most of the therapeutic benefit results from a dominant, myeloid-biased cell clone, in which the integrated vector causes transcriptional activation of HMGA2 in erythroid cells with further increased expression of a truncated HMGA2 mRNA insensitive to degradation by let-7 microRNAs. The clonal dominance that accompanies therapeutic efficacy may be coincidental and stochastic or result from a hitherto benign cell expansion caused by dysregulation of the HMGA2 gene in stem/progenitor cells.

Are there fetal stem cells in the maternal brain?

Institute of Scientific and Technical Information of China (English)

Osman Demirhan; Necmi (C)ekin; Deniz Ta(s)temir; Erdal Tun(c); Ali irfan Güzel; Demet Meral; Bülent Demirbek

2013-01-01

Fetal cells can enter maternal blood during pregnancy but whether they can also cross the blood-brain barrier to enter the maternal brain remains poorly understood. Previous results suggest that fetal cells are summoned to repair damage to the mother's brain. If this is confirmed, it would open up new and safer avenues of treatment for brain damage caused by strokes and neural diseases. In this study, we aimed to investigate whether a baby's stem cells can enter the maternal brain during pregnancy. Deceased patients who had at least one male offspring and no history of abortion and blood transfusion were included in this study. DNA was extracted from brain tissue samples of deceased women using standard phenol-chloroform extraction and ethanol precipitation methods. Genomic DNA was screened by quantitative fluorescent-polymerase chain reaction amplification together with short tandem repeat markers specific to the Y chromosome, and 13, 18, 21 and X. Any foreign DNA residues that could be used to interpret the presence of fetal stem cells in the maternal brain were monitored. Results indicated that fetal stem cells can not cross the blood-brain barrier to enter the maternal brain.

Secretome of Aggregated Embryonic Stem Cell-Derived Mesenchymal Stem Cell Modulates the Release of Inflammatory Factors in Lipopolysaccharide-Induced Peripheral Blood Mononuclear Cells

Science.gov (United States)

Mohammadi Ghahhari, Nastaran; Maghsood, Faezeh; Jahandideh, Saeed; Lotfinia, Majid; Lak, Shirin; Johari, Behrooz; Azarnezhad, Asaad; Kadivar, Mehdi

2018-07-01

Bone marrow mesenchymal stem cells (BM-MSCs) have emerged as a potential therapy for various inflammatory diseases. Because of some limitations, several recent studies have suggested the use of embryonic stem cell-derived MSCs (ESC-MSCs) as an alternative for BM-MSCs. Some of the therapeutic effects of the ESC-MSCs are related to the secretion of a broad array of cytokines and growth factors, known as secretome. Harnessing this secretome for therapeutic applications requires the optimization of production of secretary molecules. It has been shown that aggregation of MSCs into 3D spheroids, as a preconditioning strategy, can enhance immunomodulatory potential of such cells. In this study, we investigated the effect of secretome derived from human ESC-MSCs (hESC-MSCs) spheroids on secretion of IL-1β, IL-10, and tumor necrosis factor α (TNF-α) from lipopolysaccharide (LPS)-induced peripheral blood mononuclear cells (PBMCs). In the present study, after immunophenotyping and considering mesodermal differentiation of hESC-MSCs, the cells were non-adherently grown to prepare 3D aggregates, and then conditioned medium or secretome was extracted from the cultures. Afterwards, the anti-inflammatory effects of the secretome were assessed in an in vitro model of inflammation. Results from this study showed that aggregate-prepared secretome from hESC-MSCs was able to significantly decrease the secretion of TNF-α (301.7 ± 5.906, p strategy to increase immunomodulatory characteristics of hESC-MSCs.

Re-using blood products as an alternative supplement in the optimisation of clinical-grade adipose-derived mesenchymal stem cell culture

Science.gov (United States)

Phetfong, J.; Tawonsawatruk, T.; Seenprachawong, K.; Srisarin, A.; Isarankura-Na-Ayudhya, C.

2017-01-01

Objectives Adipose-derived mesenchymal stem cells (ADMSCs) are a promising strategy for orthopaedic applications, particularly in bone repair. Ex vivo expansion of ADMSCs is required to obtain sufficient cell numbers. Xenogenic supplements should be avoided in order to minimise the risk of infections and immunological reactions. Human platelet lysate and human plasma may be an excellent material source for ADMSC expansion. In the present study, use of blood products after their recommended transfusion date to prepare human platelet lysate (HPL) and human plasma (Hplasma) was evaluated for in vitro culture expansion and osteogenesis of ADMSCs. Methods Human ADMSCs were cultured in medium supplemented with HPL, Hplasma and a combination of HPL and Hplasma (HPL+Hplasma). Characteristics of these ADMSCs, including osteogenesis, were evaluated in comparison with those cultured in fetal bovine serum (FBS). Results HPL and HPL+Hplasma had a significantly greater growth-promoting effect than FBS, while Hplasma exhibited a similar growth-promoting effect to that of FBS. ADMSCs cultured in HPL and/or Hplasma generated more colony-forming unit fibroblasts (CFU-F) than those cultured in FBS. After long-term culture, ADMSCs cultured in HPL and/or Hplasma showed reduced cellular senescence, retained typical cell phenotypes, and retained differentiation capacities into osteogenic and adipogenic lineages. Conclusion HPL and Hplasma prepared from blood products after their recommended transfusion date can be used as an alternative and effective source for large-scale ex vivo expansion of ADMSCs. Cite this article: J. Phetfong, T. Tawonsawatruk, K. Seenprachawong, A. Srisarin, C. Isarankura-Na-Ayudhya, A. Supokawej. Re-using blood products as an alternative supplement in the optimisation of clinical-grade adipose-derived mesenchymal stem cell culture. Bone Joint Res 2017;6:414–422. DOI: 10.1302/2046-3758.67.BJR-2016-0342.R1. PMID:28720606

High dose melphalan in the treatment of advanced neuroblastoma: results of a randomised trial (ENSG-1) by the European Neuroblastoma Study Group

NARCIS (Netherlands)

Pritchard, Jon; Cotterill, Simon J.; Germond, Shirley M.; Imeson, John; de Kraker, Jan; Jones, David R.

2005-01-01

High dose myeloablative chemotherapy ("megatherapy"), with haematopoietic stem cell support, is now widely used to consolidate response to induction chemotherapy in patients with advanced neuroblastoma. In this study (European Neuroblastoma Study Group, ENSG1), the value of melphalan myeloablative

Umbilical Cord Blood-Derived Stem Cells Improve Heat Tolerance and Hypothalamic Damage in Heat Stressed Mice

Directory of Open Access Journals (Sweden)

Ling-Shu Tseng

2014-01-01

Full Text Available Heatstroke is characterized by excessive hyperthermia associated with systemic inflammatory responses, which leads to multiple organ failure, in which brain disorders predominate. This definition can be almost fulfilled by a mouse model of heatstroke used in the present study. Unanesthetized mice were exposed to whole body heating (41.2°C for 1 hour and then returned to room temperature (26°C for recovery. Immediately after termination of whole body heating, heated mice displayed excessive hyperthermia (body core temperature ~42.5°C. Four hours after termination of heat stress, heated mice displayed (i systemic inflammation; (ii ischemic, hypoxic, and oxidative damage to the hypothalamus; (iii hypothalamo-pituitary-adrenocortical axis impairment (reflected by plasma levels of both adrenocorticotrophic-hormone and corticosterone; (iv decreased fractional survival; and (v thermoregulatory deficits (e.g., they became hypothermia when they were exposed to room temperature. These heatstroke reactions can be significantly attenuated by human umbilical cord blood-derived CD34+ cells therapy. Our data suggest that human umbilical cord blood-derived stem cells therapy may improve outcomes of heatstroke in mice by reducing systemic inflammation as well as hypothalamo-pituitary-adrenocortical axis impairment.

Increased Proportion of Hematopoietic Stem and Progenitor Cell Population in Cord Blood of Neonates Born to Mothers with Gestational Diabetes Mellitus.

Science.gov (United States)

Hadarits, Orsolya; Zóka, András; Barna, Gábor; Al-Aissa, Zahra; Rosta, Klára; Rigó, János; Kautzky-Willer, Alexandra; Somogyi, Anikó; Firneisz, Gábor

2016-01-01

We assessed the hematopoietic stem and progenitor cell (HSPC) population in the cord blood of neonates born to mothers with gestational diabetes mellitus (GDM) in a hypothesis generating pilot study, due to that, neonatal polycythemia may be the consequence of GDM pregnancy. Forty-five pregnant women with GDM (last trimester mean HbA1C = 33.9 mmol/mol) and 42 (nondiabetic) control pregnant women were enrolled after their routine 75 g oral glucose tolerance test (OGTT) between the 24th and 28th gestational week (with expected differences in their mean routine clinical characteristics: plasma glucose at OGTT: 0' = 5.07 vs. 4.62 mM, 120' = 8.9 vs. 5.76 mM, age = 35.07 vs. 31.66 years, prepregnancy body mass index = 27.9 vs. 23.9 kg/m(2), GDM vs. control, respectively) on a voluntary basis after signing the informed consent. EDTA-treated cord blood samples were analyzed by flow cytometry and the software Kaluza1.2 using CD45 and CD34-specific fluorescent antibodies to identify the HSPC population (CD34(+) cells within the CD45(dim) blast gate). The proportion of CD34(+)CD45(dim) HSPCs among the nucleated cells was significantly (P mothers with GDM (median 0.38%) compared to neonates born to nondiabetic mothers (median 0.32%) and according to treatment types (P cells in the cord blood may possibly be related to altered fetal stem cell mobilization in GDM pregnancy, yet these results should be interpreted only as preliminary due to the small sample sizes.

Stem Cell Banking for Regenerative and Personalized Medicine

Directory of Open Access Journals (Sweden)

David T. Harris

2014-02-01

Full Text Available Regenerative medicine, tissue engineering and gene therapy offer the opportunity to treat and cure many of today’s intractable afflictions. These approaches to personalized medicine often utilize stem cells to accomplish these goals. However, stem cells can be negatively affected by donor variables such as age and health status at the time of collection, compromising their efficacy. Stem cell banking offers the opportunity to cryogenically preserve stem cells at their most potent state for later use in these applications. Practical stem cell sources include bone marrow, umbilical cord blood and tissue, and adipose tissue. Each of these sources contains stem cells that can be obtained from most individuals, without too much difficulty and in an economical fashion. This review will discuss the advantages and disadvantages of each stem cell source, factors to be considered when contemplating banking each stem cell source, the methodology required to bank each stem cell source, and finally, current and future clinical uses of each stem cell source.

Stem Cell Banking for Regenerative and Personalized Medicine

Science.gov (United States)

Harris, David T.

2014-01-01

Regenerative medicine, tissue engineering and gene therapy offer the opportunity to treat and cure many of today’s intractable afflictions. These approaches to personalized medicine often utilize stem cells to accomplish these goals. However, stem cells can be negatively affected by donor variables such as age and health status at the time of collection, compromising their efficacy. Stem cell banking offers the opportunity to cryogenically preserve stem cells at their most potent state for later use in these applications. Practical stem cell sources include bone marrow, umbilical cord blood and tissue, and adipose tissue. Each of these sources contains stem cells that can be obtained from most individuals, without too much difficulty and in an economical fashion. This review will discuss the advantages and disadvantages of each stem cell source, factors to be considered when contemplating banking each stem cell source, the methodology required to bank each stem cell source, and finally, current and future clinical uses of each stem cell source. PMID:28548060

Awareness of cord blood banking among pregnant women in semi urban area

OpenAIRE

Poomalar G. K.; Jayasree M.

2016-01-01

Background: Hematopoietic stem cells (HSCs) are multipotent stem cells, derived from bone marrow, peripheral blood and umbilical cord. These HSC are accepted method of treatment for various disorders. Cord blood can be stored either in private or public bank. Awareness about cord blood banking among semi urban and rural population is less compared to urban population. The aim of our study is to evaluate the awareness of cord blood banking among pregnant women in semi urban area and to evaluat...

Mouse preantral follicle growth in 3D co-culture system using human menstrual blood mesenchymal stem cell.

Science.gov (United States)

Rajabi, Zahra; Yazdekhasti, Hossein; Noori Mugahi, Seyed Mohammad Hossein; Abbasi, Mehdi; Kazemnejad, Somaieh; Shirazi, Abolfazl; Majidi, Masoumeh; Zarnani, Amir-Hassan

2018-03-01

Follicle culture provides a condition which can help investigators to evaluate various aspects of ovarian follicle growth and development and impact of different components and supplementations as well as presumably application of follicle culture approach in fertility preservation procedures. Mesenchymal Stem Cells (MSCs), particularly those isolated from menstrual blood has the potential to be used as a tool for improvement of fertility. In the current study, a 3D co-culture system with mice preantral follicles and human Menstrual Blood Mesenchymal Stem Cells (MenSCs) using either collagen or alginate beads was designed to investigate whether this system allows better preantral follicles growth and development. Results showed that MenSCs increase the indices of follicular growth including survival rate, diameter, and antrum formation as well as the rate of in vitro maturation (IVM) in both collagen and alginates beads. Although statistically not significant, alginate was found to be superior in terms of supporting survival rate and antrum formation. Hormone assay demonstrated that the amount of secreted 17 β-estradiol and progesterone in both 3D systems increased dramatically after 12 days, with the highest levels in system employing MenSCs. Data also demonstrated that relative expression of studied genes increased for Bmp15 and Gdf9 and decreased for Mater when follicles were cultured in the presence of MenSCs. Collectively, results of the present study showed that MenSCs could improve indices of follicular growth and maturation in vitro. Further studies are needed before a clinical application of MenSCs-induced IVM is considered. Copyright © 2018 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. All rights reserved.

Sodium Caseinate (CasNa) Induces Mobilization of Hematopoietic Stem Cells in a BALB/c Mouse Model.

Science.gov (United States)

Santiago-Osorio, Edelmiro; Ledesma-Martínez, Edgar; Aguiñiga-Sánchez, Itzen; Poblano-Pérez, Ignacio; Weiss-Steider, Benny; Montesinos-Montesinos, Juan José; Mora-García, María de Lourdes

2015-09-25

BACKGROUND Hematopoietic stem cells transplantation has high clinical potential against a wide variety of hematologic, metabolic, and autoimmune diseases and solid tumors. Clinically, hematopoietic stem cells derived from peripheral blood are currently used more than those obtained from sources such as bone marrow. However, mobilizing agents used in the clinic tend to fail in high rates, making the number of mobilized cells insufficient for transplantation. We investigated whether sodium caseinate induces functional mobilization of hematopoietic stem cells into peripheral blood of Balb/c mice. MATERIAL AND METHODS Using a mouse model, we administrated sodium caseinate or Plerixafor, a commercial mobilizing agent, and analyzed counts of hematopoietic stem cells in peripheral blood, and then cells were transplanted into lethally irradiated mice to restore hematopoiesis. All assays were performed at least twice. RESULTS We found that sodium caseinate increases the number of mononuclear cells in peripheral blood with the immunophenotype of hematopoietic stem cells (0.2 to 0.5% LSK cells), allowing them to form colonies of various cell lineages in semisolid medium (psodium caseinate as a mobilizer of hematopoietic stem cells and its potential clinical application in transplantation settings.

Blood compatibility--a perspective.

Science.gov (United States)

Ratner, B D

2000-01-01

This perspective on blood- materials interactions is intended to introduce the set of papers stemming from the symposium, "Devices and Diagnostics in Contact with Blood: Issues in Blood Compatibility at the Close of the 20th Century," organized on August 4-6, 1999 at the University of Washington by the University of Washington Engineered Biomaterials (UWEB) Engineering Research Center. This article outlines some of the history of blood contacting materials, overviews the work that has originated at the University of Washington over the past 28 years, speculates on the origins of the controversies on blood compatibility and considers the issues that should be addressed in future studies.

Enhancing endogenous stem cells in the newbornvia delayed umbilical cord clamping

Institute of Scientific and Technical Information of China (English)

Christopher Lawton; Sandra Acosta; Nate Watson; Chiara Gonzales-Portillo; hTeo Diamandis; Naoki Tajiri; Yuji Kaneko; Paul R. Sanberg; Cesar V. Borlongan

2015-01-01

There is currently no consensus among clinicians and scientists over the appropriate or optimal timing for umbilical cord clamping. However, many clinical studies have suggested that delayed cord clamping is associated with various neonatal beneifts including increased blood volume, reduced need for blood transfusion, increased cerebral oxygenation in pre-term infants, and decreased frequency of iron deifciency anemia in term infants. Human umbilical cord blood con-tains signiifcant amounts of stem and progenitor cells and is currently used in the treatment of several life-threatening diseases. We propose that delayed cord clamping be encouraged as it en-hances blood lfow from the placenta to the neonate, which is accompanied by an increase supply of valuable stem and progenitor cells, as well as may improve blood oxygenation and increase blood volume, altogether reducing the infant’s susceptibility to both neonatal and age-related diseases.

Day 100 Peripheral Blood Absolute Lymphocyte/Monocyte Ratio and Survival in Classical Hodgkin's Lymphoma Postautologous Peripheral Blood Hematopoietic Stem Cell Transplantation

Directory of Open Access Journals (Sweden)

Luis F. Porrata

2013-01-01

Full Text Available Day 100 prognostic factors of postautologous peripheral blood hematopoietic stem cell transplantation (APBHSCT to predict clinical outcome in classical Hodgkin lymphoma (cHL patients have not been evaluated. Thus, we studied if the day 100 peripheral blood absolute lymphocyte/monocyte ratio (Day 100 ALC/AMC affects clinical outcomes by landmark analysis from day 100 post-APBHSCT. Only cHL patients achieving a complete remission at day 100 post-APBHSCT were studied. From 2000 to 2010, 131 cHL consecutive patients qualified for the study. The median followup from day 100 was 4.1 years (range: 0.2–12.3 years. Patients with a Day 100 ALC/AMC ≥ 1.3 experienced superior overall survival (OS and progression-free survival (PFS compared with Day 100 ALC/AMC < 1.3 (from day 100: OS, median not reached versus 2.8 years; 5 years OS rates of 93% (95% CI, 83%–97% versus 35% (95% CI, 19%–51%, resp., P<0.0001; from day 100: PFS, median not reached versus 1.2 years; 5 years PFS rates of 79% (95% CI, 69%–86% versus 27% (95% CI, 14%–45%, resp., P<0.0001. Day ALC/AMC ratio was an independent predictor for OS and PFS. Thus, Day 100 ALC/AMC ratio is a simple biomarker that can help to assess clinical outcomes from day 100 post-APBHSCT in cHL patients.

Therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells on the radiation-induced GI syndrome

Energy Technology Data Exchange (ETDEWEB)

Shim, Se Hwan; Jang, Won Suk; Lee, Sun Joo; Park, Eun Young; Kim, Youn Joo; Jin, Sung Ho; Park, Sun Hoo; Lee, Seung Sook [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2011-05-15

The gastrointestinal (GI) tract is one of the most radiosensitive organ systems in the body. Radiation-induced GI injury is described as destruction of crypt cell, decrease in villous height and number, ulceration, and necrosis of intestinal epithelium. Studies show that mesenchymal stem cells (MSCs) treatment may be useful in the repair or regeneration of damaged organs including bone, cartilage, or myocardium. MSCs from umbilical cord blood (UCB) have many advantages because of the immature nature of newborn cells compared to bone marrow derived MSCs. Moreover, UCB-MSCs provide no ethical barriers for basic studies and clinical applications. In this study, we explore the regeneration capability of human UCB-MSCs after radiation-induced GI injury