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Sample records for stem cell study congestive

  1. Stem Cell Therapy for Congestive Heart Failure

    Directory of Open Access Journals (Sweden)

    Gunduz E

    2011-01-01

    experience from this patient. ConclusionStudies in the era of cardiac stem cell therapy are heterogenous. It is not yet possible to comment on the most appropriate stem cell type and route of administration. When we assess the results from literature and the improvement in our own patient we think stem cell therapy can be an option for bridging to heart transplantation or an adjuvant therapy for CHF.References1.Ohnishi S, Ohgushi H, Kitamura S, Nagaya N. Mesenchymal stem cells for the treatment of heart failure. Int J Hematol 2007; 86: 17-21.2.Bukharovich IF, Kukin M. Optimal medical therapy for heart failure. Prog Cardiovasc Dis 2006; 48: 372-385.3.Tongers J, Losordo DW, Landmesser U. Stem and progenitor cell-based therapy in ischaemic heart disease: promise, uncertainties and challenges. Eur Heart J 2011. Epub ahead of print.4.Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R, Neutzel S, Sharkis SJ. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 2001; 105:369-377.5.Strauer BE, Yousef M, Schannwell CM. the acute and long term effects of intracoronary stem cell transplantation in 191 patients with chronic heart failure: the STAR-heart study. Eur J Heart Fail 2010; 12:721-729.6.Hamano K, Nishida M, Mirata K, Mikarno A, Li TS, Harada M, Miura T, Matsuzaki M, Esato K. Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ishemic heart disease: clinical trial and preliminary results Jpn Circ J. 2001; 65:845-847.7.Brehm M, Zeus T, Strauer BE. Stem cells-clinical application and perspectives. Herz 2002; 27:611-620.8.Ozbaran M, Omay SB, Nalbantgil S, Kultursay H, Kumanlioglu K, Nart D, Pektok E. Autologous peripheral stem cell transplantation in patients with congestive heart failure due to ischemic heart disease. Eur J Cardiothorac Surg. 2004; 25:342-350.9.Abdel-Latif A, Bolli R, Tleyjeh IM, Montori VM, Perin EC, Hornung CA, Zuba-Surma EK, Al-Mallah M, Dawn B. Adult bone marrow

  2. Effect of repeated intracoronary injection of bone marrow cells in patients with ischaemic heart failure the Danish stem cell study--congestive heart failure trial (DanCell-CHF)

    DEFF Research Database (Denmark)

    Diederichsen, Axel Cosmus Pyndt; Møller, Jacob E; Thayssen, Per

    2008-01-01

    BACKGROUND: It has been suggested that myocardial regeneration may be achieved by a single intracoronary bone marrow derived stem cell infusion in selected patients with ischaemic heart disease. The effect is uncertain in patients with chronic ischaemic heart failure and it is not known whether r...

  3. Stem Cells

    Science.gov (United States)

    Stem cells are cells with the potential to develop into many different types of cells in the body. ... the body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...

  4. Proteomics in studying cancer stem cell biology.

    Science.gov (United States)

    Kranenburg, Onno; Emmink, Benjamin L; Knol, Jaco; van Houdt, Winan J; Rinkes, Inne H M Borel; Jimenez, Connie R

    2012-06-01

    Normal multipotent tissue stem cells (SCs) are the driving force behind tissue turnover and repair. The cancer stem cell theory holds that tumors also contain stem-like cells that drive tumor growth and metastasis formation. However, very little is known about the regulation of SC maintenance pathways in cancer and how these are affected by cancer-specific genetic alterations and by treatment. Proteomics is emerging as a powerful tool to identify the signaling complexes and pathways that control multi- and pluri-potency and SC differentiation. Here, the authors review the novel insights that these studies have provided and present a comprehensive strategy for the use of proteomics in studying cancer SC biology.

  5. Study on veterinary stem cells advances and applications

    OpenAIRE

    Ribalaiga Pinyol, Núria

    2016-01-01

    Regenerative medicine refers to therapies that seek to restore the form and function of normal cells using the body's own biological machinery, as are stem cells. Since the first study succeeded in achieving pluripotent stem cells in 1981, the aim of the research has been changing diversely, from preclinical model in experimental studies for human diseases to clinical therapeutic applications in animals.

  6. Stem cells

    NARCIS (Netherlands)

    Jukes, Jojanneke; Both, Sanne; Post, Janine; van Blitterswijk, Clemens; Karperien, Marcel; de Boer, Jan; van Blitterswijk, Clemens A.

    2008-01-01

    This chapter defines stem cells and their properties. It identifies the major differences between embryonic and adult stem cells. Stem cells can be defined by two properties: the ability to make identical copies of themselves and the ability to form other cell types of the body. These properties are

  7. Types of Stem Cells

    Science.gov (United States)

    ... Stem Cell Glossary Search Toggle Nav Types of Stem Cells Stem cells are the foundation from which all ... Learn About Stem Cells > Types of Stem Cells Stem cells Stem cells are the foundation for every organ ...

  8. Stem cells in dentistry: A study regarding awareness of stem cells among dental professionals

    OpenAIRE

    Parita K Chitroda; Girish Katti; Nikhat M Attar; Syed Shahbaz; G Sreenivasarao; Ambika Patil

    2017-01-01

    Background: Dental stem cell, a type of adult stem cell, exhibits multipotent differentiation capacity and is drawing worldwide attention because of its numerous applications. The advances in applications of dental stem cells seem to be unsurpassed in the near future, for which specialized skills and knowledge in this arena are of prime significance. Hence, there is a need to acquire more knowledge about dental stem cells to obtain maximum benefits from it in the coming years. Dental stem cel...

  9. Learn About Stem Cells

    Science.gov (United States)

    ... Patient Handbook Stem Cell Glossary Search Toggle Nav Stem Cell Basics Stem cells are the foundation from which ... original cell’s DNA, cytoplasm and cell membrane. About stem cells Stem cells are the foundation of development in ...

  10. Chronic congestive heart failure is associated with a phenotypic shift of intramyocardial endothelial cells

    NARCIS (Netherlands)

    Marijianowski, M. M.; van Laar, M.; Bras, J.; Becker, A. E.

    1995-01-01

    There is evidence that patients with chronic congestive heart failure have endothelial cell-related abnormalities of the peripheral circulation and the coronary microvasculature. For that reason, we have studied the phenotypic expression of endothelial cells in hearts of patients with congestive

  11. Studies of hematopoietic stem cells spared by 5-fluorouracil

    International Nuclear Information System (INIS)

    Van Zant, G.

    1984-01-01

    Mouse marrow cells were exposed to 5-fluorouracil (FU) either in vivo or in vitro and the effects on the hematopoietic stem cell compartment were studied. The drug was highly toxic to bone marrow cells including the spleen colony-forming unit (CFU-S) population. The small population of stem cells surviving FU, however, caused a different pattern of spleen colony growth when injected into lethally irradiated mice. Whereas numbers of spleen colonies caused by normal marrow cells remained constant during an 8-14 d period after transplantation, spleen colonies derived from FU-treated marrow cells increased by as much as 100-fold during this time. This effect on stem cells was dose dependent both in vitro and in vivo. When FU was given in vivo, the day 14/day 8 ratio of colonies was greatest 1 d after injection and, over the next 7 d, returned to a near-normal value, that is, unity. A number of studies have shown that the stem cell compartment is heterogeneous with respect to self-replicative capacity and developmental potential. An age structure for the stem cell compartment has been proposed wherein cells with a short mitotic history are more likely to self-replicate than they are to differentiate; hence they are more primitive. I propose that the delayed spleen colony appearance in normal hosts is the result of developmental maturation of the primitive stem cell compartment that survives FU and is responsible for spleen colonies arising around day 14. This maturation, at least initially, occurs in the marrow and leads to the replenishment of the more differentiated CFU-S subsets ablated by FU, which are normally responsible for spleen colonies appearing earlier after transplantation

  12. Tumorigenicity studies for human pluripotent stem cell-derived products.

    Science.gov (United States)

    Kuroda, Takuya; Yasuda, Satoshi; Sato, Yoji

    2013-01-01

    Human pluripotent stem cells (hPSCs), i.e. human embryonic stem cells and human induced pluripotent stem cells, are able to self-renew and differentiate into multiple cell types. Because of these abilities, numerous attempts have been made to utilize hPSCs in regenerative medicine/cell therapy. hPSCs are, however, also tumorigenic, that is, they can give rise to the progressive growth of tumor nodules in immunologically unresponsive animals. Therefore, assessing and managing the tumorigenicity of all final products is essential in order to prevent ectopic tissue formation, tumor development, and/or malignant transformation elicited by residual pluripotent stem cells after implantation. No detailed guideline for the tumorigenicity testing of hPSC-derived products has yet been issued for regenerative medicine/cell therapy, despite the urgent necessity. Here, we describe the current situations and issues related to the tumorigenicity testing of hPSC-derived products and we review the advantages and disadvantages of several types of tumorigenicity-associated tests. We also refer to important considerations in the execution and design of specific studies to monitor the tumorigenicity of hPSC-derived products.

  13. Stem Cells

    DEFF Research Database (Denmark)

    Sommerlund, Julie

    2004-01-01

    In his influential essay on markets, An essay on framing and overflowing (1998), Michel Callon writes that `the growing complexity of industrialized societies [is] due in large part to the movements of the technosciences, which are causing connections and interdependencies to proliferate'. This p...... and tantalizing than stem cells, in research, in medicine, or as products.......'. This paper is about tech-noscience, and about the proliferation of connections and interdependencies created by it.More specifically, the paper is about stem cells. Biotechnology in general has the power to capture the imagination. Within the field of biotechnology nothing seems more provocative...

  14. Stem Cell Basics

    Science.gov (United States)

    ... Tips Info Center Research Topics Federal Policy Glossary Stem Cell Information General Information Clinical Trials Funding Information Current ... Basics » Stem Cell Basics I. Back to top Stem Cell Basics I. Introduction: What are stem cells, and ...

  15. Dental pulp stem cells

    DEFF Research Database (Denmark)

    Ashri, N. Y.; Ajlan, S. A.; Aldahmash, Abdullah M.

    2015-01-01

    scaffold, and guided through signaling molecules. Dental pulp stem cells have been used in an increasing number of studies in dental tissue engineering. Those cells show mesenchymal (stromal) stem cell-like properties including self-renewal and multilineage differentiation potentials, aside from...... an updated review on dental pulp stem cells and their applications in periodontal regeneration, in combination with different scaffolds and growth factors....

  16. Prospects in the Study of Stem-Cell Kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Till, J. E. [Department of Medical Biophysics, University of Toronto (Canada); Ontario Cancer Instute, Toronto, ON (Canada)

    1968-08-15

    The recent rapid progress in the field of stem-cell kinetics has been due in large part to the development of reliable in-vivo assays for the functions of haemopoietic stem cells. As a direct result of the availability of these assays, several novel and interesting phenomena have been described. What is now needed is not so much further search for new phenomena as an understanding of the phenomena that have already been uncovered. It is postulated that new approaches will be required for the analysis of these phenomena, and that future progress in the field will be strongly dependent on the development of methods suitable for the detailed study of the growth and differentiation of populations of haemopoietic cells in culture systems. (author)

  17. Aneuploidy in stem cells

    NARCIS (Netherlands)

    Garcia-Martinez, Jorge; Bakker, Bjorn; Schukken, Klaske M; Simon, Judith E; Foijer, Floris

    2016-01-01

    Stem cells hold enormous promise for regenerative medicine as well as for engineering of model systems to study diseases and develop new drugs. The discovery of protocols that allow for generating induced pluripotent stem cells (IPSCs) from somatic cells has brought this promise steps closer to

  18. Stem cell biobanks.

    Science.gov (United States)

    Bardelli, Silvana

    2010-04-01

    Stem cells contribute to innate healing and harbor a promising role for regenerative medicine. Stem cell banking through long-term storage of different stem cell platforms represents a fundamental source to preserve original features of stem cells for patient-specific clinical applications. Stem cell research and clinical translation constitute fundamental and indivisible modules catalyzed through biobanking activity, generating a return of investment.

  19. Stem cell plasticity.

    Science.gov (United States)

    Lakshmipathy, Uma; Verfaillie, Catherine

    2005-01-01

    The central dogma in stem cell biology has been that cells isolated from a particular tissue can renew and differentiate into lineages of the tissue it resides in. Several studies have challenged this idea by demonstrating that tissue specific cell have considerable plasticity and can cross-lineage restriction boundary and give rise to cell types of other lineages. However, the lack of a clear definition for plasticity has led to confusion with several reports failing to demonstrate that a single cell can indeed differentiate into multiple lineages at significant levels. Further, differences between results obtained in different labs has cast doubt on some results and several studies still await independent confirmation. In this review, we critically evaluate studies that report stem cell plasticity using three rigid criteria to define stem cell plasticity; differentiation of a single cell into multiple cell lineages, functionality of differentiated cells in vitro and in vivo, robust and persistent engraft of transplanted cells.

  20. Skeletal (stromal) stem cells

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Kermani, Abbas Jafari; Zaher, Walid

    2015-01-01

    Skeletal (marrow stromal) stem cells (BMSCs) are a group of multipotent cells that reside in the bone marrow stroma and can differentiate into osteoblasts, chondrocytes and adipocytes. Studying signaling pathways that regulate BMSC differentiation into osteoblastic cells is a strategy....../preadipocyte factor 1 (Dlk1/Pref-1), the Wnt co-receptor Lrp5 and intracellular kinases. This article is part of a Special Issue entitled: Stem Cells and Bone....

  1. 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.

  2. Potency of Stem Cells

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Potency of Stem Cells. Totipotent Stem Cells (Zygote + first 2 divisions). -Can form placenta, embryo, and any cell of the body. Pluripotent (Embryonic Stem Cells). -Can form any cell of the body but can not form placenta, hence no embryo. Multipotent (Adult stem cells).

  3. Comparative Study on New AQM Mechanisms for Congestion Control

    Directory of Open Access Journals (Sweden)

    Ramakrishna B B

    2013-09-01

    Full Text Available As usage of network goes increasing day by day, managing network traffic becomes a very difficult task. It is important to avoid high packet loss rates in the Internet. Congestion is the one of the major issue in the present networks. Congestion Control is one of the solutions adopted to solve the congestion issue and to control it. Numbers of queue management algorithms are proposed for congestion control and to reduce high packet loss rates. Active Queue Management (AQM is one such mechanism which provides better control over congestion. In this paper a study is made on recent load based AQM techniques that are proposed and its merits and shortfall is presented.

  4. Stem Cells in Burn Eschar

    NARCIS (Netherlands)

    van der Veen, V. C.; Vlig, M.; van Milligen-Kummer, F.J.; de Vries, S.I.; Middelkoop, E.; Ulrich, M.

    2012-01-01

    This study compares mesenchymal cells isolated from excised burn wound eschar with adipose-derived stem cells (ASCs) and dermal fibroblasts in their ability to conform to the requirements for multipotent mesenchymal stem cells (MSCs). A population of multipotent stem cells in burn eschar could be an

  5. Specialized mouse embryonic stem cells for studying vascular development.

    Science.gov (United States)

    Glaser, Drew E; Burns, Andrew B; Hatano, Rachel; Medrzycki, Magdalena; Fan, Yuhong; McCloskey, Kara E

    2014-01-01

    Vascular progenitor cells are desirable in a variety of therapeutic strategies; however, the lineage commitment of endothelial and smooth muscle cell from a common progenitor is not well-understood. Here, we report the generation of the first dual reporter mouse embryonic stem cell (mESC) lines designed to facilitate the study of vascular endothelial and smooth muscle development in vitro. These mESC lines express green fluorescent protein (GFP) under the endothelial promoter, Tie-2, and Discomsoma sp. red fluorescent protein (RFP) under the promoter for alpha-smooth muscle actin (α-SMA). The lines were then characterized for morphology, marker expression, and pluripotency. The mESC colonies were found to exhibit dome-shaped morphology, alkaline phosphotase activity, as well as expression of Oct 3/4 and stage-specific embryonic antigen-1. The mESC colonies were also found to display normal karyotypes and are able to generate cells from all three germ layers, verifying pluripotency. Tissue staining confirmed the coexpression of VE (vascular endothelial)-cadherin with the Tie-2 GFP+ expression on endothelial structures and smooth muscle myosin heavy chain with the α-SMA RFP+ smooth muscle cells. Lastly, it was verified that the developing mESC do express Tie-2 GFP+ and α-SMA RFP+ cells during differentiation and that the GFP+ cells colocalize with the vascular-like structures surrounded by α-SMA-RFP cells. These dual reporter vascular-specific mESC permit visualization and cell tracking of individual endothelial and smooth muscle cells over time and in multiple dimensions, a powerful new tool for studying vascular development in real time.

  6. Stem cell therapy for diabetes

    Directory of Open Access Journals (Sweden)

    K O Lee

    2012-01-01

    Full Text Available Stem cell therapy holds immense promise for the treatment of patients with diabetes mellitus. Research on the ability of human embryonic stem cells to differentiate into islet cells has defined the developmental stages and transcription factors involved in this process. However, the clinical applications of human embryonic stem cells are limited by ethical concerns, as well as the potential for teratoma formation. As a consequence, alternative forms of stem cell therapies, such as induced pluripotent stem cells, umbilical cord stem cells and bone marrow-derived mesenchymal stem cells, have become an area of intense study. Recent advances in stem cell therapy may turn this into a realistic treatment for diabetes in the near future.

  7. Comparative study of adipose-derived stem cells and bone marrow-derived stem cells in similar microenvironmental conditions

    Energy Technology Data Exchange (ETDEWEB)

    Guneta, Vipra [Division of Materials Technology, School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798 (Singapore); Tan, Nguan Soon [School of Biological Science, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); KK Research Centre, KK Women' s and Children Hospital, 100 Bukit Timah Road, Singapore 229899 (Singapore); Institute of Molecular and Cell Biology, Agency for Science Technology & Research - A*STAR, 61 Biopolis Drive, Proteos, Singapore 138673 (Singapore); Chan, Soon Kiat Jeremy [School of Biological Science, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Tanavde, Vivek [Bioinformatics Institute, Agency for Science Technology & Research - A*STAR, 30 Biopolis Street, Matrix, Singapore 138671 (Singapore); Lim, Thiam Chye [Division of Plastic, Reconstructive and Aesthetic Surgery, Department of Surgery, National University Hospital (NUH) and National University of Singapore (NUS), Kent Ridge Wing, Singapore 119074 (Singapore); Wong, Thien Chong Marcus [Plastic, Reconstructive and Aesthetic Surgery Section, Tan Tock Seng Hospital (TTSH), 11, Jalan Tan Tock Seng, Singapore 308433 (Singapore); Choong, Cleo, E-mail: cleochoong@ntu.edu.sg [Division of Materials Technology, School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798 (Singapore); KK Research Centre, KK Women' s and Children Hospital, 100 Bukit Timah Road, Singapore 229899 (Singapore)

    2016-11-01

    Mesenchymal stem cells (MSCs), which were first isolated from the bone marrow, are now being extracted from various other tissues in the body, including the adipose tissue. The current study presents systematic evidence of how the adipose tissue-derived stem cells (ASCs) and bone marrow-derived mesenchymal stem cells (Bm-MSCs) behave when cultured in specific pro-adipogenic microenvironments. The cells were first characterized and identified as MSCs in terms of their morphology, phenotypic expression, self-renewal capabilities and multi-lineage potential. Subsequently, the proliferation and gene expression profiles of the cell populations cultured on two-dimensional (2D) adipose tissue extracellular matrix (ECM)-coated tissue culture plastic (TCP) and in three-dimensional (3D) AlgiMatrix® microenvironments were analyzed. Overall, it was found that adipogenesis was triggered in both cell populations due to the presence of adipose tissue ECM. However, in 3D microenvironments, ASCs and Bm-MSCs were predisposed to the adipogenic and osteogenic lineages respectively. Overall, findings from this study will contribute to ongoing efforts in adipose tissue engineering as well as provide new insights into the role of the ECM and cues provided by the immediate microenvironment for stem cell differentiation. - Highlights: • Native adipose tissue ECM coated on 2D TCP triggers adipogenesis in both ASCs and Bm-MSCs. • A 3D microenvironment with similar stiffness to adipose tissue induces adipogenic differentiation of ASCs. • ASCs cultured in 3D alginate scaffolds exhibit predisposition to adipogenesis. • Bm-MSCs cultured in 3D alginate scaffolds exhibit predisposition to osteogenesis. • The native microenvironment of the cells affects their differentiation behaviour in vitro.

  8. Comparative study of adipose-derived stem cells and bone marrow-derived stem cells in similar microenvironmental conditions

    International Nuclear Information System (INIS)

    Guneta, Vipra; Tan, Nguan Soon; Chan, Soon Kiat Jeremy; Tanavde, Vivek; Lim, Thiam Chye; Wong, Thien Chong Marcus; Choong, Cleo

    2016-01-01

    Mesenchymal stem cells (MSCs), which were first isolated from the bone marrow, are now being extracted from various other tissues in the body, including the adipose tissue. The current study presents systematic evidence of how the adipose tissue-derived stem cells (ASCs) and bone marrow-derived mesenchymal stem cells (Bm-MSCs) behave when cultured in specific pro-adipogenic microenvironments. The cells were first characterized and identified as MSCs in terms of their morphology, phenotypic expression, self-renewal capabilities and multi-lineage potential. Subsequently, the proliferation and gene expression profiles of the cell populations cultured on two-dimensional (2D) adipose tissue extracellular matrix (ECM)-coated tissue culture plastic (TCP) and in three-dimensional (3D) AlgiMatrix® microenvironments were analyzed. Overall, it was found that adipogenesis was triggered in both cell populations due to the presence of adipose tissue ECM. However, in 3D microenvironments, ASCs and Bm-MSCs were predisposed to the adipogenic and osteogenic lineages respectively. Overall, findings from this study will contribute to ongoing efforts in adipose tissue engineering as well as provide new insights into the role of the ECM and cues provided by the immediate microenvironment for stem cell differentiation. - Highlights: • Native adipose tissue ECM coated on 2D TCP triggers adipogenesis in both ASCs and Bm-MSCs. • A 3D microenvironment with similar stiffness to adipose tissue induces adipogenic differentiation of ASCs. • ASCs cultured in 3D alginate scaffolds exhibit predisposition to adipogenesis. • Bm-MSCs cultured in 3D alginate scaffolds exhibit predisposition to osteogenesis. • The native microenvironment of the cells affects their differentiation behaviour in vitro.

  9. Fake news portrayals of stem cells and stem cell research.

    Science.gov (United States)

    Marcon, Alessandro R; Murdoch, Blake; Caulfield, Timothy

    2017-10-01

    This study examines how stem cells and stem cell research are portrayed on websites deemed to be purveyors of distorted and dubious information. Content analysis was conducted on 224 articles from 2015 to 2016, compiled by searching with the keywords 'stem cell(s)' on a list of websites flagged for containing either 'fake' or 'junk science' news. Articles contained various exaggerated positive and negative claims about stem cells and stem cell science, health and science related conspiracy theories, and statements promoting fear and mistrust of conventional medicine. Findings demonstrate the existence of organized misinformation networks, which may lead the public away from accurate information and facilitate a polarization of public discourse.

  10. "NeuroStem Chip": a novel highly specialized tool to study neural differentiation pathways in human stem cells

    Directory of Open Access Journals (Sweden)

    Li Jia-Yi

    2007-02-01

    Full Text Available Abstract Background Human stem cells are viewed as a possible source of neurons for a cell-based therapy of neurodegenerative disorders, such as Parkinson's disease. Several protocols that generate different types of neurons from human stem cells (hSCs have been developed. Nevertheless, the cellular mechanisms that underlie the development of neurons in vitro as they are subjected to the specific differentiation protocols are often poorly understood. Results We have designed a focused DNA (oligonucleotide-based large-scale microarray platform (named "NeuroStem Chip" and used it to study gene expression patterns in hSCs as they differentiate into neurons. We have selected genes that are relevant to cells (i being stem cells, (ii becoming neurons, and (iii being neurons. The NeuroStem Chip has over 1,300 pre-selected gene targets and multiple controls spotted in quadruplicates (~46,000 spots total. In this study, we present the NeuroStem Chip in detail and describe the special advantages it offers to the fields of experimental neurology and stem cell biology. To illustrate the utility of NeuroStem Chip platform, we have characterized an undifferentiated population of pluripotent human embryonic stem cells (hESCs, cell line SA02. In addition, we have performed a comparative gene expression analysis of those cells versus a heterogeneous population of hESC-derived cells committed towards neuronal/dopaminergic differentiation pathway by co-culturing with PA6 stromal cells for 16 days and containing a few tyrosine hydroxylase-positive dopaminergic neurons. Conclusion We characterized the gene expression profiles of undifferentiated and dopaminergic lineage-committed hESC-derived cells using a highly focused custom microarray platform (NeuroStem Chip that can become an important research tool in human stem cell biology. We propose that the areas of application for NeuroStem microarray platform could be the following: (i characterization of the

  11. Mendenhall Glacier Visitor Center vehicular and pedestrian traffic congestion study

    Science.gov (United States)

    2007-05-01

    The Mendenhall Glacier Visitor Center of Tongass National Forest in Juneau, Alaska is experiencing vehicular and pedestrian congestion. This study was initiated by the United States Forest Service, Alaska Region, in cooperation with Western Federal L...

  12. Big Animal Cloning Using Transgenic Induced Pluripotent Stem Cells: A Case Study of Goat Transgenic Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Song, Hui; Li, Hui; Huang, Mingrui; Xu, Dan; Wang, Ziyu; Wang, Feng

    2016-02-01

    Using of embryonic stem cells (ESCs) could improve production traits and disease resistance by improving the efficiency of somatic cell nuclear transfer (SCNT) technology. However, robust ESCs have not been established from domestic ungulates. In the present study, we generated goat induced pluripotent stem cells (giPSCs) and transgenic cloned dairy goat induced pluripotent stem cells (tgiPSCs) from dairy goat fibroblasts (gFs) and transgenic cloned dairy goat fibroblasts (tgFs), respectively, using lentiviruses that contained hOCT4, hSOX2, hMYC, and hKLF4 without chemical compounds. The giPSCs and tgiPSCs expressed endogenous pluripotent markers, including OCT4, SOX2, MYC, KLF4, and NANOG. Moreover, they were able to maintain a normal karyotype and differentiate into derivatives from all three germ layers in vitro and in vivo. Using SCNT, tgFs and tgiPSCs were used as donor cells to produce embryos, which were named tgF-Embryos and tgiPSC-Embryos. The fusion rates and cleavage rates had no significant differences between tgF-Embryos and tgiPSC-Embryos. However, the expression of IGF-2, which is an important gene associated with embryonic development, was significantly lower in tgiPSC-Embryos than in tgF-Embryos and was not significantly different from vivo-Embryos.

  13. The Need to Study, Mimic, and Target Stem Cell Niches

    NARCIS (Netherlands)

    Vishwakarma, Ajaykumar; Rouwkema, Jeroen; Jones, Peter Anthony; Karp, Jeffrey M.; Vishwakarma, Ajaykumar; Karp, Jeffrey M.

    2017-01-01

    Despite important advances in tissue repair and regeneration over the past few decades, complete functional repair of damaged or diseased human tissues has remained elusive. Recent discoveries in stem cell niche molecular biology and biomaterials engineering may hold the key to true regeneration.

  14. Biochemistry of epidermal stem cells.

    Science.gov (United States)

    Eckert, Richard L; Adhikary, Gautam; Balasubramanian, Sivaprakasam; Rorke, Ellen A; Vemuri, Mohan C; Boucher, Shayne E; Bickenbach, Jackie R; Kerr, Candace

    2013-02-01

    The epidermis is an important protective barrier that is essential for maintenance of life. Maintaining this barrier requires continuous cell proliferation and differentiation. Moreover, these processes must be balanced to produce a normal epidermis. The stem cells of the epidermis reside in specific locations in the basal epidermis, hair follicle and sebaceous glands and these cells are responsible for replenishment of this tissue. A great deal of effort has gone into identifying protein epitopes that mark stem cells, in identifying stem cell niche locations, and in understanding how stem cell populations are related. We discuss these studies as they apply to understanding normal epidermal homeostasis and skin cancer. An assortment of stem cell markers have been identified that permit assignment of stem cells to specific regions of the epidermis, and progress has been made in understanding the role of these cells in normal epidermal homeostasis and in conditions of tissue stress. A key finding is the multiple stem cell populations exist in epidermis that give rise to different structures, and that multiple stem cell types may contribute to repair in damaged epidermis. Understanding epidermal stem cell biology is likely to lead to important therapies for treating skin diseases and cancer, and will also contribute to our understanding of stem cells in other systems. This article is part of a Special Issue entitled Biochemistry of Stem Cells. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Stem Cell Ophthalmology Treatment Study (SCOTS): bone marrow-derived stem cells in the treatment of Leber's hereditary optic neuropathy

    Science.gov (United States)

    Weiss, Jeffrey N.; Levy, Steven; Benes, Susan C.

    2016-01-01

    The Stem Cell Ophthalmology Treatment Study (SCOTS) is currently the largest-scale stem cell ophthalmology trial registered at ClinicalTrials.gov (identifier: NCT01920867). SCOTS utilizes autologous bone marrow-derived stem cells (BMSCs) to treat optic nerve and retinal diseases. Treatment approaches include a combination of retrobulbar, subtenon, intravitreal, intra-optic nerve, subretinal, and intravenous injection of autologous BMSCs according to the nature of the disease, the degree of visual loss, and any risk factors related to the treatments. Patients with Leber's hereditary optic neuropathy had visual acuity gains on the Early Treatment Diabetic Retinopathy Study (ETDRS) of up to 35 letters and Snellen acuity improvements from hand motion to 20/200 and from counting fingers to 20/100. Visual field improvements were noted. Macular and optic nerve head nerve fiber layer typically thickened. No serious complications were seen. The increases in visual acuity obtained in our study were encouraging and suggest that the use of autologous BMSCs as provided in SCOTS for ophthalmologic mitochondrial diseases including Leber's hereditary optic neuropathy may be a viable treatment option. PMID:27904503

  16. Stem Cell Information: Glossary

    Science.gov (United States)

    ... Tips Info Center Research Topics Federal Policy Glossary Stem Cell Information General Information Clinical Trials Funding Information Current ... here Home » Glossary Back to top Glossary Adult stem cell Astrocyte Blastocoel Blastocyst Bone marrow stromal cells Bone ...

  17. Progress of PET imaging in the study of neural stem cell transplantation treating Parkinson's disease

    International Nuclear Information System (INIS)

    Tan Haibo; Liu Xingdang

    2004-01-01

    PET imaging has important value in the study of neural stem cell transplantation treating Parkinson's disease, especial in the evaluation of the effect, the study of treating mechanisms and the comparation of effect in different transplantation places. PET imaging as a non-invasive method plays a more and more important role in the study of neural stem cell transplantation treating Parkinson's disease. (authors)

  18. Induced Pluripotent Stem Cells: A novel frontier in the study of human primary immunodeficiencies

    Science.gov (United States)

    Pessach, Itai M.; Ordovas-Montanes, Jose; Zhang, Shen-Ying; Casanova, Jean-Laurent; Giliani, Silvia; Gennery, Andrew R.; Al-Herz, Waleed; Manos, Philip D.; Schlaeger, Thorsten M.; Park, In-Hyun; Rucci, Francesca; Agarwal, Suneet; Mostoslavsky, Gustavo; Daley, George Q.; Notarangelo, Luigi D.

    2010-01-01

    Background The novel ability to epigenetically reprogram somatic cells into induced pluripotent stem cells through the exogenous expression of transcription promises to revolutionize the study of human diseases. Objective Here we report on the generation of 25 induced pluripotent stem cell lines from 6 patients with various forms of Primary Immunodeficiencies, affecting adaptive and/or innate immunity. Methods Patients’ dermal fibroblasts were reprogrammed by expression of four transcription factors, OCT4, SOX2, KLF4, and c-MYC using a single excisable polycistronic lentiviral vector. Results Induced pluripotent stem cells derived from patients with primary immunodeficiencies show a stemness profile that is comparable to that observed in human embryonic stem cells. Following in vitro differentiation into embryoid bodies, pluripotency of the patient-derived indiced pluripotent stem cells lines was demonstrated by expression of genes characteristic of each of the three embryonic layers. We have confirmed the patient-specific origin of the induced pluripotent stem cell lines, and ascertained maintenance of karyotypic integrity. Conclusion By providing a limitless source of diseased stem cells that can be differentiated into various cell types in vitro, the repository of induced pluripotent stem cell lines from patients with primary immunodeficiencies represents a unique resource to investigate the pathophysiology of hematopoietic and extra-hematopoietic manifestations of these diseases, and may assist in the development of novel therapeutic approaches based on gene correction. PMID:21185069

  19. Plant stem cell niches.

    Science.gov (United States)

    Stahl, Yvonne; Simon, Rüdiger

    2005-01-01

    Stem cells are required to support the indeterminate growth style of plants. Meristems are a plants stem cell niches that foster stem cell survival and the production of descendants destined for differentiation. In shoot meristems, stem cell fate is decided at the populational level. The size of the stem cell domain at the meristem tip depends on signals that are exchanged with cells of the organizing centre underneath. In root meristems, individual stem cells are controlled by direct interaction with cells of the quiescent centre that lie in the immediate neighbourhood. Analysis of the interactions and signaling processes in the stem cell niches has delivered some insights into the molecules that are involved and revealed that the two major niches for plant stem cells are more similar than anticipated.

  20. Biomechanics of stem cells

    Science.gov (United States)

    Spector, A. A.; Yuan, D.; Somers, S.; Grayson, W. L.

    2018-04-01

    Stem cells play a key role in the healthy development and maintenance of organisms. They are also critically important in medical treatments of various diseases. It has been recently demonstrated that the mechanical factors such as forces, adhesion, stiffness, relaxation, etc. have significant effects on stem cell functions. Under physiological conditions, cells (stem cells) in muscles, heart, and blood vessels are under the action of externally applied strains. We consider the stem cell microenvironment and performance associated with their conversion (differentiation) into skeletal muscle cells. Two problems are studied by using mathematical models whose parameters are then optimized by fitting experiments. First, we present our analysis of the process of stem cell differentiation under the application of cyclic unidirectional strain. This process is interpreted as a transition through several (six) stages where each of them is defined in terms of expression of a set of factors typical to skeletal muscle cells. The stem cell evolution toward muscle cells is described by a system of nonlinear ODEs. The parameters of the model are determined by fitting the experimental data on the time course of expression of the factors under consideration. Second, we analyse the mechanical (relaxation) properties of a scaffold that serves as the microenvironment for stem cells differentiation into skeletal muscle cells. This scaffold (surrounded by a liquid solution) is composed of unidirectional fibers with pores between them. The relaxation properties of the scaffold are studied in an experiment where a long cylindrical specimen is loaded by the application of ramp displacement until the strain reaches a prescribed value. The magnitude of the corresponding load is recorded. The specimen is considered as transversely isotropic poroelastic cylinder whose force relaxation is associated with liquid diffusion through the pores. An analytical solution for the total force applied to

  1. 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 ...

  2. A Comparative Study of the Therapeutic Potential of Mesenchymal Stem Cells and Limbal Epithelial Stem Cells for Ocular Surface Reconstruction

    Czech Academy of Sciences Publication Activity Database

    Holáň, Vladimír; Trošan, Peter; Čejka, Čestmír; Javorková, Eliška; Zajícová, Alena; Heřmánková, Barbora; Chudíčková, Milada; Čejková, Jitka

    2015-01-01

    Roč. 4, č. 9 (2015), s. 1052-1063 ISSN 2157-6564 R&D Projects: GA ČR(CZ) GA14-12580S; GA MZd NT14102; GA MŠk(CZ) LO1309; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378041 Keywords : limbal stem cells * mesenchymal stem cells * alkali-injured ocular surface * corneal regeneration * stem cell-based therapy Subject RIV: FF - HEENT, Dentistry Impact factor: 4.247, year: 2015

  3. Plant stem cell niches.

    Science.gov (United States)

    Aichinger, Ernst; Kornet, Noortje; Friedrich, Thomas; Laux, Thomas

    2012-01-01

    Multicellular organisms possess pluripotent stem cells to form new organs, replenish the daily loss of cells, or regenerate organs after injury. Stem cells are maintained in specific environments, the stem cell niches, that provide signals to block differentiation. In plants, stem cell niches are situated in the shoot, root, and vascular meristems-self-perpetuating units of organ formation. Plants' lifelong activity-which, as in the case of trees, can extend over more than a thousand years-requires that a robust regulatory network keep the balance between pluripotent stem cells and differentiating descendants. In this review, we focus on current models in plant stem cell research elaborated during the past two decades, mainly in the model plant Arabidopsis thaliana. We address the roles of mobile signals on transcriptional modules involved in balancing cell fates. In addition, we discuss shared features of and differences between the distinct stem cell niches of Arabidopsis.

  4. [A comparative study on inducing non-homologous mesenchymal stem cells to differentiate into neural stem cells using non-homologous cerebrospinal fluid].

    Science.gov (United States)

    Ren, Chao; Liu, Xiaoyun; Wan, Meirong; Geng, Deqin; Ge, Wei; Li, Jinmei; Zhang, Weiwei

    2013-12-01

    In order to set up a base for stem cells to be widely used in clinical medicine, we tried to optimize, in this study, the technique that induces human mesenchymal stem cells (hMSCs) to differentiate into neural stem cells by using cerebrospinal fluid (CSF) from the different groups. After the induction, presence of neural stem cells was confirmed with microscope observation, flow cytometry analysis, immunohistochemistry and fluorescent immunohistochemistry. At the same time, we also compared and analysed the data of the number of stem cells when it totally met the requirements for clinical treatment and the days required. At last, we confirmed that hMSCs could be induced to differentiate into neural stem cells, and that the number of cells totally met the requirements for clinical treatment. But there were some differences both in the number of cells and the days required. Among the groups, the group that marrow mesenchymal stem cells from patients own induced by CSF from healthy volunteers used the shortest time and the quantity of the cells was significantly higher than those of the others.

  5. Research on Analysis Method of Traffic Congestion Mechanism Based on Improved Cell Transmission Model

    Directory of Open Access Journals (Sweden)

    Hongzhao Dong

    2012-01-01

    Full Text Available To analyze the spreading regularity of the initial traffic congestion, the improved cell transmission model (CTM is proposed to describe the evolution mechanism of traffic congestion in regional road grid. Ordinary cells and oriented cells are applied to render the crowd roads and their adjacent roads. Therefore the traffic flow could be simulated by these cells. Resorting to the proposed model, the duration of the initial traffic congestion could be predicted and the subsequent secondary congestion could be located. Accordingly, the spatial diffusion of traffic congestion could be estimated. At last, taking a road network region of Hangzhou city as an example, the simulation experiment is implemented to verify the proposed method by PARAMICS software. The result shows that the method could predict the duration of the initial congestion and estimate its spatial diffusion accurately.

  6. Stem Cell Pathology.

    Science.gov (United States)

    Fu, Dah-Jiun; Miller, Andrew D; Southard, Teresa L; Flesken-Nikitin, Andrea; Ellenson, Lora H; Nikitin, Alexander Yu

    2018-01-24

    Rapid advances in stem cell biology and regenerative medicine have opened new opportunities for better understanding disease pathogenesis and the development of new diagnostic, prognostic, and treatment approaches. Many stem cell niches are well defined anatomically, thereby allowing their routine pathological evaluation during disease initiation and progression. Evaluation of the consequences of genetic manipulations in stem cells and investigation of the roles of stem cells in regenerative medicine and pathogenesis of various diseases such as cancer require significant expertise in pathology for accurate interpretation of novel findings. Therefore, there is an urgent need for developing stem cell pathology as a discipline to facilitate stem cell research and regenerative medicine. This review provides examples of anatomically defined niches suitable for evaluation by diagnostic pathologists, describes neoplastic lesions associated with them, and discusses further directions of stem cell pathology.

  7. Assessment of Surface Markers Derived from Human Periodontal Ligament Stem Cells: An In Vitro Study

    Directory of Open Access Journals (Sweden)

    Zainab Kadkhoda

    2016-12-01

    Full Text Available Objectives: Periodontal tissue regeneration for treatment of periodontal disease has not yet been mastered in tissue engineering. Stem cells, scaffold, and growth factors are the three main basic components of tissue engineering. Periodontal ligament (PDL contains stem cells; however, the number, potency and features of these cells have not yet been understood. This study aimed to isolate and characterize the properties of PDL stem cells. Materials and Methods: In this experimental study, samples were isolated from the PDL of extracted teeth of five patients and then stained immunohistochemically for detection of cell surface markers. Cells were then examined by immuno-flow cytometry for mesenchymal markers as well as for osteogenic and adipogenic differentiation.Results: The isolated cell population had fibroblast-like morphology and flow cytometry revealed that the mesenchymal surface markers were (means: CD90 (84.55, CD31 (39.97, CD166 (33.77, CD105 (31.19, CD45 (32/44, CD44 (462.11, CD34 (227.33, CD38 (86.94, CD13 (34.52 and CD73 (50.39. The PDL stem cells also differentiated into osteoblasts and adipocytes in osteogenic and adipogenic media, respectively.Conclusions: PDL stem cells expressed mesenchymal stem cell (MSC markers and differentiated into osteoblasts and adipocytes in osteogenic and adipogenic media, respectively.Keywords: Adipocytes; Antigens; Mesenchymal Stromal Cells; Osteoblasts; Periodontal Ligament

  8. Alginate hydrogel as a promising scaffold for dental-derived stem cells: an in vitro study.

    Science.gov (United States)

    Moshaverinia, Alireza; Chen, Chider; Akiyama, Kentaro; Ansari, Sahar; Xu, Xingtian; Chee, Winston W; Schricker, Scott R; Shi, Songtao

    2012-12-01

    The objectives of this study were to: (1) develop an injectable and biodegradable scaffold based on oxidized alginate microbeads encapsulating periodontal ligament (PDLSCs) and gingival mesenchymal stem cells (GMSCs); and (2) investigate the stem cell viability, and osteogenic differentiation of the stem cells in vitro. Stem cells were encapsulated using alginate hydrogel. The stem cell viability, proliferation and differentiation to adipogenic and osteogenic tissues were studied. To investigate the expression of both adipogenesis and ontogenesis related genes, the RNA was extracted and RT-PCR was performed. The degradation behavior of hydrogel based on oxidized sodium alginate with different degrees of oxidation was studied in PBS at 37 °C as a function of time by monitoring the changes in weight loss. The swelling kinetics of alginate hydrogel was also investigated. The results showed that alginate is a promising candidate as a non-toxic scaffold for PDLSCs and GMSCs. It also has the ability to direct the differentiation of these stem cells to osteogenic and adipogenic tissues as compared to the control group in vitro. The encapsulated stem cells remained viable in vitro and both osteo-differentiated and adipo-differentiated after 4 weeks of culturing in the induction media. It was found that the degradation profile and swelling kinetics of alginate hydrogel strongly depends on the degree of oxidation showing its tunable chemistry and degradation rate. These findings demonstrate for the first time that immobilization of PDLSCs and GMSCs in the alginate microspheres provides a promising strategy for bone tissue engineering.

  9. Putative Stem Cells in Human Dental Pulp with Irreversible Pulpitis-An Exploratory Study

    Science.gov (United States)

    Wang, Z.; Pan, J.; Wright, JT; Bencharit, S.; Zhang, S.; Everett, ET; Teixeira, FB; Preisser, JS

    2010-01-01

    Introduction Although human dental pulp stem cells isolated from healthy teeth have been extensively characterized, it is unknown whether stem cells also exist in clinically compromised teeth with irreversible pulpitis. Here we explored whether cells retrieved from clinically compromised dental pulp have stem cell-like properties. Methods Pulp cells were isolated from healthy teeth (control group) and from teeth with clinically diagnosed irreversible pulpitis (diseased group). Cell proliferation, stem cell marker STRO-1 expression and cell odonto-osteo-genic differentiation competence were compared. Results Cells from the diseased group demonstrated decreased colony formation capacity and a slightly decreased cell proliferation rate but had similar STRO-1 expression, and exhibited a similar percentage of positive ex vivo osteogenic induction and dentin sialophosphoprotein expression from STRO-1-enriched pulp cells. Conclusion Our study provides preliminary evidence that clinically compromised dental pulp may contain putative cells with certain stem cell properties. Further characterization of these cells will provide insight regarding whether they could serve as a source of endogenous multipotent cells in tissue regeneration based dental pulp therapy. PMID:20416426

  10. Counting stem cells : methodological constraints

    NARCIS (Netherlands)

    Bystrykh, Leonid V.; Verovskaya, Evgenia; Zwart, Erik; Broekhuis, Mathilde; de Haan, Gerald

    The number of stem cells contributing to hematopoiesis has been a matter of debate. Many studies use retroviral tagging of stem cells to measure clonal contribution. Here we argue that methodological factors can impact such clonal analyses. Whereas early studies had low resolution, leading to

  11. Stem Cells and Aging.

    Science.gov (United States)

    Koliakos, George

    2017-02-01

    The article is a presentation at the 4th Conference of ESAAM, which took place on October 30-31, 2015, in Athens, Greece. Its purpose was not to cover all aspects of cellular aging but to share with the audience of the Conference, in a 15-minute presentation, current knowledge about the rejuvenating and repairing somatic stem cells that are distinct from other stem cell types (such as embryonic or induced pluripotent stem cells), emphasize that our body in old age cannot take advantage of these rejuvenating cells, and provide some examples of novel experimental stem cell applications in the field of rejuvenation and antiaging biomedical research.

  12. Colorectal cancer stem cells.

    Science.gov (United States)

    Salama, Paul; Platell, Cameron

    2009-10-01

    Somatic stem cells reside at the base of the crypts throughout the colonic mucosa. These cells are essential for the normal regeneration of the colonic epithelium. The stem cells reside within a special 'niche' comprised of intestinal sub-epithelial myofibroblasts that tightly control their function. It has been postulated that mutations within these adult colonic stem cells may induce neoplastic changes. Such cells can then dissociate from the epithelium and travel into the mesenchyme and thus form invasive cancers. This theory is based on the observation that within a colon cancer, less than 1% of the neoplastic cells have the ability to regenerate the tumour. It is this group of cells that exhibits characteristics of colonic stem cells. Although anti-neoplastic agents can induce remissions by inhibiting cell division, the stem cells appear to be remarkably resistant to both standard chemotherapy and radiotherapy. These stem cells may therefore persist after treatment and form the nucleus for cancer recurrence. Hence, future treatment modalities should focus specifically on controlling the cancer stem cells. In this review, we discuss the biology of normal and malignant colonic stem cells.

  13. Aging, metabolism and stem cells: Spotlight on muscle stem cells.

    Science.gov (United States)

    García-Prat, Laura; Muñoz-Cánoves, Pura

    2017-04-15

    All tissues and organs undergo a progressive regenerative decline as they age. This decline has been mainly attributed to loss of stem cell number and/or function, and both stem cell-intrinsic changes and alterations in local niches and/or systemic environment over time are known to contribute to the stem cell aging phenotype. Advancing in the molecular understanding of the deterioration of stem cell cells with aging is key for targeting the specific causes of tissue regenerative dysfunction at advanced stages of life. Here, we revise exciting recent findings on why stem cells age and the consequences on tissue regeneration, with a special focus on regeneration of skeletal muscle. We also highlight newly identified common molecular pathways affecting diverse types of aging stem cells, such as altered proteostasis, metabolism, or senescence entry, and discuss the questions raised by these findings. Finally, we comment on emerging stem cell rejuvenation strategies, principally emanating from studies on muscle stem cells, which will surely burst tissue regeneration research for future benefit of the increasing human aging population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Dazlin' pluripotent stem cells

    NARCIS (Netherlands)

    Welling, M.A.

    2014-01-01

    Pluripotent embryonic stem cells (ESCs) can be isolated from the inner cell mass (ICM) of blastocyst embryos and differentiate into all three germ layers in vitro. However, despite their similar origin, mouse embryonic stem cells represent a more naïve ICM-like pluripotent state whereas human

  15. Stem cells and respiratory diseases

    Energy Technology Data Exchange (ETDEWEB)

    Abreu, Soraia Carvalho; Maron-Gutierrez, Tatiana; Garcia, Cristiane Sousa Nascimento Baez; Morales, Marcelo Marcos; Rocco, Patricia Rieken Macedo [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. de Biofisica Carlos Chagas Filho. Lab. de Investigacao]. E-mail: prmrocco@biof.ufrj.br

    2008-12-15

    Stem cells have a multitude of clinical implications in the lung. This article is a critical review that includes clinical and experimental studies of MedLine and SciElo database in the last 10 years, where we highlight the effects of stem cell therapy in acute respiratory distress syndrome or more chronic disorders such as lung fibrosis and emphysema. Although, many studies have shown the beneficial effects of stem cells in lung development, repair and remodeling; some important questions need to be answered to better understand the mechanisms that control cell division and differentiation, therefore enabling the use of cell therapy in human respiratory diseases. (author)

  16. Stem cells and respiratory diseases

    International Nuclear Information System (INIS)

    Abreu, Soraia Carvalho; Maron-Gutierrez, Tatiana; Garcia, Cristiane Sousa Nascimento Baez; Morales, Marcelo Marcos; Rocco, Patricia Rieken Macedo

    2008-01-01

    Stem cells have a multitude of clinical implications in the lung. This article is a critical review that includes clinical and experimental studies of MedLine and SciElo database in the last 10 years, where we highlight the effects of stem cell therapy in acute respiratory distress syndrome or more chronic disorders such as lung fibrosis and emphysema. Although, many studies have shown the beneficial effects of stem cells in lung development, repair and remodeling; some important questions need to be answered to better understand the mechanisms that control cell division and differentiation, therefore enabling the use of cell therapy in human respiratory diseases. (author)

  17. Stem cell function and maintenance

    Indian Academy of Sciences (India)

    Stem cell research holds a promise to treat and prevent age-related degenerative changes in humans. Literature is replete with studies showing that stem cell function declines with aging, especially in highly proliferative tissues/organs. Among others, telomerase and telomere damage is one of the intrinsic physical ...

  18. Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures

    Directory of Open Access Journals (Sweden)

    Melissa Lo Monaco

    2018-01-01

    Full Text Available Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs or induced pluripotent stem cells (iPSCs have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recent in vitro data and from in vivo preclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair.

  19. Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures.

    Science.gov (United States)

    Lo Monaco, Melissa; Merckx, Greet; Ratajczak, Jessica; Gervois, Pascal; Hilkens, Petra; Clegg, Peter; Bronckaers, Annelies; Vandeweerd, Jean-Michel; Lambrichts, Ivo

    2018-01-01

    Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recent in vitro data and from in vivo preclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair.

  20. The Core of Sibling Stem Cell Donation – A Grounded Theory Study

    Science.gov (United States)

    Kisch, Annika M; Forsberg, Anna

    2017-01-01

    Background: There is a lack of theoretical framework supporting stem cell transplant nurses in their assessment, judgment and caring interventions of sibling stem cell donors. Objective: The purpose of this study was to explore sibling stem cell donors’ main concerns and how they deal with them before and after donation. Method: Ten healthy sibling donors, 5 men and 5 women, with a median age of 54 years were included in this study when they were due to donate stem cells to a brother or sister. Data were collected prospectively on three occasions (before the donation and three and twelve months after it) through in-depth interviews, which were recorded and transcribed verbatim for analysis by the Grounded Theory method according to Charmaz. Results: This study describes the efforts of the ten donors to fulfil their duty as a sibling by doing what they considered necessary in order to help. Their efforts were summarised in a process wherein the grounded theory generated three main categories; Prepare, Promote and Preserve. A clear path of transition leading to fulfilment is evident, starting before the donation and continuing for one year afterwards. Conclusions: Being a sibling stem cell donor means doing what you have to do to fulfil your duty and if possible, saving the life of a seriously ill brother or sister. The relationship between the siblings is strengthened by the donation process. Sibling stem cell donation appears to be about fulfilment and the theoretical framework may support clinicians in their evaluation and support of donors. PMID:28839511

  1. The Core of Sibling Stem Cell Donation - A Grounded Theory Study.

    Science.gov (United States)

    Kisch, Annika M; Forsberg, Anna

    2017-01-01

    There is a lack of theoretical framework supporting stem cell transplant nurses in their assessment, judgment and caring interventions of sibling stem cell donors. The purpose of this study was to explore sibling stem cell donors' main concerns and how they deal with them before and after donation. Ten healthy sibling donors, 5 men and 5 women, with a median age of 54 years were included in this study when they were due to donate stem cells to a brother or sister. Data were collected prospectively on three occasions (before the donation and three and twelve months after it) through in-depth interviews, which were recorded and transcribed verbatim for analysis by the Grounded Theory method according to Charmaz. This study describes the efforts of the ten donors to fulfil their duty as a sibling by doing what they considered necessary in order to help. Their efforts were summarised in a process wherein the grounded theory generated three main categories; Prepare, Promote and Preserve. A clear path of transition leading to fulfilment is evident, starting before the donation and continuing for one year afterwards. Being a sibling stem cell donor means doing what you have to do to fulfil your duty and if possible, saving the life of a seriously ill brother or sister. The relationship between the siblings is strengthened by the donation process. Sibling stem cell donation appears to be about fulfilment and the theoretical framework may support clinicians in their evaluation and support of donors.

  2. Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures

    OpenAIRE

    Lo Monaco, Melissa; Merckx, Greet; Ratajczak, Jessica; Gervois, Pascal; Hilkens, Petra; Clegg, Peter; Bronckaers, Annelies; Vandeweerd, Jean-Michel; Lambrichts, Ivo

    2018-01-01

    Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain...

  3. College Students' Conceptions of Stem Cells, Stem Cell Research, and Cloning

    Science.gov (United States)

    Concannon, James P.; Siegel, Marcelle A.; Halverson, Kristy; Freyermuth, Sharyn

    2010-01-01

    In this study, we examined 96 undergraduate non-science majors' conceptions of stem cells, stem cell research, and cloning. This study was performed at a large, Midwest, research extensive university. Participants in the study were asked to answer 23 questions relating to stem cells, stem cell research, and cloning in an on-line assessment before…

  4. Cell lineage identification and stem cell culture in a porcine model for the study of intestinal epithelial regeneration.

    Directory of Open Access Journals (Sweden)

    Liara M Gonzalez

    Full Text Available Significant advances in intestinal stem cell biology have been made in murine models; however, anatomical and physiological differences between mice and humans limit mice as a translational model for stem cell based research. The pig has been an effective translational model, and represents a candidate species to study intestinal epithelial stem cell (IESC driven regeneration. The lack of validated reagents and epithelial culture methods is an obstacle to investigating IESC driven regeneration in a pig model. In this study, antibodies against Epithelial Adhesion Molecule 1 (EpCAM and Villin marked cells of epithelial origin. Antibodies against Proliferative Cell Nuclear Antigen (PCNA, Minichromosome Maintenance Complex 2 (MCM2, Bromodeoxyuridine (BrdU and phosphorylated Histone H3 (pH3 distinguished proliferating cells at various stages of the cell cycle. SOX9, localized to the stem/progenitor cells zone, while HOPX was restricted to the +4/'reserve' stem cell zone. Immunostaining also identified major differentiated lineages. Goblet cells were identified by Mucin 2 (MUC2; enteroendocrine cells by Chromogranin A (CGA, Gastrin and Somatostatin; and absorptive enterocytes by carbonic anhydrase II (CAII and sucrase isomaltase (SIM. Transmission electron microscopy demonstrated morphologic and sub-cellular characteristics of stem cell and differentiated intestinal epithelial cell types. Quantitative PCR gene expression analysis enabled identification of stem/progenitor cells, post mitotic cell lineages, and important growth and differentiation pathways. Additionally, a method for long-term culture of porcine crypts was developed. Biomarker characterization and development of IESC culture in the porcine model represents a foundation for translational studies of IESC-driven regeneration of the intestinal epithelium in physiology and disease.

  5. Cancer stem cells revisited

    NARCIS (Netherlands)

    Batlle, Eduard; Clevers, Hans

    2017-01-01

    The cancer stem cell (CSC) concept was proposed four decades ago, and states that tumor growth, analogous to the renewal of healthy tissues, is fueled by small numbers of dedicated stem cells. It has gradually become clear that many tumors harbor CSCs in dedicated niches, and yet their

  6. 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 ...

  7. Stem Cell Transplants (For Teens)

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Stem Cell Transplants KidsHealth / For Teens / Stem Cell Transplants What's ... Take to Recover? Coping Print What Are Stem Cells? As you probably remember from biology class, every ...

  8. Transmission economic expansion and congestion relief : a case study

    Energy Technology Data Exchange (ETDEWEB)

    Chao, H.; Trinh, L.H.; Moore, M. [ABB Consulting, Raleigh, NC (United States); Brown, L.; Patel, K. [SDG and E, San Diego, CA (United States)

    2006-07-01

    Transmission capacity additions have lagged behind load growth and generation expansion in the United States. This paper provided an economic analysis of various transmission upgrade options designed to address anticipated congestion of the electricity grid. A market-based transmission planning method was used to assess the economics of transmission expansion. The analysis accounted for the minimum costs of generation dispatch to satisfy transmission constraints, as well as a locational marginal price for each bus in the system. Marginal congestion costs for all major transmission facilities were monitored and recorded. Hourly simulations of load, generation, and transmission system interactions were conducted. Contract costs and economic measures were then calculated for each scenario run. A case study for the Sunrise Powerlink project was used to demonstrate the efficacy of the method. The study demonstrated that the Sunrise Powerlink project will eliminate significant congestion in California load centers. Results also showed that the analytical method provided critical information for decision-makers in weighing the costs with benefits for transmission projects. 5 refs., 2 tabs., 1 fig.

  9. What is a stem cell?

    Science.gov (United States)

    Slack, Jonathan M W

    2018-05-15

    The historical roots of the stem cell concept are traced with respect to its usage in embryology and in hematology. The modern consensus definition of stem cells, comprising both pluripotent stem cells in culture and tissue-specific stem cells in vivo, is explained and explored. Methods for identifying stem cells are discussed with respect to cell surface markers, telomerase, label retention and transplantability, and properties of the stem cell niche are explored. The CreER method for identifying stem cells in vivo is explained, as is evidence in favor of a stochastic rather than an obligate asymmetric form of cell division. In conclusion, it is found that stem cells do not possess any unique and specific molecular markers; and stem cell behavior depends on the environment of the cell as well as the stem cell's intrinsic qualities. Furthermore, the stochastic mode of division implies that stem cell behavior is a property of a cell population not of an individual cell. In this sense, stem cells do not exist in isolation but only as a part of multicellular system. This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Tissue Stem Cells and Niches Adult Stem Cells, Tissue Renewal, and Regeneration > Methods and Principles Adult Stem Cells, Tissue Renewal, and Regeneration > Environmental Control of Stem Cells. © 2018 Wiley Periodicals, Inc.

  10. Stem cells for tooth engineering

    Directory of Open Access Journals (Sweden)

    G Bluteau

    2008-07-01

    Full Text Available Tooth development results from sequential and reciprocal interactions between the oral epithelium and the underlying neural crest-derived mesenchyme. The generation of dental structures and/or entire teeth in the laboratory depends upon the manipulation of stem cells and requires a synergy of all cellular and molecular events that finally lead to the formation of tooth-specific hard tissues, dentin and enamel. Although mesenchymal stem cells from different origins have been extensively studied in their capacity to form dentin in vitro, information is not yet available concerning the use of epithelial stem cells. The odontogenic potential resides in the oral epithelium and thus epithelial stem cells are necessary for both the initiation of tooth formation and enamel matrix production. This review focuses on the different sources of stem cells that have been used for making teeth in vitro and their relative efficiency. Embryonic, post-natal or even adult stem cells were assessed and proved to possess an enormous regenerative potential, but their application in dental practice is still problematic and limited due to various parameters that are not yet under control such as the high risk of rejection, cell behaviour, long tooth eruption period, appropriate crown morphology and suitable colour. Nevertheless, the development of biological approaches for dental reconstruction using stem cells is promising and remains one of the greatest challenges in the dental field for the years to come.

  11. Functional Studies of Missense TREM2 Mutations in Human Stem Cell-Derived Microglia

    Directory of Open Access Journals (Sweden)

    Philip W. Brownjohn

    2018-04-01

    Full Text Available Summary: The derivation of microglia from human stem cells provides systems for understanding microglial biology and enables functional studies of disease-causing mutations. We describe a robust method for the derivation of human microglia from stem cells, which are phenotypically and functionally comparable with primary microglia. We used stem cell-derived microglia to study the consequences of missense mutations in the microglial-expressed protein triggering receptor expressed on myeloid cells 2 (TREM2, which are causal for frontotemporal dementia-like syndrome and Nasu-Hakola disease. We find that mutant TREM2 accumulates in its immature form, does not undergo typical proteolysis, and is not trafficked to the plasma membrane. However, in the absence of plasma membrane TREM2, microglia differentiate normally, respond to stimulation with lipopolysaccharide, and are phagocytically competent. These data indicate that dementia-associated TREM2 mutations have subtle effects on microglia biology, consistent with the adult onset of disease in individuals with these mutations. : Brownjohn and colleagues report methods to generate microglia from induced pluripotent human stem cells, which they demonstrate are highly similar to cultured primary human microglia. Microglia differentiated from patient-derived stem cells carrying neurological disease-causing mutations in the TREM2 receptor differentiate normally and respond appropriately to pathogenic stimuli, despite the absence of functional TREM2 receptor on the plasma membrane. Keywords: dementia, microglia, TREM2, Nasu-Hakola disease, frontotemporal dementia, iPSC-microglia, neuroinflammation

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

    Directory of Open Access Journals (Sweden)

    Ravikumar R

    2007-01-01

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

  13. Mesenchymal Stem Cells

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  14. Retinal stem cells and potential cell transplantation treatments

    Directory of Open Access Journals (Sweden)

    Tai-Chi Lin

    2014-11-01

    Full Text Available The retina, histologically composed of ten delicate layers, is responsible for light perception and relaying electrochemical signals to the secondary neurons and visual cortex. Retinal disease is one of the leading clinical causes of severe vision loss, including age-related macular degeneration, Stargardt's disease, and retinitis pigmentosa. As a result of the discovery of various somatic stem cells, advances in exploring the identities of embryonic stem cells, and the development of induced pluripotent stem cells, cell transplantation treatment for retinal diseases is currently attracting much attention. The sources of stem cells for retinal regeneration include endogenous retinal stem cells (e.g., neuronal stem cells, Müller cells, and retinal stem cells from the ciliary marginal zone and exogenous stem cells (e.g., bone mesenchymal stem cells, adipose-derived stem cells, embryonic stem cells, and induced pluripotent stem cells. The success of cell transplantation treatment depends mainly on the cell source, the timing of cell harvesting, the protocol of cell induction/transplantation, and the microenvironment of the recipient's retina. This review summarizes the different sources of stem cells for regeneration treatment in retinal diseases and surveys the more recent achievements in animal studies and clinical trials. Future directions and challenges in stem cell transplantation are also discussed.

  15. Culture of Mouse Neural Stem Cell Precursors

    OpenAIRE

    Currle, D. Spencer; Hu, Jia Sheng; Kolski-Andreaco, Aaron; Monuki, Edwin S.

    2007-01-01

    Primary neural stem cell cultures are useful for studying the mechanisms underlying central nervous system development. Stem cell research will increase our understanding of the nervous system and may allow us to develop treatments for currently incurable brain diseases and injuries. In addition, stem cells should be used for stem cell research aimed at the detailed study of mechanisms of neural differentiation and transdifferentiation and the genetic and environmental signals that direct the...

  16. Myeloproliferative neoplasm stem cells.

    Science.gov (United States)

    Mead, Adam J; Mullally, Ann

    2017-03-23

    Myeloproliferative neoplasms (MPNs) arise in the hematopoietic stem cell (HSC) compartment as a result of the acquisition of somatic mutations in a single HSC that provides a selective advantage to mutant HSC over normal HSC and promotes myeloid differentiation to engender a myeloproliferative phenotype. This population of somatically mutated HSC, which initiates and sustains MPNs, is termed MPN stem cells. In >95% of cases, mutations that drive the development of an MPN phenotype occur in a mutually exclusive manner in 1 of 3 genes: JAK2 , CALR , or MPL The thrombopoietin receptor, MPL, is the key cytokine receptor in MPN development, and these mutations all activate MPL-JAK-STAT signaling in MPN stem cells. Despite common biological features, MPNs display diverse disease phenotypes as a result of both constitutional and acquired factors that influence MPN stem cells, and likely also as a result of heterogeneity in the HSC in which MPN-initiating mutations arise. As the MPN clone expands, it exerts cell-extrinsic effects on components of the bone marrow niche that can favor the survival and expansion of MPN stem cells over normal HSC, further sustaining and driving malignant hematopoiesis. Although developed as targeted therapies for MPNs, current JAK2 inhibitors do not preferentially target MPN stem cells, and as a result, rarely induce molecular remissions in MPN patients. As the understanding of the molecular mechanisms underlying the clonal dominance of MPN stem cells advances, this will help facilitate the development of therapies that preferentially target MPN stem cells over normal HSC. © 2017 by The American Society of Hematology.

  17. Human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Abdallah, Basem; Kassem, Moustapha

    2008-01-01

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

  18. In vitro study of stem cell communication via gap junctions for fibrocartilage regeneration at entheses.

    Science.gov (United States)

    Nayak, Bibhukalyan Prasad; Goh, James Cho Hong; Toh, Siew Lok; Satpathy, Gyan Ranjan

    2010-03-01

    Entheses are fibrocartilaginous organs that bridge ligament with bone at their interface and add significant insertional strength. To replace a severely damaged ligament, a tissue-engineered graft preinstalled with interfacial fibrocartilage, which is being regenerated from stem cells, appears to be more promising than ligament-alone graft. Such a concept can be realized by a biomimetic approach of establishing a dynamic communication of stem cells with bone cells and/or ligament fibroblasts in vitro. The current study has two objectives. The first objective is to demonstrate functional coculture of bone marrow-derived stem cells (BMSCs) with mature bone cells/ligament fibroblasts as evidenced by gap-junctional communication in vitro. The second objective is to investigate the role of BMSCs in the regeneration of fibrocartilage within the coculture. Rabbit bone/ligament fibroblasts were dual-stained with DiI-Red and calcein (gap-junction permeable dye), and cocultured with unlabeled BMSCs at fixed ratio (1:10). The functional gap junction was demonstrated by the transfer of calcein from donor to recipient cells that was confirmed and quantified by flow cytometry. Type 2 collagen (cartilage extracellular matrix-specific protein) expressed by the mixed cell lines in the cocultures were estimated by real-time reverse transcription PCR and compared with that of the ligament-bone coculture (control). Significant transfer of calcein into BMSCs was observed and flow cytometry analyses showed a gradual increase in the percentage of BMSCs acquiring calcein with time. Cocultures that included BMSCs expressed significantly more type 2 collagen compared with the control. The current study, for the first time, reported the expression of gap-junctional communication of BMSCs with two adherent cell lines of musculoskeletal system in vitro and also confirmed that incorporation of stem cells augments fibrocartilage regeneration. The results open up a path to envisage a composite

  19. [Genetic regulation of plant shoot stem cells].

    Science.gov (United States)

    Al'bert, E V; Ezhova, T A

    2013-02-01

    This article describes the main features of plant stem cells and summarizes the results of studies of the genetic control of stem cell maintenance in the apical meristem of the shoot. It is demonstrated that the WUS-CLV gene system plays a key role in the maintenance of shoot apical stem cells and the formation of adventitious buds and somatic embryos. Unconventional concepts of plant stem cells are considered.

  20. In Vitro Chondrogenesis Transformation Study of Mouse Dental Pulp Stem Cells

    Directory of Open Access Journals (Sweden)

    Shahrul Hisham Zainal Ariffin

    2012-01-01

    Full Text Available A major challenge in the application of mesenchymal stem cells in cartilage reconstruction is that whether the cells are able to differentiate into fully mature chondrocytes before grafting. The aim of this study was to isolate mouse dental pulp stem cells (DPSC and differentiate them into chondrocytes. For this investigation, morphological, molecular, and biochemical analyses for differentiated cells were used. To induce the chondrocyte differentiation, DPSC were cultured in chondrogenic medium (Zen-Bio, Inc.. Based on morphological analyses using toluidine blue staining, proteoglycan products appear in DPSC after 21 days of chondrocyte induction. Biochemical analyses in differentiated group showed that alkaline phosphatase activity was significantly increased at day 14 as compared to control (P<0.05. Cell viability analyses during the differentiation to chondrocytes also showed that these cells were viable during differentiation. However, after the 14th day of differentiation, there was a significant decrease (P<0.05 in the viability proportion among differentiated cells as compared to the control cells. In RT-PCR molecular analyses, mouse DPSC expressed Cd146 and Cd166 which indicated that these cells belong to mesenchymal stem cells. Coll I and Coll II markers showed high expression after 14 and 21 days, respectively. In conclusion, this study showed that DPSC successfully differentiated into chondrocytes.

  1. Mammary gland stem cells

    DEFF Research Database (Denmark)

    Fridriksdottir, Agla J R; Petersen, Ole W; Rønnov-Jessen, Lone

    2011-01-01

    Distinct subsets of cells, including cells with stem cell-like properties, have been proposed to exist in normal human breast epithelium and breast carcinomas. The cellular origins of epithelial cells contributing to gland development, tissue homeostasis and cancer are, however, still poorly...... and differences between mouse and human gland development with particular emphasis on the identity and localization of stem cells, and the influence of the surrounding microenvironment. It is concluded that while recent advances in the field have contributed immense insight into how the normal mammary gland...... develops and is maintained, significant discrepancies exist between the mouse and human gland which should be taken into consideration in current and future models of mammary stem cell biology....

  2. Stem cell heterogeneity revealed

    DEFF Research Database (Denmark)

    Andersen, Marianne S; Jensen, Kim B

    2016-01-01

    The skin forms a protective, water-impermeable barrier consisting of heavily crosslinked epithelial cells. However, the specific role of stem cells in sustaining this barrier remains a contentious issue. A detailed analysis of the interfollicular epidermis now proposes a model for how a composite...... of cells with different properties are involved in its maintenance....

  3. Comparative study of human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC) as a treatment for retinal dystrophies

    Science.gov (United States)

    Riera, Marina; Fontrodona, Laura; Albert, Silvia; Ramirez, Diana Mora; Seriola, Anna; Salas, Anna; Muñoz, Yolanda; Ramos, David; Villegas-Perez, Maria Paz; Zapata, Miguel Angel; Raya, Angel; Ruberte, Jesus; Veiga, Anna; Garcia-Arumi, Jose

    2016-01-01

    Retinal dystrophies (RD) are major causes of familial blindness and are characterized by progressive dysfunction of photoreceptor and/or retinal pigment epithelium (RPE) cells. In this study, we aimed to evaluate and compare the therapeutic effects of two pluripotent stem cell (PSC)-based therapies. We differentiated RPE from human embryonic stem cells (hESCs) or human-induced pluripotent stem cells (hiPSCs) and transplanted them into the subretinal space of the Royal College of Surgeons (RCS) rat. Once differentiated, cells from either source of PSC resembled mature RPE in their morphology and gene expression profile. Following transplantation, both hESC- and hiPSC-derived cells maintained the expression of specific RPE markers, lost their proliferative capacity, established tight junctions, and were able to perform phagocytosis of photoreceptor outer segments. Remarkably, grafted areas showed increased numbers of photoreceptor nuclei and outer segment disk membranes. Regardless of the cell source, human transplants protected retina from cell apoptosis, glial stress and accumulation of autofluorescence, and responded better to light stimuli. Altogether, our results show that hESC- and hiPSC-derived cells survived, migrated, integrated, and functioned as RPE in the RCS rat retina, providing preclinical evidence that either PSC source could be of potential benefit for treating RD. PMID:27006969

  4. Comparative study of human embryonic stem cells (hESC and human induced pluripotent stem cells (hiPSC as a treatment for retinal dystrophies

    Directory of Open Access Journals (Sweden)

    Marina Riera

    2016-01-01

    Full Text Available Retinal dystrophies (RD are major causes of familial blindness and are characterized by progressive dysfunction of photoreceptor and/or retinal pigment epithelium (RPE cells. In this study, we aimed to evaluate and compare the therapeutic effects of two pluripotent stem cell (PSC-based therapies. We differentiated RPE from human embryonic stem cells (hESCs or human-induced pluripotent stem cells (hiPSCs and transplanted them into the subretinal space of the Royal College of Surgeons (RCS rat. Once differentiated, cells from either source of PSC resembled mature RPE in their morphology and gene expression profile. Following transplantation, both hESC- and hiPSC-derived cells maintained the expression of specific RPE markers, lost their proliferative capacity, established tight junctions, and were able to perform phagocytosis of photoreceptor outer segments. Remarkably, grafted areas showed increased numbers of photoreceptor nuclei and outer segment disk membranes. Regardless of the cell source, human transplants protected retina from cell apoptosis, glial stress and accumulation of autofluorescence, and responded better to light stimuli. Altogether, our results show that hESC- and hiPSC-derived cells survived, migrated, integrated, and functioned as RPE in the RCS rat retina, providing preclinical evidence that either PSC source could be of potential benefit for treating RD.

  5. Plasticity of spermatogonial stem cells

    Directory of Open Access Journals (Sweden)

    Paul S Cooke

    2015-06-01

    Full Text Available There have been significant breakthroughs over the past decade in the development and use of pluripotent stem cells as a potential source of cells for applications in regenerative medicine. It is likely that this methodology will begin to play an important role in human clinical medicine in the years to come. This review describes the plasticity of one type of pluripotent cell, spermatogonial stem cells (SSCs, and their potential therapeutic applications in regenerative medicine and male infertility. Normally, SSCs give rise to sperm when in the testis. However, both human and murine SSCs can give rise to cells with embryonic stem (ES cell-like characteristics that can be directed to differentiate into tissues of all three embryonic germ layers when placed in an appropriate inductive microenvironment, which is in contrast to other postnatal stem cells. Previous studies have reported that SSCs expressed an intermediate pluripotent phenotype before differentiating into a specific cell type and that extended culture was necessary for this to occur. However, recent studies from our group using a tissue recombination model demonstrated that SSCs differentiated rapidly into another tissue, in this case, prostatic epithelium, without expression of pluripotent ES cell markers before differentiation. These results suggest that SSCs are capable of directly differentiating into other cell types without going through an intermediate ES cell-like stage. Because SSCs do not require reprogramming to achieve a pluripotent state, they are an attractive source of pluripotent cells for use in regenerative medicine.

  6. Induced pluripotent stem cell - derived neurons for the study of spinocerebellar ataxia type 3

    DEFF Research Database (Denmark)

    Hansen, Susanne Kofoed; Stummann, Tina C.; Madsen, Helena Borland

    2016-01-01

    The neurodegenerative disease spinocerebellar ataxia type 3 (SCA3) is caused by a CAG-repeat expansion in the ATXN3 gene. In this study, induced pluripotent stem cell (iPSC) lines were established from two SCA3 patients. Dermal fibroblasts were reprogrammed using an integration-free method...

  7. Induced Pluripotent Stem Cell Technology and Direct Conversion : New Possibilities to Study and Treat Parkinson's Disease

    NARCIS (Netherlands)

    Roessler, Reinhard; Boddeke, Erik; Copray, Sjef

    Recent developments in in vitro disease modeling and regenerative medicine have placed induced pluripotent stem cells (iPSCs) in the center of attention as a unique source to study Parkinson's disease. After only 5 years of intensive research, human iPSCs can be generated without viral integration

  8. Human embryonic stem cells handbook

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2013-03-01

    Full Text Available After the Nobel prize in physiology or medicine was awarded jointly to Sir John Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent it became imperative to write down the review for a book entirely devoted to human embryonic stem cells (hES, those cells that are a urgent need for researchers, those cells that rekindle the ethical debates and finally, last but not least, those cells whose study paved the way to obtain induced pluripotent stem cells by the OSKC’s Yamanaka method (the OSKC acronim refers, for those not familiar with the topic, to the four stemness genes used to transfect somatic fibroblasts: Oct4, Sox2, Klf4 and c-Myc....

  9. Current status of stem cells in cardiac repair.

    Science.gov (United States)

    Henning, Robert J

    2018-03-01

    One out of every two men and one out of every three women greater than the age of 40 will experience an acute myocardial infarction (AMI) at some time during their lifetime. As more patients survive their AMIs, the incidence of congestive heart failure (CHF) is increasing. 6 million people in the USA have ischemic cardiomyopathies and CHF. The search for new and innovative treatments for patients with AMI and CHF has led to investigations and use of human embryonic stem cells, cardiac stem/progenitor cells, bone marrow-derived mononuclear cells and mesenchymal stem cells for treatment of these heart conditions. This paper reviews current investigations with human embryonic, cardiac, bone marrow and mesenchymal stem cells, and also stem cell paracrine factors and exosomes.

  10. Induced pluripotent stem cells as a cellular model for studying Down Syndrome

    Directory of Open Access Journals (Sweden)

    Brigida AL

    2016-11-01

    Full Text Available Down Syndrome (DS, or Trisomy 21 Syndrome, is one of the most common genetic diseases. It is a chromosomal abnormality caused by a duplication of chromosome 21. DS patients show the presence of a third copy (or a partial third copy of chromosome 21 (trisomy, as result of meiotic errors. These patients suffer of many health problems, such as intellectual disability, congenital heart disease, duodenal stenosis, Alzheimer's disease, leukemia, immune system deficiencies, muscle hypotonia and motor disorders. About one in 1000 babies born each year are affected by DS. Alterations in the dosage of genes located on chromosome 21 (also called HSA21 are responsible for the DS phenotype. However, the molecular pathogenic mechanisms of DS triggering are still not understood; newest evidences suggest the involvement of epigenetic mechanisms. For obvious ethical reasons, studies performed on DS patients, as well as on human trisomic tissues are limited. Some authors have proposed mouse models of this syndrome. However, not all the features of the syndrome are represented. Stem cells are considered the future of molecular and regenerative medicine. Several types of stem cells could provide a valid approach to offer a potential treatment for some untreatable human diseases. Stem cells also represent a valid system to develop new cell-based drugs and/or a model to study molecular disease pathways. Among stem cell types, patient-derived induced pluripotent stem (iPS cells offer some advantages for cell and tissue replacement, engineering and studying: self-renewal capacity, pluripotency and ease of accessibility to donor tissues. These cells can be reprogrammed into completely different cellular types. They are derived from adult somatic cells via reprogramming with ectopic expression of four transcription factors (Oct3/4, Sox2, c-Myc and Klf4; or, Oct3/4, Sox2, Nanog, and Lin28. By reprogramming cells from DS patients, it is possible to obtain new tissue with

  11. Gastric stem cells and gastric cancer stem cells

    OpenAIRE

    Han, Myoung-Eun; Oh, Sae-Ock

    2013-01-01

    The gastric epithelium is continuously regenerated by gastric stem cells, which give rise to various kinds of daughter cells, including parietal cells, chief cells, surface mucous cells, mucous neck cells, and enteroendocrine cells. The self-renewal and differentiation of gastric stem cells need delicate regulation to maintain the normal physiology of the stomach. Recently, it was hypothesized that cancer stem cells drive the cancer growth and metastasis. In contrast to conventional clonal ev...

  12. Influence of oxygen in the cultivation of human mesenchymal stem cells in simulated microgravity: an explorative study

    NARCIS (Netherlands)

    Versari, S.; Klein-Nulend, J.; van Loon, J.; Bradamante, S.

    2013-01-01

    Previous studies indicated that human Adipose Tissue-derived Mesenchymal Stem Cells (AT-MSCs) cultured in simulated microgravity (sim-μg) in standard laboratory incubators alter their proliferation and differentiation. Recent studies on the stem cell (SC) niches and the influence of oxygen on SC

  13. Influence of Oxygen in the Cultivation of Human Mesenchymal Stem Cells in Simulated Microgravity: An Explorative Study

    NARCIS (Netherlands)

    Versari, S.; Klein-Nulend, J.; van Loon, J.J.W.A.; Bradamante, S.

    2013-01-01

    Previous studies indicated that human Adipose Tissue-derived Mesenchymal Stem Cells (AT-MSCs) cultured in simulated microgravity (sim-μg) in standard laboratory incubators alter their proliferation and differentiation. Recent studies on the stem cell (SC) niches and the influence of oxygen on SC

  14. Cancer stem cells and differentiation therapy.

    Science.gov (United States)

    Jin, Xiong; Jin, Xun; Kim, Hyunggee

    2017-10-01

    Cancer stem cells can generate tumors from only a small number of cells, whereas differentiated cancer cells cannot. The prominent feature of cancer stem cells is its ability to self-renew and differentiate into multiple types of cancer cells. Cancer stem cells have several distinct tumorigenic abilities, including stem cell signal transduction, tumorigenicity, metastasis, and resistance to anticancer drugs, which are regulated by genetic or epigenetic changes. Like normal adult stem cells involved in various developmental processes and tissue homeostasis, cancer stem cells maintain their self-renewal capacity by activating multiple stem cell signaling pathways and inhibiting differentiation signaling pathways during cancer initiation and progression. Recently, many studies have focused on targeting cancer stem cells to eradicate malignancies by regulating stem cell signaling pathways, and products of some of these strategies are in preclinical and clinical trials. In this review, we describe the crucial features of cancer stem cells related to tumor relapse and drug resistance, as well as the new therapeutic strategy to target cancer stem cells named "differentiation therapy."

  15. Mitochondrial biogenesis and energy production in differentiating murine stem cells: a functional metabolic study.

    Science.gov (United States)

    Han, Sungwon; Auger, Christopher; Thomas, Sean C; Beites, Crestina L; Appanna, Vasu D

    2014-02-01

    The significance of metabolic networks in guiding the fate of the stem cell differentiation is only beginning to emerge. Oxidative metabolism has been suggested to play a major role during this process. Therefore, it is critical to understand the underlying mechanisms of metabolic alterations occurring in stem cells to manipulate the ultimate outcome of these pluripotent cells. Here, using P19 murine embryonal carcinoma cells as a model system, the role of mitochondrial biogenesis and the modulation of metabolic networks during dimethyl sulfoxide (DMSO)-induced differentiation are revealed. Blue native polyacrylamide gel electrophoresis (BN-PAGE) technology aided in profiling key enzymes, such as hexokinase (HK) [EC 2.7.1.1], glucose-6-phosphate isomerase (GPI) [EC 5.3.1.9], pyruvate kinase (PK) [EC 2.7.1.40], Complex I [EC 1.6.5.3], and Complex IV [EC 1.9.3.1], that are involved in the energy budget of the differentiated cells. Mitochondrial adenosine triphosphate (ATP) production was shown to be increased in DMSO-treated cells upon exposure to the tricarboxylic acid (TCA) cycle substrates, such as succinate and malate. The increased mitochondrial activity and biogenesis were further confirmed by immunofluorescence microscopy. Collectively, the results indicate that oxidative energy metabolism and mitochondrial biogenesis were sharply upregulated in DMSO-differentiated P19 cells. This functional metabolic and proteomic study provides further evidence that modulation of mitochondrial energy metabolism is a pivotal component of the cellular differentiation process and may dictate the final destiny of stem cells.

  16. Preclinical Studies of Induced Pluripotent Stem Cell-Derived Astrocyte Transplantation in ALS

    Science.gov (United States)

    2012-10-01

    Pluripotent Stem Cell -Derived Astrocyte Transplantation in ALS PRINCIPAL INVESTIGATOR: Nicholas J. Maragakis, M.D...Pluripotent Stem Cell -Derived Astrocyte Transplantation in ALS 5b. GRANT NUMBER W81XWH-10-1-0520 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...into astrocytes following transplantation. 15. SUBJECT TERMS Stem Cells , iPS cells, astrocytes, familial ALS 16. SECURITY CLASSIFICATION OF

  17. Subsequent vitiligo after hematopoietic stem cell transplantation: A nationwide population-based cohort study from Korea.

    Science.gov (United States)

    Bae, Jung Min; Choi, Kwang Hyun; Jung, Han Mi; Kim, Sook Young; Kim, Miri; Kim, Gyung Moon; Yu, Dong Soo; Lee, Young Bok

    2017-03-01

    Subsequent vitiligo after hematopoietic stem cell transplantation (HSCT) has been described sporadically in case series. To investigate the incidence and risk factors of subsequent vitiligo after HSCT. A nationwide, population-based cohort study was performed using the Korean National Health Insurance Claims Database from 2009 to 2013. All HSCT recipients who had undergone HSCT between 2010 and 2011 and not treatment for vitiligo in 2009 (to exclude preexisting active vitiligo) were included in the HSCT recipient group, and an age- and sex-matched control group without HSCT was also established. A total of 2747 HSCT recipients and 8241 controls were enrolled. Newly acquired vitiligo occurred in 1.06% of HSCT recipients between 2010 and 2013, and there was a significant increase (OR 3.130, 95% CI 1.859-5.271) in cases of vitiligo in HSCT recipients compared with controls (0.34%). Allogeneic HSCT (OR 5.593, 95% CI 1.628-19.213) and bone marrow-sourced stem cells (as compared with peripheral blood-sourced stem cells; OR 2.492, 95% CI 1.114-5.576) were independently associated with the development of vitiligo after HSCT. Medical record review was not available. Vitiligo developed at a significantly increased rate after HSCT compared with controls. Allogeneic HSCT and bone marrow-sourced stem cells were independent risk factors. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  18. Stem cells therapy for ALS.

    Science.gov (United States)

    Mazzini, Letizia; Vescovi, Angelo; Cantello, Roberto; Gelati, Maurizio; Vercelli, Alessandro

    2016-01-01

    Despite knowledge on the molecular basis of amyotrophic lateral sclerosis (ALS) having quickly progressed over the last few years, such discoveries have not yet translated into new therapeutics. With the advancement of stem cell technologies there is hope for stem cell therapeutics as novel treatments for ALS. We discuss in detail the therapeutic potential of different types of stem cells in preclinical and clinical works. Moreover, we address many open questions in clinical translation. SC therapy is a potentially promising new treatment for ALS and the need to better understand how to develop cell-based experimental treatments, and how to implement them in clinical trials, becomes more pressing. Mesenchymal stem cells and neural fetal stem cells have emerged as safe and potentially effective cell types, but there is a need to carry out appropriately designed experimental studies to verify their long-term safety and possibly efficacy. Moreover, the cost-benefit analysis of the results must take into account the quality of life of the patients as a major end point. It is our opinion that a multicenter international clinical program aime d at fine-tuning and coordinating transplantation procedures and protocols is mandatory.

  19. Studies on the effects of ionizing radiation and chemotherapeutic agents on hematopoiesis according to the stem-cell kinetics

    International Nuclear Information System (INIS)

    Hirashima, Kunitake

    1975-01-01

    The fundamental problem of the effects of ionizing radiation and antineoplastic drugs on hematopoiesis can be explained by the kinetic study on the hematopoietic stem-cell population. Quantitative comparison of a single x-irradiation and a single administration of several antineoplastic drugs on the stem-cell population was performed by the splenic colony-forming method. The repopulation pattern of stem-cells in mice after a single 150 rad irradiation was compared with that after the administration of corresponding dose of cyclophosphamide. It was demonstrated that the additional administration of cyclophosphamide immediately after the x-irradiation significantly accelerated repopulation of the stem-cell compartment. The mechanism of repopulation of the stem-cell compartment after partial irradiation was also studied according to the immigration theory of stem-cells. An in vitro colony-forming technique for the human bone marrow cells was introduced and compared with other assay methods for stem-cells. From the hematological observations of accidentally irradiated patients, it was determined that the thromboelastogram values were regarded as one of the most useful indicators for detecting the earliest recovery sign of the hematopoietic stem-cells. (Evans, J.)

  20. Comparative study of human-induced pluripotent stem cells derived from bone marrow cells, hair keratinocytes, and skin fibroblasts.

    Science.gov (United States)

    Streckfuss-Bömeke, Katrin; Wolf, Frieder; Azizian, Azadeh; Stauske, Michael; Tiburcy, Malte; Wagner, Stefan; Hübscher, Daniela; Dressel, Ralf; Chen, Simin; Jende, Jörg; Wulf, Gerald; Lorenz, Verena; Schön, Michael P; Maier, Lars S; Zimmermann, Wolfram H; Hasenfuss, Gerd; Guan, Kaomei

    2013-09-01

    Induced pluripotent stem cells (iPSCs) provide a unique opportunity for the generation of patient-specific cells for use in disease modelling, drug screening, and regenerative medicine. The aim of this study was to compare human-induced pluripotent stem cells (hiPSCs) derived from different somatic cell sources regarding their generation efficiency and cardiac differentiation potential, and functionalities of cardiomyocytes. We generated hiPSCs from hair keratinocytes, bone marrow mesenchymal stem cells (MSCs), and skin fibroblasts by using two different virus systems. We show that MSCs and fibroblasts are more easily reprogrammed than keratinocytes. This corresponds to higher methylation levels of minimal promoter regions of the OCT4 and NANOG genes in keratinocytes than in MSCs and fibroblasts. The success rate and reprogramming efficiency was significantly higher by using the STEMCCA system than the OSNL system. All analysed hiPSCs are pluripotent and show phenotypical characteristics similar to human embryonic stem cells. We studied the cardiac differentiation efficiency of generated hiPSC lines (n = 24) and found that MSC-derived hiPSCs exhibited a significantly higher efficiency to spontaneously differentiate into beating cardiomyocytes when compared with keratinocyte-, and fibroblast-derived hiPSCs. There was no significant difference in the functionalities of the cardiomyocytes derived from hiPSCs with different origins, showing the presence of pacemaker-, atrial-, ventricular- and Purkinje-like cardiomyocytes, and exhibiting rhythmic Ca2+ transients and Ca2+ sparks in hiPSC-derived cardiomyocytes. Furthermore, spontaneously and synchronously beating and force-developing engineered heart tissues were generated. Human-induced pluripotent stem cells can be reprogrammed from all three somatic cell types, but with different efficiency. All analysed iPSCs can differentiate into cardiomyocytes, and the functionalities of cardiomyocytes derived from different cell

  1. Advancing Stem Cell Biology toward Stem Cell Therapeutics

    OpenAIRE

    Scadden, David; Srivastava, Alok

    2012-01-01

    Here, the International Society for Stem Cell Research (ISSCR) Clinical Translation Committee introduces a series of articles outlining the current status, opportunities, and challenges surrounding the clinical translation of stem cell therapeutics for specific medical conditions.

  2. Stem Cells in Regenerative Medicine

    Czech Academy of Sciences Publication Activity Database

    Syková, Eva; Forostyak, Serhiy

    2013-01-01

    Roč. 22, č. 2 (2013), s. 87-92 ISSN 0898-5901 R&D Projects: GA ČR(CZ) GAP304/11/0189; GA ČR(CZ) GBP304/12/G069 Institutional research plan: CEZ:AV0Z50390703 Institutional support: RVO:68378041 Keywords : cell therapy * stem cells * clinical study Subject RIV: FH - Neurology

  3. Combination cell therapy with mesenchymal stem cells and neural stem cells for brain stroke in rats.

    Science.gov (United States)

    Hosseini, Seyed Mojtaba; Farahmandnia, Mohammad; Razi, Zahra; Delavari, Somayeh; Shakibajahromi, Benafsheh; Sarvestani, Fatemeh Sabet; Kazemi, Sepehr; Semsar, Maryam

    2015-05-01

    Brain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stroke. The Mesenchymal stem cells were isolated from adult rat bone marrow and the neural stem cells were isolated from ganglion eminence of rat embryo 14 days. The Mesenchymal stem cells were injected 1 day after middle cerebral artery occlusion (MCAO) and the neural stem cells transplanted 7 day after MCAO. After 28 days, the neurological outcomes and brain lesion volumes were evaluated. Also, the activity of Caspase 3 was assessed in different groups. The group which received combination cell therapy had better neurological examination and less brain lesion. Also the combination cell therapy group had the least Caspase 3 activity among the groups. The combination cell therapy is more effective than Mesenchymal stem cell therapy and neural stem cell therapy separately in treating the brain stroke in rats.

  4. Stem cell organization in Arabidopsis

    NARCIS (Netherlands)

    Wendrich, J.R.

    2016-01-01

    Growth of plant tissues and organs depends on continuous production of new cells, by niches of stem cells. Stem cells typically divide to give rise to one differentiating daughter and one non-differentiating daughter. This constant process of self-renewal ensures that the niches of stem cells or

  5. Engineering stem cell niches in bioreactors

    OpenAIRE

    Liu, Meimei; Liu, Ning; Zang, Ru; Li, Yan; Yang, Shang-Tian

    2013-01-01

    Stem cells, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells and amniotic fluid stem cells have the potential to be expanded and differentiated into various cell types in the body. Efficient differentiation of stem cells with the desired tissue-specific function is critical for stem cell-based cell therapy, tissue engineering, drug discovery and disease modeling. Bioreactors provide a great platform to regulate the stem cell microenvironment, known as “ni...

  6. Pluripotent Stem Cell Studies Elucidate the Underlying Mechanisms of Early Embryonic Development

    Directory of Open Access Journals (Sweden)

    Lingyu Li

    2011-03-01

    Full Text Available Early embryonic development is a multi-step process that is intensively regulated by various signaling pathways. Because of the complexity of the embryo and the interactions between the germ layers, it is very difficult to fully understand how these signals regulate embryo patterning. Recently, pluripotent stem cell lines derived from different developmental stages have provided an in vitro system for investigating molecular mechanisms regulating cell fate decisions. In this review, we summarize the major functions of the BMP, FGF, Nodal and Wnt signaling pathways, which have well-established roles in vertebrate embryogenesis. Then, we highlight recent studies in pluripotent stem cells that have revealed the stage-specific roles of BMP,FGF and Nodal pathways during neural differentiation. These findings enhance our understanding of the stepwise regulation of embryo patterning by particular signaling pathways and provide new insight into the mechanisms underlying early embryonic development.

  7. Proliferative capacity of murine hematopoietic stem cells

    International Nuclear Information System (INIS)

    Hellman, S.; Botnick, L.E.; Hannon, E.C.; Vigneulle, R.M.

    1978-01-01

    The present study demonstrates a decrease in self-renewal capacity with serial transfer of murine hematopoietic stem cells. Production of differentiated cell progeny is maintained longer than stem cell self-renewal. In normal animals the capacity for self-renewal is not decreased with increasing donor age. The stem cell compartment in normal animals, both young and old, appears to be proliferatively quiescent. After apparent recovery from the alkylating agent busulfan, the probability of stem cell self-renewal is decreased, there is a permanent defect in the capacity of the bone marrow for serial transplantation, and the stem cells are proliferatively active. These findings support a model of the hematopoietic stem cell compartment as a continuum of cells with decreasing capacities for self-renewal, increasing likelihood for differentiation, and increasing proliferative activity. Cells progress in the continuum in one direction and such progression is not reversible

  8. [Progress in epidermal stem cells].

    Science.gov (United States)

    Wang, Li-Juan; Wang, You-Liang; Yang, Xiao

    2010-03-01

    Mammalian skin epidermis contains different epidermal stem cell pools which contribute to the homeostasis and repair of skin epithelium. Epidermal stem cells possess two essential features common to all stem cells: self-renewal and differentiation. Disturbing the balance between self-renewal and differentiation of epidermal stem cell often causes tumors or other skin diseases. Epidermal stem cell niches provide a special microenvironment that maintains a balance of stem cell quiescence and activity. This review primarily concentrates on the following points of the epidermal stem cells: the existing evidences, the self-renewal and differentiation, the division pattern, the signal pathways regulating self-renewal and differentiation, and the microenvironment (niche) and macroenvironment maintaining the homeostasis of stem cells.

  9. Mismatch repair deficient hematopoietic stem cells are preleukemic stem cells.

    Directory of Open Access Journals (Sweden)

    Yulan Qing

    Full Text Available Whereas transformation events in hematopoietic malignancies may occur at different developmental stages, the initial mutation originates in hematopoietic stem cells (HSCs, creating a preleukemic stem cell (PLSC. Subsequent mutations at either stem cell or progenitor cell levels transform the PLSC into lymphoma/leukemia initiating cells (LIC. Thymic lymphomas have been thought to develop from developing thymocytes. T cell progenitors are generated from HSCs in the bone marrow (BM, but maturation and proliferation of T cells as well as T-lymphomagenesis depends on both regulatory mechanisms and microenvironment within the thymus. We studied PLSC linked to thymic lymphomas. In this study, we use MSH2-/- mice as a model to investigate the existence of PLSC and the evolution of PLSC to LIC. Following BM transplantation, we found that MSH2-/- BM cells from young mice are able to fully reconstitute multiple hematopoietic lineages of lethally irradiated wild-type recipients. However, all recipients developed thymic lymphomas within three and four months post transplantation. Transplantation of different fractions of BM cells or thymocytes from young health MSH2-/- mice showed that an HSC enriched fraction always reconstituted hematopoiesis followed by lymphoma development. In addition, lymphomas did not occur in thymectomized recipients of MSH2-/- BM. These results suggest that HSCs with DNA repair defects such as MSH2-/- are PLSCs because they retain hematopoietic function, but also carry an obligate lymphomagenic potential within their T-cell progeny that is dependent on the thymic microenvironment.

  10. Porcine embryonic stem cells

    DEFF Research Database (Denmark)

    Hall, Vanessa Jane

    2008-01-01

    The development of porcine embryonic stem cell lines (pESC) has received renewed interest given the advances being made in the production of immunocompatible transgenic pigs. However, difficulties are evident in the production of pESCs in-vitro. This may largely be attributable to differences...

  11. Redox regulation of plant stem cell fate.

    Science.gov (United States)

    Zeng, Jian; Dong, Zhicheng; Wu, Haijun; Tian, Zhaoxia; Zhao, Zhong

    2017-10-02

    Despite the importance of stem cells in plant and animal development, the common mechanisms of stem cell maintenance in both systems have remained elusive. Recently, the importance of hydrogen peroxide (H 2 O 2 ) signaling in priming stem cell differentiation has been extensively studied in animals. Here, we show that different forms of reactive oxygen species (ROS) have antagonistic roles in plant stem cell regulation, which were established by distinct spatiotemporal patterns of ROS-metabolizing enzymes. The superoxide anion (O2·-) is markedly enriched in stem cells to activate WUSCHEL and maintain stemness, whereas H 2 O 2 is more abundant in the differentiating peripheral zone to promote stem cell differentiation. Moreover, H 2 O 2 negatively regulates O2·- biosynthesis in stem cells, and increasing H 2 O 2 levels or scavenging O2·- leads to the termination of stem cells. Our results provide a mechanistic framework for ROS-mediated control of plant stem cell fate and demonstrate that the balance between O2·- and H 2 O 2 is key to stem cell maintenance and differentiation. © 2017 The Authors.

  12. Materials as stem cell regulators

    Science.gov (United States)

    Murphy, William L.; McDevitt, Todd C.; Engler, Adam J.

    2014-01-01

    The stem cell/material interface is a complex, dynamic microenvironment in which the cell and the material cooperatively dictate one another's fate: the cell by remodelling its surroundings, and the material through its inherent properties (such as adhesivity, stiffness, nanostructure or degradability). Stem cells in contact with materials are able to sense their properties, integrate cues via signal propagation and ultimately translate parallel signalling information into cell fate decisions. However, discovering the mechanisms by which stem cells respond to inherent material characteristics is challenging because of the highly complex, multicomponent signalling milieu present in the stem cell environment. In this Review, we discuss recent evidence that shows that inherent material properties may be engineered to dictate stem cell fate decisions, and overview a subset of the operative signal transduction mechanisms that have begun to emerge. Further developments in stem cell engineering and mechanotransduction are poised to have substantial implications for stem cell biology and regenerative medicine. PMID:24845994

  13. Stem cells in psoriasis.

    Science.gov (United States)

    Hou, Ruixia; Li, Junqin; Niu, Xuping; Liu, Ruifeng; Chang, Wenjuan; Zhao, Xincheng; Wang, Qiang; Li, Xinhua; Yin, Guohua; Zhang, Kaiming

    2017-06-01

    Psoriasis is a complex chronic relapsing inflammatory disease. Although the exact mechanism remains unknown, it is commonly accepted that the development of psoriasis is a result of multi-system interactions among the epidermis, dermis, blood vessels, immune system, neuroendocrine system, metabolic system, and hematopoietic system. Many cell types have been confirmed to participate in the pathogenesis of psoriasis. Here, we review the stem cell abnormalities related to psoriasis that have been investigated recently. Copyright © 2016. Published by Elsevier B.V.

  14. Stem cell therapy to treat heart ischaemia

    DEFF Research Database (Denmark)

    Ali Qayyum, Abbas; Mathiasen, Anders Bruun; Kastrup, Jens

    2014-01-01

    (CABG), morbidity and mortality is still high in patients with CAD. Along with PCI and CABG or in patients without options for revascularization, stem cell regenerative therapy in controlled trials is a possibility. Stem cells are believed to exert their actions by angiogenesis and regeneration...... of cardiomyocytes. Recently published clinical trials and meta-analysis of stem cell studies have shown encouraging results with increased left ventricle ejection fraction and reduced symptoms in patients with CAD and heart failure. There is some evidence of mesenchymal stem cell being more effective compared...... to other cell types and cell therapy may be more effective in patients with known diabetes mellitus. However, further investigations are warranted....

  15. International Society for Stem Cell Research

    Science.gov (United States)

    ... renowned stem cell and regenerative medicine community. More stem cell research Take a closer look Recent Blogs View ... story independent nonprofit organization & the voice of the stem cell research community The International Society for Stem Cell ...

  16. Information on Stem Cell Research

    Science.gov (United States)

    ... Home » Current Research » Focus on Research Focus on Stem Cell Research Stem cells possess the unique ability to differentiate into ... virus infection. To search the complete list of stem cell research projects funded by NIH please go to NIH ...

  17. Strategies to improve homing of mesenchymal stem cells for greater efficacy in stem cell therapy.

    Science.gov (United States)

    Naderi-Meshkin, Hojjat; Bahrami, Ahmad Reza; Bidkhori, Hamid Reza; Mirahmadi, Mahdi; Ahmadiankia, Naghmeh

    2015-01-01

    Stem/progenitor cell-based therapeutic approach in clinical practice has been an elusive dream in medical sciences, and improvement of stem cell homing is one of major challenges in cell therapy programs. Stem/progenitor cells have a homing response to injured tissues/organs, mediated by interactions of chemokine receptors expressed on the cells and chemokines secreted by the injured tissue. For improvement of directed homing of the cells, many techniques have been developed either to engineer stem/progenitor cells with higher amount of chemokine receptors (stem cell-based strategies) or to modulate the target tissues to release higher level of the corresponding chemokines (target tissue-based strategies). This review discusses both of these strategies involved in the improvement of stem cell homing focusing on mesenchymal stem cells as most frequent studied model in cellular therapies. © 2014 International Federation for Cell Biology.

  18. Engineering Stem Cells for Biomedical Applications

    Science.gov (United States)

    Yin, Perry T.; Han, Edward

    2018-01-01

    Stem cells are characterized by a number of useful properties, including their ability to migrate, differentiate, and secrete a variety of therapeutic molecules such as immunomodulatory factors. As such, numerous pre-clinical and clinical studies have utilized stem cell-based therapies and demonstrated their tremendous potential for the treatment of various human diseases and disorders. Recently, efforts have focused on engineering stem cells in order to further enhance their innate abilities as well as to confer them with new functionalities, which can then be used in various biomedical applications. These engineered stem cells can take on a number of forms. For instance, engineered stem cells encompass the genetic modification of stem cells as well as the use of stem cells for gene delivery, nanoparticle loading and delivery, and even small molecule drug delivery. The present Review gives an in-depth account of the current status of engineered stem cells, including potential cell sources, the most common methods used to engineer stem cells, and the utilization of engineered stem cells in various biomedical applications, with a particular focus on tissue regeneration, the treatment of immunodeficiency diseases, and cancer. PMID:25772134

  19. Engineering Stem Cells for Biomedical Applications.

    Science.gov (United States)

    Yin, Perry T; Han, Edward; Lee, Ki-Bum

    2016-01-07

    Stem cells are characterized by a number of useful properties, including their ability to migrate, differentiate, and secrete a variety of therapeutic molecules such as immunomodulatory factors. As such, numerous pre-clinical and clinical studies have utilized stem cell-based therapies and demonstrated their tremendous potential for the treatment of various human diseases and disorders. Recently, efforts have focused on engineering stem cells in order to further enhance their innate abilities as well as to confer them with new functionalities, which can then be used in various biomedical applications. These engineered stem cells can take on a number of forms. For instance, engineered stem cells encompass the genetic modification of stem cells as well as the use of stem cells for gene delivery, nanoparticle loading and delivery, and even small molecule drug delivery. The present Review gives an in-depth account of the current status of engineered stem cells, including potential cell sources, the most common methods used to engineer stem cells, and the utilization of engineered stem cells in various biomedical applications, with a particular focus on tissue regeneration, the treatment of immunodeficiency diseases, and cancer. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. A Pilot Study of Mesenchymal Stem Cell Therapy for Acute Liver Allograft Rejection

    OpenAIRE

    Shi, Ming; Liu, Zhenwen; Wang, Ying; Xu, Rounan; Sun, Yanling; Zhang, Min; Yu, Xi; Wang, Hongbo; Meng, Lingzhan; Su, Haibin; Jin, Lei; Wang, Fu‐Sheng

    2017-01-01

    Abstract Acute allograft rejection remains common after liver transplantation despite modern immunosuppressive agents. In addition, the long‐term side effects of these regimens, including opportunistic infections, are challenging. This study evaluated the safety and clinical feasibility of umbilical cord‐derived mesenchymal stem cell (UC‐MSC) therapy in liver transplant patients with acute graft rejection. Twenty‐seven liver allograft recipients with acute rejection were randomly assigned int...

  1. 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.)

  2. [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.

  3. 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.

  4. Comparing independent microarray studies: the case of human embryonic stem cells

    Directory of Open Access Journals (Sweden)

    Hemmati-Brivanlou Ali

    2005-07-01

    Full Text Available Abstract Background Microarray studies of the same phenomenon in different labs often appear at variance because the published lists of regulated transcripts have disproportionately small intersections. We demonstrate that comparing studies by intersecting lists in this manner is methodologically flawed by reanalyzing three studies of the molecular signature of "stemness" in human embryonic stem cells. There are only 7 genes common to all three published lists, suggesting disagreement. Results Carefully reanalyzing all three together from the raw data we detect 111 genes upregulated and 95 downregulated in all three studies. The upregulated list was subject to rtRTPCR analysis and 75% of the genes were confirmed. Conclusion Our findings show that the three studies have a substantial core of common genes, which is missed if only the published lists are examined. Combined analysis of multiple experiments can be a powerful way to distil coherent conclusions.

  5. A genome editing approach to study cancer stem cells in human tumors.

    Science.gov (United States)

    Cortina, Carme; Turon, Gemma; Stork, Diana; Hernando-Momblona, Xavier; Sevillano, Marta; Aguilera, Mònica; Tosi, Sébastien; Merlos-Suárez, Anna; Stephan-Otto Attolini, Camille; Sancho, Elena; Batlle, Eduard

    2017-07-01

    The analysis of stem cell hierarchies in human cancers has been hampered by the impossibility of identifying or tracking tumor cell populations in an intact environment. To overcome this limitation, we devised a strategy based on editing the genomes of patient-derived tumor organoids using CRISPR/Cas9 technology to integrate reporter cassettes at desired marker genes. As proof of concept, we engineered human colorectal cancer (CRC) organoids that carry EGFP and lineage-tracing cassettes knocked in the LGR5 locus. Analysis of LGR5-EGFP + cells isolated from organoid-derived xenografts demonstrated that these cells express a gene program similar to that of normal intestinal stem cells and that they propagate the disease to recipient mice very efficiently. Lineage-tracing experiments showed that LGR5 + CRC cells self-renew and generate progeny over long time periods that undergo differentiation toward mucosecreting- and absorptive-like phenotypes. These genetic experiments confirm that human CRCs adopt a hierarchical organization reminiscent of that of the normal colonic epithelium. The strategy described herein may have broad applications to study cell heterogeneity in human tumors. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  6. Stem Cell Ophthalmology Treatment Study (SCOTS for retinal and optic nerve diseases: a preliminary report

    Directory of Open Access Journals (Sweden)

    Jeffrey N Weiss

    2015-01-01

    Full Text Available In this report, we present the results of a single patient with optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study (SCOTS. SCOTS is an Institutional Review Board approved clinical trial and is the largest ophthalmology stem cell study registered at the National Institutes of Health to date- www.clinicaltrials.gov Identifier NCT 01920867. SCOTS utilizes autologous bone marrow-derived stem cells in the treatment of optic nerve and retinal diseases. Pre- and post-treatment comprehensive eye exams were independently performed at the Wilmer Eye Institute at the Johns Hopkins Hospital, USA. A 27 year old female patient had lost vision approximately 5 years prior to enrollment in SCOTS. Pre-treatment best-corrected visual acuity at the Wilmer Eye Institute was 20/800 Right Eye (OD and 20/4,000 Left Eye (OS. Four months following treatment in SCOTS, the central visual acuity had improved to 20/100 OD and 20/40 OS.

  7. 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...

  8. 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)

  9. Of Microenvironments and Mammary Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    LaBarge, Mark A; Petersen, Ole W; Bissell, Mina J

    2007-06-01

    In most adult tissues there reside pools of stem and progenitor cells inside specialized microenvironments referred to as niches. The niche protects the stem cells from inappropriate expansion and directs their critical functions. Thus guided, stem cells are able to maintain tissue homeostasis throughout the ebb and flow of metabolic and physical demands encountered over a lifetime. Indeed, a pool of stem cells maintains mammary gland structure throughout development, and responds to the physiological demands associated with pregnancy. This review discusses how stem cells were identified in both human and mouse mammary glands; each requiring different techniques that were determined by differing biological needs and ethical constraints. These studies together create a robust portrait of mammary gland biology and identify the location of the stem cell niche, elucidate a developmental hierarchy, and suggest how the niche might be manipulated for therapeutic benefit.

  10. Experimental studies on the mechanism of leukemogenesis following the hemopoietic stem cell kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Bessho, Masami; Hirashima, Kunitake (National Inst. of Radiological Sciences, Chiba (Japan))

    1982-12-01

    The mechanism of radiation-induced myeloid leukemogenesis was studied experimentally following the hemopoietic stem cell kinetics. Pluripotent stem cells (CFU-S) regarded as target cells to Friend virus (FV) were highly susceptible to leukemic cell transformation by FV during the regeneration period after irradiation. Experimental studies using RFM mice revealed that (1) the period of leukemic transformation closely corresponded to the prolonged suppressive period of CFU-C after irradiation, when significantly increased fraction of CFU-C is in S-phase, (2) the leukemic cell transformation after irradiation occurred earlier and more frequently than the overt leukemia, (3) some unknown host factors except cellular immunity played an important role in the establishment of overt leukemia, (4) lipopolysaccharide administrated after irradiation increased the incidence of myeloid leukemia whereas urethane decreased it. Another experimental systems using C3H/He mice bearing CSF-producing tumor revealed that the incidence of myeloid leukemia after a low-dose irradiation increased when CFU-S and CFU-C were proliferating and differentiating actively by the stimulus of CSF produced by the tumor. The mechanism of this phenomenon can be regarded as the activation of leukemia virus in irradiated bodies.

  11. Limbal Stem Cell Deficiency and Treatment with Stem Cell Transplantation.

    Science.gov (United States)

    Barut Selver, Özlem; Yağcı, Ayşe; Eğrilmez, Sait; Gürdal, Mehmet; Palamar, Melis; Çavuşoğlu, Türker; Ateş, Utku; Veral, Ali; Güven, Çağrı; Wolosin, Jose Mario

    2017-10-01

    The cornea is the outermost tissue of the eye and it must be transparent for the maintenance of good visual function. The superficial epithelium of the cornea, which is renewed continuously by corneal stem cells, plays a critical role in the permanence of this transparency. These stem cells are localized at the cornea-conjunctival transition zone, referred to as the limbus. When this zone is affected/destroyed, limbal stem cell deficiency ensues. Loss of limbal stem cell function allows colonization of the corneal surface by conjunctival epithelium. Over 6 million people worldwide are affected by corneal blindness, and limbal stem cell deficiency is one of the main causes. Fortunately, it is becoming possible to recover vision by autologous transplantation of limbal cells obtained from the contralateral eye in unilateral cases. Due to the potential risks to the donor eye, only a small amount of tissue can be obtained, in which only 1-2% of the limbal epithelial cells are actually limbal stem cells. Vigorous attempts are being made to expand limbal stem cells in culture to preserve or even enrich the stem cell population. Ex vivo expanded limbal stem cell treatment in limbal stem cell deficiency was first reported in 1997. In the 20 years since, various protocols have been developed for the cultivation of limbal epithelial cells. It is still not clear which method promotes effective stem cell viability and this remains a subject of ongoing research. The most preferred technique for limbal cell culture is the explant culture model. In this approach, a small donor eye limbal biopsy is placed as an explant onto a biocompatible substrate (preferably human amniotic membrane) for expansion. The outgrowth (cultivated limbal epithelial cells) is then surgically transferred to the recipient eye. Due to changing regulations concerning cell-based therapy, the implementation of cultivated limbal epithelial transplantation in accordance with Good Laboratory Practice using

  12. Stem cells and cancer: A review

    Directory of Open Access Journals (Sweden)

    Najeeb Ullah

    2016-05-01

    Full Text Available Stem cells are the small units of multicellular creature. Regeneration and self-renewal are the ability of the stem cells. Each tissue is having particular stem cells, specific to it. These normal stem cells are converted into cancer stem cells through mutations in it. Although the expression of oncogenes is enhanced a lot, the tumor-supressing gene is lessened. Cancer stem cells are isolated and visualized through different techniques like immunocytochemical staining, spectral karyotyping, immunohistochemistry, induction method and dissection measures, then are performed histological procedures which include fascination, immunohistochemistry, dispensation, in situ hybridization and also quantitative examination of tissue flow cytometric analysis. For the analysis of quantization, statistical tests are also performed as two-sample t-test, Chi-square test, SD and arithmetic mean. Tumor cells generate glioma spheres. These are used in cancer study. Axin 1 is the gene suppressing cancer. Its removal causes the generation of liver cancer. Curcumin is the most effective for suppressing cancer as it increases the normal stem cell function and decreases the cancer stem cell function. Brahma-related gene 1 is crucial for the safeguarding of the stem cell residents in tissue-specific comportment. Different types of cancers originate through genetic mutation, tissue disorganization and cell proliferation. Tumor configuration is produced by the alteration in original cell culture having stem cells and progenitor cell populations. The developmental facets about cancer cells and cancer stem cells as well as their personal natal functions sustain an intricate steadiness to settle on their personal donations to the efficacy or harmfulness of the biological organization.

  13. Stem cells in dentistry--part I: stem cell sources.

    Science.gov (United States)

    Egusa, Hiroshi; Sonoyama, Wataru; Nishimura, Masahiro; Atsuta, Ikiru; Akiyama, Kentaro

    2012-07-01

    Stem cells can self-renew and produce different cell types, thus providing new strategies to regenerate missing tissues and treat diseases. In the field of dentistry, adult mesenchymal stem/stromal cells (MSCs) have been identified in several oral and maxillofacial tissues, which suggests that the oral tissues are a rich source of stem cells, and oral stem and mucosal cells are expected to provide an ideal source for genetically reprogrammed cells such as induced pluripotent stem (iPS) cells. Furthermore, oral tissues are expected to be not only a source but also a therapeutic target for stem cells, as stem cell and tissue engineering therapies in dentistry continue to attract increasing clinical interest. Part I of this review outlines various types of intra- and extra-oral tissue-derived stem cells with regard to clinical availability and applications in dentistry. Additionally, appropriate sources of stem cells for regenerative dentistry are discussed with regard to differentiation capacity, accessibility and possible immunomodulatory properties. Copyright © 2012 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  14. 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.

  15. Stem Cells for Skeletal Muscle Tissue Engineering.

    Science.gov (United States)

    Pantelic, Molly N; Larkin, Lisa M

    2018-04-19

    Volumetric muscle loss (VML) is a debilitating condition wherein muscle loss overwhelms the body's normal physiological repair mechanism. VML is particularly common among military service members who have sustained war injuries. Because of the high social and medical cost associated with VML and suboptimal current surgical treatments, there is great interest in developing better VML therapies. Skeletal muscle tissue engineering (SMTE) is a promising alternative to traditional VML surgical treatments that use autogenic tissue grafts, and rather uses isolated stem cells with myogenic potential to generate de novo skeletal muscle tissues to treat VML. Satellite cells are the native precursors to skeletal muscle tissue, and are thus the most commonly studied starting source for SMTE. However, satellite cells are difficult to isolate and purify, and it is presently unknown whether they would be a practical source in clinical SMTE applications. Alternative myogenic stem cells, including adipose-derived stem cells, bone marrow-derived mesenchymal stem cells, perivascular stem cells, umbilical cord mesenchymal stem cells, induced pluripotent stem cells, and embryonic stem cells, each have myogenic potential and have been identified as possible starting sources for SMTE, although they have yet to be studied in detail for this purpose. These alternative stem cell varieties offer unique advantages and disadvantages that are worth exploring further to advance the SMTE field toward highly functional, safe, and practical VML treatments. The following review summarizes the current state of satellite cell-based SMTE, details the properties and practical advantages of alternative myogenic stem cells, and offers guidance to tissue engineers on how alternative myogenic stem cells can be incorporated into SMTE research.

  16. Application of hanging drop technique for stem cell differentiation and cytotoxicity studies.

    Science.gov (United States)

    Banerjee, Meenal; Bhonde, Ramesh R

    2006-05-01

    The aim of our study is to explore the possibility of using an ancient method of culture technique- the hanging drop technique for stem cell differentiation and cytotoxicity testing. We demonstrate here a variety of novel applications of this age old technique not only to harness the differentiation potential of stem cells into specific lineages but also for cytotoxicity studies. Here we have prepared hanging drop cultures by placing 20 microl micro-drops of nutrient media and 10% Fetal Calf Serum (FCS) containing cells of interest on the lids of 60 mm dishes. Bottom plates of the dishes were filled with sterile Phosphate Buffer Saline (PBS) to avoid desiccation of samples. Lids were then placed on the bottom plates to achieve hanging drop cultures. We utilized this technique for cultivation of ciliated epithelia to study cytotoxicity and differentiation of bone marrow stromal cells. Most importantly the modified culture technique presented here is simple, economical and cost effective in terms of the time taken and the reagents required and are amenable to goal specific modification such as cytotoxicity testing. It is advantageous over the existing system in terms of retention of viability and functionality for longer duration and for providing three dimensional growth micro-environment making it useful for organotypic cultures and in vivo simulation.

  17. Study and Analysis of Congestion Management in Hybrid Electric Market

    Directory of Open Access Journals (Sweden)

    Moayed Mohseni

    2013-01-01

    Full Text Available The congestion management system is a systematic approach, collaboratively developed and implemented throughout a metropolitan region that provides for the safe and effective management and operation of new and existing transportation facilities through the use of demand reduction and operational management strat­e­gies. In this paper we try to present some points which should be investigated in congestion management problems. We calculate different kinds of congestion problems which may be occurred in our network. Here, the hybrid model is used to solve problems in the electricity market to solve the congestion problem in the network and Benders techniques is used together with an optimal power flow (OPF. In fact, by using of Benders algorithm the problem is divided into two major and minor problems. Therefore, the major problem related to the economy sector and no network is included and the minor problem is to solve the network and examine the accuracy of the network. Benders algorithm has been tested on a standard network IEEE 24 bus and Matlab software is used to implement the algorithm.

  18. Modelling and experimental study for automated congestion driving

    NARCIS (Netherlands)

    Urhahne, Joseph; Piastowski, P.; van der Voort, Mascha C.; Bebis, G; Boyle, R.; Parvin, B.; Koracin, D.; Pavlidis, I.; Feris, R.; McGraw, T.; Elendt, M.; Kopper, R.; Ragan, E.; Ye, Z.; Weber, G.

    2015-01-01

    Taking a collaborative approach in automated congestion driving with a Traffic Jam Assist system requires the driver to take over control in certain traffic situations. In order to warn the driver appropriately, warnings are issued (“pay attention” vs. “take action”) due to a control transition

  19. Characterization of neurons from immortalized dental pulp stem cells for the study of neurogenetic disorders

    Directory of Open Access Journals (Sweden)

    Nora Urraca

    2015-11-01

    Full Text Available A major challenge to the study and treatment of neurogenetic syndromes is accessing live neurons for study from affected individuals. Although several sources of stem cells are currently available, acquiring these involve invasive procedures, may be difficult or expensive to generate and are limited in number. Dental pulp stem cells (DPSCs are multipotent stem cells that reside deep the pulp of shed teeth. To investigate the characteristics of DPSCs that make them a valuable resource for translational research, we performed a set of viability, senescence, immortalization and gene expression studies on control DPSC and derived neurons. We investigated the basic transport conditions and maximum passage number for primary DPSCs. We immortalized control DPSCs using human telomerase reverse transcriptase (hTERT and evaluated neuronal differentiation potential and global gene expression changes by RNA-seq. We show that neurons from immortalized DPSCs share morphological and electrophysiological properties with non-immortalized DPSCs. We also show that differentiation of DPSCs into neurons significantly alters gene expression for 1305 transcripts. Here we show that these changes in gene expression are concurrent with changes in protein levels of the transcriptional repressor REST/NRSF, which is known to be involved in neuronal differentiation. Immortalization significantly altered the expression of 183 genes after neuronal differentiation, 94 of which also changed during differentiation. Our studies indicate that viable DPSCs can be obtained from teeth stored for ≥72 h, these can then be immortalized and still produce functional neurons for in vitro studies, but that constitutive hTERT immortalization is not be the best approach for long term use of patient derived DPSCs for the study of disease.

  20. Characterization of neurons from immortalized dental pulp stem cells for the study of neurogenetic disorders.

    Science.gov (United States)

    Urraca, Nora; Memon, Rawaha; El-Iyachi, Ikbale; Goorha, Sarita; Valdez, Colleen; Tran, Quynh T; Scroggs, Reese; Miranda-Carboni, Gustavo A; Donaldson, Martin; Bridges, Dave; Reiter, Lawrence T

    2015-11-01

    A major challenge to the study and treatment of neurogenetic syndromes is accessing live neurons for study from affected individuals. Although several sources of stem cells are currently available, acquiring these involve invasive procedures, may be difficult or expensive to generate and are limited in number. Dental pulp stem cells (DPSCs) are multipotent stem cells that reside deep the pulp of shed teeth. To investigate the characteristics of DPSCs that make them a valuable resource for translational research, we performed a set of viability, senescence, immortalization and gene expression studies on control DPSC and derived neurons. We investigated the basic transport conditions and maximum passage number for primary DPSCs. We immortalized control DPSCs using human telomerase reverse transcriptase (hTERT) and evaluated neuronal differentiation potential and global gene expression changes by RNA-seq. We show that neurons from immortalized DPSCs share morphological and electrophysiological properties with non-immortalized DPSCs. We also show that differentiation of DPSCs into neurons significantly alters gene expression for 1305 transcripts. Here we show that these changes in gene expression are concurrent with changes in protein levels of the transcriptional repressor REST/NRSF, which is known to be involved in neuronal differentiation. Immortalization significantly altered the expression of 183 genes after neuronal differentiation, 94 of which also changed during differentiation. Our studies indicate that viable DPSCs can be obtained from teeth stored for ≥72 h, these can then be immortalized and still produce functional neurons for in vitro studies, but that constitutive hTERT immortalization is not be the best approach for long term use of patient derived DPSCs for the study of disease. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Stem cell-based approaches in dentistry

    Directory of Open Access Journals (Sweden)

    TA Mitsiadis

    2011-11-01

    Full Text Available Repair of dental pulp and periodontal lesions remains a major clinical challenge. Classical dental treatments require the use of specialised tissue-adapted materials with still questionable efficacy and durability. Stem cell-based therapeutic approaches could offer an attractive alternative in dentistry since they can promise physiologically improved structural and functional outcomes. These therapies necessitate a sufficient number of specific stem cell populations for implantation. Dental mesenchymal stem cells can be easily isolated and are amenable to in vitro expansion while retaining their stemness. In vivo studies realised in small and large animals have evidenced the potential of dental mesenchymal stem cells to promote pulp and periodontal regeneration, but have also underlined new important challenges. The homogeneity of stem cell populations and their quality control, the delivery method, the quality of the regenerated dental tissues and their integration to the host tissue are some of the key challenges. The use of bioactive scaffolds that can elicit effective tissue repair response, through activation and mobilisation of endogenous stem cell populations, constitutes another emerging therapeutic strategy. Finally, the use of stem cells and induced pluripotent cells for the regeneration of entire teeth represents a novel promising alternative to dental implant treatment after tooth loss. In this mini-review, we present the currently applied techniques in restorative dentistry and the various attempts that are made to bridge gaps in knowledge regarding treatment strategies by translating basic stem cell research into the dental practice.

  2. Biochip-based study of unidirectional mitochondrial transfer from stem cells to myocytes via tunneling nanotubes

    International Nuclear Information System (INIS)

    Yang, Huaxiao; Gao, Bruce Z; Borg, Thomas K; Markwald, Roger; Ma, Zhen; Xu, Meifeng; Wetzel, George; Saraf, Laxmikant V; Runyan, Raymond B

    2016-01-01

    Tunneling nanotubes (TNTs) are small membranous tubes of 50–1000 nm diameter observed to connect cells in culture. Transfer of subcellular organelles through TNTs was observed in vitro and in vivo, but the formation and significance of these structures is not well understood. A polydimethylsiloxane biochip-based coculture model was devised to constrain TNT orientation and explore both TNT-formation and TNT-mediated mitochondrial transfer. Two parallel microfluidic channels connected by an array of smaller microchannels enabled localization of stem cell and cardiomyocyte populations while allowing connections to form between them. Stem cells and cardiomyocytes were deposited in their respective microfluidic channels, and stem cell-cardiomyocyte pairs were formed via the microchannels. Formation of TNTs and transfer of stained mitochondria through TNTs was observed by 24 h real-time video recording. The data show that stem cells are 7.7 times more likely to initiate contact by initial extension of filopodia. By 24 h, 67% of nanotube connections through the microchannels are composed of cardiomyocyte membrane. Filopodial extension and retraction by stem cells draws an extension of TNTs from cardiomyocytes. MitoTracker staining shows that unidirectional transfer of mitochondria between stem cell-cardiomyocyte pairs invariably originates from stem cells. Control experiments with cardiac fibroblasts and cardiomyocytes show little nanotube formation between homotypic or mixed cell pairs and no mitochondrial transfer. These data identify a novel biological process, unidirectional mitochondrial transfer, mediated by heterotypic TNT connections. This suggests that the enhancement of cardiomyocyte function seen after stem-cell injection may be due to a bioenergetic stimulus provided by mitochondrial transfer. (paper)

  3. Solid organ transplantation after allogeneic hematopoietic stem cell transplantation: a retrospective, multicenter study of the EBMT

    DEFF Research Database (Denmark)

    Koenecke, C; Hertenstein, B; Schetelig, J

    2010-01-01

    To analyze the outcome of solid organ transplantation (SOT) in patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT), a questionnaire survey was carried out within 107 European Group of Blood and Marrow Transplantation centers. This study covered HSCT between 1984...... for underlying malignant diseases was 4% at 5 years (95% CI, 0% to 12%). In summary, this study shows that selected patients receiving SOT after HSCT have a remarkably good overall and organ survival. These data indicate that SOT should be considered in selected patients with single organ failure after HSCT....

  4. Nonclinical safety strategies for stem cell therapies

    Energy Technology Data Exchange (ETDEWEB)

    Sharpe, Michaela E., E-mail: michaela_sharpe@yahoo.com [Investigative Toxicology, Drug Safety Research and Development, Pfizer Ltd, Ramsgate Road, Sandwich, CT13 9NJ (United Kingdom); Morton, Daniel [Exploratory Drug Safety, Drug Safety Research and Development, Pfizer Inc, Cambridge, 02140 (United States); Rossi, Annamaria [Investigative Toxicology, Drug Safety Research and Development, Pfizer Ltd, Ramsgate Road, Sandwich, CT13 9NJ (United Kingdom)

    2012-08-01

    Recent breakthroughs in stem cell biology, especially the development of the induced pluripotent stem cell techniques, have generated tremendous enthusiasm and efforts to explore the therapeutic potential of stem cells in regenerative medicine. Stem cell therapies are being considered for the treatment of degenerative diseases, inflammatory conditions, cancer and repair of damaged tissue. The safety of a stem cell therapy depends on many factors including the type of cell therapy, the differentiation status and proliferation capacity of the cells, the route of administration, the intended clinical location, long term survival of the product and/or engraftment, the need for repeated administration, the disease to be treated and the age of the population. Understanding the product profile of the intended therapy is crucial to the development of the nonclinical safety study design.

  5. Nonclinical safety strategies for stem cell therapies

    International Nuclear Information System (INIS)

    Sharpe, Michaela E.; Morton, Daniel; Rossi, Annamaria

    2012-01-01

    Recent breakthroughs in stem cell biology, especially the development of the induced pluripotent stem cell techniques, have generated tremendous enthusiasm and efforts to explore the therapeutic potential of stem cells in regenerative medicine. Stem cell therapies are being considered for the treatment of degenerative diseases, inflammatory conditions, cancer and repair of damaged tissue. The safety of a stem cell therapy depends on many factors including the type of cell therapy, the differentiation status and proliferation capacity of the cells, the route of administration, the intended clinical location, long term survival of the product and/or engraftment, the need for repeated administration, the disease to be treated and the age of the population. Understanding the product profile of the intended therapy is crucial to the development of the nonclinical safety study design.

  6. Open for business: a comparative study of websites selling autologous stem cells in Australia and Japan.

    Science.gov (United States)

    Munsie, Megan; Lysaght, Tamra; Hendl, Tereza; Tan, Hui-Yin Lynn; Kerridge, Ian; Stewart, Cameron

    2017-11-10

    This article examines online marketing practices of Japanese and Australian clinics offering putative autologous stem cell treatments. We conducted google searches for keywords related to stem cell therapy and stem cell clinics in English and Japanese. We identified websites promoting 88 point-of-sale clinics in Japan and 70 in Australia. Our findings provide further evidence of the rapid global growth in clinics offering unproven stem cell interventions. We also show that these clinics adopt strategies to promote their services as though they are consistent with evidentiary and ethical standards of science, research and medicine. Unless addressed, these practices risk harming not only vulnerable patients but also undermining public trust in science and medicine.

  7. Planarians as a model of aging to study the interaction between stem cells and senescent cells in vivo

    Directory of Open Access Journals (Sweden)

    Patrick M. Perrigue

    2015-12-01

    Full Text Available The depletion of stem cell pools and the accumulation of senescent cells in animal tissues are linked to aging. Planarians are invertebrate flatworms and are unusual in that their stem cells, called neoblasts, are constantly replacing old and dying cells. By eliminating neoblasts in worms via irradiation, the biological principles of aging are exposed in the absence of wound healing and regeneration, making planaria a powerful tool for aging research.

  8. Identification of WOX family genes in Selaginella kraussiana for studies on stem cells and regeneration in lycophytes

    Directory of Open Access Journals (Sweden)

    Yachao eGe

    2016-02-01

    Full Text Available Plant stem cells give rise to all tissues and organs and also serve as the source for plant regeneration. The organization of plant stem cells has undergone a progressive change from simple to complex during the evolution of vascular plants. Most studies on plant stem cells have focused on model angiosperms, the most recently diverged branch of vascular plants. However, our knowledge of stem cell function in other vascular plants is limited. Lycophytes and euphyllophytes (ferns, gymnosperms, and angiosperms are two existing branches of vascular plants that separated more than 400 million years ago. Lycophytes retain many of the features of early vascular plants. Based on genome and transcriptome data, we identified WUSCHEL-RELATED HOMEOBOX (WOX genes in Selaginella kraussiana, a model lycophyte that is convenient for in vitro culture and observations of organ formation and regeneration. WOX genes are key players controlling stem cells in plants. Our results showed that the S. kraussiana genome encodes at least eight members of the WOX family, which represent an early stage of WOX family evolution. Identification of WOX genes in S. kraussiana could be a useful tool for molecular studies on the function of stem cells in lycophytes.

  9. Mesenchymal stem cells in oral reconstructive surgery

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  10. Sensing radiosensitivity of human epidermal stem cells

    International Nuclear Information System (INIS)

    Rachidi, Walid; Harfourche, Ghida; Lemaitre, Gilles; Amiot, Franck; Vaigot, Pierre; Martin, Michele T.

    2007-01-01

    Purpose: Radiosensitivity of stem cells is a matter of debate. For mouse somatic stem cells, both radiosensitive and radioresistant stem cells have been described. By contrast, the response of human stem cells to radiation has been poorly studied. As epidermis is a radiosensitive tissue, we evaluated in the present work the radiosensitivity of cell populations enriched for epithelial stem cells of human epidermis. Methods and materials: The total keratinocyte population was enzymatically isolated from normal human skin. We used flow cytometry and antibodies against cell surface markers to isolate basal cell populations from human foreskin. Cell survival was measured after a dose of 2 Gy with the XTT assay at 72 h after exposure and with a clonogenic assay at 2 weeks. Transcriptome analysis using oligonucleotide microarrays was performed to assess the genomic cell responses to radiation. Results: Cell sorting based on two membrane proteins, α6 integrin and the transferrin receptor CD71, allowed isolation of keratinocyte populations enriched for the two types of cells found in the basal layer of epidermis: stem cells and progenitors. Both the XTT assay and the clonogenic assay showed that the stem cells were radioresistant whereas the progenitors were radiosensitive. We made the hypothesis that upstream DNA damage signalling might be different in the stem cells and used microarray technology to test this hypothesis. The stem cells exhibited a much more reduced gene response to a dose of 2 Gy than the progenitors, as we found that 6% of the spotted genes were regulated in the stem cells and 20% in the progenitors. Using Ingenuity Pathway Analysis software, we found that radiation exposure induced very specific pathways in the stem cells. The most striking responses were the repression of a network of genes involved in apoptosis and the induction of a network of cytokines and growth factors. Conclusion: These results show for the first time that keratinocyte

  11. Identification of Hematopoietic Stem Cell Engraftment Genes in Gene Therapy Studies.

    Science.gov (United States)

    Powers, John M; Trobridge, Grant D

    2013-09-01

    Hematopoietic stem cell (HSC) therapy using replication-incompetent retroviral vectors is a promising approach to provide life-long correction for genetic defects. HSC gene therapy clinical studies have resulted in functional cures for several diseases, but in some studies clonal expansion or leukemia has occurred. This is due to the dyregulation of endogenous host gene expression from vector provirus insertional mutagenesis. Insertional mutagenesis screens using replicating retroviruses have been used extensively to identify genes that influence oncogenesis. However, retroviral mutagenesis screens can also be used to determine the role of genes in biological processes such as stem cell engraftment. The aim of this review is to describe the potential for vector insertion site data from gene therapy studies to provide novel insights into mechanisms of HSC engraftment. In HSC gene therapy studies dysregulation of host genes by replication-incompetent vector proviruses may lead to enrichment of repopulating clones with vector integrants near genes that influence engraftment. Thus, data from HSC gene therapy studies can be used to identify novel candidate engraftment genes. As HSC gene therapy use continues to expand, the vector insertion site data collected will be of great interest to help identify novel engraftment genes and may ultimately lead to new therapies to improve engraftment.

  12. Study of internalization and viability of multimodal nanoparticles for labeling of human umbilical cord mesenchymal stem cells

    International Nuclear Information System (INIS)

    Miyaki, Liza Aya Mabuchi; Sibov, Tatiana Tais; Pavon, Lorena Favaro; Mamani, Javier Bustamante; Gamarra, Lionel Fernel

    2012-01-01

    Objective: To analyze multimodal magnetic nanoparticles-Rhodamine B in culture media for cell labeling, and to establish a study of multimodal magnetic nanoparticles-Rhodamine B detection at labeled cells evaluating they viability at concentrations of 10 μg Fe/mL and 100μg Fe/mL. Methods: We performed the analysis of stability of multimodal magnetic nanoparticles-Rhodamine B in different culture media; the mesenchymal stem cells labeling with multimodal magnetic nanoparticles-Rhodamine B; the intracellular detection of multimodal magnetic nanoparticles-Rhodamine B in mesenchymal stem cells, and assessment of the viability of labeled cells by kinetic proliferation. Results: The stability analysis showed that multimodal magnetic nanoparticles-Rhodamine B had good stability in cultured Dulbecco's Modified Eagle's-Low Glucose medium and RPMI 1640 medium. The mesenchymal stem cell with multimodal magnetic nanoparticles-Rhodamine B described location of intracellular nanoparticles, which were shown as blue granules co-localized in fluorescent clusters, thus characterizing magnetic and fluorescent properties of multimodal magnetic nanoparticles Rhodamine B. Conclusion: The stability of multimodal magnetic nanoparticles-Rhodamine B found in cultured Dulbecco's Modified Eagle's-Low Glucose medium and RPMI 1640 medium assured intracellular mesenchymal stem cells labeling. This cell labeling did not affect viability of labeled mesenchymal stem cells since they continued to proliferate for five days. (author)

  13. Stem Cell Transplantation from Bench to Bedside

    Indian Academy of Sciences (India)

    Table of contents. Stem Cell Transplantation from Bench to Bedside · Slide 2 · Slide 3 · Slide 4 · Principles of an allogeneic stem cell transplant · Principle of an allogeneic stem cell transplant · Principle of an autologous Stem Cell Transplant · Slide 8 · Conditioning · Slide 10 · Slide 11 · Stem Cell Transplantation · Slide 13.

  14. Congestion relief by travel time minimization in near real time : Detroit area I-75 corridor study.

    Science.gov (United States)

    2008-12-01

    "This document summarizes the activities concerning the project: Congestion Relief by : Travel Time Minimization in Near Real Time -- Detroit Area I-75 Corridor Study since : the inception of the project (Nov. 22, 2006 through September 30, 2008). : ...

  15. In Vitro Cardiomyogenic Potential of Human Amniotic Fluid Stem Cells

    OpenAIRE

    Guan, Xuan; Delo, Dawn M.; Atala, Anthony; Soker, Shay

    2011-01-01

    Stem cell therapy for damaged cardiac tissue is currently limited by a number of factors, including the inability to obtain sufficient cell numbers, the potential tumorigenicity of certain types of stem cells, and the possible link between stem cell therapy and the development of malignant arrhythmias. In this study, we investigated whether human amniotic fluid-derived stem (hAFS) cells could be a potential source of cells for cardiac cell therapy by testing the in vitro differentiation capab...

  16. Muscle Stem Cells: A Model System for Adult Stem Cell Biology.

    Science.gov (United States)

    Cornelison, Ddw; Perdiguero, Eusebio

    2017-01-01

    Skeletal muscle stem cells, originally termed satellite cells for their position adjacent to differentiated muscle fibers, are absolutely required for the process of skeletal muscle repair and regeneration. In the last decade, satellite cells have become one of the most studied adult stem cell systems and have emerged as a standard model not only in the field of stem cell-driven tissue regeneration but also in stem cell dysfunction and aging. Here, we provide background in the field and discuss recent advances in our understanding of muscle stem cell function and dysfunction, particularly in the case of aging, and the potential involvement of muscle stem cells in genetic diseases such as the muscular dystrophies.

  17. Stem cell Transplantation for Eradication of Minimal PAncreatic Cancer persisting after surgical Excision (STEM PACE Trial, ISRCTN47877138): study protocol for a phase II study

    International Nuclear Information System (INIS)

    Schmitz-Winnenthal, Friedrich H; Schmidt, Thomas; Lehmann, Monika; Beckhove, Philipp; Kieser, Meinhard; Ho, Anthony D; Dreger, Peter; Büchler, Markus W

    2014-01-01

    Pancreatic cancer is the third most common cancer related cause of death. Even in the 15% of patients who are eligible for surgical resection the outlook is dismal with less than 10% of patients surviving after 5 years. Allogeneic hematopoietic (allo-HSCT) stem cell transplantation is an established treatment capable of to providing cure in a variety of hematopoietic malignancies. Best results are achieved when the underlying neoplasm has been turned into a stage of minimal disease by chemotherapy. Allo-HSCT in advanced solid tumors including pancreatic cancer have been of limited success, however studies of allo-HSCT in solid tumors in minimal disease situations have never been performed. The aim of this trial is to provide evidence for the clinical value of allo-HSCT in pancreatic cancer put into a minimal disease status by effective surgical resection and standard adjuvant chemotherapy. The STEM PACE trial is a single center, phase II study to evaluate adjuvant allogeneic hematopoietic stem cell transplantation in pancreatic cancer after surgical resection. The study will evaluate as primary endpoint 2 year progression free survival and will generate first time state-of-the-art scientific clinical evidence if allo-HSCT is feasible and if it can provide long term disease control in patients with effectively resected pancreatic cancer. Screened eligible patients after surgical resection and standard adjuvant chemotherapy with HLA matched related stem cell donor can participate. Patients without a matched donor will be used as a historical control. Study patients will undergo standard conditioning for allo-HSCT followed by transplantation of allogeneic unmanipulated peripheral blood stem cells. The follow up of the patients will continue for 2 years. Secondary endpoints will be evaluated on 7 postintervention visits. The principal question addressed in this trial is whether allo-HSCT can change the unfavourable natural course of this disease. The underlying

  18. Biophysical regulation of stem cell differentiation.

    Science.gov (United States)

    Govey, Peter M; Loiselle, Alayna E; Donahue, Henry J

    2013-06-01

    Bone adaptation to its mechanical environment, from embryonic through adult life, is thought to be the product of increased osteoblastic differentiation from mesenchymal stem cells. In parallel with tissue-scale loading, these heterogeneous populations of multipotent stem cells are subject to a variety of biophysical cues within their native microenvironments. Bone marrow-derived mesenchymal stem cells-the most broadly studied source of osteoblastic progenitors-undergo osteoblastic differentiation in vitro in response to biophysical signals, including hydrostatic pressure, fluid flow and accompanying shear stress, substrate strain and stiffness, substrate topography, and electromagnetic fields. Furthermore, stem cells may be subject to indirect regulation by mechano-sensing osteocytes positioned to more readily detect these same loading-induced signals within the bone matrix. Such paracrine and juxtacrine regulation of differentiation by osteocytes occurs in vitro. Further studies are needed to confirm both direct and indirect mechanisms of biophysical regulation within the in vivo stem cell niche.

  19. Cartilage Repair With Autologous Bone Marrow Mesenchymal Stem Cell Transplantation: Review of Preclinical and Clinical Studies.

    Science.gov (United States)

    Yamasaki, Shinya; Mera, Hisashi; Itokazu, Maki; Hashimoto, Yusuke; Wakitani, Shigeyuki

    2014-10-01

    Clinical trials of various procedures, including bone marrow stimulation, mosaicplasty, and autologous chondrocyte implantation, have been explored to treat articular cartilage defects. However, all of them have some demerits. We focused on autologous culture-expanded bone marrow mesenchymal stem cells (BMSC), which can proliferate without losing their capacity for differentiation. First, we transplanted BMSC into the defective articular cartilage of rabbit and succeeded in regenerating osteochondral tissue. We then applied this transplantation in humans. Our previous reports showed that treatment with BMSC relieves the clinical symptoms of chondral defects in the knee and elbow joint. We investigated the efficacy of BMSC for osteoarthritic knee treated with high tibial osteotomy, by comparing 12 BMSC-transplanted patients with 12 cell-free patients. At 16-month follow-up, although the difference in clinical improvement between both groups was not significant, the arthroscopic and histological grading score was better in the cell-transplanted group. At the over 10-year follow-up, Hospital for Special Surgery knee scores improved to 76 and 73 in the BMSC-transplanted and cell-free groups, respectively, which were better than preoperative scores. Additionally, neither tumors nor infections were observed in all patients, and in the clinical study, we have never observed hypertrophy of repaired tissue, thereby guaranteeing the clinical safety of this therapy. Although we have never observed calcification above the tidemark in rabbit model and human histologically, the repair cartilage was not completely hyaline cartilage. To elucidate the optimum conditions for cell therapy, other stem cells, culture conditions, growth factors, and gene transfection methods should be explored.

  20. Human stromal (mesenchymal) stem cells

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  1. Haematopoietic stem and progenitor cells from human pluripotent stem cells

    Science.gov (United States)

    Sugimura, Ryohichi; Jha, Deepak Kumar; Han, Areum; Soria-Valles, Clara; da Rocha, Edroaldo Lummertz; Lu, Yi-Fen; Goettel, Jeremy A.; Serrao, Erik; Rowe, R. Grant; Malleshaiah, Mohan; Wong, Irene; Sousa, Patricia; Zhu, Ted N.; Ditadi, Andrea; Keller, Gordon; Engelman, Alan N.; Snapper, Scott B.; Doulatov, Sergei; Daley, George Q.

    2018-01-01

    A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts. We recover seven transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that are sufficient to convert haemogenic endothelium into haematopoietic stem and progenitor cells that engraft myeloid, B and T cells in primary and secondary mouse recipients. Our combined approach of morphogen-driven differentiation and transcription-factor-mediated cell fate conversion produces haematopoietic stem and progenitor cells from pluripotent stem cells and holds promise for modelling haematopoietic disease in humanized mice and for therapeutic strategies in genetic blood disorders. PMID:28514439

  2. Involvement of plant stem cells or stem cell-like cells in dedifferentiation

    Directory of Open Access Journals (Sweden)

    Fangwei eJiang

    2015-11-01

    Full Text Available Dedifferentiation is the transformation of cells from a given differentiated state to a less differentiated or stem cell-like state. Stem cell-related genes play important roles in dedifferentiation, which exhibits similar histone modification and DNA methylation features to stem cell maintenance. Hence, stem cell-related factors possibly synergistically function to provide a specific niche beneficial to dedifferentiation. During callus formation in Arabidopsis petioles, cells adjacent to procambium cells (stem cell-like cells are dedifferentiated and survive more easily than other cell types. This finding indicates that stem cells or stem cell-like cells may influence the dedifferentiating niche. In this paper, we provide a brief overview of stem cell maintenance and dedifferentiation regulation. We also summarize current knowledge of genetic and epigenetic mechanisms underlying the balance between differentiation and dedifferentiation. Furthermore, we discuss the correlation of stem cells or stem cell-like cells with dedifferentiation.

  3. Pluripotent stem cells and reprogrammed cells in farm animals.

    Science.gov (United States)

    Nowak-Imialek, Monika; Kues, Wilfried; Carnwath, Joseph W; Niemann, Heiner

    2011-08-01

    Pluripotent cells are unique because of their ability to differentiate into the cell lineages forming the entire organism. True pluripotent stem cells with germ line contribution have been reported for mice and rats. Human pluripotent cells share numerous features of pluripotentiality, but confirmation of their in vivo capacity for germ line contribution is impossible due to ethical and legal restrictions. Progress toward derivation of embryonic stem cells from domestic species has been made, but the derived cells were not able to produce germ line chimeras and thus are termed embryonic stem-like cells. However, domestic animals, in particular the domestic pig (Sus scrofa), are excellent large animals models, in which the clinical potential of stem cell therapies can be studied. Reprogramming technologies for somatic cells, including somatic cell nuclear transfer, cell fusion, in vitro culture in the presence of cell extracts, in vitro conversion of adult unipotent spermatogonial stem cells into germ line derived pluripotent stem cells, and transduction with reprogramming factors have been developed with the goal of obtaining pluripotent, germ line competent stem cells from domestic animals. This review summarizes the present state of the art in the derivation and maintenance of pluripotent stem cells in domestic animals.

  4. Stem cell therapy for inflammatory bowel disease

    OpenAIRE

    Duijvestein, Marjolijn

    2012-01-01

    Hematopoietic stem cell transplantation (HSCT) and mesenchymal stromal (MSC) cell therapy are currently under investigation as novel therapies for inflammatory bowel diseases (IBD). Hematopoietic stem cells are thought to repopulate the immune system and reset the immunological response to luminal antigens. MSCs have the capacity to differentiate into a wide variety of distinct cell lineages and to suppress immune responses in vitro and in vivo. The main goal of this thesis was to study the s...

  5. Stem cells in pharmaceutical biotechnology.

    Science.gov (United States)

    Zuba-Surma, Ewa K; Józkowicz, Alicja; Dulak, Józef

    2011-11-01

    Multiple populations of stem cells have been indicated to potentially participate in regeneration of injured organs. Especially, embryonic stem cells (ESC) and recently inducible pluripotent stem cells (iPS) receive a marked attention from scientists and clinicians for regenerative medicine because of their high proliferative and differentiation capacities. Despite that ESC and iPS cells are expected to give rise into multiple regenerative applications when their side effects are overcame during appropriate preparation procedures, in fact their most recent application of human ESC may, however, reside in their use as a tool in drug development and disease modeling. This review focuses on the applications of stem cells in pharmaceutical biotechnology. We discuss possible relevance of pluripotent cell stem populations in developing physiological models for any human tissue cell type useful for pharmacological, metabolic and toxicity evaluation necessary in the earliest steps of drug development. The present models applied for preclinical drug testing consist of primary cells or immortalized cell lines that show limitations in terms of accessibility or relevance to their in vivo counterparts. The availability of renewable human cells with functional similarities to their in vivo counterparts is the first landmark for a new generation of cell-based assays. We discuss the approaches for using stem cells as valuable physiological targets of drug activity which may increase the strength of target validation and efficacy potentially resulting in introducing new safer remedies into clinical trials and the marketplace. Moreover, we discuss the possible applications of stem cells for elucidating mechanisms of disease pathogenesis. The knowledge about the mechanisms governing the development and progression of multitude disorders which would come from the cellular models established based on stem cells, may give rise to new therapeutical strategies for such diseases. All

  6. Traffic congestion and blood pressure elevation: A comparative cross-sectional study in Lebanon.

    Science.gov (United States)

    Bou Samra, Patrick; El Tomb, Paul; Hosni, Mohammad; Kassem, Ahmad; Rizk, Robin; Shayya, Sami; Assaad, Sarah

    2017-12-01

    This comparative cross-sectional study examines the association between traffic congestion and elevation of systolic and/or diastolic blood pressure levels among a convenience sample of 310 drivers. Data collection took place during a gas station pause at a fixed time of day. Higher average systolic (142 vs 123 mm Hg) and diastolic (87 vs 78 mm Hg) blood pressures were detected among drivers exposed to traffic congestion compared with those who were not exposed (P<.001), while controlling for body mass index, age, sex, pack-year smoking, driving hours per week, and occupational driving. Moreover, among persons exposed to traffic congestion, longer exposure time was associated with higher systolic and diastolic blood pressures. Further studies are needed to better understand the mechanisms of the significant association between elevated blood pressure and traffic congestion. ©2017 Wiley Periodicals, Inc.

  7. Bioprinting for stem cell research

    Science.gov (United States)

    Tasoglu, Savas; Demirci, Utkan

    2012-01-01

    Recently, there has been a growing interest to apply bioprinting techniques to stem cell research. Several bioprinting methods have been developed utilizing acoustics, piezoelectricity, and lasers to deposit living cells onto receiving substrates. Using these technologies, spatially defined gradients of immobilized proteins can be engineered to direct stem cell differentiation into multiple subpopulations of different lineages. Stem cells can also be patterned in a high-throughput manner onto flexible implementation patches for tissue regeneration or onto substrates with the goal of accessing encapsulated stem cell of interest for genomic analysis. Here, we review recent achievements with bioprinting technologies in stem cell research, and identify future challenges and potential applications including tissue engineering and regenerative medicine, wound healing, and genomics. PMID:23260439

  8. Skin Stem Cells in Skin Cell Therapy

    Directory of Open Access Journals (Sweden)

    Mollapour Sisakht

    2015-12-01

    Full Text Available Context Preclinical and clinical research has shown that stem cell therapy is a promising therapeutic option for many diseases. This article describes skin stem cells sources and their therapeutic applications. Evidence Acquisition Compared with conventional methods, cell therapy reduces the surgical burden for patients because it is simple and less time-consuming. Skin cell therapy has been developed for variety of diseases. By isolation of the skin stem cell from the niche, in vitro expansion and transplantation of cells offers a surprising healing capacity profile. Results Stem cells located in skin cells have shown interesting properties such as plasticity, transdifferentiation, and specificity. Mesenchymal cells of the dermis, hypodermis, and other sources are currently being investigated to promote regeneration. Conclusions Because skin stem cells are highly accessible from autologous sources and their immunological profile is unique, they are ideal for therapeutic approaches. Optimization of administrative routes requires more investigation own to the lack of a standard protocol.

  9. A small molecule (pluripotin as a tool for studying cancer stem cell biology: proof of concept.

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    Susan D Mertins

    Full Text Available BACKGROUND: Cancer stem cells (CSC are thought to be responsible for tumor maintenance and heterogeneity. Bona fide CSC purified from tumor biopsies are limited in supply and this hampers study of CSC biology. Furthermore, purified stem-like CSC subpopulations from existing tumor lines are unstable in culture. Finding a means to overcome these technical challenges would be a useful goal. In a first effort towards this, we examined whether a chemical probe that promotes survival of murine embryonic stem cells without added exogenous factors can alter functional characteristics in extant tumor lines in a fashion consistent with a CSC phenotype. METHODOLOGY/PRINCIPAL FINDINGS: The seven tumor lines of the NCI60 colon subpanel were exposed to SC-1 (pluripotin, a dual kinase and GTPase inhibitor that promotes self-renewal, and then examined for tumorigenicity under limiting dilution conditions and clonogenic activity in soft agar. A statistically significant increase in tumor formation following SC-1 treatment was observed (p<0.04. Cloning efficiencies and expression of putative CSC surface antigens (CD133 and CD44 were also increased. SC-1 treatment led to sphere formation in some colon tumor lines. Finally, SC-1 inhibited in vitro kinase activity of RSK2, and another RSK2 inhibitor increased colony formation implicating a role for this kinase in eliciting a CSC phenotype. CONCLUSIONS/SIGNIFICANCE: These findings validate a proof of concept study exposure of extant tumor lines to a small molecule may provide a tractable in vitro model for understanding CSC biology.

  10. Stem cell-based treatments against stroke: observations from human proof-of-concept studies and considerations regarding clinical applicability

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    Thorsten Roland Doeppner

    2014-10-01

    Full Text Available Ischemic stroke remains a heavy burden for industrialized countries. The only causal therapy is the recanalization of occluded vessels via thrombolysis, which due to a narrow time window still can be offered only to a minority of patients. Since the majority of patients continues to exhibit neurological deficits even following successful thrombolysis, restorative therapies are urgently needed that promote brain remodeling and repair once stroke injury has occurred. Due to their unique properties of action, stem cell-based strategies gained increasing interest during recent years. Using various stroke models in both rodents and primates, the transplantation of stem cells, namely of bone marrow derived mesenchymal stem cells (MSCs or neural progenitor cells (NPCs, has been shown to promote neurological recovery most likely via indirect bystander actions. In view of promising observations, clinical proof-of-concept studies are currently under way, in which effects of stem and precursor cells are evaluated in human stroke patients. In this review we summarize already published studies, which due to the broad experience in other medical contexts mostly employed bone marrow-derived MSCs by means of intravenous transplantation. With the overall number of clinical trials limited in number, only a fraction of these studies used non-treated control groups, and only single studies were adequately blinded. Despite these limitations, first promising results justify the need for more elaborate clinical trials in order to make stem cell transplantation a success for stroke treatment in the future.

  11. Stem Cells and Tissue Engineering

    CERN Document Server

    Pavlovic, Mirjana

    2013-01-01

    Stem cells are the building blocks for all other cells in an organism. The human body has about 200 different types of cells and any of those cells can be produced by a stem cell. This fact emphasizes the significance of stem cells in transplantational medicine, regenerative therapy and bioengineering. Whether embryonic or adult, these cells can be used for the successful treatment of a wide range of diseases that were not treatable before, such as osteogenesis imperfecta in children, different forms of leukemias, acute myocardial infarction, some neural damages and diseases, etc. Bioengineering, e.g. successful manipulation of these cells with multipotential capacity of differentiation toward appropriate patterns and precise quantity, are the prerequisites for successful outcome and treatment. By combining in vivo and in vitro techniques, it is now possible to manage the wide spectrum of tissue damages and organ diseases. Although the stem-cell therapy is not a response to all the questions, it provides more...

  12. Spermatogonial stem cells: Progress and prospects

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    Mitsuru Komeya

    2015-01-01

    Full Text Available Twenty years ago, the transplantation of spermatogonial stem cells (SSCs from a mouse to other recipient mice was shown to be feasible, which clearly demonstrated the functional identity of SSCs. Since then, several important new findings and other technical developments have followed, which included a new hypothesis on their cell kinetics and spermatogonial hierarchy in the testis, a culture method allowing their self-renewal and proliferation, a testis tissue organ culture method, which induced their complete differentiation up to sperm, and the in vitro induction of germ cells from embryonic stem cells and induced pluripotent stem cells. These advancements reinforced or advanced our understanding of this unique cell. Nonetheless, there are many unresolved questions in the study of spermatogonial stem cells and a long road remains until these cells can be used clinically in reproductive medicine.

  13. Stem Cell-Based Therapies for Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Lei Hao

    2014-01-01

    Full Text Available In recent years, stem cell-based approaches have attracted more attention from scientists and clinicians due to their possible therapeutical effect on stroke. Animal studies have demonstrated that the beneficial effects of stem cells including embryonic stem cells (ESCs, inducible pluripotent stem cells (iPSCs, neural stem cells (NSCs, and mesenchymal stem cell (MSCs might be due to cell replacement, neuroprotection, endogenous neurogenesis, angiogenesis, and modulation on inflammation and immune response. Although several clinical studies have shown the high efficiency and safety of stem cell in stroke management, mainly MSCs, some issues regarding to cell homing, survival, tracking, safety, and optimal cell transplantation protocol, such as cell dose and time window, should be addressed. Undoubtably, stem cell-based gene therapy represents a novel potential therapeutic strategy for stroke in future.

  14. Milestones of Hematopoietic Stem Cell Transplantation – From First Human Studies to Current Developments

    Science.gov (United States)

    Juric, Mateja Kralj; Ghimire, Sakhila; Ogonek, Justyna; Weissinger, Eva M.; Holler, Ernst; van Rood, Jon J.; Oudshoorn, Machteld; Dickinson, Anne; Greinix, Hildegard T.

    2016-01-01

    Since the early beginnings, in the 1950s, hematopoietic stem cell transplantation (HSCT) has become an established curative treatment for an increasing number of patients with life-threatening hematological, oncological, hereditary, and immunological diseases. This has become possible due to worldwide efforts of preclinical and clinical research focusing on issues of transplant immunology, reduction of transplant-associated morbidity, and mortality and efficient malignant disease eradication. The latter has been accomplished by potent graft-versus-leukemia (GvL) effector cells contained in the stem cell graft. Exciting insights into the genetics of the human leukocyte antigen (HLA) system allowed improved donor selection, including HLA-identical related and unrelated donors. Besides bone marrow, other stem cell sources like granulocyte-colony stimulating-mobilized peripheral blood stem cells and cord blood stem cells have been established in clinical routine. Use of reduced-intensity or non-myeloablative conditioning regimens has been associated with a marked reduction of non-hematological toxicities and eventually, non-relapse mortality allowing older patients and individuals with comorbidities to undergo allogeneic HSCT and to benefit from GvL or antitumor effects. Whereas in the early years, malignant disease eradication by high-dose chemotherapy or radiotherapy was the ultimate goal; nowadays, allogeneic HSCT has been recognized as cellular immunotherapy relying prominently on immune mechanisms and to a lesser extent on non-specific direct cellular toxicity. This chapter will summarize the key milestones of HSCT and introduce current developments. PMID:27881982

  15. The Rabbit as a Model for Studying Lung Disease and Stem Cell Therapy

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    Nurfatin Asyikhin Kamaruzaman

    2013-01-01

    Full Text Available No single animal model can reproduce all of the human features of both acute and chronic lung diseases. However, the rabbit is a reliable model and clinically relevant facsimile of human disease. The similarities between rabbits and humans in terms of airway anatomy and responses to inflammatory mediators highlight the value of this species in the investigation of lung disease pathophysiology and in the development of therapeutic agents. The inflammatory responses shown by the rabbit model, especially in the case of asthma, are comparable with those that occur in humans. The allergic rabbit model has been used extensively in drug screening tests, and this model and humans appear to be sensitive to similar drugs. In addition, recent studies have shown that the rabbit serves as a good platform for cell delivery for the purpose of stem-cell-based therapy.

  16. Stem cells in endodontic therapy

    Directory of Open Access Journals (Sweden)

    Sita Rama Kumar M, Madhu Varma K, Kalyan Satish R, Manikya kumar Nanduri.R, Murali Krishnam Raju S, Mohan rao

    2014-11-01

    Full Text Available Stem cells have the remarkable potential to develop into many different cell types in the body. Serving as a sort of repair system for the body, they can theoretically divide without limit to replenish other cells as long as the person or animal is still alive. However, progress in stem cell biology and tissue engineering may present new options for replacing heavily damaged or lost teeth, or even individual tooth structures. The goal of this review is to discuss the potential impact of dental pulp stem cells on regenerative endodontics.

  17. Study on human mesenchymal stem cells from bone marrow pretreated with low dose radiation

    International Nuclear Information System (INIS)

    Yang Yan; Wang Guangjun; Wang Juan

    2008-01-01

    Objective: To study effects of human bone marrow mesenchymal stem cells (hBM-MSC) from bone marrow pretreated with low dose radiation (LDR). Methods: The cells were the hBM-MSC. They were exposed to X rays at the dose of 50 mGy, 75 mGy, 100 mGy (dose rate 12.5 mGy/min). The growth curve, cell cycle and apoptosis of hBM-MSC treated by LDR were investigated. The content changes of stem cell factor(SCF), interleukin-6 (IL-6), macrophage colony stimulating factor(M-CSF) secreted by hBM-MSC after treated by LDR were determined by enzyme linked immunosorbent assay method. Results: The growth rates of hBM-MSC treated by LDR obviously increase from 72 h. The cell cycle and apoptosis were examined with FORTRAN Atomatic Checkout Systom. The results show that the G 0 /G 1 stage cells decrease after exposure to LDR, the percent of G 0 /G 1 stage cells of 75 mGy at 72 h is the lowest(30.86%). However, the S stage cells percentage gradually increase at 48 h and 72 h. The most one is 75 mGy group at 72 h, which reaches to 68.88%. The apoptosis percentages have increased tendency at 24 h and 48h in all dose groups, especially in 100 mGy at 24 h(25.99%), while have decreased tendency at 72 h and the most decreased group is the 50 mGy(6.8%), transient enhancement of apoptosis in the early stage and soon being decreased. The contents of SCF have increased tendency at 24 h, 48 h. As for IL-6, the contents in different dose groups at 24 h and 48 h have up-regulation. These groups, 50 mGy at 24 h, 48 h, 75 mGy at 24 h, 48 h, 100 mGy at 24 h have statistical difference compared with their control groups respectively. The content of IL-6 has greatest enhancement at dose of 50 mGy. The contents of M-SCF in all the groups at 24 h, 48 h and 72 h except for the 50 mGy dose at 72 h have also been found increased. The greatest increased content occur in the 75 mGy dose group at 72 h. Conclusion: This conclusion show that LDR has hormesis effect on hBM-MSC in cell growth, cell cycle and content

  18. The experimental study of genetic engineering human neural stem cells mediated by lentivirus to express multigene.

    Science.gov (United States)

    Cai, Pei-qiang; Tang, Xun; Lin, Yue-qiu; Martin, Oudega; Sun, Guang-yun; Xu, Lin; Yang, Yun-kang; Zhou, Tian-hua

    2006-02-01

    To explore the feasibility to construct genetic engineering human neural stem cells (hNSCs) mediated by lentivirus to express multigene in order to provide a graft source for further studies of spinal cord injury (SCI). Human neural stem cells from the brain cortex of human abortus were isolated and cultured, then gene was modified by lentivirus to express both green fluorescence protein (GFP) and rat neurotrophin-3 (NT-3); the transgenic expression was detected by the methods of fluorescence microscope, dorsal root ganglion of fetal rats and slot blot. Genetic engineering hNSCs were successfully constructed. All of the genetic engineering hNSCs which expressed bright green fluorescence were observed under the fluorescence microscope. The conditioned medium of transgenic hNSCs could induce neurite flourishing outgrowth from dorsal root ganglion (DRG). The genetic engineering hNSCs expressed high level NT-3 which could be detected by using slot blot. Genetic engineering hNSCs mediated by lentivirus can be constructed to express multigene successfully.

  19. Stem Cell Transplants (For Parents)

    Science.gov (United States)

    ... of Transplants Transplantation Recovery Coping Print en español Trasplantes de células madre Stem cells are cells in ... finding a match is called tissue typing (or HLA [human leukocyte antigen] typing). HLA is a protein ...

  20. Lasers, stem cells, and COPD

    Directory of Open Access Journals (Sweden)

    De Necochea-Campion Rosalia

    2010-02-01

    Full Text Available Abstract The medical use of low level laser (LLL irradiation has been occurring for decades, primarily in the area of tissue healing and inflammatory conditions. Despite little mechanistic knowledge, the concept of a non-invasive, non-thermal intervention that has the potential to modulate regenerative processes is worthy of attention when searching for novel methods of augmenting stem cell-based therapies. Here we discuss the use of LLL irradiation as a "photoceutical" for enhancing production of stem cell growth/chemoattractant factors, stimulation of angiogenesis, and directly augmenting proliferation of stem cells. The combination of LLL together with allogeneic and autologous stem cells, as well as post-mobilization directing of stem cells will be discussed.

  1. Mesenchymal stem cells with osteogenic potential in human maxillary sinus membrane: an in vitro study.

    Science.gov (United States)

    Berbéri, Antoine; Al-Nemer, Fatima; Hamade, Eva; Noujeim, Ziad; Badran, Bassam; Zibara, Kazem

    2017-06-01

    The aim of our study is to prove and validate the existence of an osteogenic progenitor cell population within the human maxillary Schneiderian sinus membrane (hMSSM) and to demonstrate their potential for bone formation. Ten hMSSM samples of approximately 2 × 2 cm were obtained during a surgical nasal approach for treatment of chronic rhinosinusitis and were retained for this study. The derived cells were isolated, cultured, and assayed at passage 3 for their osteogenic potential using the expression of Alkaline phosphatase, alizarin red and Von Kossa staining, flow cytometry, and quantitative real-time polymerase chain reaction. hMSSM-derived cells were isolated, showed homogenous spindle-shaped fibroblast-like morphology, characteristic of mesenchymal progenitor cells (MPCs), and demonstrated very high expression of MPC markers such as STRO-1, CD44, CD90, CD105, and CD73 in all tested passages. In addition, von Kossa and Alizarin red staining showed significant mineralization, a typical feature of osteoblasts. Moreover, alkaline phosphatase (ALP) activity was significantly increased at days 7, 14, 21, and 28 of culture in hMSSM-derived cells grown in osteogenic medium, in comparison to controls. Furthermore, osteogenic differentiation significantly upregulated the transcriptional expression of osteogenic markers such as ALP, Runt-related transcription factor 2 (Runx-2), bone morphogenetic protein (BMP)-2, osteocalcin (OCN), osteonectin (ON), and osteopontin (OPN), confirming that hMSSM-derived cells are of osteoprogenitor origin. Finally, hMSSM-derived cells were also capable of producing OPN proteins upon culturing in an osteogenic medium. Our data showed that hMSSM holds mesenchymal osteoprogenitor cells capable of differentiating to the osteogenic lineage. hMSSM contains potentially multipotent postnatal stem cells providing a promising clinical application in preimplant and implant therapy.

  2. A multifunctional 3D co-culture system for studies of mammary tissue morphogenesis and stem cell biology.

    Directory of Open Access Journals (Sweden)

    Jonathan J Campbell

    Full Text Available Studies on the stem cell niche and the efficacy of cancer therapeutics require complex multicellular structures and interactions between different cell types and extracellular matrix (ECM in three dimensional (3D space. We have engineered a 3D in vitro model of mammary gland that encompasses a defined, porous collagen/hyaluronic acid (HA scaffold forming a physiologically relevant foundation for epithelial and adipocyte co-culture. Polarized ductal and acinar structures form within this scaffold recapitulating normal tissue morphology in the absence of reconstituted basement membrane (rBM hydrogel. Furthermore, organoid developmental outcome can be controlled by the ratio of collagen to HA, with a higher HA concentration favouring acinar morphological development. Importantly, this culture system recapitulates the stem cell niche as primary mammary stem cells form complex organoids, emphasising the utility of this approach for developmental and tumorigenic studies using genetically altered animals or human biopsy material, and for screening cancer therapeutics for personalised medicine.

  3. Stem cell factor supports migration in canine mesenchymal stem cells.

    Science.gov (United States)

    Enciso, Nathaly; Ostronoff, Luciana L K; Mejías, Guillermo; León, Leticia G; Fermín, María Luisa; Merino, Elena; Fragio, Cristina; Avedillo, Luis; Tejero, Concepción

    2018-03-01

    Adult Mesenchymal Stem Cells (MSC) are cells that can be defined as multipotent cells able to differentiate into diverse lineages, under appropriate conditions. These cells have been widely used in regenerative medicine, both in preclinical and clinical settings. Initially discovered in bone marrow, MSC can now be isolated from a wide spectrum of adult and foetal tissues. Studies to evaluate the therapeutic potential of these cells are based on their ability to arrive to damaged tissues. In this paper we have done a comparative study analyzing proliferation, surface markers and OCT4, SOX9, RUNX2, PPARG genes expression in MSC cells from Bone marrow (BMMSC) and Adipose tissue (ASC). We also analyzed the role of Stem Cell Factor (SCF) on MSC proliferation and on ASCs metalloproteinases MMP-2, MMP-9 secretion. Healthy dogs were used as BMMSC donors, and ASC were collected from omentum during elective ovariohysterectomy surgery. Both cell types were cultured in IMDM medium with or without SCF, 10% Dog Serum (DS), and incubated at 38 °C with 5% CO2. Growth of BMMSCs and ASCs was exponential until 25-30 days. Flow citometry of MSCs revealed positive results for CD90 and negative for CD34, CD45 and MCH-II. Genes were evaluated by RT-PCR and metalloproteinases by zymografy. Our findings indicate morphological and immunological similarities as well as expression of genes from both origins on analyzed cells. Furthermore, SCF did not affect proliferation of MSCs, however it up-regulated MMP-2 and MMP-9 secretion in ASCs. These results suggest that metalloproteinases are possibly essential molecules pivoting migration.

  4. Connecting Mitochondria, Metabolism, and Stem Cell Fate

    Science.gov (United States)

    Wanet, Anaïs; Arnould, Thierry; Najimi, Mustapha

    2015-01-01

    As sites of cellular respiration and energy production, mitochondria play a central role in cell metabolism. Cell differentiation is associated with an increase in mitochondrial content and activity and with a metabolic shift toward increased oxidative phosphorylation activity. The opposite occurs during reprogramming of somatic cells into induced pluripotent stem cells. Studies have provided evidence of mitochondrial and metabolic changes during the differentiation of both embryonic and somatic (or adult) stem cells (SSCs), such as hematopoietic stem cells, mesenchymal stem cells, and tissue-specific progenitor cells. We thus propose to consider those mitochondrial and metabolic changes as hallmarks of differentiation processes. We review how mitochondrial biogenesis, dynamics, and function are directly involved in embryonic and SSC differentiation and how metabolic and sensing pathways connect mitochondria and metabolism with cell fate and pluripotency. Understanding the basis of the crosstalk between mitochondria and cell fate is of critical importance, given the promising application of stem cells in regenerative medicine. In addition to the development of novel strategies to improve the in vitro lineage-directed differentiation of stem cells, understanding the molecular basis of this interplay could lead to the identification of novel targets to improve the treatment of degenerative diseases. PMID:26134242

  5. Congestive heart failure effects on atrial fibroblast phenotype: differences between freshly-isolated and cultured cells.

    Directory of Open Access Journals (Sweden)

    Kristin Dawson

    Full Text Available Fibroblasts are important in the atrial fibrillation (AF substrate resulting from congestive heart failure (CHF. We previously noted changes in in vivo indices of fibroblast function in a CHF dog model, but could not detect changes in isolated cells. This study assessed CHF-induced changes in the phenotype of fibroblasts freshly isolated from control versus CHF dogs, and examined effects of cell culture on these differences.Left-atrial fibroblasts were isolated from control and CHF dogs (ventricular tachypacing 240 bpm × 2 weeks. Freshly-isolated fibroblasts were compared to fibroblasts in primary culture. Extracellular-matrix (ECM gene-expression was assessed by qPCR, protein by Western blot, fibroblast morphology with immunocytochemistry, and K(+-current with patch-clamp. Freshly-isolated CHF fibroblasts had increased expression-levels of collagen-1 (10-fold, collagen-3 (5-fold, and fibronectin-1 (3-fold vs. control, along with increased cell diameter (13.4 ± 0.4 µm vs control 8.4 ± 0.3 µm and cell spreading (shape factor 0.81 ± 0.02 vs. control 0.87 ± 0.02, consistent with an activated phenotype. Freshly-isolated control fibroblasts displayed robust tetraethylammonium (TEA-sensitive K(+-currents that were strongly downregulated in CHF. The TEA-sensitive K(+-current differences between control and CHF fibroblasts were attenuated after 2-day culture and eliminated after 7 days. Similarly, cell-culture eliminated the ECM protein-expression and shape differences between control and CHF fibroblasts.Freshly-isolated CHF and control atrial fibroblasts display distinct ECM-gene and morphological differences consistent with in vivo pathology. Culture for as little as 48 hours activates fibroblasts and obscures the effects of CHF. These results demonstrate potentially-important atrial-fibroblast phenotype changes in CHF and emphasize the need for caution in relating properties of cultured fibroblasts to in vivo systems.

  6. Bone regeneration and stem cells

    Science.gov (United States)

    Arvidson, K; Abdallah, B M; Applegate, L A; Baldini, N; Cenni, E; Gomez-Barrena, E; Granchi, D; Kassem, M; Konttinen, Y T; Mustafa, K; Pioletti, D P; Sillat, T; Finne-Wistrand, A

    2011-01-01

    Abstract This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed. PMID:21129153

  7. Bone regeneration and stem cells

    DEFF Research Database (Denmark)

    Arvidson, K; Abdallah, B M; Applegate, L A

    2011-01-01

    cells, use of platelet rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed.......This invited review covers research areas of central importance for orthopedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and fetal stem cells, effects of sex steroids on mesenchymal stem...

  8. Culture & differentiation of mesenchymal stem cell into osteoblast on degradable biomedical composite scaffold: In vitro study

    Directory of Open Access Journals (Sweden)

    Krishan G Jain

    2015-01-01

    Full Text Available Background & objectives: There is a significant bone tissue loss in patients from diseases and traumatic injury. The current autograft transplantation gold standard treatment has drawbacks, namely donor site morbidity and limited supply. The field of tissue engineering has emerged with a goal to provide alternative sources for transplantations to bridge this gap between the need and lack of bone graft. The aim of this study was to prepare biocomposite scaffolds based on chitosan (CHT, polycaprolactone (PCL and hydroxyapatite (HAP by freeze drying method and to assess the role of scaffolds in spatial organization, proliferation, and osteogenic differentiation of human mesenchymal stem cells (hMSCs in vitro, in order to achieve bone graft substitutes with improved physical-chemical and biological properties. Methods: Pure chitosan (100CHT and composites (40CHT/HAP, 30CHT/HAP/PCL and 25CHT/HAP/PCL scaffolds containing 40, 30, 25 parts per hundred resin (phr filler, respectively in acetic acid were freeze dried and the porous foams were studied for physicochemical and in vitro biological properties. Results: Scanning electron microscope (SEM images of the scaffolds showed porous microstructure (20-300 μm with uniform pore distribution in all compositions. Materials were tested under compressive load in wet condition (using phosphate buffered saline at pH 7.4. The in vitro studies showed that all the scaffold compositions supported mesenchymal stem cell attachment, proliferation and differentiation as visible from SEM images, [3-(4,5-dimethylthiazole-2-yl-2,5-diphenyltetrazolium bromide] (MTT assay, alkaline phosphatase (ALP assay and quantitative reverse transcription (qRT-PCR. Interpretation & conclusions: Scaffold composition 25CHT/HAP/PCL showed better biomechanical and osteoinductive properties as evident by mechanical test and alkaline phosphatase activity and osteoblast specific gene expression studies. This study suggests that this novel

  9. Study of the application potential of synthetic and natural polymeric coatings in stem cell research

    OpenAIRE

    Perestrelo, Ana Rubina

    2014-01-01

    Self-renewability and the ability to differentiate into various functional cells are characteristics of embryonic stem cells (ESCs) that make them attractive for applications in biomedical field, namely in restoring the function of damaged cells/tissues. In research, ESCs are usually cultured in gelatin or over a monolayer of mitotically inactivated mouse embryonic fibroblasts (MEFsi). The latter is the gold standard to maintain pluripotent ESCs in culture. A variety of alterna...

  10. Therapeutic potential of stem cells in auditory hair cell repair

    Directory of Open Access Journals (Sweden)

    Ryuji Hata

    2009-01-01

    Full Text Available The prevalence of acquired hearing loss is very high. About 10% of the total population and more than one third of the population over 65 years suffer from debilitating hearing loss. The most common type of hearing loss in adults is idiopathic sudden sensorineural hearing loss (ISSHL. In the majority of cases, ISSHL is permanent and typically associated with loss of sensory hair cells in the organ of Corti. Following the loss of sensory hair cells, the auditory neurons undergo secondary degeneration. Sensory hair cells and auditory neurons do not regenerate throughout life, and loss of these cells is irreversible and cumulative. However, recent advances in stem cell biology have gained hope that stem cell therapy comes closer to regenerating sensory hair cells in humans. A major advance in the prospects for the use of stem cells to restore normal hearing comes with the recent discovery that hair cells can be generated ex vivo from embryonic stem (ES cells, adult inner ear stem cells and neural stem cells. Furthermore, there is increasing evidence that stem cells can promote damaged cell repair in part by secreting diffusible molecules such as growth factors. These results suggest that stem-cell-based treatment regimens can be applicable to the damaged inner ear as future clinical applications.Previously we have established an animal model of cochlear ischemia in gerbils and showed progressive hair cell loss up to 4 days after ischemia. Auditory brain stem response (ABR recordings have demonstrated that this gerbil model displays severe deafness just after cochlear ischemia and gradually recovers thereafter. These pathological findings and clinical manifestations are reminiscent of ISSHL in humans. In this study, we have shown the effectiveness of stem cell therapy by using this animal model of ISSHL.

  11. Mammary Stem Cells and Breast Cancer Stem Cells: Molecular Connections and Clinical Implications.

    Science.gov (United States)

    Celià-Terrassa, Toni

    2018-05-04

    Cancer arises from subpopulations of transformed cells with high tumor initiation and repopulation ability, known as cancer stem cells (CSCs), which share many similarities with their normal counterparts. In the mammary gland, several studies have shown common molecular regulators between adult mammary stem cells (MaSCs) and breast cancer stem cells (bCSCs). Cell plasticity and self-renewal are essential abilities for MaSCs to maintain tissue homeostasis and regenerate the gland after pregnancy. Intriguingly, these properties are similarly executed in breast cancer stem cells to drive tumor initiation, tumor heterogeneity and recurrence after chemotherapy. In addition, both stem cell phenotypes are strongly influenced by external signals from the microenvironment, immune cells and supportive specific niches. This review focuses on the intrinsic and extrinsic connections of MaSC and bCSCs with clinical implications for breast cancer progression and their possible therapeutic applications.

  12. Stem cells and respiratory diseases

    Directory of Open Access Journals (Sweden)

    Soraia Carvalho Abreu

    2008-12-01

    Full Text Available Stem cells have a multitude of clinical implications in the lung. This article is a critical review that includes clinical and experimental studies of MedLine and SciElo database in the last 10 years, where we highlight the effects of stem cell therapy in acute respiratory distress syndrome or more chronic disorders such as lung fibrosis and emphysema. Although, many studies have shown the beneficial effects of stem cells in lung development, repair and remodeling; some important questions need to be answered to better understand the mechanisms that control cell division and differentiation, therefore enabling the use of cell therapy in human respiratory diseases.As células-tronco têm uma infinidade de implicações clínicas no pulmão. Este artigo é uma revisão crítica que inclui estudos clínicos e experimentais advindos do banco de dados do MEDLINE e SciElo nos últimos 10 anos, onde foram destacados os efeitos da terapia celular na síndrome do desconforto respiratório agudo ou doenças mais crônicas, como fibrose pulmonar e enfisema. Apesar de muitos estudos demonstrarem os efeitos benéficos das células-tronco no desenvolvimento, reparo e remodelamento pulmonar; algumas questões ainda precisam ser respondidas para um melhor entendimento dos mecanismos que controlam a divisão celular e diferenciação, permitindo o uso da terapia celular nas doenças respiratórias.

  13. Stem Cells in Regenerative Medicine

    OpenAIRE

    Sykova, Eva; Forostyak, Serhiy

    2013-01-01

    Background: A number of cardiovascular, neurological, musculoskeletal and other diseases have a limited capacity for repair and only a modest progress has been made in treatment of brain diseases. The discovery of stem cells has opened new possibilities for the treatment of these maladies, and cell therapy now stands at the cutting-edge of modern regenerative medicine and tissue engineering. Experimental data and the first clinical trials employing stem cells have shown their broad therapeuti...

  14. Immunological characteristics of mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Cíntia de Vasconcellos Machado

    2013-01-01

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

  15. Alfalfa stem tissues: Cell wall deposition, composition, and degradability

    NARCIS (Netherlands)

    Jung, H.G.; Engels, F.M.

    2002-01-01

    Declining cell wall degradability of alfalfa (Medicago sativa L.) stems with maturation limits the nutritional value of alfalfa for ruminants. This study characterized changes in cell wall concentration, composition, and degradability by rumen microbes resulting from alfalfa stem tissue

  16. Functional studies of microRNAs in neural stem cells: problems and perspectives.

    Directory of Open Access Journals (Sweden)

    Malin eÅkerblom

    2012-02-01

    Full Text Available In adult mammals, neural stem cells (NSCs are found in two niches of the brain; the subventricular zone at the lateral ventricle and the subgranular zone of the dentate gyrus in the hippocampus. Neurogenesis is a complex process that is tightly controlled on a molecular level. Recently, microRNAs (miRNAs have been implicated to play a central role in the regulation of NCSs. miRNAs are small, endogenously expressed RNAs that regulate gene expression at the post-transcriptional level. However, functional studies of miRNAs are complicated due to current technical limitations. In this review we describe recent findings about miRNAs in NSCs looking closely at miR-124, miR-9 and let-7. We also highlight technical strategies used to investigate miRNA function, accentuating limitations and potentials.

  17. Adult Stem Cells and Diseases of Aging

    Directory of Open Access Journals (Sweden)

    Lisa B. Boyette

    2014-01-01

    Full Text Available Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan.

  18. Identification and Characterization of Adult Porcine Muscle Stem Cells

    OpenAIRE

    Wilschut, K.J.

    2009-01-01

    In the past decade, tissue-specific stem cell research has been emerging. Stem cells are characterized by a long-term expansion and a broad developmental potential in vitro. Pre-clinical studies appear promising, but still many limitations have to be overcome before broad therapeutic use of stem cells is save and efficient. Meanwhile, the use of stem cells for drug screening and toxicology studies are also beneficial to biomedical science. To cure muscular dystrophy no efficient therapy exist...

  19. Hematopoietic stem cell origin of connective tissues.

    Science.gov (United States)

    Ogawa, Makio; Larue, Amanda C; Watson, Patricia M; Watson, Dennis K

    2010-07-01

    Connective tissue consists of "connective tissue proper," which is further divided into loose and dense (fibrous) connective tissues and "specialized connective tissues." Specialized connective tissues consist of blood, adipose tissue, cartilage, and bone. In both loose and dense connective tissues, the principal cellular element is fibroblasts. It has been generally believed that all cellular elements of connective tissue, including fibroblasts, adipocytes, chondrocytes, and bone cells, are generated solely by mesenchymal stem cells. Recently, a number of studies, including those from our laboratory based on transplantation of single hematopoietic stem cells, strongly suggested a hematopoietic stem cell origin of these adult mesenchymal tissues. This review summarizes the experimental evidence for this new paradigm and discusses its translational implications. Copyright 2010 ISEH - Society for Hematology and Stem Cells. All rights reserved.

  20. Differentiation-Dependent Energy Production and Metabolite Utilization: A Comparative Study on Neural Stem Cells, Neurons, and Astrocytes

    Science.gov (United States)

    Jády, Attila Gy.; Nagy, Ádám M.; Kőhidi, Tímea; Ferenczi, Szilamér; Tretter, László

    2016-01-01

    While it is evident that the metabolic machinery of stem cells should be fairly different from that of differentiated neurons, the basic energy production pathways in neural stem cells (NSCs) or in neurons are far from clear. Using the model of in vitro neuron production by NE-4C NSCs, this study focused on the metabolic changes taking place during the in vitro neuronal differentiation. O2 consumption, H+ production, and metabolic responses to single metabolites were measured in cultures of NSCs and in their neuronal derivatives, as well as in primary neuronal and astroglial cultures. In metabolite-free solutions, NSCs consumed little O2 and displayed a higher level of mitochondrial proton leak than neurons. In stem cells, glycolysis was the main source of energy for the survival of a 2.5-h period of metabolite deprivation. In contrast, stem cell-derived or primary neurons sustained a high-level oxidative phosphorylation during metabolite deprivation, indicating the consumption of own cellular material for energy production. The stem cells increased O2 consumption and mitochondrial ATP production in response to single metabolites (with the exception of glucose), showing rapid adaptation of the metabolic machinery to the available resources. In contrast, single metabolites did not increase the O2 consumption of neurons or astrocytes. In “starving” neurons, neither lactate nor pyruvate was utilized for mitochondrial ATP production. Gene expression studies also suggested that aerobic glycolysis and rapid metabolic adaptation characterize the NE-4C NSCs, while autophagy and alternative glucose utilization play important roles in the metabolism of stem cell-derived neurons. PMID:27116891

  1. Animal and plant stem cells concepts, propagation and engineering

    CERN Document Server

    Pavlović, Mirjana

    2017-01-01

    This book provides a multifaceted look into the world of stem cells and explains the similarities and differences between plant and human stem cells. It explores the intersection between animals and plants and explains their cooperative role in bioengineering studies. The book treats both theoretical and practical aspects of stem cell research. It covers the advantages and limitations of many common applications related to stem cells: their sources, categories, engineering of these cells, reprogramming of their functions, and their role as novel cellular therapeutic approach. Written by experts in the field, the book focuses on aspects of stem cells ranging from expansion-propagation to metabolic reprogramming. It introduces the emergence of cancer stem cells and different modalities in targeted cancer stem cell therapies. It is a valuable source of fresh information for academics and researchers, examining molecular mechanisms of animal and plant stem cell regulation and their usage for therapeutic applicati...

  2. Bioengineering Embryonic Stem Cell Microenvironments for the Study of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Yubing Xie

    2011-11-01

    Full Text Available Breast cancer is the most prevalent disease amongst women worldwide and metastasis is the main cause of death due to breast cancer. Metastatic breast cancer cells and embryonic stem (ES cells display similar characteristics. However, unlike metastatic breast cancer cells, ES cells are nonmalignant. Furthermore, embryonic microenvironments have the potential to convert metastatic breast cancer cells into a less invasive phenotype. The creation of in vitro embryonic microenvironments will enable better understanding of ES cell-breast cancer cell interactions, help elucidate tumorigenesis, and lead to the restriction of breast cancer metastasis. In this article, we will present the characteristics of breast cancer cells and ES cells as well as their microenvironments, importance of embryonic microenvironments in inhibiting tumorigenesis, convergence of tumorigenic and embryonic signaling pathways, and state of the art in bioengineering embryonic microenvironments for breast cancer research. Additionally, the potential application of bioengineered embryonic microenvironments for the prevention and treatment of invasive breast cancer will be discussed.

  3. A Scaled Framework for CRISPR Editing of Human Pluripotent Stem Cells to Study Psychiatric Disease.

    Science.gov (United States)

    Hazelbaker, Dane Z; Beccard, Amanda; Bara, Anne M; Dabkowski, Nicole; Messana, Angelica; Mazzucato, Patrizia; Lam, Daisy; Manning, Danielle; Eggan, Kevin; Barrett, Lindy E

    2017-10-10

    Scaling of CRISPR-Cas9 technology in human pluripotent stem cells (hPSCs) represents an important step for modeling complex disease and developing drug screens in human cells. However, variables affecting the scaling efficiency of gene editing in hPSCs remain poorly understood. Here, we report a standardized CRISPR-Cas9 approach, with robust benchmarking at each step, to successfully target and genotype a set of psychiatric disease-implicated genes in hPSCs and provide a resource of edited hPSC lines for six of these genes. We found that transcriptional state and nucleosome positioning around targeted loci was not correlated with editing efficiency. However, editing frequencies varied between different hPSC lines and correlated with genomic stability, underscoring the need for careful cell line selection and unbiased assessments of genomic integrity. Together, our step-by-step quantification and in-depth analyses provide an experimental roadmap for scaling Cas9-mediated editing in hPSCs to study psychiatric disease, with broader applicability for other polygenic diseases. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  4. Bone regeneration: stem cell therapies and clinical studies in orthopaedics and traumatology.

    Science.gov (United States)

    Gómez-Barrena, Enrique; Rosset, Philippe; Müller, Ingo; Giordano, Rosaria; Bunu, Carmen; Layrolle, Pierre; Konttinen, Yrjö T; Luyten, Frank P

    2011-06-01

    Regenerative medicine seeks to repair or replace damaged tissues or organs, with the goal to fully restore structure and function without the formation of scar tissue. Cell based therapies are promising new therapeutic approaches in regenerative medicine. By using mesenchymal stem cells, good results have been reported for bone engineering in a number of clinical studies, most of them investigator initiated trials with limited scope with respect to controls and outcome. With the implementation of a new regulatory framework for advanced therapeutic medicinal products, the stage is set to improve both the characterization of the cells and combination products, and pave the way for improved controlled and well-designed clinical trials. The incorporation of more personalized medicine approaches, including the use of biomarkers to identify the proper patients and the responders to treatment, will be contributing to progress in the field. Both translational and clinical research will move the boundaries in the field of regenerative medicine, and a coordinated effort will provide the clinical breakthroughs, particularly in the many applications of bone engineering. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  5. Association between thymic function and allogeneic hematopoietic stem cell transplantation outcome: results of a pediatric study.

    Science.gov (United States)

    Saglio, Francesco; Cena, Silvia; Berger, Massimo; Quarello, Paola; Boccasavia, Viola; Ferrando, Federica; Pittana, Laura; Bruno, Benedetto; Fagioli, Franca

    2015-06-01

    Robust T cell function recovery has been shown to be crucial in determining allogeneic hematopoietic stem cell transplantation (HSCT) outcome, and there is growing evidence that the thymus plays a central role in regulating this process. We performed a long-term analysis of the role of thymic activity recovery in a population of pediatric patients undergoing allogeneic HSCT by signal joint T cell receptor excision circle (sjTREC) quantification. In this study, characterized by a long-term follow-up (median, 72 months), we found patients with higher levels of sjTRECs before transplantation had a statistically significant reduced risk of death compared with patients with lower values (relative risk, .31; 95% confidence interval, .30 to .32; P = .02), showing this different outcome was mainly related to a reduction of relapse incidence (14% versus 43%, P = .02). Unlike previous reports, we observed no correlation between sjTREC levels and lymphocyte recovery. Moreover, we confirmed that only graft-versus-host disease influenced thymic activity after transplantation. In conclusion, our results suggest an association between pretransplantation thymic activity and the long-term outcome of pediatric patients undergoing HSCT, mainly through a reduction of relapse opportunities. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  6. Stem cells: Concepts and prospects

    Indian Academy of Sciences (India)

    development exemplified by murine experiments motivated the ... from specific regions of the brain, cardiac stem cells from atrial ..... have also been shown to integrate and differentiate .... to vascular network structures in three dimensional.

  7. Effect of Cell Seeding Density and Inflammatory Cytokines on Adipose Tissue-Derived Stem Cells : an in Vitro Study

    NARCIS (Netherlands)

    Sukho, Panithi; Kirpensteijn, Jolle; Hesselink, Jan Willem; van Osch, Gerjo J V M; Verseijden, Femke; Bastiaansen-Jenniskens, Yvonne M

    Adipose tissue-derived stem cells (ASCs) are known to be able to promote repair of injured tissue via paracrine factors. However, the effect of cell density and inflammatory cytokines on the paracrine ability of ASCs remains largely unknown. To investigate these effects, ASCs were cultured in 8000

  8. Effect of Cell Seeding Density and Inflammatory Cytokines on Adipose Tissue-Derived Stem Cells: an in Vitro Study

    NARCIS (Netherlands)

    Sukho, P. (Panithi); J. Kirpensteijn (Jolle); Hesselink, J.W. (Jan Willem); G.J.V.M. van Osch (Gerjo); F. Verseijden (Femke); Y.M. Bastiaansen-Jenniskens (Yvonne)

    2017-01-01

    textabstractAdipose tissue-derived stem cells (ASCs) are known to be able to promote repair of injured tissue via paracrine factors. However, the effect of cell density and inflammatory cytokines on the paracrine ability of ASCs remains largely unknown. To investigate these effects, ASCs were

  9. [Progress in stem cells and regenerative medicine].

    Science.gov (United States)

    Wang, Libin; Zhu, He; Hao, Jie; Zhou, Qi

    2015-06-01

    Stem cells have the ability to differentiate into all types of cells in the body and therefore have great application potential in regenerative medicine, in vitro disease modelling and drug screening. In recent years, stem cell technology has made great progress, and induced pluripotent stem cell technology revolutionizes the whole stem cell field. At the same time, stem cell research in our country has also achieved great progress and becomes an indispensable power in the worldwide stem cell research field. This review mainly focuses on the research progress in stem cells and regenerative medicine in our country since the advent of induced pluripotent stem cell technology, including induced pluripotent stem cells, transdifferentiation, haploid stem cells, and new gene editing tools.

  10. Exosomes as potential alternatives to stem cell therapy for intervertebral disc degeneration: in-vitro study on exosomes in interaction of nucleus pulposus cells and bone marrow mesenchymal stem cells.

    Science.gov (United States)

    Lu, Kang; Li, Hai-Yin; Yang, Kuang; Wu, Jun-Long; Cai, Xiao-Wei; Zhou, Yue; Li, Chang-Qing

    2017-05-10

    The stem cell-based therapies for intervertebral disc degeneration have been widely studied. However, the mechanisms of mesenchymal stem cells interacting with intervertebral disc cells, such as nucleus pulposus cells (NPCs), remain unknown. Exosomes as a vital paracrine mechanism in cell-cell communication have been highly focused on. The purpose of this study was to detect the role of exosomes derived from bone marrow mesenchymal stem cells (BM-MSCs) and NPCs in their interaction with corresponding cells. The exosomes secreted by BM-MSCs and NPCs were purified by differential centrifugation and identified by transmission electron microscope and immunoblot analysis of exosomal marker proteins. Fluorescence confocal microscopy was used to examine the uptake of exosomes by recipient cells. The effects of NPC exosomes on the migration and differentiation of BM-MSCs were determined by transwell migration assays and quantitative RT-PCR analysis of NPC phenotypic genes. Western blot analysis was performed to examine proteins such as aggrecan, sox-9, collagen II and hif-1α in the induced BM-MSCs. Proliferation and the gene expression profile of NPCs induced by BM-MSC exosomes were measured by Cell Counting Kit-8 and qRT-PCR analysis, respectively. Both the NPCs and BM-MSCs secreted exosomes, and these exosomes underwent uptake by the corresponding cells. NPC-derived exosomes promoted BM-MSC migration and induced BM-MSC differentiation to a nucleus pulposus-like phenotype. BM-MSC-derived exosomes promoted NPC proliferation and healthier extracellular matrix production in the degenerate NPCs. Our study indicates that the exosomes act as an important vehicle in information exchange between BM-MSCs and NPCs. Given a variety of functions and multiple advantages, exosomes alone or loaded with specific genes and drugs would be an appropriate option in a cell-free therapy strategy for intervertebral disc degeneration.

  11. [Study of the role of miRNA in mesenchymal stem cells isolated from osteoarthritis patients].

    Science.gov (United States)

    Tornero-Esteban, P; Hoyas, J A; Villafuertes, E; Garcia-Bullón, I; Moro, E; Fernández-Gutiérrez, B; Marco, F

    2014-01-01

    MiRNAs act as gene silencers that are involved in the regulation of essential cell functions. miR-335 is involved in regulating cell differentiation processes in progenitor cells. Mesenchymal stem cells (MSCs) are progenitor cells of chondrocytes and osteoblasts responsible for homeostatic maintenance of cartilage and bone. The aim of this study was to determine a possible relationship between the expression of miR-335 and osteoarthritis. MSCs obtained from the bone marrow of 3 osteoarthritic patients and 3 controls with no clinical signs of osteoarthritis or osteoporosis were cultured and phenotypically and functionally characterised in a 3-step culture. Expression levels of miR-335 and the mesoderm-specific transcript gene -MEST- that controls its expression were determined by quantitative PCR. Differences in the expression levels of miR-335 and MEST (median [interquartile range]: 1.69 [0.85-1.74], and 3.85 [3.20-5.67] were detected between MSCs isolated from patients with osteoarthritis and controls. Although the differences detected did not reach statistical significance (P=.1), a clear trend towards lower expression of miR-335 in osteoarthritis MSCs was observed. Given that miR-335 has the different genes involved in the Wnt signalling pathway as potential targets, the observed trend may help to ascertain, at least partially, some of the alterations which determine the onset or progression of osteoarthritis, and can therefore serve for the design of future therapeutic targets for the treatment of this disease. Copyright © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

  12. Stem Cell Lineages: Between Cell and Organism

    Directory of Open Access Journals (Sweden)

    Melinda Bonnie Fagan

    2017-01-01

    Full Text Available Ontologies of living things are increasingly grounded on the concepts and practices of current life science. Biological development is a process, undergone by living things, which begins with a single cell and (in an important class of cases ends with formation of a multicellular organism. The process of development is thus prima facie central for ideas about biological individuality and organismality. However, recent accounts of these concepts do not engage developmental biology. This paper aims to fill the gap, proposing the lineage view of stem cells as an ontological framework for conceptualizing organismal development. This account is grounded on experimental practices of stem cell research, with emphasis on new techniques for generating biological organization in vitro. On the lineage view, a stem cell is the starting point of a cell lineage with a specific organismal source, time-interval of existence, and ‘tree topology’ of branch-points linking the stem to developmental termini. The concept of ‘enkapsis’ accommodates the cell-organism relation within the lineage view; this hierarchical notion is further explicated by considering the methods and results of stem cell experiments. Results of this examination include a (partial characterization of stem cells’ developmental versatility, and the context-dependence of developmental processes involving stem cells.

  13. Nanotechnology in the regulation of stem cell behavior

    International Nuclear Information System (INIS)

    Wu, King-Chuen; Tseng, Ching-Li; Wu, Chi-Chang; Wang, Yang-Kao; Kao, Feng-Chen; Tu, Yuan-Kun; C So, Edmund

    2013-01-01

    Stem cells are known for their potential to repair damaged tissues. The adhesion, growth and differentiation of stem cells are likely controlled by the surrounding microenvironment which contains both chemical and physical cues. Physical cues in the microenvironment, for example, nanotopography, were shown to play important roles in stem cell fate decisions. Thus, controlling stem cell behavior by nanoscale topography has become an important issue in stem cell biology. Nanotechnology has emerged as a new exciting field and research from this field has greatly advanced. Nanotechnology allows the manipulation of sophisticated surfaces/scaffolds which can mimic the cellular environment for regulating cellular behaviors. Thus, we summarize recent studies on nanotechnology with applications to stem cell biology, including the regulation of stem cell adhesion, growth, differentiation, tracking and imaging. Understanding the interactions of nanomaterials with stem cells may provide the knowledge to apply to cell–scaffold combinations in tissue engineering and regenerative medicine. (review)

  14. The Use of Induced Pluripotent Stem Cells for the Study and Treatment of Liver Diseases.

    Science.gov (United States)

    Hansel, Marc C; Davila, Julio C; Vosough, Massoud; Gramignoli, Roberto; Skvorak, Kristen J; Dorko, Kenneth; Marongiu, Fabio; Blake, William; Strom, Stephen C

    2016-02-01

    Liver disease is a major global health concern. Liver cirrhosis is one of the leading causes of death in the world and currently the only therapeutic option for end-stage liver disease (e.g., acute liver failure, cirrhosis, chronic hepatitis, cholestatic diseases, metabolic diseases, and malignant neoplasms) is orthotropic liver transplantation. Transplantation of hepatocytes has been proposed and used as an alternative to whole organ transplant to stabilize and prolong the lives of patients in some clinical cases. Although these experimental therapies have demonstrated promising and beneficial results, their routine use remains a challenge due to the shortage of donor livers available for cell isolation, variable quality of those tissues, the potential need for lifelong immunosuppression in the transplant recipient, and high costs. Therefore, new therapeutic strategies and more reliable clinical treatments are urgently needed. Recent and continuous technological advances in the development of stem cells suggest they may be beneficial in this respect. In this review, we summarize the history of stem cell and induced pluripotent stem cell (iPSC) technology in the context of hepatic differentiation and discuss the potential applications the technology may offer for human liver disease modeling and treatment. This includes developing safer drugs and cell-based therapies to improve the outcomes of patients with currently incurable health illnesses. We also review promising advances in other disease areas to highlight how the stem cell technology could be applied to liver diseases in the future. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

  15. Culture conditions for bovine embryonic stem cell-like cells isolated from blastocysts after external fertilization

    OpenAIRE

    Jin, Muzi; Wu, Asga; Dorzhin, Sergei; Yue, Qunhua; Ma, Yuzhen; Liu, Dongjun

    2012-01-01

    Although isolation and characterization of embryonic stem cells have been successful in cattle, maintenance of bovine embryonic stem cells in culture remains difficult. In this study, we compared different methods of cell passaging, feeder cell layers and medium conditions for bovine embryonic stem cell-like cells. We found that a murine embryonic fibroblast feeder layer is more suitable for embryonic stem cell-like cells than bovine embryonic fibroblasts. When murine embryonic fibroblasts we...

  16. [Induced pluripotent stem cells: a new paradigm to study human tissues].

    Science.gov (United States)

    Sansac, Caroline; Assou, Said; Bouckenheimer, Julien; Lemaître, Jean-Marc; De Vos, John

    2016-01-01

    Induced pluripotent stem cells (iPSCs) are obtained by reprogramming differentiated cells through forced expression of four embryonic transcription factors. The discovery of this technology, able to transform a differentiated cell into a pluripotent cell, has profoundly shifted the paradigm of the concept of cell identity, since it is now possible to obtain in vitro any cell type from an initial sample of skin or blood cells from a healthy volunteer or patient. Applications of iPSCs are exceedingly large, and comprise the in vitro modeling of normal or pathological tissues, including for massive drug screening. They also open new therapeutic avenues in the field of regenerative medicine. © Société de Biologie, 2016.

  17. Stem cell tracking using iron oxide nanoparticles

    Directory of Open Access Journals (Sweden)

    Bull E

    2014-03-01

    Full Text Available Elizabeth Bull,1 Seyed Yazdan Madani,1 Roosey Sheth,1 Amelia Seifalian,1 Mark Green,2 Alexander M Seifalian1,31UCL Centre for Nanotechnology and Regenerative Medicine, Division of Surgery and Interventional Science, University College London, London, 2Department of Physics, King’s College London, Strand Campus, London, UK; 3Royal Free London National Health Service Foundation Trust Hospital, London, UKAbstract: Superparamagnetic iron oxide nanoparticles (SPIONs are an exciting advancement in the field of nanotechnology. They expand the possibilities of noninvasive analysis and have many useful properties, making them potential candidates for numerous novel applications. Notably, they have been shown that they can be tracked by magnetic resonance imaging (MRI and are capable of conjugation with various cell types, including stem cells. In-depth research has been undertaken to establish these benefits, so that a deeper level of understanding of stem cell migratory pathways and differentiation, tumor migration, and improved drug delivery can be achieved. Stem cells have the ability to treat and cure many debilitating diseases with limited side effects, but a main problem that arises is in the noninvasive tracking and analysis of these stem cells. Recently, researchers have acknowledged the use of SPIONs for this purpose and have set out to establish suitable protocols for coating and attachment, so as to bring MRI tracking of SPION-labeled stem cells into common practice. This review paper explains the manner in which SPIONs are produced, conjugated, and tracked using MRI, as well as a discussion on their limitations. A concise summary of recently researched magnetic particle coatings is provided, and the effects of SPIONs on stem cells are evaluated, while animal and human studies investigating the role of SPIONs in stem cell tracking will be explored.Keywords: stem cells, nanoparticle, magnetic

  18. Stem cells and bone: a historical perspective.

    Science.gov (United States)

    Bianco, Paolo

    2015-01-01

    Bone physiology and stem cells were tightly intertwined with one another, both conceptually and experimentally, long before the current explosion of interest in stem cells and so-called regenerative medicine. Bone is home to the two best known and best characterized systems of postnatal stem cells, and it is the only organ in which two stem cells and their dependent lineages coordinate the overall adaptive responses of two major physiological systems. All along, the nature and the evolutionary significance of the interplay of bone and hematopoiesis have remained a major scientific challenge, but also allowed for some of the most spectacular developments in cell biology-based medicine, such as hematopoietic stem cell transplantation. This question recurs in novel forms at multiple turning points over time: today, it finds in the biology of the "niche" its popular phrasing. Entirely new avenues of investigation emerge as a new view of bone in physiology and medicine is progressively established. Looking at bone and stem cells in a historical perspective provides a unique case study to highlight the general evolution of science in biomedicine since the end of World War II to the present day. A paradigm shift in science and in its relation to society and policies occurred in the second half of the XXth century, with major implications thereof for health, industry, drug development, market and society. Current interest in stem cells in bone as in other fields is intertwined with that shift. New opportunities and also new challenges arise. This article is part of a Special Issue entitled "Stem cells and bone". Copyright © 2014. Published by Elsevier Inc.

  19. Road for understanding cancer stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Erzik, Can

    2007-01-01

    There is increasing evidence suggesting that stem cells are susceptive to carcinogenesis and, consequently, can be the origin of many cancers. Recently, the neoplastic potential of stem cells has been supported by many groups showing the existence of subpopulations with stem cell characteristics...... in tumor biopsies such as brain and breast. Evidence supporting the cancer stem cell hypothesis has gained impact due to progress in stem cell biology and development of new models to validate the self-renewal potential of stem cells. Recent evidence on the possible identification of cancer stem cells may...... offer an opportunity to use these cells as future therapeutic targets. Therefore, model systems in this field have become very important and useful. This review will focus on the state of knowledge on cancer stem cell research, including cell line models for cancer stem cells. The latter will, as models...

  20. Eckol suppresses maintenance of stemness and malignancies in glioma stem-like cells

    International Nuclear Information System (INIS)

    Hyun, Kyung-Hwan; Yoon, Chang-Hwan; Kim, Rae-Kwon; Lim, Eun-Jung; An, Sungkwan; Park, Myung-Jin; Hyun, Jin-Won; Suh, Yongjoon; Kim, Min-Jung; Lee, Su-Jae

    2011-01-01

    A subpopulation of cancer cells with stem cell properties is responsible for tumor maintenance and progression, and may contribute to resistance to anticancer treatments. Thus, compounds that target cancer stem-like cells could be usefully applied to destroy cancer. In this study, we investigated the effect of Eckol, a phlorotannin compound, on stemness and malignancies in glioma stem-like cells. To determine whether Eckol targets glioma stem-like cells, we examined whether Eckol treatment could change the expression levels of glioma stem-like cell markers and self-renewal-related proteins as well as the sphere forming ability, and the sensitivity to anticancer treatments. Alterations in the malignant properties of sphere-derived cells by Eckol were also investigated by soft-agar colony forming assay, by xenograft assay in nude mice, and by cell invasion assay. Treatment of sphere-forming glioma cells with Eckol effectively decreased the sphere formation as well as the CD133 + cell population. Eckol treatment suppressed expression of the glioma stem-like cell markers and the self-renewal-related proteins without cell death. Moreover, treatment of glioma stem-like cells with Eckol significantly attenuated anchorage-independent growth on soft agar and tumor formation in xenograft mice. Importantly, Eckol treatment effectively reduced the resistance of glioma stem-like cells to ionizing radiation and temozolomide. Treatment of glioma stem-like cells with Eckol markedly blocked both phosphoinositide 3-kinase-Akt and Ras-Raf-1-Erk signaling pathways. These results indicate that the natural phlorotannin Eckol suppresses stemness and malignancies in glioma stem-like cells, and thereby makes glioma stem-like cells more sensitive to anticancer treatments, providing novel therapeutic strategies targeting specifically cancer stem-like cells.

  1. Cell Cycle Regulation of Stem Cells by MicroRNAs.

    Science.gov (United States)

    Mens, Michelle M J; Ghanbari, Mohsen

    2018-06-01

    MicroRNAs (miRNAs) are a class of small non-coding RNA molecules involved in the regulation of gene expression. They are involved in the fine-tuning of fundamental biological processes such as proliferation, differentiation, survival and apoptosis in many cell types. Emerging evidence suggests that miRNAs regulate critical pathways involved in stem cell function. Several miRNAs have been suggested to target transcripts that directly or indirectly coordinate the cell cycle progression of stem cells. Moreover, previous studies have shown that altered expression levels of miRNAs can contribute to pathological conditions, such as cancer, due to the loss of cell cycle regulation. However, the precise mechanism underlying miRNA-mediated regulation of cell cycle in stem cells is still incompletely understood. In this review, we discuss current knowledge of miRNAs regulatory role in cell cycle progression of stem cells. We describe how specific miRNAs may control cell cycle associated molecules and checkpoints in embryonic, somatic and cancer stem cells. We further outline how these miRNAs could be regulated to influence cell cycle progression in stem cells as a potential clinical application.

  2. Advances in reprogramming somatic cells to induced pluripotent stem cells.

    Science.gov (United States)

    Patel, Minal; Yang, Shuying

    2010-09-01

    Traditionally, nuclear reprogramming of cells has been performed by transferring somatic cell nuclei into oocytes, by combining somatic and pluripotent cells together through cell fusion and through genetic integration of factors through somatic cell chromatin. All of these techniques changes gene expression which further leads to a change in cell fate. Here we discuss recent advances in generating induced pluripotent stem cells, different reprogramming methods and clinical applications of iPS cells. Viral vectors have been used to transfer transcription factors (Oct4, Sox2, c-myc, Klf4, and nanog) to induce reprogramming of mouse fibroblasts, neural stem cells, neural progenitor cells, keratinocytes, B lymphocytes and meningeal membrane cells towards pluripotency. Human fibroblasts, neural cells, blood and keratinocytes have also been reprogrammed towards pluripotency. In this review we have discussed the use of viral vectors for reprogramming both animal and human stem cells. Currently, many studies are also involved in finding alternatives to using viral vectors carrying transcription factors for reprogramming cells. These include using plasmid transfection, piggyback transposon system and piggyback transposon system combined with a non viral vector system. Applications of these techniques have been discussed in detail including its advantages and disadvantages. Finally, current clinical applications of induced pluripotent stem cells and its limitations have also been reviewed. Thus, this review is a summary of current research advances in reprogramming cells into induced pluripotent stem cells.

  3. A proteomic approach to studying the differentiation of neural stem cells

    Czech Academy of Sciences Publication Activity Database

    Skalníková, Helena; Halada, Petr; Vodička, Petr; Motlík, Jan; Řehulka, Pavel; Horning, O.; Chmelík, Josef; Norregaard Jensen, O.; Kovářová, Hana

    2007-01-01

    Roč. 7, 11 (2007), s. 1825-1838 ISSN 1615-9853 R&D Projects: GA MŠk 1M0538; GA MŠk LC545 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50200510; CEZ:AV0Z40310501 Keywords : differentiation * neural stem cells * two-dimensional gel electrophoresis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.479, year: 2007

  4. Multipotent stem cells of mother's milk

    Directory of Open Access Journals (Sweden)

    Alessandra Reali

    2016-03-01

    Full Text Available In recent years the presence of stem cells (hBSCs: human breastmilk-derived stem cells and epithelial progenitors has been demonstrated in mother’s milk (MM. Stem cells present in samples of fresh MM exhibit a high degree of vitality and this makes possible the performance of cell cultures and to evaluate the differentiation capacity of the hBSCs. The most important datum that expresses the enormous potential of the use of MM stem cells is the presence of a cell population capable of differentiating into the three mesoderm, endoderm and ectoderm lines. The small number of studies and MM samples analyzed and the different sampling methods applied suggest standardization in the collection, analysis and culture of MM in future studies, in consideration of the well-known extreme variability of MM composition, also from the standpoint of cells.The analysis of literature data confirms the uniqueness of MM and its enormous potential.Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015 · Cagliari (Italy · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

  5. Dental Stem Cell in Tooth Development and Advances of Adult Dental Stem Cell in Regenerative Therapies.

    Science.gov (United States)

    Tan, Jiali; Xu, Xin; Lin, Jiong; Fan, Li; Zheng, Yuting; Kuang, Wei

    2015-01-01

    Stem cell-based therapies are considered as a promising treatment for many clinical usage such as tooth regeneration, bone repairation, spinal cord injury, and so on. However, the ideal stem cell for stem cell-based therapy still remains to be elucidated. In the past decades, several types of stem cells have been isolated from teeth, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), dental follicle progenitor stem cells (DFPCs) and stem cells from apical papilla (SCAP), which may be a good source for stem cell-based therapy in certain disease, especially when they origin from neural crest is considered. In this review, the specific characteristics and advantages of the adult dental stem cell population will be summarized and the molecular mechanisms of the differentiation of dental stem cell during tooth development will be also discussed.

  6. Epigenetics in cancer stem cells.

    Science.gov (United States)

    Toh, Tan Boon; Lim, Jhin Jieh; Chow, Edward Kai-Hua

    2017-02-01

    Compelling evidence have demonstrated that bulk tumors can arise from a unique subset of cells commonly termed "cancer stem cells" that has been proposed to be a strong driving force of tumorigenesis and a key mechanism of therapeutic resistance. Recent advances in epigenomics have illuminated key mechanisms by which epigenetic regulation contribute to cancer progression. In this review, we present a discussion of how deregulation of various epigenetic pathways can contribute to cancer initiation and tumorigenesis, particularly with respect to maintenance and survival of cancer stem cells. This information, together with several promising clinical and preclinical trials of epigenetic modulating drugs, offer new possibilities for targeting cancer stem cells as well as improving cancer therapy overall.

  7. Ex vivo assays to study self-renewal and long-term expansion of genetically modified primary human acute myeloid leukemia stem cells

    NARCIS (Netherlands)

    Schuringa, Jan Jacob; Schepers, Hein

    2009-01-01

    With the emergence of the concept of the leukemia stem cell, assays to study them remain pivotal in understanding (leukemic) stem cell biology. Although the in vivo NOD-SCID xenotransplantation model is still the favored model of choice in most cases, this system has some limitations as well, such

  8. Ex vivo assays to study self-renewal, long-term expansion, and leukemic transformation of genetically modified human hematopoietic and patient-derived leukemic stem cells

    NARCIS (Netherlands)

    Sontakke, Pallavi; Carretta, Marco; Capala, Marta; Schepers, Hein; Schuringa, Jan Jacob

    2014-01-01

    With the emergence of the concept of the leukemic stem cell (LSC), assays to study them remain pivotal in understanding (leukemic) stem cell biology. Although the in vivo NOD-SCID or NSG xenotransplantation model is currently still the favored assay of choice in most cases, this system has some

  9. A bioengineered murine model using CD24+CD44+ pancreatic cancer stem cells for chemotherapy study

    International Nuclear Information System (INIS)

    Qin, Shengqi; Li, Jianshe; Zhang, Zhongtao; Deng, Yiming

    2015-01-01

    In this work we first developed a murine pancreatic tumor model using CD24 + CD44 + pancreatic cancer stem cells (CSC) supported by an electrospun scaffold. Unlike conventional models, the use of CSC and the scaffold, which were biologically and chemically defined, afforded scientists a reliable platform to evaluate novel chemotherapy regimens. CD24 + CD44 + CSC successfully initiated tumorigenesis in vitro on the scaffold without suffering apoptosis, evidencing the lack of cytotoxicity of scaffolding materials. Also, the scaffold contributed to the acceleration of in vivo tumorigenesis and increased the likelihood of tumor formation. Using this model, we set out to explore the effectiveness of irinotecan/gemcitabine (IRIN-GEM), a chemotherapy regimen, for pancreatic cancer. Our study showed that IRIN-GEM induced a tumor regression whereas gemcitabine alone could only arrest the tumor growth. Further study suggested that the superior performance of IRIN-GEM could be attributed to its capacity to demolish the CD24 + CD44 + CSC sub-population by inducing a large-scale apoptosis. The use of highly proliferative yet homogenous CD24 + CD44 + CSC along with a chemically defined scaffold accelerated the tumor formation and significantly reduced the variability associated with conventional murine models. Armed with this new model, we discovered that IRIN-GEM would be a promising chemotherapy candidate for patients with advanced pancreatic cancer. (paper)

  10. Pulp regeneration by transplantation of dental pulp stem cells in pulpitis: a pilot clinical study.

    Science.gov (United States)

    Nakashima, Misako; Iohara, Koichiro; Murakami, Masashi; Nakamura, Hiroshi; Sato, Yayoi; Ariji, Yoshiko; Matsushita, Kenji

    2017-03-09

    Experiments have previously demonstrated the therapeutic potential of mobilized dental pulp stem cells (MDPSCs) for complete pulp regeneration. The aim of the present pilot clinical study is to assess the safety, potential efficacy, and feasibility of autologous transplantation of MDPSCs in pulpectomized teeth. Five patients with irreversible pulpitis were enrolled and monitored for up to 24 weeks following MDPSC transplantation. The MDPSCs were isolated from discarded teeth and expanded based on good manufacturing practice (GMP). The quality of the MDPSCs at passages 9 or 10 was ascertained by karyotype analyses. The MDPSCs were transplanted with granulocyte colony-stimulating factor (G-CSF) in atelocollagen into pulpectomized teeth. The clinical and laboratory evaluations demonstrated no adverse events or toxicity. The electric pulp test (EPT) of the pulp at 4 weeks demonstrated a robust positive response. The signal intensity of magnetic resonance imaging (MRI) of the regenerated tissue in the root canal after 24 weeks was similar to that of normal dental pulp in the untreated control. Finally, cone beam computed tomography demonstrated functional dentin formation in three of the five patients. Human MDPSCs are safe and efficacious for complete pulp regeneration in humans in this pilot clinical study.

  11. Stem cells and regenerative medicine

    Czech Academy of Sciences Publication Activity Database

    Syková, Eva

    2005-01-01

    Roč. 3, - (2005), s. 45-46 ISSN 1214-021X. [Cells VI - Biological Days /18./. 24.10.2005-26.10.2005, České Budějovice] R&D Projects: GA MŠk(CZ) 1M0538 Institutional research plan: CEZ:AV0Z5039906 Keywords : stem cells Subject RIV: FH - Neurology

  12. The spermatogonial stem cell niche

    NARCIS (Netherlands)

    de Rooij, Dirk G.

    2009-01-01

    Spermatogonial stem cells (SSCs; A(s) spermatogonia) and their direct descendants (A(pr) and A(al) spermatogonia) are preferentially located in those areas of the seminiferous tubules that border on the interstitial tissue. Fewer of these cells are present in tubule areas directly bordering on

  13. [Human myoblast culture as muscle stem cells in medical and biological studies].

    Science.gov (United States)

    Terekhov, S M; Krokhina, T B; Shishkin, S S; Krakhmaleva, I N; Zakharov, S F; Ershova, E S

    2001-01-01

    The method for obtaining human myoblast culture has been modified to consider the specific histological localization of the satellite cells as well as their growth properties; the cultivation conditions have been selected to grow up to 150000 cells/cm2. At high densities, the cells remain mononuclear and preserve their typical myoblast morphology as well as the capacity for fusion and the formation of myotubes. By contrast to fibroblasts, up to 80% of the cells in the myoblast culture were positive in the acid phosphatase test, which indicates their stem nature. The obtained myoblast cultures were used in the clinical tests of cell-mediated gene therapy of Duchenne's muscular dystrophy as well as in the bioassay for the effects of biologically active compounds.

  14. Stem cell therapy for inflammatory bowel disease

    NARCIS (Netherlands)

    Duijvestein, Marjolijn

    2012-01-01

    Hematopoietic stem cell transplantation (HSCT) and mesenchymal stromal (MSC) cell therapy are currently under investigation as novel therapies for inflammatory bowel diseases (IBD). Hematopoietic stem cells are thought to repopulate the immune system and reset the immunological response to luminal

  15. 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.

  16. What's missing? Discussing stem cell translational research in educational information on stem cell "tourism".

    Science.gov (United States)

    Master, Zubin; Zarzeczny, Amy; Rachul, Christen; Caulfield, Timothy

    2013-01-01

    Stem cell tourism is a growing industry in which patients pursue unproven stem cell therapies for a wide variety of illnesses and conditions. It is a challenging market to regulate due to a number of factors including its international, online, direct-to-consumer approach. Calls to provide education and information to patients, their families, physicians, and the general public about the risks associated with stem cell tourism are mounting. Initial studies examining the perceptions of patients who have pursued stem cell tourism indicate many are highly critical of the research and regulatory systems in their home countries and believe them to be stagnant and unresponsive to patient needs. We suggest that educational material should include an explanation of the translational research process, in addition to other aspects of stem cell tourism, as one means to help promote greater understanding and, ideally, curb patient demand for unproven stem cell interventions. The material provided must stress that strong scientific research is required in order for therapies to be safe and have a greater chance at being effective. Through an analysis of educational material on stem cell tourism and translational stem cell research from patient groups and scientific societies, we describe essential elements that should be conveyed in educational material provided to patients. Although we support the broad dissemination of educational material on stem cell translational research, we also acknowledge that education may simply not be enough to engender patient and public trust in domestic research and regulatory systems. However, promoting patient autonomy by providing good quality information to patients so they can make better informed decisions is valuable in itself, irrespective of whether it serves as an effective deterrent of stem cell tourism. © 2013 American Society of Law, Medicine & Ethics, Inc.

  17. Patterning of Endothelial Cells and Mesenchymal Stem Cells by Laser-Assisted Bioprinting to Study Cell Migration

    Directory of Open Access Journals (Sweden)

    Jean-Michel Bourget

    2016-01-01

    Full Text Available Tissue engineering of large organs is currently limited by the lack of potent vascularization in vitro. Tissue-engineered bone grafts can be prevascularized in vitro using endothelial cells (ECs. The microvascular network architecture could be controlled by printing ECs following a specific pattern. Using laser-assisted bioprinting, we investigated the effect of distance between printed cell islets and the influence of coprinted mesenchymal cells on migration. When printed alone, ECs spread out evenly on the collagen hydrogel, regardless of the distance between cell islets. However, when printed in coculture with mesenchymal cells by laser-assisted bioprinting, they remained in the printed area. Therefore, the presence of mesenchymal cell is mandatory in order to create a pattern that will be conserved over time. This work describes an interesting approach to study cell migration that could be reproduced to study the effect of trophic factors.

  18. Patterning of Endothelial Cells and Mesenchymal Stem Cells by Laser-Assisted Bioprinting to Study Cell Migration.

    Science.gov (United States)

    Bourget, Jean-Michel; Kérourédan, Olivia; Medina, Manuela; Rémy, Murielle; Thébaud, Noélie Brunehilde; Bareille, Reine; Chassande, Olivier; Amédée, Joëlle; Catros, Sylvain; Devillard, Raphaël

    2016-01-01

    Tissue engineering of large organs is currently limited by the lack of potent vascularization in vitro . Tissue-engineered bone grafts can be prevascularized in vitro using endothelial cells (ECs). The microvascular network architecture could be controlled by printing ECs following a specific pattern. Using laser-assisted bioprinting, we investigated the effect of distance between printed cell islets and the influence of coprinted mesenchymal cells on migration. When printed alone, ECs spread out evenly on the collagen hydrogel, regardless of the distance between cell islets. However, when printed in coculture with mesenchymal cells by laser-assisted bioprinting, they remained in the printed area. Therefore, the presence of mesenchymal cell is mandatory in order to create a pattern that will be conserved over time. This work describes an interesting approach to study cell migration that could be reproduced to study the effect of trophic factors.

  19. Cancer Stem Cells – New Approach to Cancerogenensis and Treatment

    Directory of Open Access Journals (Sweden)

    Zuzana Mačingová

    2008-01-01

    Full Text Available Recently, there is an increasing evidence supporting the theory of cancer stem cells not only in leukemia but also in solid cancer. To date, the existence of cancer stem cells has been proven in acute and chronic myeloid leukemia, in breast cancer, in brain tumors, in lung cancer and gastrointestinal tumors. This review is focusing on the recent discovery of stem cells in leukemia, human brain tumors and breast cancer. A small population of cells in the tumor (less than 1 % shows the potential to give rise to the tumor and its growth. These cells have a substantial characteristic of stem cells – ability for self-renewal without loss of proliferation capacity with each cell division. Furthermore they are immortal, rather resistant to treatment and express typical markers of stem cells. The origin of these resident cancer stem cells is not clear. Whether the cancer stem cells originate from normal stem cells in consequence of genetic and epigenetic changes and/or redifferentiation from somatic tumor cells to the stem-like cells remains to be investigated. We propose the idea of the relation between normal tissue stem cells and cancer stem cells and their populations – progenitor cells. Based on this we highlight one of the major characteristic of stem cell – plasticity, which is equally important in the physiological regeneration process as well as carcinogenesis. Furthermore, we consider the microenvironment as a limiting factor for tumor genesis in AML, breast cancer and brain tumors. Thus the biological properties of cancer stem cells are just beginning to be revealed, the continuation of these studies should lead to the development of cancer stem cells target therapies for cancer treatment.

  20. Intestinal stem cells in the adult Drosophila midgut

    International Nuclear Information System (INIS)

    Jiang, Huaqi; Edgar, Bruce A.

    2011-01-01

    Drosophila has long been an excellent model organism for studying stem cell biology. Notably, studies of Drosophila's germline stem cells have been instrumental in developing the stem cell niche concept. The recent discovery of somatic stem cells in adult Drosophila, particularly the intestinal stem cells (ISCs) of the midgut, has established Drosophila as an exciting model to study stem cell-mediated adult tissue homeostasis and regeneration. Here, we review the major signaling pathways that regulate the self-renewal, proliferation and differentiation of Drosophila ISCs, discussing how this regulation maintains midgut homeostasis and mediates regeneration of the intestinal epithelium after injury. -- Highlights: ► The homeostasis and regeneration of adult fly midguts are mediated by ISCs. ► Damaged enterocytes induce the proliferation of intestinal stem cells (ISC). ► EGFR and Jak/Stat signalings mediate compensatory ISC proliferation. ► Notch signaling regulates ISC self-renewal and differentiation.

  1. Comparative study of hematopoietic stem and progenitor cells between sexes in mice under physiological conditions along time.

    Science.gov (United States)

    Gasco, Samanta; Rando, Amaya; Zaragoza, Pilar; García-Redondo, Alberto; Calvo, Ana Cristina; Osta, Rosario

    2017-12-01

    Hematopoietic stem and progenitor cells (HSPCs) are attractive targets in regenerative medicine, although the differences in their homeostatic maintenance between sexes along time are still under debate. We accurately monitored hematopoietic stem cells (HSCs), common lymphoid progenitors (CLPs), and common myeloid progenitors (CMPs) frequencies by flow cytometry, by performing serial peripheral blood extractions from male and female B6SJL wild-type mice and found no significant differences. Only modest differences were found in the gene expression profile of Slamf1 and Gata2. Our findings suggest that both sexes could be used indistinctly to perform descriptive studies in the murine hematopoietic system, especially for flow cytometry studies in peripheral blood. This would allow diminishing the number of animals needed for the experimental procedures. In addition, the use of serial extractions in the same animals drastically decreases the number of animals needed. © 2017 International Federation for Cell Biology.

  2. Stem cell assays: Something old, something new, something borrowed : Something old, something new, something borrowed

    NARCIS (Netherlands)

    van Os, R.; Kamminga, Leonie; de Haan, G.

    2004-01-01

    Numerous assays exist that measure the function of stem cells. In this article, we review in detail the history and future of existing stem cell assays. Hematopoietic stem cells (HSCs) are historically the most well studied, but new developments in stem cell research, including the claim of stem

  3. 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.

  4. Experimental approaches to the study of radiation effects on haemopoietic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Silini, G; Pozzi, L V

    1971-04-01

    It is possible to distinguish between those techniques that allow a direct estimate of the number of stem cells based on their capacity for indefinite reproduction (viability) and those that evaluate this number indirectly by measuring some functions of the progenitor cells or of their descendants, like the incorporation of {sup 59}Fe into haemoglobin or the uptake of DNA precursors into the dividing cells. To obtain comparable estimates, indirect techniques should always be standardized in any given experimental system in relation to the number of cells causing any particular function, which is usually done through experiments on quantitative transplantation. Our present knowledge of methodology is, however, not such as to allow with certainty any absolute correlation between direct and indirect assays. Irrespective of the technique used, there are basically two methods for assaying the stem cell number or functions in the haemopoietic tissues of an animal: (a) directly on the entire animal, in which case the method may be referred to as 'endogenous'; and (b) the tissue to be assayed is transplanted into a heavily irradiated, genetic ally compatible host on which the final titration takes place. This type of assay is called 'exogenous'.

  5. The evolution of chicken stem cell culture methods.

    Science.gov (United States)

    Farzaneh, M; Attari, F; Mozdziak, P E; Khoshnam, S E

    2017-12-01

    1. The avian embryo is an excellent model for studying embryology and the production of pharmaceutical proteins in transgenic chickens. Furthermore, chicken stem cells have the potential for proliferation and differentiation and emerged as an attractive tool for various cell-based technologies. 2. The objective of these studies is the derivation and culture of these stem cells is the production of transgenic birds for recombinant biomaterials and vaccine manufacture, drug and cytotoxicity testing, as well as to gain insight into basic science, including cell tracking. 3. Despite similarities among the established chicken stem cell lines, fundamental differences have been reported between their culture conditions and applications. Recent conventional protocols used for expansion and culture of chicken stem cells mostly depend on feeder cells, serum-containing media and static culture. 4. Utilising chicken stem cells for generation of cell-based transgenic birds and a variety of vaccines requires large-scale cell production. However, scaling up the conventional adherent chicken stem cells is challenging and labour intensive. Development of a suspension cell culture process for chicken embryonic stem cells (cESCs), chicken primordial germ cells (PGCs) and chicken induced pluripotent stem cells (ciPSCs) will be an important advance for increasing the growth kinetics of these cells. 6. This review describes various approaches and suggestions to achieve optimal cell growth for defined chicken stem cells cultures and use in future manufacturing applications.

  6. Epidermal stem cells: location, potential and contribution to cancer.

    Science.gov (United States)

    Ambler, C A; Määttä, A

    2009-01-01

    Epidermal stem cells have been classically characterized as slow-cycling, long-lived cells that reside in discrete niches in the skin. Gene expression studies of niche-resident cells have revealed a number of stem cell markers and regulators, including the Wnt/beta-catenin, Notch, p63, c-Myc and Hedgehog pathways. A new study challenges the traditional developmental paradigm of slow-cycling stem cells and rapid-cycling transit amplifying cells in some epidermal regions, and there is mounting evidence to suggest that multi-lineage epidermal progenitors can be isolated from highly proliferative, non-niche regions. Whether there is a unique microenvironment surrounding these progenitors remains to be determined. Interestingly, cancer stem cells derived from epidermal tumours exist independent of the classic skin stem cell niche, yet also have stem cell properties, including multi-lineage differentiation. This review summarizes recent studies identifying the location and regulators of mouse and human epidermal stem cells and highlights the strategies used to identify cancer stem cells, including expression of normal epidermal stem cell markers, expression of cancer stem cell markers identified in other epidermal tumours and characterization of side-population tumour cells.

  7. Multifaceted Interpretation of Colon Cancer Stem Cells.

    Science.gov (United States)

    Hatano, Yuichiro; Fukuda, Shinya; Hisamatsu, Kenji; Hirata, Akihiro; Hara, Akira; Tomita, Hiroyuki

    2017-07-05

    Colon cancer is one of the leading causes of cancer-related deaths worldwide, despite recent advances in clinical oncology. Accumulating evidence sheds light on the existence of cancer stem cells and their role in conferring therapeutic resistance. Cancer stem cells are a minor fraction of cancer cells, which enable tumor heterogeneity and initiate tumor formation. In addition, these cells are resistant to various cytotoxic factors. Therefore, elimination of cancer stem cells is difficult but essential to cure the malignant foci completely. Herein, we review the recent evidence for intestinal stem cells and colon cancer stem cells, methods to detect the tumor-initiating cells, and clinical significance of cancer stem cell markers. We also describe the emerging problems of cancer stem cell theory, including bidirectional conversion and intertumoral heterogeneity of stem cell phenotype.

  8. Stem cell self-renewal in intestinal crypt

    International Nuclear Information System (INIS)

    Simons, Benjamin D.; Clevers, Hans

    2011-01-01

    As a rapidly cycling tissue capable of fast repair and regeneration, the intestinal epithelium has emerged as a favored model system to explore the principles of adult stem cell biology. However, until recently, the identity and characteristics of the stem cell population in both the small intestine and colon has remained the subject of debate. Recent studies based on targeted lineage tracing strategies, combined with the development of an organotypic culture system, have identified the crypt base columnar cell as the intestinal stem cell, and have unveiled the strategy by which the balance between proliferation and differentiation is maintained. These results show that intestinal stem cells operate in a dynamic environment in which frequent and stochastic stem cell loss is compensated by the proliferation of neighboring stem cells. We review the basis of these experimental findings and the insights they offer into the mechanisms of homeostatic stem cell regulation.

  9. Identification and Characterization of Adult Porcine Muscle Stem Cells

    NARCIS (Netherlands)

    Wilschut, K.J.

    2009-01-01

    In the past decade, tissue-specific stem cell research has been emerging. Stem cells are characterized by a long-term expansion and a broad developmental potential in vitro. Pre-clinical studies appear promising, but still many limitations have to be overcome before broad therapeutic use of stem

  10. 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.

  11. Lymphoscintigraphy and autologous stem cell implantation

    International Nuclear Information System (INIS)

    Peña, Yamile; Batista, Juan F.; Perera, Alejandro; Torres, Leonel A.; Sánchez, Elvia L.; Sánchez, Yolaine; Ducat, Luis; Prats, Anais; Hernández, Porfirio; Romero, Susana; Goicochea, Pedro; Quintela, Ana M.

    2016-01-01

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

  12. The Efficacy of Mesenchymal Stem Cell Transplantation in Caustic Esophagus Injury: An Experimental Study

    Directory of Open Access Journals (Sweden)

    Murat Kantarcioglu

    2014-01-01

    Full Text Available Introduction. Ingestion of corrosive substances may lead to stricture formation in esophagus as a late complication. Full thickness injury seems to exterminate tissue stem cells of esophagus. Mesenchymal stem cells (MSCs can differentiate into specific cell lineages and have the capacity of homing in sites of injury. Aim and Methods. We aimed to investigate the efficacy of MSC transplantation, on prevention of esophageal damage and stricture formation after caustic esophagus injury in rats. 54 rats were allocated into four groups; 4 rats were sacrificed for MSC production. Group 1, untreated controls (n: 10. Group 2, membrane labeled MSCs-treated rats (n: 20. Group 3, biodistribution of fluorodeoxyglucose labeled MSCs via positron emission tomography (PET imaging (n: 10. Group 4, sham operated (n: 10. Standard caustic esophageal burns were created and MSCs were transplanted 24 hours after. All rats were sacrificed at the 21st days. Results. PET scan images revealed the homing behavior of MSCs to the injury site. The histopathology damage score was not significantly different from controls. However, we demonstrated Dil labeled epithelial and muscle cells which were originating from transplanted MSCs. Conclusion. MSC transplantation after caustic esophageal injury may be a helpful treatment modality; however, probably repeated infusions are needed.

  13. Stem cell sources for cardiac regeneration

    NARCIS (Netherlands)

    Roccio, M.; Goumans, M. J.; Sluijter, J. P. G.; Doevendans, P. A.

    Cell-based cardiac repair has the ambitious aim to replace the malfunctioning cardiac muscle developed after myocardial infarction, with new contractile cardiomyocytes and vessels. Different stem cell populations have been intensively studied in the last decade as a potential source of new

  14. Prospective study establishing a management plan for impacted third molar in patients undergoing hematopoietic stem cell transplantation

    OpenAIRE

    Yamagata, Kenji; Onizawa, Kojiro; Yanagawa, Toru; Takeuchi, Yasutoshi; Hasegawa, Yuichi; Chiba, Shigeru; Bukawa, Hiroki

    2011-01-01

    ObjectiveAlthough dental treatment before hematopoietic stem cell transplantation (HSCT) is essential to prevent serious infections from oral sources, the best management plan for impacted third molar (ITM) is unclear.Study designThis study was planned to establish a management plan for ITM. Eighty-four candidates for HSCT therapy were consecutively enrolled in the prospective trial. The management plan, which was evidence based and prospectively decided, was to extract the symptomatic ITMs a...

  15. A family business: stem cell progeny join the niche to regulate homeostasis.

    Science.gov (United States)

    Hsu, Ya-Chieh; Fuchs, Elaine

    2012-01-23

    Stem cell niches, the discrete microenvironments in which the stem cells reside, play a dominant part in regulating stem cell activity and behaviours. Recent studies suggest that committed stem cell progeny become indispensable components of the niche in a wide range of stem cell systems. These unexpected niche inhabitants provide versatile feedback signals to their stem cell parents. Together with other heterologous cell types that constitute the niche, they contribute to the dynamics of the microenvironment. As progeny are often located in close proximity to stem cell niches, similar feedback regulations may be the underlying principles shared by different stem cell systems.

  16. Stem Cell Therapies in Retinal Disorders

    Directory of Open Access Journals (Sweden)

    Aakriti Garg

    2017-02-01

    Full Text Available Stem cell therapy has long been considered a promising mode of treatment for retinal conditions. While human embryonic stem cells (ESCs have provided the precedent for regenerative medicine, the development of induced pluripotent stem cells (iPSCs revolutionized this field. iPSCs allow for the development of many types of retinal cells, including those of the retinal pigment epithelium, photoreceptors, and ganglion cells, and can model polygenic diseases such as age-related macular degeneration. Cellular programming and reprogramming technology is especially useful in retinal diseases, as it allows for the study of living cells that have genetic variants that are specific to patients’ diseases. Since iPSCs are a self-renewing resource, scientists can experiment with an unlimited number of pluripotent cells to perfect the process of targeted differentiation, transplantation, and more, for personalized medicine. Challenges in the use of stem cells are present from the scientific, ethical, and political realms. These include transplant complications leading to anatomically incorrect placement, concern for tumorigenesis, and incomplete targeting of differentiation leading to contamination by different types of cells. Despite these limitations, human ESCs and iPSCs specific to individual patients can revolutionize the study of retinal disease and may be effective therapies for conditions currently considered incurable.

  17. Preclinical study of mouse pluripotent parthenogenetic embryonic stem cell derivatives for the construction of tissue-engineered skin equivalent.

    Science.gov (United States)

    Rao, Yang; Cui, Jihong; Yin, Lu; Liu, Wei; Liu, Wenguang; Sun, Mei; Yan, Xingrong; Wang, Ling; Chen, Fulin

    2016-10-22

    Embryonic stem cell (ESC) derivatives hold great promise for the construction of tissue-engineered skin equivalents (TESE). However, harvesting of ESCs destroys viable embryos and may lead to political and ethical concerns over their application. In the current study, we directed mouse parthenogenetic embryonic stem cells (pESCs) to differentiate into fibroblasts, constructed TESE, and evaluated its function in vivo. The stemness marker expression and the pluripotent differentiation ability of pESCs were tested. After embryoid body (EB) formation and adherence culture, mesenchymal stem cells (MSCs) were enriched and directed to differentiate into fibroblastic lineage. Characteristics of derived fibroblasts were assessed by quantitative real-time PCR and ELISA. Functional ability of the constructed TESE was tested by a mouse skin defects repair model. Mouse pESCs expressed stemness marker and could form teratoma containing three germ layers. MSCs could be enriched from outgrowths of EBs and directed to differentiate into fibroblastic lineage. These cells express a high level of growth factors including FGF, EGF, VEGF, TGF, PDGF, and IGF1, similar to those of ESC-derived fibroblasts and mouse fibroblasts. Seeded into collagen gels, the fibroblasts derived from pESCs could form TESE. Mouse skin defects could be successfully repaired 15 days after transplantation of TESE constructed by fibroblasts derived from pESCs. pESCs could be induced to differentiate into fibroblastic lineage, which could be applied to the construction of TESE and skin defect repair. Particularly, pESC derivatives avoid the limitations of political and ethical concerns, and provide a promising source for regenerative medicine.

  18. Stem cell technology for drug discovery and development.

    Science.gov (United States)

    Hook, Lilian A

    2012-04-01

    Stem cells have enormous potential to revolutionise the drug discovery process at all stages, from target identification through to toxicology studies. Their ability to generate physiologically relevant cells in limitless supply makes them an attractive alternative to currently used recombinant cell lines or primary cells. However, realisation of the full potential of stem cells is currently hampered by the difficulty in routinely directing stem cell differentiation to reproducibly and cost effectively generate pure populations of specific cell types. In this article we discuss how stem cells have already been used in the drug discovery process and how novel technologies, particularly in relation to stem cell differentiation, can be applied to attain widespread adoption of stem cell technology by the pharmaceutical industry. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. A revisionist history of adult marrow stem cell biology or 'they forgot about the discard'.

    Science.gov (United States)

    Quesenberry, P; Goldberg, L

    2017-08-01

    The adult marrow hematopoietic stem cell biology has largely been based on studies of highly purified stem cells. This is unfortunate because during the stem cell purification the great bulk of stem cells are discarded. These cells are actively proliferating. The final purified stem cell is dormant and not representative of the whole stem cell compartment. Thus, a large number of studies on the cellular characteristics, regulators and molecular details of stem cells have been carried on out of non-represented cells. Niche studies have largely pursued using these purified stem cells and these are largely un-interpretable. Other considerations include the distinction between baseline and transplant stem cells and the modulation of stem cell phenotype by extracellular vesicles, to cite a non-inclusive list. Work needs to proceed on characterizing the true stem cell population.

  20. An endoscopic study of upper-GI mucosal changes in patients with congestive heart failure.

    Science.gov (United States)

    Raja, Kaiser; Kochhar, Rakesh; Sethy, Pradeepta K; Dutta, Usha; Bali, Harinder K; Varma, Jagmohan S

    2004-12-01

    Congestive heart failure results in an increase in systemic venous pressure that is transmitted to the inferior vena cava and to the hepatic veins. This can cause GI vascular and mucosal congestion. The aim of this study was to define upper-GI mucosal changes in patients with congestive heart failure. A total of 57 patients with congestive heart failure presenting with GI symptoms underwent upper endoscopy. Echocardiography was performed in all patients to determine the ejection fraction and the degree of tricuspid regurgitation. Transabdominal US was performed to measure the diameters of the hepatic veins, the inferior vena cava, and the portal vein. The presence and the severity of gastropathy and duodenopathy were compared with the parameters relating to severity of cardiac failure. Of the 57 patients studied, gastric mucosal changes were observed in 50 (88%), duodenal mucosal changes in 31 (54%), and esophageal mucosal changes in none. Gastric mucosal changes were the following: mosaic-like pattern (n = 50), punctate spots (n = 34), thickened folds (n = 5), watermelon stomach (n = 3), and telangiectasia (n = 10). Duodenal mucosal changes were the following: mosaic-like pattern (n = 29), thickened folds (n = 8), and telangiectasia (n = 2). Upper-GI symptoms were associated with gastropathy ( p = 0.027) and duodenopathy ( p = 0.003). The presence and the severity of duodenopathy showed a high degree of positive correlation with the presence and the severity of gastropathy (gamma value 0.690; p value <0.001). Patients with gastropathy and duodenopathy had higher mean inferior vena cava and hepatic vein diameters than those without gastropathy and duodenopathy. The severity of duodenopathy but not that of gastropathy was significantly associated with increasing severity of tricuspid regurgitation ( p = 0.001), larger portal vein diameter ( p = 0.02), and lower ejection fraction ( p = 0.008). Among patients with congestive cardiac failure with GI symptoms, changes

  1. A scale out approach towards neural induction of human induced pluripotent stem cells for neurodevelopmental toxicity studies.

    Science.gov (United States)

    Miranda, Cláudia C; Fernandes, Tiago G; Pinto, Sandra N; Prieto, Manuel; Diogo, M Margarida; Cabral, Joaquim M S

    2018-05-21

    Stem cell's unique properties confer them a multitude of potential applications in the fields of cellular therapy, disease modelling and drug screening fields. In particular, the ability to differentiate neural progenitors (NP) from human induced pluripotent stem cells (hiPSCs) using chemically-defined conditions provides an opportunity to create a simple and straightforward culture platform for application in these fields. Here, we demonstrated that hiPSCs are capable of undergoing neural commitment inside microwells, forming characteristic neural structures resembling neural rosettes and further give rise to glial and neuronal cells. Furthermore, this platform can be applied towards the study of the effect of neurotoxic molecules that impair normal embryonic development. As a proof of concept, the neural teratogenic potential of the antiepileptic drug valproic acid (VPA) was analyzed. It was verified that exposure to VPA, close to typical dosage values (0.3 to 0.75 mM), led to a prevalence of NP structures over neuronal differentiation, as confirmed by analysis of the expression of neural cell adhesion molecule, as well as neural rosette number and morphology assessment. The methodology proposed herein for the generation and neural differentiation of hiPSC aggregates can potentially complement current toxicity tests such as the humanized embryonic stem cell test for the detection of teratogenic compounds that can interfere with normal embryonic development. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Therapeutic Potential of Dental Pulp Stem Cell Secretome for Alzheimer’s Disease Treatment: An In Vitro Study

    Directory of Open Access Journals (Sweden)

    Nermeen El-Moataz Bellah Ahmed

    2016-01-01

    Full Text Available The secretome obtained from stem cell cultures contains an array of neurotrophic factors and cytokines that might have the potential to treat neurodegenerative conditions. Alzheimer’s disease (AD is one of the most common human late onset and sporadic neurodegenerative disorders. Here, we investigated the therapeutic potential of secretome derived from dental pulp stem cells (DPSCs to reduce cytotoxicity and apoptosis caused by amyloid beta (Aβ peptide. We determined whether DPSCs can secrete the Aβ-degrading enzyme, neprilysin (NEP, and evaluated the effects of NEP expression in vitro by quantitating Aβ-degrading activity. The results showed that DPSC secretome contains higher concentrations of VEGF, Fractalkine, RANTES, MCP-1, and GM-CSF compared to those of bone marrow and adipose stem cells. Moreover, treatment with DPSC secretome significantly decreased the cytotoxicity of Aβ peptide by increasing cell viability compared to nontreated cells. In addition, DPSC secretome stimulated the endogenous survival factor Bcl-2 and decreased the apoptotic regulator Bax. Furthermore, neprilysin enzyme was detected in DPSC secretome and succeeded in degrading Aβ1–42 in vitro in 12 hours. In conclusion, our study demonstrates that DPSCs may serve as a promising source for secretome-based treatment of Alzheimer’s disease.

  3. Organizing Organoids: Stem Cells Branch Out.

    Science.gov (United States)

    Davies, Jamie A

    2017-12-07

    In this issue of Cell Stem Cell, Taguchi and Nishinakamura (2017) describe a carefully optimized method for making a branch-competent ureteric bud, a tissue fundamental to kidney development, from mouse embryonic stem cells and human induced pluripotent stem cells. The work illuminates embryology and has important implications for making more realistic kidney organoids. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. nduced pluripotent stem cells and cell therapy

    Directory of Open Access Journals (Sweden)

    Banu İskender

    2013-12-01

    Full Text Available Human embryonic stem cells are derived from the inner cell mass of a blastocyst-stage embryo. They hold a huge promise for cell therapy with their self-renewing ability and pluripotency, which is known as the potential to differentiate into all cell types originating from three embryonic germ layers. However, their unique pluripotent feature could not be utilised for therapeutic purposes due to the ethical and legal problems during derivation. Recently, it was shown that the cells from adult tissues could be reverted into embryonic state, thereby restoring their pluripotent feature. This has strenghtened the possiblity of directed differentition of the reprogrammed somatic cells into the desired cell types in vitro and their use in regenerative medicine. Although these cells were termed as induced pluripotent cells, the mechanism of pluripotency has yet to be understood. Still, induced pluripotent stem cell technology is considered to be significant by proposing novel approaches in disease modelling, drug screening and cell therapy. Besides their self-renewing ability and their potential to differentiate into all cell types in a human body, they arouse a great interest in scientific world by being far from the ethical concerns regarding their embryonic counterparts and their unique feature of being patient-specific in prospective cell therapies. In this review, induced pluripotent stem cell technology and its role in cell-based therapies from past to present will be discussed. J Clin Exp Invest 2013; 4 (4: 550-561

  5. Characterization and comparison of osteoblasts derived from mouse embryonic stem cells and induced pluripotent stem cells

    NARCIS (Netherlands)

    Ma, Ming San; Kannan, Vishnu; de Vries, Anneriek E; Czepiel, Marcin; Wesseling, Evelyn; Balasubramaniyan, Veerakumar; Kuijer, Roelof; Vissink, Arjan; Copray, Sjef; Raghoebar, Gerry

    New developments in stem cell biology offer alternatives for the reconstruction of critical-sized bone defects. One of these developments is the use of induced pluripotent stem (iPS) cells. These stem cells are similar to embryonic stem (ES) cells, but can be generated from adult somatic cells and

  6. The Extracellular Environment's Effect on Cellular Processes: An In Vitro Study of Mechanical and Chemical Cues on Human Mesenchymal Stem Cells and C17.2 Neural Stem Cells

    Science.gov (United States)

    Casey, Meghan E.

    Stem cells are widely used in the area of tissue engineering. The ability of cells to interact with materials on the nano- and micro- level is important in the success of the biomaterial. It is well-known that cells respond to their micro- and nano-environments through a process termed chemo-mechanotransduction. It is important to establish standard protocols for cellular experiments, as chemical modifications to maintenance environments can alter long-term research results. In this work, the effects of different media compositions on human mesenchymal stem cells (hMSCs) throughout normal in vitro maintenance are investigated. Changes in RNA regulation, protein expression and proliferation are studied via quantitative polymerase chain reaction (qPCR), immunocytochemistry (ICC) and cell counts, respectively. Morphological differences are also observed throughout the experiment. Results of this study illustrate the dynamic response of hMSC maintenance to differences in growth medium and passage number. These experiments highlight the effect growth medium has on in vitro experiments and the need of consistent protocols in hMSC research. A substantial opportunity exists in neuronal research to develop a material platform that allows for both the proliferation and differentiation of stem cells into neurons and the ability to quantify the secretome of neuronal cells. Anodic aluminum oxide (AAO) membranes are fabricated in a two-step anodization procedure where voltage is varied to control the pore size and morphology of the membranes. C17.2 neural stem cells are differentiated on the membranes via serum-withdrawal. Cellular growth is characterized by scanning electron microscopy (SEM), ICC and qPCR. ImageJ software is used to obtain phenotypic cell counts and neurite outgrowth lengths. Results indicate a highly tunable correlation between AAO nanopore sizes and differentiated cell populations. By selecting AAO membranes with specific pore size ranges, control of neuronal

  7. Keeping stem cells under control: new insights into the mechanisms that limit niche-stem cell signaling within the reproductive system

    OpenAIRE

    Inaba, Mayu; Yamashita, Yukiko M.; Buszczak, Michael

    2016-01-01

    Adult stem cells reside in specialized microenvironments called niches that maintain stem cells in an undifferentiated and self-renewing state. Despite extensive studies on the signaling pathways that operate within stem cells and their niches, the mechanisms that restrict niche signal exclusively to stem cells remained elusive: such a mechanism is crucially important to ensure that stem cells undergo self-renewal while their progeny, often located just one cell diameter away from the niche, ...

  8. Epigenetic control of embryonic stem cell fate

    DEFF Research Database (Denmark)

    Christophersen, Nicolaj Strøyer; Helin, Kristian

    2010-01-01

    Embryonic stem (ES) cells are derived from the inner cell mass of the preimplantation embryo and are pluripotent, as they are able to differentiate into all cell types of the adult organism. Once established, the pluripotent ES cells can be maintained under defined culture conditions, but can also...... be induced rapidly to differentiate. Maintaining this balance of stability versus plasticity is a challenge, and extensive studies in recent years have focused on understanding the contributions of transcription factors and epigenetic enzymes to the "stemness" properties of these cells. Identifying...... the molecular switches that regulate ES cell self-renewal versus differentiation can provide insights into the nature of the pluripotent state and enhance the potential use of these cells in therapeutic applications. Here, we review the latest models for how changes in chromatin methylation can modulate ES cell...

  9. Systems Biology and Stem Cell Pluripotency

    DEFF Research Database (Denmark)

    Mashayekhi, Kaveh; Hall, Vanessa Jane; Freude, Kristine

    2016-01-01

    Recent breakthroughs in stem cell biology have accelerated research in the area of regenerative medicine. Over the past years, it has become possible to derive patient-specific stem cells which can be used to generate different cell populations for potential cell therapy. Systems biological...... modeling of stem cell pluripotency and differentiation have largely been based on prior knowledge of signaling pathways, gene regulatory networks, and epigenetic factors. However, there is a great need to extend the complexity of the modeling and to integrate different types of data, which would further...... improve systems biology and its uses in the field. In this chapter, we first give a general background on stem cell biology and regenerative medicine. Stem cell potency is introduced together with the hierarchy of stem cells ranging from pluripotent embryonic stem cells (ESCs) and induced pluripotent stem...

  10. 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

  11. Extracellular Matrix as a Regulator of Epidermal Stem Cell Fate.

    Science.gov (United States)

    Chermnykh, Elina; Kalabusheva, Ekaterina; Vorotelyak, Ekaterina

    2018-03-27

    Epidermal stem cells reside within the specific anatomic location, called niche, which is a microenvironment that interacts with stem cells to regulate their fate. Regulation of many important processes, including maintenance of stem cell quiescence, self-renewal, and homeostasis, as well as the regulation of division and differentiation, are common functions of the stem cell niche. As it was shown in multiple studies, extracellular matrix (ECM) contributes a lot to stem cell niches in various tissues, including that of skin. In epidermis, ECM is represented, primarily, by a highly specialized ECM structure, basement membrane (BM), which separates the epidermal and dermal compartments. Epidermal stem cells contact with BM, but when they lose the contact and migrate to the overlying layers, they undergo terminal differentiation. When considering all of these factors, ECM is of fundamental importance in regulating epidermal stem cells maintenance, proper mobilization, and differentiation. Here, we summarize the remarkable progress that has recently been made in the research of ECM role in regulating epidermal stem cell fate, paying special attention to the hair follicle stem cell niche. We show that the destruction of ECM components impairs epidermal stem cell morphogenesis and homeostasis. A deep understanding of ECM molecular structure as well as the development of in vitro system for stem cell maintaining by ECM proteins may bring us to developing new approaches for regenerative medicine.

  12. Glucocorticoids and hemopoietic stem cells

    International Nuclear Information System (INIS)

    Romashko, O.O.; Berin, G.I.

    1978-01-01

    Analyzing the data of home and foreign investigators the problems of the glucocorticoid effect on blood and bone marrow of experimental (including irradiated ones) animals are discussed. Considered are a character and mechanism of the adrenal cortex hormones effect on blood formation, as well as the effect of pharmacological doses of corticosteroids on CFU, their erythropoietic effect in physiological doses on a morphological picture of bone marrow after irradiation and subsequent introduction of hormones and the hormone effect on intensity of erythropoiesis recovery in irradiated mice. Presented are the experimental data on studying the effect of endogenic hypercorticoidism and a reduced level of endogenic corticosteroids on blood-forming stem cells in the irradiated mice and the data on the ACTH injection effect on CFU migration after irradiation. Evaluated are already available data and further investigations to ground advisability and conditions of using corticosteroids as well as determining rational therapeutic effects on secretion of endogenic glucocorticoids when treating blood system diseases

  13. Perspectives on stem cell therapy for cardiac regeneration. Advances and challenges.

    Science.gov (United States)

    Choi, Sung Hyun; Jung, Seok Yun; Kwon, Sang-Mo; Baek, Sang Hong

    2012-01-01

    Ischemic heart disease (IHD) accelerates cardiomyocyte loss, but the developing stem cell research could be useful for regenerating a variety of tissue cells, including cardiomyocytes. Diverse sources of stem cells for IHD have been reported, including embryonic stem cells, induced pluripotent stem cells, skeletal myoblasts, bone marrow-derived stem cells, mesenchymal stem cells, and cardiac stem cells. However, stem cells have unique advantages and disadvantages for cardiac tissue regeneration, which are important considerations in determining the specific cells for improving cell survival and long-term engraftment after transplantation. Additionally, the dosage and administration method of stem cells need to be standardized to increase stability and efficacy for clinical applications. Accordingly, this review presents a summary of the stem cell therapies that have been studied for cardiac regeneration thus far, and discusses the direction of future cardiac regeneration research for stem cells.

  14. Human Embryonic Stem Cells: A Model for the Study of Neural Development and Neurological Diseases

    Directory of Open Access Journals (Sweden)

    Piya Prajumwongs

    2016-01-01

    Full Text Available Although the mechanism of neurogenesis has been well documented in other organisms, there might be fundamental differences between human and those species referring to species-specific context. Based on principles learned from other systems, it is found that the signaling pathways required for neural induction and specification of human embryonic stem cells (hESCs recapitulated those in the early embryo development in vivo at certain degree. This underscores the usefulness of hESCs in understanding early human neural development and reinforces the need to integrate the principles of developmental biology and hESC biology for an efficient neural differentiation.

  15. Mesenchymal stem cell therapy for salivary gland dysfunction and xerostomia: a systematic review of preclinical studies

    DEFF Research Database (Denmark)

    Jensen, David Hebbelstrup; Oliveri, Roberto Stefan; Trojahn-Kølle, Stig-Frederik

    2014-01-01

    was to assess, through systematic review, the potential benefit of mesenchymal stem cell (MSC) therapy in radiation-induced and SS-related salivary gland dysfunction and xerostomia. We searched PubMed/MEDLINE, Embase, Web of Science, the Cochrane Database of Systematic Reviews, the World Health Organization......The most severe forms of xerostomia and salivary gland dysfunction, as well as a severely reduced quality of life, are seen in Sjögren syndrome (SS) and after radiotherapy for head and neck cancer. For both conditions, no effective regenerative therapies yet exist. Thus, the aim of this article...

  16. Adipose-derived mesenchymal stem cells for cartilage tissue engineering: state-of-the-art in in vivo studies.

    Science.gov (United States)

    Veronesi, Francesca; Maglio, Melania; Tschon, Matilde; Aldini, Nicolò Nicoli; Fini, Milena

    2014-07-01

    Several therapeutic approaches have been developed to address hyaline cartilage regeneration, but to date, there is no universal procedure to promote the restoration of mechanical and functional properties of native cartilage, which is one of the most important challenges in orthopedic surgery. For cartilage tissue engineering, adult mesenchymal stem cells (MSCs) are considered as an alternative cell source to chondrocytes. Since little is known about adipose-derived mesenchymal stem cell (ADSC) cartilage regeneration potential, the aim of this review was to give an overview of in vivo studies about the chondrogenic potential and regeneration ability of culture-expanded ADSCs when implanted in heterotopic sites or in osteoarthritic and osteochondral defects. The review compares the different studies in terms of number of implanted cells and animals, cell harvesting sites, in vitro expansion and chondrogenic induction conditions, length of experimental time, defect dimensions, used scaffolds and post-explant analyses of the cartilage regeneration. Despite variability of the in vivo protocols, it seems that good cartilage formation and regeneration were obtained with chondrogenically predifferentiated ADSCs (1 × 10(7) cells for heterotopic cartilage formation and 1 × 10(6) cells/scaffold for cartilage defect regeneration) and polymeric scaffolds, even if many other aspects need to be clarified in future studies. © 2013 Wiley Periodicals, Inc.

  17. Stem cell and gene therapies for diabetes mellitus.

    Science.gov (United States)

    Calne, Roy Y; Gan, Shu Uin; Lee, Kok Onn

    2010-03-01

    In this Perspectives article, we comment on the progress in experimental stem cell and gene therapies that might one day become a clinical reality for the treatment of patients with diabetes mellitus. Research on the ability of human embryonic stem cells to differentiate into islet cells has defined the developmental stages and transcription factors involved in this process. However, the clinical applications of human embryonic stem cells are limited by ethical concerns, as well as the potential for teratoma formation. As a consequence, alternative forms of stem cell therapies, such as induced pluripotent stem cells and bone marrow-derived mesenchymal stem cells, have become an area of intense study. Finally, gene therapy shows some promise for the generation of insulin-producing cells. Here, we discuss two of the most frequently used approaches: in vitro gene delivery into cells which are then transplanted into the recipient and direct delivery of genes in vivo.

  18. Stem cells: a plant biology perspective

    NARCIS (Netherlands)

    Scheres, B.J.G.

    2005-01-01

    A recent meeting at the Juan March Foundation in Madrid, Spain brought together plant biologists to discuss the characteristics of plant stem cells that are unique and those that are shared by stem cells from the animal kingdom

  19. FDA Warns About Stem Cell Therapies

    Science.gov (United States)

    ... Home For Consumers Consumer Updates FDA Warns About Stem Cell Therapies Share Tweet Linkedin Pin it More sharing ... see the boxed section below for more advice. Stem Cell Uses and FDA Regulation The FDA has the ...

  20. Stem Cell Transplant Patients and Fungal Infections

    Science.gov (United States)

    ... Foodborne, Waterborne, and Environmental Diseases Mycotic Diseases Branch Stem Cell Transplant Patients and Fungal Infections Recommend on Facebook ... Mold . Top of Page Preventing fungal infections in stem cell transplant patients Fungi are difficult to avoid because ...

  1. 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 ...

  2. Molecular mechanisms of adult stem cell aging

    National Research Council Canada - National Science Library

    Rudolph, K. Lenhard

    2010-01-01

    "There is growing evidence that adult stem cells age. This process can result in alterations in the number and function of stem cells, leading to distinct phenotypic outcomes in different organ systems...

  3. Stem Cell Therapy for Erectile Dysfunction.

    Science.gov (United States)

    Matz, Ethan L; Terlecki, Ryan; Zhang, Yuanyuan; Jackson, John; Atala, Anthony

    2018-04-06

    The prevalence of erectile dysfunction (ED) is substantial and continues to rise. Current therapeutics for ED consist of oral medications, intracavernosal injections, vacuum erection devices, and penile implants. While such options may manage the disease state, none of these modalities, however, restore function. Stem cell therapy has been evaluated for erectile restoration in animal models. These cells have been derived from multiple tissues, have varied potential, and may function via local engraftment or paracrine signaling. Bone marrow-derived stem cells (BMSC) and adipose-derived stem cells (ASC) have both been used in these models with noteworthy effects. Herein, we will review the pathophysiology of ED, animal models, current and novel stem-cell based therapeutics, clinical trials and areas for future research. The relevant literature and contemporary data using keywords, "stem cells and erectile dysfunction" was reviewed. Examination of evidence supporting the association between erectile dysfunction and adipose derived stem cells, bone marrow derived stem cells, placental stem cells, urine stem cells and stem cell therapy respectively. Placental-derived stem cells and urine-derived stem cells possess many similar properties as BMSC and ASC, but the methods of acquisition are favorable. Human clinical trials have already demonstrated successful use of stem cells for improvement of erectile function. The future of stem cell research is constantly being evaluated, although, the evidence suggests a place for stem cells in erectile dysfunction therapeutics. Matz EL, Terlecki R, Zhang Y, et al. Stem Cell Therapy for Erectile Dysfunction. Sex Med Rev 2018;XX:XXX-XXX. Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  4. Propagation of human spermatogonial stem cells in vitro.

    Science.gov (United States)

    Sadri-Ardekani, Hooman; Mizrak, Sefika C; van Daalen, Saskia K M; Korver, Cindy M; Roepers-Gajadien, Hermien L; Koruji, Morteza; Hovingh, Suzanne; de Reijke, Theo M; de la Rosette, Jean J M C H; van der Veen, Fulco; de Rooij, Dirk G; Repping, Sjoerd; van Pelt, Ans M M

    2009-11-18

    Young boys treated with high-dose chemotherapy are often confronted with infertility once they reach adulthood. Cryopreserving testicular tissue before chemotherapy and autotransplantation of spermatogonial stem cells at a later stage could theoretically allow for restoration of fertility. To establish in vitro propagation of human spermatogonial stem cells from small testicular biopsies to obtain an adequate number of cells for successful transplantation. Study performed from April 2007 to July 2009 using testis material donated by 6 adult men who underwent orchidectomy as part of prostate cancer treatment. Testicular cells were isolated and cultured in supplemented StemPro medium; germline stem cell clusters that arose were subcultured on human placental laminin-coated dishes in the same medium. Presence of spermatogonia was determined by reverse transcriptase polymerase chain reaction and immunofluorescence for spermatogonial markers. To test for the presence of functional spermatogonial stem cells in culture, xenotransplantation to testes of immunodeficient mice was performed, and migrated human spermatogonial stem cells after transplantation were detected by COT-1 fluorescence in situ hybridization. The number of colonized spermatogonial stem cells transplanted at early and later points during culture were counted to determine propagation. Propagation of spermatogonial stem cells over time. Testicular cells could be cultured and propagated up to 15 weeks. Germline stem cell clusters arose in the testicular cell cultures from all 6 men and could be subcultured and propagated up to 28 weeks. Expression of spermatogonial markers on both the RNA and protein level was maintained throughout the entire culture period. In 4 of 6 men, xenotransplantation to mice demonstrated the presence of functional spermatogonial stem cells, even after prolonged in vitro culture. Spermatogonial stem cell numbers increased 53-fold within 19 days in the testicular cell culture and

  5. Adipose-Derived Stem Cells

    NARCIS (Netherlands)

    Gathier, WA; Türktas, Z; Duckers, HJ

    2015-01-01

    Until recently bone marrow was perceived to be the only significant reservoir of stem cells in the body. However, it is now recognized that there are other and perhaps even more abundant sources, which include adipose tissue. Subcutaneous fat is readily available in most patients, and can easily be

  6. New perspectives in human stem cell therapeutic research

    Directory of Open Access Journals (Sweden)

    Trounson Alan

    2009-06-01

    Full Text Available Abstract Human stem cells are in evaluation in clinical stem cell trials, primarily as autologous bone marrow studies, autologous and allogenic mesenchymal stem cell trials, and some allogenic neural stem cell transplantation projects. Safety and efficacy are being addressed for a number of disease state applications. There is considerable data supporting safety of bone marrow and mesenchymal stem cell transplants but the efficacy data are variable and of mixed benefit. Mechanisms of action of many of these cells are unknown and this raises the concern of unpredictable results in the future. Nevertheless there is considerable optimism that immune suppression and anti-inflammatory properties of mesenchymal stem cells will be of benefit for many conditions such as graft versus host disease, solid organ transplants and pulmonary fibrosis. Where bone marrow and mesenchymal stem cells are being studied for heart disease, stroke and other neurodegenerative disorders, again progress is mixed and mostly without significant benefit. However, correction of multiple sclerosis, at least in the short term is encouraging. Clinical trials on the use of embryonic stem cell derivatives for spinal injury and macular degeneration are beginning and a raft of other clinical trials can be expected soon, for example, the use of neural stem cells for killing inoperable glioma and embryonic stem cells for regenerating β islet cells for diabetes. The change in attitude to embryonic stem cell research with the incoming Obama administration heralds a new co-operative environment for study and evaluation of stem cell therapies. The Californian stem cell initiative (California Institute for Regenerative Medicine has engendered global collaboration for this new medicine that will now also be supported by the US Federal Government. The active participation of governments, academia, biotechnology, pharmaceutical companies, and private investment is a powerful consortium for

  7. Differentiation of Neonatal Human-Induced Pluripotent Stem Cells to Prostate Epithelial Cells: A Model to Study Prostate Cancer Development

    Science.gov (United States)

    2013-06-01

    38, 40, 41]. Because these “ mela - noma stem cells” (MSC) are sometimes so numerous, some have argued that the CSC model may not apply to melanoma...40]. There are data from two groups indicating that mela - noma lesions contain a CSC subset character- ized by CD271 expression [25, 26]. In a...neuronal proteins and neuron- like differentiation has been long recognized in neoplastic melanocytes [46, 47]. Certain mela - noma cell lines that

  8. Comparative study of expression and activity of glucose transporters between stem cell-derived brain microvascular endothelial cells and hCMEC/D3 cells.

    Science.gov (United States)

    Al-Ahmad, Abraham J

    2017-10-01

    Glucose constitutes a major source of energy of mammalian brains. Glucose uptake at the blood-brain barrier (BBB) occurs through a facilitated glucose transport, through glucose transporter 1 (GLUT1), although other isoforms have been described at the BBB. Mutations in GLUT1 are associated with the GLUT1 deficiency syndrome, yet none of the current in vitro models of the human BBB maybe suited for modeling such a disorder. In this study, we investigated the expression of glucose transporters and glucose diffusion across brain microvascular endothelial cells (BMECs) derived from healthy patient-derived induced pluripotent stem cells (iPSCs). We investigated the expression of different glucose transporters at the BBB using immunocytochemistry and flow cytometry and measured glucose uptake and diffusion across BMEC monolayers obtained from two iPSC lines and from hCMEC/D3 cells. BMEC monolayers showed expression of several glucose transporters, in particular GLUT1, GLUT3, and GLUT4. Diffusion of glucose across the monolayers was mediated via a saturable transcellular mechanism and partially inhibited by pharmacological inhibitors. Taken together, our study suggests the presence of several glucose transporters isoforms at the human BBB and demonstrates the feasibility of modeling glucose across the BBB using patient-derived stem cells. Copyright © 2017 the American Physiological Society.

  9. The stem-cell application in ischemic heart disease: Basic principles, specifics and practical experience from clinical studies

    Directory of Open Access Journals (Sweden)

    Banović Marko

    2015-01-01

    Full Text Available Longer life duration, different clinical presentations of coronary disease, as well as high incidence of comorbidity in patients with ischemic heart disease have led to an increase in the incidence of ischemic heart failure. Despite numerous and new treatment methods that act on different pathophysiological mechanisms that cause heart failure, and whose aim is to slowdown or stop the progression of this devastating disease, morbidity and mortality in these patients remain high. These facts have firstly led to the introduction of the experimental, and then clinical studies with the application of stem cells in patients with ischemic heart disease. Previous studies have shown that the application of stem cells is a feasible and safe method in patients with acute coronary syndrome, as well as in patients with chronic ischemic cardiomyopathy, but the efficacy of these methods in both of the abovementioned clinical syndromes has yet to be established. This review paper outlines the basic principles of treatment of ischemic heart disease with stem cells, as well as the experience and knowledge gained in previous clinical studies.

  10. Pluripotent Stem Cells for Schwann Cell Engineering

    NARCIS (Netherlands)

    Ma, Ming-San; Boddeke, Erik; Copray, Sjef

    Tissue engineering of Schwann cells (SCs) can serve a number of purposes, such as in vitro SC-related disease modeling, treatment of peripheral nerve diseases or peripheral nerve injury, and, potentially, treatment of CNS diseases. SCs can be generated from autologous stem cells in vitro by

  11. Ovary and fimbrial stem cells: biology, niche and cancer origins.

    Science.gov (United States)

    Ng, Annie; Barker, Nick

    2015-10-01

    The mammalian ovary is covered by a single-layered epithelium that undergoes rupture and remodelling following each ovulation. Although resident stem cells are presumed to be crucial for this cyclic regeneration, their identity and mode of action have been elusive. Surrogate stemness assays and in vivo fate-mapping studies using recently discovered stem cell markers have identified stem cell pools in the ovary and fimbria that ensure epithelial homeostasis. Recent findings provide insights into intrinsic mechanisms and local extrinsic cues that govern the function of ovarian and fimbrial stem cells. These discoveries have advanced our understanding of stem cell biology in the ovary and fimbria, and lay the foundations for evaluating the contribution of resident stem cells to the initiation and progression of human epithelial ovarian cancer.

  12. Music Therapy for Symptom Management After Autologous Stem Cell Transplantation: Results From a Randomized Study.

    Science.gov (United States)

    Bates, Debbie; Bolwell, Brian; Majhail, Navneet S; Rybicki, Lisa; Yurch, Melissa; Abounader, Donna; Kohuth, Joseph; Jarancik, Shannon; Koniarczyk, Heather; McLellan, Linda; Dabney, Jane; Lawrence, Christine; Gallagher, Lisa; Kalaycio, Matt; Sobecks, Ronald; Dean, Robert; Hill, Brian; Pohlman, Brad; Hamilton, Betty K; Gerds, Aaron T; Jagadeesh, Deepa; Liu, Hien D

    2017-09-01

    High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is frequently performed in patients with hematologic malignancies. ASCT can result in significant nausea, pain, and discomfort. Supportive care has improved, and pharmacologic therapies are frequently used, but with limitations. Music has been demonstrated to improve nausea and pain in patients undergoing chemotherapy, but little data are available regarding the effects of music therapy in the transplantation setting. In a prospective study, patients with lymphoma or multiple myeloma undergoing ASCT were randomized to receive either interactive music therapy with a board-certified music therapist or no music therapy. The music therapy arm received 2 music therapy sessions on days +1 and +5. Primary outcomes were perception of pain and nausea measured on a visual analog scale. Secondary outcomes were narcotic pain medication use from day -1 to day +5 and impact of ASCT on patient mood as assessed by Profile of Mood States (POMS) on day +5. Eighty-two patients were enrolled, with 37 in the music therapy arm and 45 in the no music therapy arm. Patients who received MT had slightly increased nausea by day +7 compared with the no music therapy patients. The music therapy and no music therapy patients had similar pain scores; however, the patients who received music therapy used significantly less narcotic pain medication (median, 24 mg versus 73 mg; P = .038). Music therapy may be a viable nonpharmacologic method of pain management for patients undergoing ASCT; the music therapy patients required significantly fewer morphine equivalent doses compared with the no music therapy patients. Additional research is needed to better understand the effects of music therapy on patient-perceived symptoms, such as pain and nausea. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  13. Intravenous mesenchymal stem cell therapy after recurrent laryngeal nerve injury: a preliminary study.

    Science.gov (United States)

    Lerner, Michael Z; Matsushita, Takashi; Lankford, Karen L; Radtke, Christine; Kocsis, Jeffery D; Young, Nwanmegha O

    2014-11-01

    Intravenous administration of mesenchymal stem cells (MSCs) has been recently shown to enhance functional recovery after stroke and spinal cord injury. The therapeutic properties of MSCs are attributed to their secretion of a variety of potent antiinflammatory and neurotrophic factors. We hypothesize that intravenous administration of MSCs after recurrent laryngeal nerve (RLN) injury in the rat may enhance functional recovery. Animal Research. Twelve 250-gram Sprague-Dawley rats underwent a controlled crush injury to the left RLN. After confirming postoperative vocal fold immobility, each rat was intravenously infused with either green fluorescent protein-expressing MSCs or control media in a randomized and blinded fashion. Videolaryngoscopy was performed weekly. The laryngoscopy video recordings were reviewed and rated by a fellowship-trained laryngologist who remained blinded to the intervention using a 0 to 3 scale. At 1 week postinjury, the MSC-infused group showed a trend for higher average functional recovery scores compared to the control group (2.2 vs 1.3), but it did not reach statistical significance (P value of 0.06). By 2 weeks, however, both groups exhibited complete return of function. These pilot data indicate that with complete nerve transection by crush injury of the RLN in rat, there is complete recovery of vocal fold mobility at 2 weeks. At 1 week postinjury, animals receiving intravenous infusion of MSCs showed a trend for greater functional recovery, suggesting a potential beneficial effect of MSCs; however, this did not reach statistical significance. Therefore, no definite conclusions can be drawn from these data and further study is required. N/A. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  14. Cytogenetic and clinicobiological features of acute leukemia with stem cell phenotype: study of nine cases.

    Science.gov (United States)

    Cuneo, A; Ferrant, A; Michaux, J L; Bosly, A; Chatelain, B; Stul, M; Dal Cin, P; Dierlamm, J; Cassiman, J J; Hossfeld, D K; Castoldi, G; Van den Berghe, H

    1996-11-01

    Morphologic, immunologic, cytogenetic, and clinical features were studied in 9 cases of acute undifferentiated leukemia (AUL). These patients were unclassifiable by FAB criteria, they were CD34+ and did not express myeloid- or lymphoid-associated antigens (CD13, CD33, CD14, CD15, CD61, CD19, CD10, CD22, CD7, CD2, CD5, CD3). Clonal abnormalities were seen in 8 of 9 cases. Del(5q) as the sole anomaly was observed in 3 cases; +13 was the primary change in 3 cases, and isolated trisomy 12 was found in 1 patient. A complex karyotype with trisomy 12q, in association with del 17p and trisomy 21q was detected in 1 case. One patient with 5q- relapsed with refractory anemia with excess of blasts; the presence of dysgranulopoiesis and a few blasts with possible monocytoid morphology in the remaining 2 patients point to a "myeloid nature" of these leukemias. Analysis of cytologic features in our 3 patients with +13, in combination with previously reported cases, suggests the occurrence of immature stem cell involvement with limited differentiation potential, possibly more along the myeloid than the lymphoid lineage. The significance of trisomy 12q in this subset of leukemia remains elusive; some clues of minimal differentiation towards the myeloid lineage in our cases are provided by positivity for the CD117 (c-kit) antigen and by relapse with acute myeloid leukemia without maturation (M1) in one patient. We conclude that, with presently available diagnostic techniques, AUL is a rare subset of leukemia, in which cytogenetic changes are confined to a few chromosomes, with prevalent involvement of 5q and of chromosomes 13 and 12. Chromosome findings may be of value in clinical practice, especially in those cases with "myeloid-oriented" karyotype.

  15. Recent Advances in Intestinal Stem Cells.

    Science.gov (United States)

    McCabe, Laura R; Parameswaran, Narayanan

    2017-09-01

    The intestine is a dynamic organ with rapid stem cell division generating epithelial cells that mature and apoptose in 3-5 days. Rapid turnover maintains the epithelial barrier and homeostasis. Current insights on intestinal stem cells (ISCs) and their regulation are discussed here. The Lgr5+ ISCs maintain intestinal homeostasis by dividing asymmetrically, but also divide symmetrically to extinguish or replace ISCs. Following radiation or mucosal injury, reserve BMI1+ ISCs as well as other crypt cells can de-differentiate into Lgr5+ ISCs. ISC niche cells, including Paneth, immune and myofibroblast cells secrete factors that regulate ISC proliferation. Finally, several studies indicate that the microbiome metabolites regulate ISC growth. ISC cells can be plastic and integrate a complexity of environmental/niche cues to trigger or suppress proliferation as needed.

  16. Identification of progenitor cancer stem cell in lentigo maligna melanoma.

    Science.gov (United States)

    Bongiorno, M R; Doukaki, S; Malleo, F; Aricò, M

    2008-07-01

    The potential role of stem cells in neoplasia has aroused considerable interest over the past few years. A number of known biologic characteristics of melanomas support the theory that they may originate in a mutated stem cell. Melanocytic stem cell markers have been described recently. Moreover, the CD133 cells that show surface markers for CD34 are stem cells primitive. These stem cells are capable of differentiating into neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. The identification of cancer stem/initiating cells with a crucial role in tumor formation may open up new pharmacologic perspectives. The purpose of this study is to detect the expression of CD133 and CD34, two putative markers of cancer stem cells in the lentigo maligna melanoma. Thirty cases of lentigo maligna melanoma were analyzed using indirect immunohistochemical staining. The vast majority of the samples analyzed showed the presence of rare cells, which were clearly positive for CD133 and CD34. Strong CD133 and CD34 staining was found in the outer root sheath of the mid-lower hair follicles, intermixed with atypical melanocytes extending along layers of the hair follicles. A number of these staminal cells were adjacent and intermixed with melanoma cells. This study supports the stem cell origin of this tumor and suggests that the precursor of the melanoma in question is a stem-like cell rather than the primitive melanoblast committed to be exclusively involved in melanocytic differentiation.

  17. Nine Things to Know About Stem Cell Treatments

    Science.gov (United States)

    ... Search Toggle Nav Nine Things To Know About Stem Cell Treatments Home > Stem Cells and Medicine > Nine Things ... Know About Stem Cell Treatments Many clinics offering stem cell treatments make claims that are not supported by ...

  18. Setting FIRES to Stem Cell Research

    Science.gov (United States)

    Miller, Roxanne Grietz

    2005-01-01

    The goal of this lesson is to present the basic scientific knowledge about stem cells, the promise of stem cell research to medicine, and the ethical considerations and arguments involved. One of the challenges of discussing stem cell research is that the field is constantly evolving and the most current information changes almost daily. Few…

  19. Adipose-Derived Mesenchymal Stem Cells in the Regeneration of Vocal Folds: A Study on a Chronic Vocal Fold Scar

    Directory of Open Access Journals (Sweden)

    Angelou Valerie

    2016-01-01

    Full Text Available Background. The aim of the study was to assess the histological effects of autologous infusion of adipose-derived stem cells (ADSC on a chronic vocal fold scar in a rabbit model as compared to an untreated scar as well as in injection of hyaluronic acid. Study Design. Animal experiment. Method. We used 74 New Zealand rabbits. Sixteen of them were used as control/normal group. We created a bilateral vocal fold wound in the remaining 58 rabbits. After 18 months we separated our population into three groups. The first group served as control/scarred group. The second one was injected with hyaluronic acid in the vocal folds, and the third received an autologous adipose-derived stem cell infusion in the scarred vocal folds (ADSC group. We measured the variation of thickness of the lamina propria of the vocal folds and analyzed histopathologic changes in each group after three months. Results. The thickness of the lamina propria was significantly reduced in the group that received the ADSC injection, as compared to the normal/scarred group. The collagen deposition, the hyaluronic acid, the elastin levels, and the organization of elastic fibers tend to return to normal after the injection of ADSC. Conclusions. Autologous injection of adipose-derived stem cells on a vocal fold chronic scar enhanced the healing of the vocal folds and the reduction of the scar tissue, even when compared to other treatments.

  20. Adipose-Derived Mesenchymal Stem Cells in the Regeneration of Vocal Folds: A Study on a Chronic Vocal Fold Scar

    Science.gov (United States)

    Vassiliki, Kalodimou; Irini, Messini; Nikolaos, Psychalakis; Karampela, Eleftheria; Apostolos, Papalois

    2016-01-01

    Background. The aim of the study was to assess the histological effects of autologous infusion of adipose-derived stem cells (ADSC) on a chronic vocal fold scar in a rabbit model as compared to an untreated scar as well as in injection of hyaluronic acid. Study Design. Animal experiment. Method. We used 74 New Zealand rabbits. Sixteen of them were used as control/normal group. We created a bilateral vocal fold wound in the remaining 58 rabbits. After 18 months we separated our population into three groups. The first group served as control/scarred group. The second one was injected with hyaluronic acid in the vocal folds, and the third received an autologous adipose-derived stem cell infusion in the scarred vocal folds (ADSC group). We measured the variation of thickness of the lamina propria of the vocal folds and analyzed histopathologic changes in each group after three months. Results. The thickness of the lamina propria was significantly reduced in the group that received the ADSC injection, as compared to the normal/scarred group. The collagen deposition, the hyaluronic acid, the elastin levels, and the organization of elastic fibers tend to return to normal after the injection of ADSC. Conclusions. Autologous injection of adipose-derived stem cells on a vocal fold chronic scar enhanced the healing of the vocal folds and the reduction of the scar tissue, even when compared to other treatments. PMID:26933440

  1. Autophagy regulates the stemness of cervical cancer stem cells

    Directory of Open Access Journals (Sweden)

    Yang Y

    2017-06-01

    Full Text Available Yi Yang,1,2 Li Yu,1 Jin Li,1 Ya Hong Yuan,1 Xiao Li Wang,1 Shi Rong Yan,1 Dong Sheng Li,1 Yan Ding1 1Hubei Key Laboratory of Embryonic Stem Cell Research, 2Reproductive Center, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China Abstract: Cancer stem cells (CSCs are a rare population of multipotent cells with the capacity to self-renew. It has been reported that there are CSCs in cervical cancer cells. Pluripotency-associated (PA transcription factors such as Oct4, Sox2, Nanog and CD44 have been used to isolate CSCs subpopulations. In this study, we showed that autophagy plays an important role in the biological behavior of cervical cancer cells. The expression of the autophagy protein Beclin 1 and LC3B was higher in tumorspheres established from human cervical cancers cell lines (and CaSki than in the parental adherent cells. It was also observed that the basal and starvation-induced autophagy flux was higher in tumorspheres than in the bulk population. Autophagy could regulate the expression level of PA proteins in cervical CSCs. In addition, CRISPR/Cas 9-mediated Beclin 1 knockout enhanced the malignancy of HeLa cells, leading to accumulation of PA proteins and promoted tumorsphere formation. Our findings suggest that autophagy modulates homeostasis of PA proteins, and Beclin 1 is critical for CSC maintenance and tumor development in nude mice. This demonstrates that a prosurvival autophagic pathway is critical for CSC maintenance. Keywords: cervical cancer, autophagy, cancer stem cell, LC3, Oct4

  2. Autophagy in Stem Cell Biology: A Perspective on Stem Cell Self-Renewal and Differentiation

    Directory of Open Access Journals (Sweden)

    Xihang Chen

    2018-01-01

    Full Text Available Autophagy is a highly conserved cellular process that degrades modified, surplus, or harmful cytoplasmic components by sequestering them in autophagosomes which then fuses with the lysosome for degradation. As a major intracellular degradation and recycling pathway, autophagy is crucial for maintaining cellular homeostasis, as well as for remodeling during normal development. Impairment of this process has been implicated in various diseases, in the pathogenic response to bacterial and viral infections, and in aging. Pluripotent stem cells, with their ability to self-replicate and to give rise to any specialized cell type, are very valuable resources for cell-based medical therapies and open a number of promising avenues for studying human development and disease. It has been suggested that autophagy is vital for the maintenance of cellular homeostasis in stem cells, and subsequently more in-depth knowledge about the regulation of autophagy in stem cell biology has been acquired recently. In this review, we describe the most significant advances in the understanding of autophagy regulation in hematopoietic and mesenchymal stem cells, as well as in induced pluripotent stem cells. In particular, we highlight the roles of various autophagy activities in the regulation of self-renewal and differentiation of these stem cells.

  3. Human skeletal muscle-derived stem cells retain stem cell properties after expansion in myosphere culture

    International Nuclear Information System (INIS)

    Wei, Yan; Li, Yuan; Chen, Chao; Stoelzel, Katharina; Kaufmann, Andreas M.; Albers, Andreas E.

    2011-01-01

    Human skeletal muscle contains an accessible adult stem-cell compartment in which differentiated myofibers are maintained and replaced by a self-renewing stem cell pool. Previously, studies using mouse models have established a critical role for resident stem cells in skeletal muscle, but little is known about this paradigm in human muscle. Here, we report the reproducible isolation of a population of cells from human skeletal muscle that is able to proliferate for extended periods of time as floating clusters of rounded cells, termed 'myospheres' or myosphere-derived progenitor cells (MDPCs). The phenotypic characteristics and functional properties of these cells were determined using reverse transcription-polymerase chain reaction (RT-PCR), flow cytometry and immunocytochemistry. Our results showed that these cells are clonogenic, express skeletal progenitor cell markers Pax7, ALDH1, Myod, and Desmin and the stem cell markers Nanog, Sox2, and Oct3/4 significantly elevated over controls. They could be maintained proliferatively active in vitro for more than 20 weeks and passaged at least 18 times, despite an average donor-age of 63 years. Individual clones (4.2%) derived from single cells were successfully expanded showing clonogenic potential and sustained proliferation of a subpopulation in the myospheres. Myosphere-derived cells were capable of spontaneous differentiation into myotubes in differentiation media and into other mesodermal cell lineages in induction media. We demonstrate here that direct culture and expansion of stem cells from human skeletal muscle is straightforward and reproducible with the appropriate technique. These cells may provide a viable resource of adult stem cells for future therapies of disease affecting skeletal muscle or mesenchymal lineage derived cell types.

  4. Extinction models for cancer stem cell therapy

    Science.gov (United States)

    Sehl, Mary; Zhou, Hua; Sinsheimer, Janet S.; Lange, Kenneth L.

    2012-01-01

    Cells with stem cell-like properties are now viewed as initiating and sustaining many cancers. This suggests that cancer can be cured by driving these cancer stem cells to extinction. The problem with this strategy is that ordinary stem cells are apt to be killed in the process. This paper sets bounds on the killing differential (difference between death rates of cancer stem cells and normal stem cells) that must exist for the survival of an adequate number of normal stem cells. Our main tools are birth–death Markov chains in continuous time. In this framework, we investigate the extinction times of cancer stem cells and normal stem cells. Application of extreme value theory from mathematical statistics yields an accurate asymptotic distribution and corresponding moments for both extinction times. We compare these distributions for the two cell populations as a function of the killing rates. Perhaps a more telling comparison involves the number of normal stem cells NH at the extinction time of the cancer stem cells. Conditioning on the asymptotic time to extinction of the cancer stem cells allows us to calculate the asymptotic mean and variance of NH. The full distribution of NH can be retrieved by the finite Fourier transform and, in some parameter regimes, by an eigenfunction expansion. Finally, we discuss the impact of quiescence (the resting state) on stem cell dynamics. Quiescence can act as a sanctuary for cancer stem cells and imperils the proposed therapy. We approach the complication of quiescence via multitype branching process models and stochastic simulation. Improvements to the τ-leaping method of stochastic simulation make it a versatile tool in this context. We conclude that the proposed therapy must target quiescent cancer stem cells as well as actively dividing cancer stem cells. The current cancer models demonstrate the virtue of attacking the same quantitative questions from a variety of modeling, mathematical, and computational perspectives

  5. Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells

    NARCIS (Netherlands)

    Guadix, Juan Antonio; Orlova, Valeria V.; Giacomelli, Elisa; Bellin, Milena; Ribeiro, Marcelo C.; Mummery, Christine L.; Pérez-Pomares, José M.; Passier, Robert

    2017-01-01

    Human pluripotent stem cells (hPSCs) are widely used to study cardiovascular cell differentiation and function. Here, we induced differentiation of hPSCs (both embryonic and induced) to proepicardial/epicardial progenitor cells that cover the heart during development. Addition of retinoic acid (RA)

  6. Limbal stem cell transplantation: current perspectives

    Directory of Open Access Journals (Sweden)

    Atallah MR

    2016-04-01

    the severity of the disease. In summary, limbal stem cell transplantation improves both vision and quality-of-life in patients with ocular surface disorders associated with LSCD, and overall, the use of autologous tissue offers the best results. Future studies aim at improving cellular expansion and finding different sources of stem cells. Keywords: limbal stem cell deficiency (LSCD, simple limbal epithelial transplantation (SLET, cultivated limbal epithelial transplantation (CLET, keratolimbal allograft (KLAL

  7. Dental pulp stem cells in regenerative dentistry.

    Science.gov (United States)

    Casagrande, Luciano; Cordeiro, Mabel M; Nör, Silvia A; Nör, Jacques E

    2011-01-01

    Stem cells constitute the source of differentiated cells for the generation of tissues during development, and for regeneration of tissues that are diseased or injured postnatally. In recent years, stem cell research has grown exponentially owing to the recognition that stem cell-based therapies have the potential to improve the life of patients with conditions that span from Alzheimer's disease to cardiac ischemia to bone or tooth loss. Growing evidence demonstrates that stem cells are primarily found in niches and that certain tissues contain more stem cells than others. Among these tissues, the dental pulp is considered a rich source of mesenchymal stem cells that are suitable for tissue engineering applications. It is known that dental pulp stem cells have the potential to differentiate into several cell types, including odontoblasts, neural progenitors, osteoblasts, chondrocytes, and adipocytes. The dental pulp stem cells are highly proliferative. This characteristic facilitates ex vivo expansion and enhances the translational potential of these cells. Notably, the dental pulp is arguably the most accessible source of postnatal stem cells. Collectively, the multipotency, high proliferation rates, and accessibility make the dental pulp an attractive source of mesenchymal stem cells for tissue regeneration. This review discusses fundamental concepts of stem cell biology and tissue engineering within the context of regenerative dentistry.

  8. Methods for Stem Cell Production and Therapy

    Science.gov (United States)

    Valluri, Jagan V. (Inventor); Claudio, Pier Paolo (Inventor)

    2015-01-01

    The present invention relates to methods for rapidly expanding a stem cell population with or without culture supplements in simulated microgravity conditions. The present invention relates to methods for rapidly increasing the life span of stem cell populations without culture supplements in simulated microgravity conditions. The present invention also relates to methods for increasing the sensitivity of cancer stem cells to chemotherapeutic agents by culturing the cancer stem cells under microgravity conditions and in the presence of omega-3 fatty acids. The methods of the present invention can also be used to proliferate cancer cells by culturing them in the presence of omega-3 fatty acids. The present invention also relates to methods for testing the sensitivity of cancer cells and cancer stem cells to chemotherapeutic agents by culturing the cancer cells and cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce tissue for use in transplantation by culturing stem cells or cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce cellular factors and growth factors by culturing stem cells or cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce cellular factors and growth factors to promote differentiation of cancer stem cells under microgravity conditions.

  9. [Embryonic stem cells. Future perspectives].

    Science.gov (United States)

    Groebner, M; David, R; Franz, W M

    2006-05-01

    Embryonic stem cells (ES cells) are able to differentiate into any cell type, and therefore represent an excellent source for cellular replacement therapies in the case of widespread diseases, for example heart failure, diabetes, Parkinson's disease and spinal cord injury. A major prerequisite for their efficient and safe clinical application is the availability of pure populations for direct cell transplantation or tissue engineering as well as the immunological compatibility of the transplanted cells. The expression of human surface markers under the control of cell type specific promoters represents a promising approach for the selection of cardiomyocytes and other cell types for therapeutic applications. The first human clinical trial using ES cells will start in the United States this year.

  10. Current applications of human pluripotent stem cells: possibilities and challenges.

    Science.gov (United States)

    Ho, Pai-Jiun; Yen, Men-Luh; Yet, Shaw-Fang; Yen, B Linju

    2012-01-01

    Stem cells are self-renewable cells with the differentiation capacity to develop into somatic cells with biological functions. This ability to sustain a renewable source of multi- and/or pluripotential differentiation has brought new hope to the field of regenerative medicine in terms of cell therapy and tissue engineering. Moreover, stem cells are invaluable tools as in vitro models for studying diverse fields, from basic scientific questions such as developmental processes and lineage commitment, to practical application including drug screening and testing. The stem cells with widest differentiation potential are pluripotent stem cells (PSCs), which are rare cells with the ability to generate somatic cells from all three germ layers. PSCs are considered the most optimal choice for therapeutic potential of stem cells, bringing new impetus to the field of regenerative medicine. In this article, we discuss the therapeutic potential of human PSCs (hPSCs) including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), reviewing the current preclinical and clinical data using these stem cells. We describe the classification of different sources of hPSCs, ongoing research, and currently encountered clinical obstacles of these novel and versatile human stem cells.

  11. Redox environment in stem and differentiated cells: A quantitative approach

    Directory of Open Access Journals (Sweden)

    O.G. Lyublinskaya

    2017-08-01

    Full Text Available Stem cells are believed to maintain a specific intracellular redox status through a combination of enhanced removal capacity and limited production of ROS. In the present study, we challenge this assumption by developing a quantitative approach for the analysis of the pro- and antioxidant ability of human embryonic stem cells in comparison with their differentiated descendants, as well as adult stem and non-stem cells. Our measurements showed that embryonic stem cells are characterized by low ROS level, low rate of extracellular hydrogen peroxide removal and low threshold for peroxide-induced cytotoxicity. However, biochemical normalization of these parameters to cell volume/protein leads to matching of normalized values in stem and differentiated cells and shows that tested in the present study cells (human embryonic stem cells and their fibroblast-like progenies, adult mesenchymal stem cells, lymphocytes, HeLa maintain similar intracellular redox status. Based on these observations, we propose to use ROS concentration averaged over the cell volume instead of ROS level as a measure of intracellular redox balance. We show that attempts to use ROS level for comparative analysis of redox status of morphologically different cells could lead to false conclusions. Methods for the assessment of ROS concentration based on flow cytometry analysis with the use of H2DCFDA dye and HyPer, genetically encoded probe for hydrogen peroxide, are discussed. Keywords: Embryonic stem cells, Differentiated cells, ROS, Redox status, H2DCFDA, HyPer, Flow cytometry, Quantitative redox biology

  12. Nuclear Mechanics and Stem Cell Differentiation.

    Science.gov (United States)

    Mao, Xinjian; Gavara, Nuria; Song, Guanbin

    2015-12-01

    Stem cells are characterized by their self-renewal and multi-lineage differentiation potential. Stem cell differentiation is a prerequisite for the application of stem cells in regenerative medicine and clinical therapy. In addition to chemical stimulation, mechanical cues play a significant role in regulating stem cell differentiation. The integrity of mechanical sensors is necessary for the ability of cells to respond to mechanical signals. The nucleus, the largest and stiffest cellular organelle, interacts with the cytoskeleton as a key mediator of cell mechanics. Nuclear mechanics are involved in the complicated interactions of lamins, chromatin and nucleoskeleton-related proteins. Thus, stem cell differentiation is intimately associated with nuclear mechanics due to its indispensable role in mechanotransduction and mechanical response. This paper reviews several main contributions of nuclear mechanics, highlights the hallmarks of the nuclear mechanics of stem cells, and provides insight into the relationship between nuclear mechanics and stem cell differentiation, which may guide clinical applications in the future.

  13. Antibody responses to vaccination and immune function in patients with haematological malignancies - studies in patients with chronic lymphocytic leukaemia autologous stem cell recipients

    NARCIS (Netherlands)

    Velden, A.M.T. van der

    2007-01-01

    This thesis concerns the antibody responses to vaccination and immune function of patients with several forms of haematological diseases. Antibody responses in patients with chronic lymphocytic leukaemia (CLL) and in autologous stem cell transplant recipients were studied. In the autologous stem

  14. The role of purinergic receptors in stem cell differentiation

    Directory of Open Access Journals (Sweden)

    Constanze Kaebisch

    2015-01-01

    Full Text Available A major challenge modern society has to face is the increasing need for tissue regeneration due to degenerative diseases or tumors, but also accidents or warlike conflicts. There is great hope that stem cell-based therapies might improve current treatments of cardiovascular diseases, osteochondral defects or nerve injury due to the unique properties of stem cells such as their self-renewal and differentiation potential. Since embryonic stem cells raise severe ethical concerns and are prone to teratoma formation, adult stem cells are still in the focus of research. Emphasis is placed on cellular signaling within these cells and in between them for a better understanding of the complex processes regulating stem cell fate. One of the oldest signaling systems is based on nucleotides as ligands for purinergic receptors playing an important role in a huge variety of cellular processes such as proliferation, migration and differentiation. Besides their natural ligands, several artificial agonists and antagonists have been identified for P1 and P2 receptors and are already used as drugs. This review outlines purinergic receptor expression and signaling in stem cells metabolism. We will briefly describe current findings in embryonic and induced pluripotent stem cells as well as in cancer-, hematopoietic-, and neural crest-derived stem cells. The major focus will be placed on recent findings of purinergic signaling in mesenchymal stem cells addressed in in vitro and in vivo studies, since stem cell fate might be manipulated by this system guiding differentiation towards the desired lineage in the future.

  15. Gastric cancer stem cells: A novel therapeutic target

    Science.gov (United States)

    Singh, Shree Ram

    2013-01-01

    Gastric cancer remains one of the leading causes of global cancer mortality. Multipotent gastric stem cells have been identified in both mouse and human stomachs, and they play an essential role in the self-renewal and homeostasis of gastric mucosa. There are several environmental and genetic factors known to promote gastric cancer. In recent years, numerous in vitro and in vivo studies suggest that gastric cancer may originate from normal stem cells or bone marrow–derived mesenchymal cells, and that gastric tumors contain cancer stem cells. Cancer stem cells are believed to share a common microenvironment with normal niche, which play an important role in gastric cancer and tumor growth. This mini-review presents a brief overview of the recent developments in gastric cancer stem cell research. The knowledge gained by studying cancer stem cells in gastric mucosa will support the development of novel therapeutic strategies for gastric cancer. PMID:23583679

  16. Immunohistochemical study of hepatocyte, cholangiocyte and stem cell markers of hepatocellular carcinoma: the second report: relationship with tumor size and cell differentiation.

    Science.gov (United States)

    Kumagai, Arisa; Kondo, Fukuo; Sano, Keiji; Inoue, Masafumi; Fujii, Takeshi; Hashimoto, Masaji; Watanabe, Masato; Soejima, Yurie; Ishida, Tsuyoshi; Tokairin, Takuo; Saito, Koji; Sasajima, Yuko; Takahashi, Yoshihisa; Uozaki, Hiroshi; Fukusato, Toshio

    2016-07-01

    The purpose of this study is to investigate whether ordinary hepatocellular carcinomas (HCCs) show positivity of stem/progenitor cell markers and cholangiocyte markers during the process of tumor progression. Ninety-four HCC lesions no larger than 8 cm from 94 patients were immuno-histochemically studied using two hepatocyte markers (Hep par 1 and α-fetoprotein), five cholangiocyte markers (cytokeratin CK7, CK19, Muc1, epithelial membrane antigen and carcinoembryonic antigen) and three hepatic stem/progenitor cell markers (CD56, c-Kit and EpCAM). The tumors were classified into three groups by tumor size: S1, tumors were also classified according to tumor differentiation: well, moderately and poorly differentiated. The relationship between the positive ratios of these markers, tumor size and tumor differentiation was examined. The positive ratios of cholangiocyte markers tended to be higher in larger sized and more poorly differentiated tumors (except for CK7). The positive ratios of stem/progenitor cell markers tended to be higher in larger sized and more poorly differentiated tumors (except for c-Kit). Ordinary HCC can acquire the characteristic of positivity of cholangiocyte and stem/progenitor cell markers during the process of tumor progression. © 2016 The Authors. Journal of Hepato-Biliary-Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  17. What Undergraduates Misunderstand about Stem Cell Research

    Science.gov (United States)

    Halverson, Kristy Lynn; Freyermuth, Sharyn K.; Siegel, Marcelle A.; Clark, Catharine G.

    2010-01-01

    As biotechnology-related scientific advances, such as stem cell research (SCR), are increasingly permeating the popular media, it has become ever more important to understand students' ideas about this issue. Very few studies have investigated learners' ideas about biotechnology. Our study was designed to understand the types of alternative…

  18. Spinning a stem cell ethics web.

    Science.gov (United States)

    McDonald, Michael; Longstaff, Holly

    2013-01-01

    The goal of this study was to provide an ethics education resource for trainees and researchers in the Canadian Stem Cell Network that would address the multiple ethical challenges in stem cell research including accountability in and for research across its multiple dimensions. The website was built using a bottom-up type approach based on an ethics needs assessment in combination with a top-down expert-driven component. There have been 3,615 visitors to the website since it was launched in July, 2011. The ongoing rate of returning visitors (20%) indicates that the website is becoming a valuable tool used multiple times.

  19. Stem cell plasticity enables hair regeneration following Lgr5+ cell loss.

    Science.gov (United States)

    Hoeck, Joerg D; Biehs, Brian; Kurtova, Antonina V; Kljavin, Noelyn M; de Sousa E Melo, Felipe; Alicke, Bruno; Koeppen, Hartmut; Modrusan, Zora; Piskol, Robert; de Sauvage, Frederic J

    2017-06-01

    Under injury conditions, dedicated stem cell populations govern tissue regeneration. However, the molecular mechanisms that induce stem cell regeneration and enable plasticity are poorly understood. Here, we investigate stem cell recovery in the context of the hair follicle to understand how two molecularly distinct stem cell populations are integrated. Utilizing diphtheria-toxin-mediated cell ablation of Lgr5 + (leucine-rich repeat-containing G-protein-coupled receptor 5) stem cells, we show that killing of Lgr5 + cells in mice abrogates hair regeneration but this is reversible. During recovery, CD34 + (CD34 antigen) stem cells activate inflammatory response programs and start dividing. Pharmacological attenuation of inflammation inhibits CD34 + cell proliferation. Subsequently, the Wnt pathway controls the recovery of Lgr5 + cells and inhibition of Wnt signalling prevents Lgr5 + cell and hair germ recovery. Thus, our study uncovers a compensatory relationship between two stem cell populations and the underlying molecular mechanisms that enable hair follicle regeneration.

  20. Recent advances in hematopoietic stem cell biology

    DEFF Research Database (Denmark)

    Bonde, Jesper; Hess, David A; Nolta, Jan A

    2004-01-01

    PURPOSE OF REVIEW: Exciting advances have been made in the field of hematopoietic stem cell biology during the past year. This review summarizes recent progress in the identification, culture, and in vivo tracking of hematopoietic stem cells. RECENT FINDINGS: The roles of Wnt and Notch proteins...... in regulating stem cell renewal in the microenvironment, and how these molecules can be exploited in ex vivo stem cell culture, are reviewed. The importance of identification of stem cells using functional as well as phenotypic markers is discussed. The novel field of nanotechnology is then discussed...... in the context of stem cell tracking in vivo. This review concludes with a section on the unexpected potential of bone marrow-derived stem cells to contribute to the repair of damaged tissues. The contribution of cell fusion to explain the latter phenomenon is discussed. SUMMARY: Because of exciting discoveries...

  1. Utilizing two-photon fluorescence and second harmonic generation microscopy to study human bone marrow mesenchymal stem cell morphogenesis in chitosan scaffold

    Science.gov (United States)

    Su, Ping-Jung; Huang, Chi-Hsiu; Huang, Yi-You; Lee, Hsuan-Sue; Dong, Chen-Yuan

    2008-02-01

    A major goal of tissue engineering is to cultivate the cartilage in vitro. One approach is to implant the human bone marrow mesenchymal stem cells into the three dimensional biocompatible and biodegradable material. Through the action of the chondrogenic factor TGF-β3, the stem cells can be induced to secrete collagen. In this study, mesenchymal stem cells are implanted on the chitosan scaffold and TGF-β3 was added to produce the cartilage tissue and TP autofluorescence and SHG microscopy was used to image the process of chondrogenesis. With additional development, multiphoton microscopy can be developed into an effective tool for evaluating the quality of tissue engineering products.

  2. 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

  3. Development of New Technologies for Stem Cell Research

    Directory of Open Access Journals (Sweden)

    Xibo Ma

    2012-01-01

    Full Text Available Since the 1960s, the stem cells have been extensively studied including embryonic stem cells, neural stem cells, bone marrow hematopoietic stem cells, and mesenchymal stem cells. In the recent years, several stem cells have been initially used in the treatment of diseases, such as in bone marrow transplant. At the same time, isolation and culture experimental technologies for stem cell research have been widely developed in recent years. In addition, molecular imaging technologies including optical molecular imaging, positron emission tomography, single-photon emission computed tomography, and computed tomography have been developed rapidly in recent the 10 years and have also been used in the research on disease mechanism and evaluation of treatment of disease related with stem cells. This paper will focus on recent typical isolation, culture, and observation techniques of stem cells followed by a concise introduction. Finally, the current challenges and the future applications of the new technologies in stem cells are given according to the understanding of the authors, and the paper is then concluded.

  4. Simple platelet markers: Mean platelet volume and congestive heart failure coexistent with periodontal disease. Pilot studies.

    Science.gov (United States)

    Czerniuk, Maciej R; Bartoszewicz, Zbigniew; Dudzik-Niewiadomska, Iwona; Pilecki, Tomasz; Górska, Renata; Filipiak, Krzysztof J

    2017-07-17

    Conducted pilot study concerning mean platelet volume parameter among patients suffering from congestive heart failure and periodontal disease. Examination of dynamic changes of platelet and periodontal markers in group of 50 patients before and an average of 6 months subsequent to professional periodontal treatment. Both platelet and periodontal parameters decreased after periodontal treatment, what is more, the decrease of mean platelet volume (MPV) value due to periodontal disease/mm improvement was shown to be statistically significant (p = 0.05). Improvement of periodontal status may influence decrease of MPV value andincrease of congestive heart failure treatment efficacy and effect patient comfort. It is a new, not frequently used pattern of chronic disease treatment optimalization.

  5. Factors controlling the recirculation of haematopoietic stem cells

    International Nuclear Information System (INIS)

    Petrov, R.V.; Khaitov, R.M.; Alejnikova, N.V.; Gulak, L.V.

    1976-01-01

    Influence of thymectomy on the rate of migration and differentiation of haematopoietic stem cells from a shielded part of the bone marrow has been studied on mice X-irradiated with a lethal dose. Inhibition of the migration rate and delay in differentiation of stem cells into colonies of granuloid type have been detected in the thymectomized mice. Transplantation of syngeneic cells of the thymus or lymph nodes to thymectomized mice increases the number of colonies in the spleen and restores the routine way of differentiation of haematopoietic stem cells. It is concluded that the processes of migration and differentiation of haematopoietic stem cells are thymus-dependent

  6. Klotho, stem cells, and aging.

    Science.gov (United States)

    Bian, Ao; Neyra, Javier A; Zhan, Ming; Hu, Ming Chang

    2015-01-01

    Aging is an inevitable and progressive biological process involving dysfunction and eventually destruction of every tissue and organ. This process is driven by a tightly regulated and complex interplay between genetic and acquired factors. Klotho is an antiaging gene encoding a single-pass transmembrane protein, klotho, which serves as an aging suppressor through a wide variety of mechanisms, such as antioxidation, antisenescence, antiautophagy, and modulation of many signaling pathways, including insulin-like growth factor and Wnt. Klotho deficiency activates Wnt expression and activity contributing to senescence and depletion of stem cells, which consequently triggers tissue atrophy and fibrosis. In contrast, the klotho protein was shown to suppress Wnt-signaling transduction, and inhibit cell senescence and preserve stem cells. A better understanding of the potential effects of klotho on stem cells could offer novel insights into the cellular and molecular mechanisms of klotho deficiency-related aging and disease. The klotho protein may be a promising therapeutic agent for aging and aging-related disorders.

  7. Strategies for future histocompatible stem cell therapy

    DEFF Research Database (Denmark)

    Nehlin, Jan; Barington, Torben

    2009-01-01

    Stem cell therapy based on the safe and unlimited self-renewal of human pluripotent stem cells is envisioned for future use in tissue or organ replacement after injury or disease. A gradual decline of regenerative capacity has been documented among the adult stem cell population in some body organs...... during the aging process. Recent progress in human somatic cell nuclear transfer and inducible pluripotent stem cell technologies has shown that patient-derived nuclei or somatic cells can be reprogrammed in vitro to become pluripotent stem cells, from which the three germ layer lineages can be generated......, genetically identical to the recipient. Once differentiation protocols and culture conditions can be defined and optimized, patient-histocompatible pluripotent stem cells could be directed towards virtually every cell type in the human body. Harnessing this capability to enrich for given cells within...

  8. Adipose-Derived Stem Cells and Application Areas

    Directory of Open Access Journals (Sweden)

    Mujde Kivanc

    2015-09-01

    Full Text Available The use of stem cells derived from adipose tissue as an autologous and self-replenishing source for a variety of differentiated cell phenotypes, provides a great deal of promise for reconstructive surgery. The secret of the human body, stem cells are reserved. Stem cells are undifferentiated cells found in the human body placed in any body tissue characteristics that differentiate and win ever known to cross the tissue instead of more than 200 diseases and thus improve and, rejuvenates the tissues. So far, the cord blood of newborn babies are used as a source of stem cells, bone marrow, and twenty years after tooth stem cells in human adipose tissue, scientists studied more than other sources of stem cells in adipose tissue and discovered that. Increase in number of in vitro studies on adult stem cells, depending on many variables is that the stem cells directly to the desired soybean optimization can be performed.. We will conclude by assessing potential avenues for developing this incredibly promising field. The aim of this paper is to review the existing literature on applications of harvest, purification, characterization and cryopreservation of adipose-derived stem cells (ASCs. [Cukurova Med J 2015; 40(3.000: 399-408

  9. Stem cells and repair of lung injuries

    Directory of Open Access Journals (Sweden)

    Randell Scott H

    2004-07-01

    Full Text Available Abstract Fueled by the promise of regenerative medicine, currently there is unprecedented interest in stem cells. Furthermore, there have been revolutionary, but somewhat controversial, advances in our understanding of stem cell biology. Stem cells likely play key roles in the repair of diverse lung injuries. However, due to very low rates of cellular proliferation in vivo in the normal steady state, cellular and architectural complexity of the respiratory tract, and the lack of an intensive research effort, lung stem cells remain poorly understood compared to those in other major organ systems. In the present review, we concisely explore the conceptual framework of stem cell biology and recent advances pertinent to the lungs. We illustrate lung diseases in which manipulation of stem cells may be physiologically significant and highlight the challenges facing stem cell-related therapy in the lung.

  10. Stem cell facelift: between reality and fiction.

    Science.gov (United States)

    Atiyeh, Bishara S; Ibrahim, Amir E; Saad, Dibo A

    2013-03-01

    Stem cells are "big business" throughout medical technology, and their potential application in cosmetic procedures is no exception. One of the latest nonsurgical facial treatments (and new catchphrases) in plastic surgery is the "stem cell facelift." It is evident from the currently available scientific literature that the use of stem cell therapy for facial rejuvenation is limited to the theoretical induction of skin tightening and can in no way be equated to a facelift. In fact, what is advertised and promoted as a new and original technique of stem cell facelifting is mostly stem cell-enriched lipofilling. Despite encouraging data suggesting that adult stem cells hold promise for future applications, the data from clinical evidence available today do not substantiate the marketing and promotional claims being made to patients. To claim that the "stem cell facelift" is a complete facial rejuvenation procedure surgery is unethical.

  11. Stem Cells, Science, and Public Reasoning

    Science.gov (United States)

    Hurlbut, J. Benjamin; Robert, Jason Scott

    2012-01-01

    These are interesting days in the scientific, social, and political debates about human embryonic stem cell research. Pluripotent stem cells--cells that can, in principle, give rise to the body's full range of cell types--were previously derivable only from human embryos that were destroyed in the process. Now, a variety of somatic cell types can…

  12. Mesenchymal Stem Cells Retain Their Defining Stem Cell Characteristics After Exposure to Ionizing Radiation

    International Nuclear Information System (INIS)

    Nicolay, Nils H.; Sommer, Eva; Lopez, Ramon; Wirkner, Ute; Trinh, Thuy; Sisombath, Sonevisay; Debus, Jürgen; Ho, Anthony D.; Saffrich, Rainer; Huber, Peter E.

    2013-01-01

    Purpose: Mesenchymal stem cells (MSCs) have the ability to migrate to lesion sites and undergo differentiation into functional tissues. Although this function may be important for tissue regeneration after radiation therapy, the influence of ionizing radiation (IR) on cellular survival and the functional aspects of differentiation and stem cell characteristics of MSCs have remained largely unknown. Methods and Materials: Radiation sensitivity of human primary MSCs from healthy volunteers and primary human fibroblast cells was examined, and cellular morphology, cell cycle effects, apoptosis, and differentiation potential after exposure to IR were assessed. Stem cell gene expression patterns after exposure to IR were studied using gene arrays. Results: MSCs were not more radiosensitive than human primary fibroblasts, whereas there were considerable differences regarding radiation sensitivity within individual MSCs. Cellular morphology, cytoskeletal architecture, and cell motility were not markedly altered by IR. Even after high radiation doses up to 10 Gy, MSCs maintained their differentiation potential. Compared to primary fibroblast cells, MSCs did not show an increase in irradiation-induced apoptosis. Gene expression analyses revealed an upregulation of various genes involved in DNA damage response and DNA repair, but expression of established MSC surface markers appeared only marginally influenced by IR. Conclusions: These data suggest that human MSCs are not more radiosensitive than differentiated primary fibroblasts. In addition, upon photon irradiation, MSCs were able to retain their defining stem cell characteristics both on a functional level and regarding stem cell marker expression

  13. Epithelial cell polarity, stem cells and cancer

    DEFF Research Database (Denmark)

    Martin-Belmonte, Fernando; Perez-Moreno, Mirna

    2011-01-01

    , deregulation of adhesion and polarity proteins can cause misoriented cell divisions and increased self-renewal of adult epithelial stem cells. In this Review, we highlight some advances in the understanding of how loss of epithelial cell polarity contributes to tumorigenesis.......After years of extensive scientific discovery much has been learned about the networks that regulate epithelial homeostasis. Loss of expression or functional activity of cell adhesion and cell polarity proteins (including the PAR, crumbs (CRB) and scribble (SCRIB) complexes) is intricately related...

  14. The pluripotency of hair follicle stem cells.

    Science.gov (United States)

    Hoffman, Robert M

    2006-02-01

    The hair follicle bulge area is an abundant, easily accessible source of actively growing, pluripotent adult stem cells. Nestin, a protein marker for neural stem cells, is also expressed in follicle stem cells as well as their immediate differentiated progeny. The nestin-expressing hair follicle stem cells differentiated into neurons, glial cells, keratinocytes and smooth muscle cells in vitro. Hair-follicle stem cells were implanted into the gap region of a severed sciatic nerve. The hair follicle stem cells greatly enhanced the rate of nerve regeneration and the restoration of nerve function. The follicle stem cells transdifferentiated largely into Schwann cells which are known to support neuron regrowth. Function of the rejoined sciatic nerve was measured by contraction of the gastrocnemius muscle upon electrical stimulation. After severing the tibial nerve and subsequent transplantation of hair-follicle stem cells, the transplanted mice recovered the ability to walk normally. These results suggest that hair-follicle stem cells provide an important accessible, autologous source of adult stem cells for regenerative medicine.

  15. Stem Cell Therapies in Orthopaedic Trauma

    OpenAIRE

    Marcucio, Ralph S.; Nauth, Aaron; Giannoudis, Peter V.; Bahney, Chelsea; Piuzzi, Nicolas S.; Muschler, George; Miclau, Theodore

    2015-01-01

    Stem cells offer great promise to help understand the normal mechanisms of tissue renewal, regeneration, and repair, and also for development of cell-based therapies to treat patients after tissue injury. Most adult tissues contain stem cells and progenitor cells that contribute to homeostasis, remodeling and repair. Multiple stem and progenitor cell populations in bone are found in the marrow, the endosteum, and the periosteum. They contribute to the fracture healing process after injury and...

  16. Comparison of chemotherapy and hematopoietic stem cell ...

    African Journals Online (AJOL)

    2013-02-19

    Feb 19, 2013 ... scores before and after hematopoietic stem cell transplantation (HSCT) and chemotherapy. Materials and Methods: Thirty-six patients undergoing HSCT were included in the study. A pre-HSCT dental treatment protocol was implemented that consisted of restoration of all active carious lesions, treatment of ...

  17. Stem cell therapy for myocardial infarction

    NARCIS (Netherlands)

    A.D. Moelker (Amber)

    2007-01-01

    textabstractCoronary heart disease and heart failure continue to be significant burdens to healthcare systems in the Western world and are predicted to become so in emerging economies. Despite mixed results in both experimental and clinical studies, stem cell therapy is a promising option for

  18. Kidney dysfunction after allogeneic stem cell transplantation

    NARCIS (Netherlands)

    Kersting, S.

    2008-01-01

    Allogeneic stem cell transplantation (SCT) is a widely accepted approach for malignant and nonmalignant hematopoietic diseases. Unfortunately complications can occur because of the treatment, leading to treatment-related mortality. We studied kidney dysfunction after allogeneic SCT in 2 cohorts of

  19. 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.

  20. Role for Adhesion Molecules in the Spermatogonial Stem Cell Niche

    NARCIS (Netherlands)

    de Rooij, Dirk G.; Repping, S.; van Pelt, Ans M. M.

    2008-01-01

    In this issue of Cell Stem Cell, Kanatsu-Shinohara et al. (2008) show that beta 1-integrin participates in normal spermatogenesis and is required for spermatogonial stem cell (SSC) homing to the basal membrane niche. The methodology used provides a powerful tool to study the role of other factors in

  1. Unmasking Stem/Progenitor Cell Properties in Differentiated Epithelial Cells Using Short-term Transplantation

    National Research Council Canada - National Science Library

    Lewis, Michael T

    2006-01-01

    ...) To determine the range of mammary stem cell types participating in gland regeneration. 2) To develop the short-term transplantation assay as a means by which critical regulators of stem and progenitor cell behavior can be discovered and evaluated. Relevance: Studies will provide a direct test of prevailing stem cell models.

  2. Unmasking Stem/Progenitor Cell Properties in Differentiated Epithelial Cells Using Short-term Transplantation

    National Research Council Canada - National Science Library

    Lewis, Michael T

    2007-01-01

    ...) To determine the range of mammary stem cell types participating in gland regeneration. 2) To develop the short-term transplantation assay as a means by which critical regulators of stem and progenitor cell behavior can be discovered and evaluated. Relevance: Studies will provide a direct test of prevailing stem cell models.

  3. Therapeutic application of multipotent stem cells

    DEFF Research Database (Denmark)

    Mirzaei, Hamed; Sahebkar, Amirhossein; Sichani, Laleh Shiri

    2018-01-01

    Cell therapy is an emerging fields in the treatment of various diseases such as cardiovascular, pulmonary, hepatic, and neoplastic diseases. Stem cells are an integral tool for cell therapy. Multipotent stem cells are an important class of stem cells which have the ability to self-renew through...... been showed that multipotent stem cells exert their therapeutic effects via inhibition/activation of a sequence of cellular and molecular pathways. Although the advantages of multipotent stem cells are numerous, further investigation is still necessary to clarify the biology and safety of these cells...... before they could be considered as a potential treatment for different types of diseases. This review summarizes different features of multipotent stem cells including isolation, differentiation, and therapeutic applications....

  4. Therapeutic potential of adult stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Keith, W. Nicol

    2006-01-01

    is the necessity to be able to identify, select, expand and manipulate cells outside the body. Recent advances in adult stem cell technologies and basic biology have accelerated therapeutic opportunities aimed at eventual clinical applications. Adult stem cells with the ability to differentiate down multiple...... lineages are an attractive alternative to human embryonic stem cells (hES) in regenerative medicine. In many countries, present legislation surrounding hES cells makes their use problematic, and indeed the origin of hES cells may represent a controversial issue for many communities. However, adult stem...... cells are not subject to these issues. This review will therefore focus on adult stem cells. Based on their extensive differentiation potential and, in some cases, the relative ease of their isolation, adult stem cells are appropriate for clinical development. Recently, several observations suggest...

  5. Nanotechnology and stem cell therapy for cardiovascular diseases: potential applications.

    Science.gov (United States)

    La Francesca, Saverio

    2012-01-01

    The use of stem cell therapy for the treatment of cardiovascular diseases has generated significant interest in recent years. Limitations to the clinical application of this therapy center on issues of stem cell delivery, engraftment, and fate. Nanotechnology-based cell labeling and imaging techniques facilitate stem cell tracking and engraftment studies. Nanotechnology also brings exciting new opportunities to translational stem cell research as it enables the controlled engineering of nanoparticles and nanomaterials that can properly relate to the physical scale of cell-cell and cell-niche interactions. This review summarizes the most relevant potential applications of nanoscale technologies to the field of stem cell therapy for the treatment of cardiovascular diseases.

  6. Olfactory stem cells, a new cellular model for studying molecular mechanisms underlying familial dysautonomia.

    Directory of Open Access Journals (Sweden)

    Nathalie Boone

    Full Text Available BACKGROUND: Familial dysautonomia (FD is a hereditary neuropathy caused by mutations in the IKBKAP gene, the most common of which results in variable tissue-specific mRNA splicing with skipping of exon 20. Defective splicing is especially severe in nervous tissue, leading to incomplete development and progressive degeneration of sensory and autonomic neurons. The specificity of neuron loss in FD is poorly understood due to the lack of an appropriate model system. To better understand and modelize the molecular mechanisms of IKBKAP mRNA splicing, we collected human olfactory ecto-mesenchymal stem cells (hOE-MSC from FD patients. hOE-MSCs have a pluripotent ability to differentiate into various cell lineages, including neurons and glial cells. METHODOLOGY/PRINCIPAL FINDINGS: We confirmed IKBKAP mRNA alternative splicing in FD hOE-MSCs and identified 2 novel spliced isoforms also present in control cells. We observed a significant lower expression of both IKBKAP transcript and IKAP/hELP1 protein in FD cells resulting from the degradation of the transcript isoform skipping exon 20. We localized IKAP/hELP1 in different cell compartments, including the nucleus, which supports multiple roles for that protein. We also investigated cellular pathways altered in FD, at the genome-wide level, and confirmed that cell migration and cytoskeleton reorganization were among the processes altered in FD. Indeed, FD hOE-MSCs exhibit impaired migration compared to control cells. Moreover, we showed that kinetin improved exon 20 inclusion and restores a normal level of IKAP/hELP1 in FD hOE-MSCs. Furthermore, we were able to modify the IKBKAP splicing ratio in FD hOE-MSCs, increasing or reducing the WT (exon 20 inclusion:MU (exon 20 skipping ratio respectively, either by producing free-floating spheres, or by inducing cells into neural differentiation. CONCLUSIONS/SIGNIFICANCE: hOE-MSCs isolated from FD patients represent a new approach for modeling FD to better

  7. New Advanced Technologies in Stem Cell Therapy

    Science.gov (United States)

    2014-11-01

    James, J. N. Zara , M. Corselli et al., “An abundant perivascular source of stem cells for bone tissue engineering,” Stem Cells Translational Medicine...vol. 1, no. 9, pp. 673–684, 2012. [89] A.W. James, J. N. Zara , X. Zhang et al., “Perivascular stem cells: a prospectively purified mesenchymal stem...1, pp. 54–63, 2009. [176] A. Askarinam, A. W. James, J. N. Zara et al., “Human perivas- cular stem cells show enhanced osteogenesis and

  8. Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Varga, Nora [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary); Vereb, Zoltan; Rajnavoelgyi, Eva [Department of Immunology, Medical and Health Science Centre, University of Debrecen, Debrecen (Hungary); Nemet, Katalin; Uher, Ferenc; Sarkadi, Balazs [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary); Apati, Agota, E-mail: apati@kkk.org.hu [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary)

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer MSC like cells were derived from hESC by a simple and reproducible method. Black-Right-Pointing-Pointer Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. Black-Right-Pointing-Pointer MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.

  9. Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

    International Nuclear Information System (INIS)

    Varga, Nóra; Veréb, Zoltán; Rajnavölgyi, Éva; Német, Katalin; Uher, Ferenc; Sarkadi, Balázs; Apáti, Ágota

    2011-01-01

    Highlights: ► MSC like cells were derived from hESC by a simple and reproducible method. ► Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. ► MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.

  10. Stem cells from birth to death : The history and the future

    NARCIS (Netherlands)

    de Haan, G; Van Zant, G

    The concept that adult stem cells, despite their impressive proliferative potential, are immortal has been challenged by experimental studies of hematopoietic stem cells. In this review, we discuss the properties that characterize a stem cell, the growing list of tissues in which stem cells are

  11. Successful isolation, in vitro expansion and characterization of stem cells from Human Dental Pulp

    OpenAIRE

    Preethy SP; Srinivasan T; Tholcopiyan L; Thamaraikannan P; Srinivasan V; Murugan P; Manjunath S; Kannan TA; Shalini R; Sunil PM; Manikandhan R; Muthu MS; Abraham S

    2010-01-01

    BACKGROUND: Recent studies have shown that mesenchymal stem cells isolated from post natal human dental pulp, (Dental pulp stem cells-DPSCs) which is from permanent teeth and SHED (stem cells from human exfoliated deciduous teeth),the Periodontal ligament stem cells (PDLSC) and Stem cells from root Apical papilla(SCAP)have the potential to differentiate into cells of a variety of tissues including heart, muscle, cartilage, bone, nerve, salivary glands, teeth etc(1,2,3,4).This multipotential a...

  12. Potential of Stem Cell-Based Therapy for Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Hany E. Marei

    2018-02-01

    Full Text Available Ischemic stroke is one of the major health problems worldwide. The only FDA approved anti-thrombotic drug for acute ischemic stroke is the tissue plasminogen activator. Several studies have been devoted to assessing the therapeutic potential of different types of stem cells such as neural stem cells (NSCs, mesenchymal stem cells, embryonic stem cells, and human induced pluripotent stem cell-derived NSCs as treatments for ischemic stroke. The results of these studies are intriguing but many of them have presented conflicting results. Additionally, the mechanism(s by which engrafted stem/progenitor cells exert their actions are to a large extent unknown. In this review, we will provide a synopsis of different preclinical and clinical studies related to the use of stem cell-based stroke therapy, and explore possible beneficial/detrimental outcomes associated with the use of different types of stem cells. Due to limited/short time window implemented in most of the recorded clinical trials about the use of stem cells as potential therapeutic intervention for stroke, further clinical trials evaluating the efficacy of the intervention in a longer time window after cellular engraftments are still needed.

  13. Stepwise development of hematopoietic stem cells from embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Kenji Matsumoto

    Full Text Available The cellular ontogeny of hematopoietic stem cells (HSCs remains poorly understood because their isolation from and their identification in early developing small embryos are difficult. We attempted to dissect early developmental stages of HSCs using an in vitro mouse embryonic stem cell (ESC differentiation system combined with inducible HOXB4 expression. Here we report the identification of pre-HSCs and an embryonic type of HSCs (embryonic HSCs as intermediate cells between ESCs and HSCs. Both pre-HSCs and embryonic HSCs were isolated by their c-Kit(+CD41(+CD45(- phenotype. Pre-HSCs did not engraft in irradiated adult mice. After co-culture with OP9 stromal cells and conditional expression of HOXB4, pre-HSCs gave rise to embryonic HSCs capable of engraftment and long-term reconstitution in irradiated adult mice. Blast colony assays revealed that most hemangioblast activity was detected apart from the pre-HSC population, implying the early divergence of pre-HSCs from hemangioblasts. Gene expression profiling suggests that a particular set of transcripts closely associated with adult HSCs is involved in the transition of pre-HSC to embryonic HSCs. We propose an HSC developmental model in which pre-HSCs and embryonic HSCs sequentially give rise to adult types of HSCs in a stepwise manner.

  14. Microgravity-Enhanced Stem Cell Selection

    Science.gov (United States)

    Claudio, Pier Paolo; Valluri, Jagan

    2011-01-01

    Stem cells, both embryonic and adult, promise to revolutionize the practice of medicine in the future. In order to realize this potential, a number of hurdles must be overcome. Most importantly, the signaling mechanisms necessary to control the differentiation of stem cells into tissues of interest remain to be elucidated, and much of the present research on stem cells is focused on this goal. Nevertheless, it will also be essential to achieve large-scale expansion and, in many cases, assemble cells in 3D as transplantable tissues. To this end, microgravity analog bioreactors can play a significant role. Microgravity bioreactors were originally conceived as a tool to study the cellular responses to microgravity. However, the technology can address some of the shortcomings of conventional cell culture systems; namely, the deficiency of mass transport in static culture and high mechanical shear forces in stirred systems. Unexpectedly, the conditions created in the vessel were ideal for 3D cell culture. Recently, investigators have demonstrated the capability of the microgravity bioreactors to expand hematopoietic stem cells compared to static culture, and facilitate the differentiation of umbilical cord stem cells into 3D liver aggregates. Stem cells are capable of differentiating into functional cells. However, there are no reliable methods to induce the stem cells to form specific cells or to gain enough cells for transplantation, which limits their application in clinical therapy. The aim of this study is to select the best experimental setup to reach high proliferation levels by culturing these cells in a microgravity-based bioreactor. In typical cell culture, the cells sediment to the bottom surface of their container and propagate as a one-cell-layer sheet. Prevention of such sedimentation affords the freedom for self-assembly and the propagation of 3D tissue arrays. Suspension of cells is easily achievable using stirred technologies. Unfortunately, in

  15. Reconstitution of mammary epithelial morphogenesis by murine embryonic stem cells undergoing hematopoietic stem cell differentiation.

    Directory of Open Access Journals (Sweden)

    Shuxian Jiang

    2010-03-01

    Full Text Available Mammary stem cells are maintained within specific microenvironments and recruited throughout lifetime to reconstitute de novo the mammary gland. Mammary stem cells have been isolated through the identification of specific cell surface markers and in vivo transplantation into cleared mammary fat pads. Accumulating evidence showed that during the reformation of mammary stem cell niches by dispersed epithelial cells in the context of the intact epithelium-free mammary stroma, non-mammary epithelial cells may be sequestered and reprogrammed to perform mammary epithelial cell functions and to adopt mammary epithelial characteristics during reconstruction of mammary epithelium in regenerating mammary tissue in vivo.To examine whether other types of progenitor cells are able to contribute to mammary branching morphogenesis, we examined the potential of murine embryonic stem (mES cells, undergoing hematopoietic differentiation, to support mammary reconstitution in vivo. We observed that cells from day 14 embryoid bodies (EBs under hematopoietic differentiation condition, but not supernatants derived from these cells, when transplanted into denuded mammary fat pads, were able to contribute to both the luminal and myoepithelial lineages in branching ductal structures resembling the ductal-alveolar architecture of the mammary tree. No teratomas were observed when these cells were transplanted in vivo.Our data provide evidence for the dominance of the tissue-specific mammary stem cell niche and its role in directing mES cells, undergoing hematopoietic differentiation, to reprogram into mammary epithelial cells and to promote mammary epithelial morphogenesis. These studies should also provide insights into regeneration of damaged mammary gland and the role of the mammary microenvironment in reprogramming cell fate.

  16. Tumorigenic hybrids between mesenchymal stem cells and gastric cancer cells enhanced cancer proliferation, migration and stemness

    International Nuclear Information System (INIS)

    Xue, Jianguo; Zhu, Yuan; Sun, Zixuan; Ji, Runbi; Zhang, Xu; Xu, Wenrong; Yuan, Xiao; Zhang, Bin; Yan, Yongmin; Yin, Lei; Xu, Huijuan; Zhang, Leilei; Zhu, Wei; Qian, Hui

    2015-01-01

    Emerging evidence indicates that inappropriate cell-cell fusion might contribute to cancer progression. Similarly, mesenchymal stem cells (MSCs) can also fuse with other cells spontaneously and capable of adopting the phenotype of other cells. The aim of our study was to investigate the role of MSCs participated cell fusion in the tumorigenesis of gastric cancer. We fused human umbilical cord mesenchymal stem cells (hucMSCs) with gastric cancer cells in vitro by polyethylene glycol (PEG), the hybrid cells were sorted by flow cytometer. The growth and migration of hybrids were assessed by cell counting, cell colony formation and transwell assays. The proteins and genes related to epithelial-mesenchymal transition and stemness were tested by western blot, immunocytochemistry and real-time RT-PCR. The expression of CD44 and CD133 was examined by immunocytochemistry and flow cytometry. The xenograft assay was used to evaluation the tumorigenesis of the hybrids. The obtained hybrids exhibited epithelial- mesenchymal transition (EMT) change with down-regulation of E-cadherin and up-regulation of Vimentin, N-cadherin, α-smooth muscle actin (α-SMA), and fibroblast activation protein (FAP). The hybrids also increased expression of stemness factors Oct4, Nanog, Sox2 and Lin28. The expression of CD44 and CD133 on hybrid cells was stronger than parental gastric cancer cells. Moreover, the migration and proliferation of heterotypic hybrids were enhanced. In addition, the heterotypic hybrids promoted the growth abilities of gastric xenograft tumor in vivo. Taken together, our results suggest that cell fusion between hucMSCs and gastric cancer cells could contribute to tumorigenic hybrids with EMT and stem cell-like properties, which may provide a flexible tool for investigating the roles of MSCs in gastric cancer. The online version of this article (doi:10.1186/s12885-015-1780-1) contains supplementary material, which is available to authorized users

  17. Cellular Mechanisms of Somatic Stem Cell Aging

    Science.gov (United States)

    Jung, Yunjoon

    2014-01-01

    Tissue homeostasis and regenerative capacity rely on rare populations of somatic stem cells endowed with the potential to self-renew and differentiate. During aging, many tissues show a decline in regenerative potential coupled with a loss of stem cell function. Cells including somatic stem cells have evolved a series of checks and balances to sense and repair cellular damage to maximize tissue function. However, during aging the mechanisms that protect normal cell function begin to fail. In this review, we will discuss how common cellular mechanisms that maintain tissue fidelity and organismal lifespan impact somatic stem cell function. We will highlight context-dependent changes and commonalities that define aging, by focusing on three age-sensitive stem cell compartments: blood, neural, and muscle. Understanding the interaction between extrinsic regulators and intrinsic effectors that operate within different stem cell compartments is likely to have important implications for identifying strategies to improve health span and treat age-related degenerative diseases. PMID:24439814

  18. The experimental study on tropism of magnetic labeled bone marrow mesenchymal stem cells for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Chen Shuangqing; Wang Peijun; Li Minghua; Zhang Wei; Dai gonghua

    2009-01-01

    Objective: To label rat bone marrow mesenchymal stem cells with superparamagnetic iron oxide (SPIO) and to explore the tropism of BMSCs for hepatocellular carcinoma cells after transplantation in vivo. Methods: BMSCs from bone marrow of Sprague-Dawly (SD) rats were cultured isolated and purified. Labeled BMSCs was achieved using Feridex. Twenty-four hepatocellular carcinoma models of SD rats were induced two weeks before transplantation. The models were divided into three groups in random: the labeled BMSCs and unlabeled BMSCs were transplanted respectively into the rat's livers of experimental group (n=12) and control group A (n=6) via spleens, and no transplant was done for control group B (n=6). MR imaging was performed to monitor the transplanted cells after 1,3,7,14 d using 1.5 T MR system. Signal intensity ratio (SI/SI * ) between tumor and hepatic tissue on T 2 * WI were measured and compared by one-factor analysis of variance. After MR imaging, Prussian blue staining was performed. MR imaging findings were compared with histological sections. Results: Prussian blue staining confirmed the labeling efficiency of BMSCs was above 90%. SI/SI * of experimental group before and 1, 3, 7, 14 d after transplantation were 3.18±0.21, 1.98±0.20, 2.38±0.28, 2.70±0.25 and 3.16±0.24 respectively. Following transplantation of BMSCs, signal intensity decrease was found in hepatocellular carcinoma of experimental group (F=56.65, P 2 * WI (P>0.05). A large number of Prussian blue staining positive cells were found in hepatocellular carcinoma in experimental group. Histological section with Prussian blue staining had a good correlation with the signal intensity changes on MR images at different time. Conclusion: BMSCs display significant tropism to hepatocellular carcinoma and may be an ideal gene therapy vehicle against hepatocellular carcinoma. (authors)

  19. Stem cell biology meets systems biology

    OpenAIRE

    Roeder, I.; Radtke, F.

    2009-01-01

    Stem cells and their descendents are the building blocks of life. How stem cell populations guarantee their maintenance and/or self-renewal, and how individual stem cells decide to transit from one cell stage to another to generate different cell types are long-standing and fascinating questions in the field. Here, we review the discussions that took place at a recent EMBO conference in Cambridge, UK, in which these questions were placed in the context of the latest advances in stem cell biol...

  20. Stem cells: limitations and opportunities in Peru

    OpenAIRE

    Amiel-Pérez, José; Laboratorio de Cultivos Celulares, Universidad Científica del Sur. Lima, Perú.; Casado, Fanny; Stem Cell and Cancer Research Institute, McMaster University. Hamilton, Canadá.

    2015-01-01

    Stem cells are defined as rare cells that are characterized by asymmetric division, a process known as self-renewal, and the potential to differentiate into more than one type of terminally differentiated cell. There is a diversity of stem cells including embryonic stem cells, which exist only during the first stages of human development, and many adult stem cells depending on the specific tissues from where they derive or the ones derived from mesenchymal or stromal tissues. On the other han...

  1. Roles of Mitochondrial DNA Mutations in Stem Cell Ageing

    Directory of Open Access Journals (Sweden)

    Tianhong Su

    2018-03-01

    Full Text Available Mitochondrial DNA (mtDNA mutations accumulate in somatic stem cells during ageing and cause mitochondrial dysfunction. In this review, we summarize the studies that link mtDNA mutations to stem cell ageing. We discuss the age-related behaviours of the somatic mtDNA mutations in stem cell populations and how they potentially contribute to stem cell ageing by altering mitochondrial properties in humans and in mtDNA-mutator mice. We also draw attention to the diverse fates of the mtDNA mutations with different origins during ageing, with potential selective pressures on the germline inherited but not the somatic mtDNA mutations.

  2. Mesenchymal stem cells induce dermal fibroblast responses to injury

    International Nuclear Information System (INIS)

    Smith, Andria N.; Willis, Elise; Chan, Vincent T.; Muffley, Lara A.; Isik, F. Frank; Gibran, Nicole S.; Hocking, Anne M.

    2010-01-01

    Although bone marrow-derived mesenchymal stem cells have been shown to promote repair when applied to cutaneous wounds, the mechanism for this response remains to be determined. The aim of this study was to determine the effects of paracrine signaling from mesenchymal stem cells on dermal fibroblast responses to injury including proliferation, migration and expression of genes important in wound repair. Dermal fibroblasts were co-cultured with bone marrow-derived mesenchymal stem cells grown in inserts, which allowed for paracrine interactions without direct cell contact. In this co-culture model, bone marrow-derived mesenchymal stem cells regulate dermal fibroblast proliferation, migration and gene expression. When co-cultured with mesenchymal stem cells, dermal fibroblasts show increased proliferation and accelerated migration in a scratch assay. A chemotaxis assay also demonstrated that dermal fibroblasts migrate towards bone marrow-derived mesenchymal stem cells. A PCR array was used to analyze the effect of mesenchymal stem cells on dermal fibroblast gene expression. In response to mesenchymal stem cells, dermal fibroblasts up-regulate integrin alpha 7 expression and down-regulate expression of ICAM1, VCAM1 and MMP11. These observations suggest that mesenchymal stem cells may provide an important early signal for dermal fibroblast responses to cutaneous injury.

  3. Studies on the biocidal and cell membrane disruption potentials of stem bark extracts of Afzelia africana (Smith

    Directory of Open Access Journals (Sweden)

    DAVID A AKINPELU

    2009-01-01

    Full Text Available We had recently reported antibacterial activity in the crude extract of the stem bark of Afzelia africana (Akinpelu et al., 2008. In this study, we assessed the biocidal and cell membrane disruption potentials of fractions obtained from the crude extract of the plant. The aqueous (AQ and butanol (BL fractions exhibited appreciable antibacterial activities against the test bacteria. The minimum inhibitory concentrations of the AQ and BL fractions ranged between 0.313 and 2.5 mg/ml, while their minimum bactericidal concentrations varied between 0.625 and 5.0 mg/ml. Also, the AQ fraction killed about 95.8% of E. coli cells within 105 min at a concentration of 5 mg/ml, while about 99.1% of Bacillus pumilus cells were killed by this fraction at the same concentration and exposure time. A similar trend was observed for the BL fraction. At a concentration of 5 mg/ml, the butanol fraction leaked 9.8 μg/ml of proteins from E. coli cells within 3 h, while the aqueous fraction leaked 6.5 μg/ml of proteins from the same organisms at the same concentration and exposure time. We propose that the stem bark of Afzelia africana is a potential source of bioactive compounds of importance to the pharmaceutical industry.

  4. Mesenchymal dental stem cells in regenerative dentistry.

    Science.gov (United States)

    Rodríguez-Lozano, Francisco-Javier; Insausti, Carmen-Luisa; Iniesta, Francisca; Blanquer, Miguel; Ramírez, María-del-Carmen; Meseguer, Luis; Meseguer-Henarejos, Ana-Belén; Marín, Noemí; Martínez, Salvador; Moraleda, José-María

    2012-11-01

    In the last decade, tissue engineering is a field that has been suffering an enormous expansion in the regenerative medicine and dentistry. The use of cells as mesenchymal dental stem cells of easy access for dentist and oral surgeon, immunosuppressive properties, high proliferation and capacity to differentiate into odontoblasts, cementoblasts, osteoblasts and other cells implicated in the teeth, suppose a good perspective of future in the clinical dentistry. However, is necessary advance in the known of growth factors and signalling molecules implicated in tooth development and regeneration of different structures of teeth. Furthermore, these cells need a fabulous scaffold that facility their integration, differentiation, matrix synthesis and promote multiple specific interactions between cells. In this review, we give a brief description of tooth development and anatomy, definition and classification of stem cells, with special attention of mesenchymal stem cells, commonly used in the cellular therapy for their trasdifferentiation ability, non ethical problems and acceptable results in preliminary clinical trials. In terms of tissue engineering, we provide an overview of different types of mesenchymal stem cells that have been isolated from teeth, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHEDs), periodontal ligament stem cells (PDLSCs), dental follicle progenitor stem cells (DFPCs), and stem cells from apical papilla (SCAPs), growth factors implicated in regeneration teeth and types of scaffolds for dental tissue regeneration.

  5. Characterizing the radioresponse of pluripotent and multipotent human stem cells.

    Directory of Open Access Journals (Sweden)

    Mary L Lan

    Full Text Available The potential capability of stem cells to restore functionality to diseased or aged tissues has prompted a surge of research, but much work remains to elucidate the response of these cells to genotoxic agents. To more fully understand the impact of irradiation on different stem cell types, the present study has analyzed the radioresponse of human pluripotent and multipotent stem cells. Human embryonic stem (ES cells, human induced pluripotent (iPS cells, and iPS-derived human neural stem cells (iPS-hNSCs cells were irradiated and analyzed for cell survival parameters, differentiation, DNA damage and repair and oxidative stress at various times after exposure. While irradiation led to dose-dependent reductions in survival, the fraction of surviving cells exhibited dose-dependent increases in metabolic activity. Irradiation did not preclude germ layer commitment of ES cells, but did promote neuronal differentiation. ES cells subjected to irradiation exhibited early apoptosis and inhibition of cell cycle progression, but otherwise showed normal repair of DNA double-strand breaks. Cells surviving irradiation also showed acute and persistent increases in reactive oxygen and nitrogen species that were significant at nearly all post-irradiation times analyzed. We suggest that stem cells alter their redox homeostasis to adapt to adverse conditions and that radiation-induced oxidative stress plays a role in regulating the function and fate of stem cells within tissues compromised by radiation injury.

  6. 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.

  7. Simultaneous detection of mRNA and protein stem cell markers in live cells

    Directory of Open Access Journals (Sweden)

    Bao Gang

    2009-04-01

    Full Text Available Abstract Background Biological studies and medical application of stem cells often require the isolation of stem cells from a mixed cell population, including the detection of cancer stem cells in tumor tissue, and isolation of induced pluripotent stem cells after eliciting the expression of specific genes in adult cells. Here we report the detection of Oct-4 mRNA and SSEA-1 protein in live carcinoma stem cells using respectively molecular beacon and dye-labeled antibody, aiming to establish a new method for stem cells detection and isolation. Results Quantification of Oct-4 mRNA and protein in P19 mouse carcinoma stem cells using respectively RT-PCR and immunocytochemistry confirmed that their levels drastically decreased after differentiation. To visualize Oct-4 mRNA in live stem cells, molecular beacons were designed, synthesized and validated, and the detection specificity was confirmed using control studies. We found that the fluorescence signal from Oct-4-targeting molecular beacons provides a clear discrimination between undifferentiated and retinoic acid-induced differentiated cells. Using deconvolution fluorescence microscopy, Oct-4 mRNAs were found to reside on one side of the cytosol. We demonstrated that, using a combination of Oct-4 mRNA-targeting molecular beacon with SSEA-1 antibody in flow cytometric analysis, undifferentiated stem cells can be clearly distinguished from differentiated cells. We revealed that Oct-4 targeting molecular beacons do not seem to affect stem cell biology. Conclusion Molecular beacons have the potential to provide a powerful tool for highly specific detection and isolation of stem cells, including cancer stem cells and induced pluripotent stem (iPS cells without disturbing cell physiology. It is advantageous to perform simultaneous detection of intracellular (mRNA and cell-surface (protein stem cell markers in flow cytometric analysis, which may lead to high detection sensitivity and efficiency.

  8. Viability of mesenchymal stem cells during electrospinning

    Directory of Open Access Journals (Sweden)

    G. Zanatta

    2012-02-01

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

  9. 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.

  10. From stem cell to embryo without centrioles.

    Science.gov (United States)

    Stevens, Naomi R; Raposo, Alexandre A S F; Basto, Renata; St Johnston, Daniel; Raff, Jordan W

    2007-09-04

    Centrosome asymmetry plays a key role in ensuring the asymmetric division of Drosophila neural stem cells (neuroblasts [NBs]) and male germline stem cells (GSCs) [1-3]. In both cases, one centrosome is anchored close to a specific cortical region during interphase, thus defining the orientation of the spindle during the ensuing mitosis. To test whether asymmetric centrosome behavior is a general feature of stem cells, we have studied female GSCs, which divide asymmetrically, producing another GSC and a cystoblast. The cystoblast then divides and matures into an oocyte, a process in which centrosomes exhibit a series of complex behaviors proposed to play a crucial role in oogenesis [4-6]. We show that the interphase centrosome does not define spindle orientation in female GSCs and that DSas-4 mutant GSCs [7], lacking centrioles and centrosomes, invariably divide asymmetrically to produce cystoblasts that proceed normally through oogenesis-remarkably, oocyte specification, microtubule organization, and mRNA localization are all unperturbed. Mature oocytes can be fertilized, but embryos that cannot support centriole replication arrest very early in development. Thus, centrosomes are dispensable for oogenesis but essential for early embryogenesis. These results reveal that asymmetric centrosome behavior is not an essential feature of stem cell divisions.

  11. Epigenetic regulation of hematopoietic stem cell aging

    International Nuclear Information System (INIS)

    Beerman, Isabel; Rossi, Derrick J.

    2014-01-01

    Aging is invariably associated with alterations of the hematopoietic stem cell (HSC) compartment, including loss of functional capacity, altered clonal composition, and changes in lineage contribution. Although accumulation of DNA damage occurs during HSC aging, it is unlikely such consistent aging phenotypes could be solely attributed to changes in DNA integrity. Another mechanism by which heritable traits could contribute to the changes in the functional potential of aged HSCs is through alterations in the epigenetic landscape of adult stem cells. Indeed, recent studies on hematopoietic stem cells have suggested that altered epigenetic profiles are associated with HSC aging and play a key role in modulating the functional potential of HSCs at different stages during ontogeny. Even small changes of the epigenetic landscape can lead to robustly altered expression patterns, either directly by loss of regulatory control or through indirect, additive effects, ultimately leading to transcriptional changes of the stem cells. Potential drivers of such changes in the epigenetic landscape of aged HSCs include proliferative history, DNA damage, and deregulation of key epigenetic enzymes and complexes. This review will focus largely on the two most characterized epigenetic marks – DNA methylation and histone modifications – but will also discuss the potential role of non-coding RNAs in regulating HSC function during aging

  12. Epigenetic regulation of hematopoietic stem cell aging

    Energy Technology Data Exchange (ETDEWEB)

    Beerman, Isabel, E-mail: isabel.beerman@childrens.harvard.edu [Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138 (United States); Department of Pediatrics, Harvard Medical School, Boston, MA 02115 (United States); Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children' s Hospital, MA 02116 (United States); Rossi, Derrick J. [Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138 (United States); Department of Pediatrics, Harvard Medical School, Boston, MA 02115 (United States); Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children' s Hospital, MA 02116 (United States)

    2014-12-10

    Aging is invariably associated with alterations of the hematopoietic stem cell (HSC) compartment, including loss of functional capacity, altered clonal composition, and changes in lineage contribution. Although accumulation of DNA damage occurs during HSC aging, it is unlikely such consistent aging phenotypes could be solely attributed to changes in DNA integrity. Another mechanism by which heritable traits could contribute to the changes in the functional potential of aged HSCs is through alterations in the epigenetic landscape of adult stem cells. Indeed, recent studies on hematopoietic stem cells have suggested that altered epigenetic profiles are associated with HSC aging and play a key role in modulating the functional potential of HSCs at different stages during ontogeny. Even small changes of the epigenetic landscape can lead to robustly altered expression patterns, either directly by loss of regulatory control or through indirect, additive effects, ultimately leading to transcriptional changes of the stem cells. Potential drivers of such changes in the epigenetic landscape of aged HSCs include proliferative history, DNA damage, and deregulation of key epigenetic enzymes and complexes. This review will focus largely on the two most characterized epigenetic marks – DNA methylation and histone modifications – but will also discuss the potential role of non-coding RNAs in regulating HSC function during aging.

  13. Stem Cell Models: A Guide to Understand and Mitigate Aging?

    Science.gov (United States)

    Brunauer, Regina; Alavez, Silvestre; Kennedy, Brian K

    2017-01-01

    Aging is studied either on a systemic level using life span and health span of animal models, or on the cellular level using replicative life span of yeast or mammalian cells. While useful in identifying general and conserved pathways of aging, both approaches provide only limited information about cell-type specific causes and mechanisms of aging. Stem cells are the regenerative units of multicellular life, and stem cell aging might be a major cause for organismal aging. Using the examples of hematopoietic stem cell aging and human pluripotent stem cell models, we propose that stem cell models of aging are valuable for studying tissue-specific causes and mechanisms of aging and can provide unique insights into the mammalian aging process that may be inaccessible in simple model organisms. © 2016 S. Karger AG, Basel.

  14. Study of mesanchymal stem cells derived from human umbilical cord vein wall and determining the Process of differentiation to cartilage and bone

    Directory of Open Access Journals (Sweden)

    MohammadAli Zare

    2015-01-01

    Full Text Available Background: Mesenchymal stem cells (MSCs comprise a rare population of multipotent progenitors capable of supporting hematopoiesis and differentiating into three (osteogenic, adipogenic, and chondrogenic or more (myogenic, cardiomyogenic, etc. lineages. Due to this ability, MSCs appear to be an attractive tool in the context of tissue engineering and cell-based therapy. Currently, bone marrow represents the main source of MSCs for both experimental and clinical studies. The purpose of this study was isolation and quantitative comparison of mesenchymal stem cells derived from umbilical vein. Materials and Methods: In this study, 35 samples of umbilical cord of healthy full- term newborn were studied. Results: The cells had fibroblastoid like appearance and had revealed the potential to differentiate into three linage of bone, Adipose and cartilage. Surface markers for mesenchymal nature were their demonstratives. Conclusion: Based on our findings the mesenchymal stem cells, from umbilical vein wall can be isolated, cultured and differentiated into three categories of bone, cartilage and adipose.

  15. Imaging of Human Hepatic Stem Cells In Vivo

    International Nuclear Information System (INIS)

    Hsu, E.W.

    2006-01-01

    Report on progress in MRI and PET of stem cell tracking. Human hepatic stem cell imaging for both MRI and PET have been accomplished within SCID/nod mice, and succeeded in cell specificity labeling with in vitro, ex vivo, and in vivo image tracking. For MRI, stem cell labeling was accomplished by two methods: (1) in vitro labeling the stem cells just prior to in vivo transplantation, and/or (2) transplanting the stem cells into SCID/nod mice and in vivo specificity labeling the cells just prior to MRI. For labeling techniques 1 and 2, multiple image controls were utilized and include: (A) stem cells(-) and contrast label(-), (B) stem cells(+) and contrast label(-), and (C) stem cells(-) and contrast label(+) help to confirm signal noise background interference, which is a result of slight nonspecific cell labeling. Contrast labeled stem cells are directly transplanted into liver tissues, the tissues excised, and immediately MR imaged to determine cell dispersion dynamics. In this method, the contrast labeled cells appear as void foci throughout the organs. The images are imported into Metamorph imaging software and analyzed for foci radii, diameter, and to discern spheroid volumes. Then, cell numbers are extrapolated to understand ''imaged'' cell aggregate requirements using this technique. For this ex vivo method, a cell aggregate of ∼100 stem cells is required to MRI monitor signal activities. For in vivo imaging, contrast labeled human stem cells within SCID/nod mice are also confirmed as small foci voids and are evident within liver tissues. Initially, these short-term studies where accomplished by in vitro labeling stem cells, transplanting the cells, then in vivo imaging the tissues between days 3-15. Next and to avoid imaged time limitations of detaching contrast agents, the proliferative stem cells were labeled after transplantation, and before MR imaging. This was accomplished to confirm the ability to specifically label unique cell subsets after the

  16. In vitro differentiation of mouse embryonic stem cells into functional ...

    African Journals Online (AJOL)

    Studies have shown that embryonic stem (ES) cells can be successfully differentiated into liver cells, which offer the potential unlimited cell source for a variety of end-stage liver disease. In our study, in order to induce mouse ES cells to differentiate into hepatocyte-like cells under chemically defined conditions, ES cells ...

  17. Stem cells: progressions and applications in clinical medicine

    Directory of Open Access Journals (Sweden)

    Ali Hosseini Bereshneh

    2016-05-01

    of them in transferring gene into different cells. Today, this method have had considerable progress in the treatment of many disease. In this review study, some aspect of stem cells like types and characteristic, origin, derivation techniques, storage conditions and differentiation to target tissues, current clinical usage and their therapeutic capabilities will be discussed.

  18. Stem Cells and Herbal Acupuncture Therapy

    Directory of Open Access Journals (Sweden)

    Ki Rok Kwon

    2005-12-01

    Full Text Available Stem cell therapy implies the birth of regenerative medicine. Regenerative medicine signify treatment through regeneration of cells which was impossible by existing medicine. Stem cell is classified into embryonic stem cell and adult stem cell and they have distinctive benefits and limitations. Researches on stem cell are already under active progression and is expected to be commercially available in the near future. One may not relate the stem cell treatment with Oriental medicine, but can be interpreted as the fundamental treatment action of Oriental medicine is being investigated in more concrete manner. When it comes to difficult to cure diseases, there is no boundary between eastern and western medicine, and one must be ready to face and overcome changes lying ahead.

  19. Redox environment in stem and differentiated cells: A quantitative approach.

    Science.gov (United States)

    Lyublinskaya, O G; Ivanova, Ju S; Pugovkina, N A; Kozhukharova, I V; Kovaleva, Z V; Shatrova, A N; Aksenov, N D; Zenin, V V; Kaulin, Yu A; Gamaley, I A; Nikolsky, N N

    2017-08-01

    Stem cells are believed to maintain a specific intracellular redox status through a combination of enhanced removal capacity and limited production of ROS. In the present study, we challenge this assumption by developing a quantitative approach for the analysis of the pro- and antioxidant ability of human embryonic stem cells in comparison with their differentiated descendants, as well as adult stem and non-stem cells. Our measurements showed that embryonic stem cells are characterized by low ROS level, low rate of extracellular hydrogen peroxide removal and low threshold for peroxide-induced cytotoxicity. However, biochemical normalization of these parameters to cell volume/protein leads to matching of normalized values in stem and differentiated cells and shows that tested in the present study cells (human embryonic stem cells and their fibroblast-like progenies, adult mesenchymal stem cells, lymphocytes, HeLa) maintain similar intracellular redox status. Based on these observations, we propose to use ROS concentration averaged over the cell volume instead of ROS level as a measure of intracellular redox balance. We show that attempts to use ROS level for comparative analysis of redox status of morphologically different cells could lead to false conclusions. Methods for the assessment of ROS concentration based on flow cytometry analysis with the use of H 2 DCFDA dye and HyPer, genetically encoded probe for hydrogen peroxide, are discussed. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  20. A Preliminary Study: Human Fibroid Stro-1+/CD44+ Stem Cells Isolated From Uterine Fibroids Demonstrate Decreased DNA Repair and Genomic Integrity Compared to Adjacent Myometrial Stro-1+/CD44+ Cells.

    Science.gov (United States)

    Prusinski Fernung, Lauren E; Al-Hendy, Ayman; Yang, Qiwei

    2018-01-01

    Although uterine fibroids (UFs) continue to place a major burden on female reproductive health, the mechanisms behind their origin remain undetermined. Normal myometrial stem cells may be transformed into tumor-initiating stem cells, causing UFs, due to unknown causes of somatic mutations in MED12, found in up to 85% of sporadically formed UFs. It is well established in other tumor types that defective DNA repair increases the risk of such tumorigenic somatic mutations, mechanisms not yet studied in UFs. To examine the putative cause(s) of this stem cell transformation, we analyzed DNA repair within stem cells from human UFs compared to those from adjacent myometrium to determine whether DNA repair in fibroid stem cells is compromised. Human fibroid (F) and adjacent myometrial (Myo) stem cells were isolated from fresh tissues, and gene expression relating to DNA repair was analyzed. Fibroid stem cells differentially expressed DNA repair genes related to DNA double- (DSBs) and single-strand breaks. DNA damage was measured using alkaline comet assay. Additionally, DNA DSBs were induced in these stem cells and DNA DSB repair evaluated (1) by determining changes in phosphorylation of DNA DSB-related proteins and (2) by determining differences in γ-H2AX foci formation and relative DNA repair protein RAD50 expression. Overall, F stem cells demonstrated increased DNA damage and altered DNA repair gene expression and signaling, suggesting that human F stem cells demonstrate impaired DNA repair. Compromised F stem cell DNA repair may contribute to further mutagenesis and, consequently, further growth and propagation of UF tumors.

  1. Stem Cell Technology in Cardiac Regeneration: A Pluripotent Stem Cell Promise.

    Science.gov (United States)

    Duelen, Robin; Sampaolesi, Maurilio

    2017-02-01

    Despite advances in cardiovascular biology and medical therapy, heart disorders are the leading cause of death worldwide. Cell-based regenerative therapies become a promising treatment for patients affected by heart failure, but also underline the need for reproducible results in preclinical and clinical studies for safety and efficacy. Enthusiasm has been tempered by poor engraftment, survival and differentiation of the injected adult stem cells. The crucial challenge is identification and selection of the most suitable stem cell type for cardiac regenerative medicine. Human pluripotent stem cells (PSCs) have emerged as attractive cell source to obtain cardiomyocytes (CMs), with potential applications, including drug discovery and toxicity screening, disease modelling and innovative cell therapies. Lessons from embryology offered important insights into the development of stem cell-derived CMs. However, the generation of a CM population, uniform in cardiac subtype, adult maturation and functional properties, is highly recommended. Moreover, hurdles regarding tumorigenesis, graft cell death, immune rejection and arrhythmogenesis need to be overcome in clinical practice. Here we highlight the recent progression in PSC technologies for the regeneration of injured heart. We review novel strategies that might overcome current obstacles in heart regenerative medicine, aiming at improving cell survival and functional integration after cell transplantation. Copyright © 2017. Published by Elsevier B.V.

  2. Stem Cell Technology in Cardiac Regeneration: A Pluripotent Stem Cell Promise

    Directory of Open Access Journals (Sweden)

    Robin Duelen

    2017-02-01

    Full Text Available Despite advances in cardiovascular biology and medical therapy, heart disorders are the leading cause of death worldwide. Cell-based regenerative therapies become a promising treatment for patients affected by heart failure, but also underline the need for reproducible results in preclinical and clinical studies for safety and efficacy. Enthusiasm has been tempered by poor engraftment, survival and differentiation of the injected adult stem cells. The crucial challenge is identification and selection of the most suitable stem cell type for cardiac regenerative medicine. Human pluripotent stem cells (PSCs have emerged as attractive cell source to obtain cardiomyocytes (CMs, with potential applications, including drug discovery and toxicity screening, disease modelling and innovative cell therapies. Lessons from embryology offered important insights into the development of stem cell-derived CMs. However, the generation of a CM population, uniform in cardiac subtype, adult maturation and functional properties, is highly recommended. Moreover, hurdles regarding tumorigenesis, graft cell death, immune rejection and arrhythmogenesis need to be overcome in clinical practice. Here we highlight the recent progression in PSC technologies for the regeneration of injured heart. We review novel strategies that might overcome current obstacles in heart regenerative medicine, aiming at improving cell survival and functional integration after cell transplantation.

  3. Induced pluripotent stem cells, from generation to application: review article

    Directory of Open Access Journals (Sweden)

    Sharif Moradi

    2014-11-01

    Full Text Available Embryonic stem cells are pluripotent stem cells which have the ability to indefinitely self-renew and differentiate into all differentiated cells of the body. Regarding their two main properties (unlimited self-renewal and multi-lineage differentiation, these cells have various biomedical applications in basic research and cell based therapy. Because the transplantation of differentiated cells that are derived from embryonic stem cells is allogenic, they face the problem of immune rejection following the transplantation of embryonic stem cell-derived cells into patients. In 2006, researchers from Japan reported the derivation of a new type of pluripotent stem cells which could overcome the problem of immune rejection that is associated with the application of embryonic stem cells. They designated these cells as induced pluripotent stem (iPS cells, because their production was ‘induced’ from differentiated somatic cells using a combination of four embryonic stem cell-associated transcription factors. Importantly, these pluripotent stem cells exhibit all the key features of embryonic stem cells including unlimited self-renewal and multi-lineage differentiation potential, and can pass the most stringent test of pluripotency which is known as the tetraploid (4n complementation. Hence, in addition to bypassing the problem of immune rejection, iPS cells have all of the potential applications of embryonic stem cells, including in developmental studies, toxicology research, drug discovery and disease modeling. Also, considering that they could be generated from patient’s own cells, iPS cells hold great promise in the future of patient-specific cell replacement therapies using pluripotent stem cells. In this review article, we will present a comprehensive review on the how and why of the generation of iPS cell from somatic cells of the body and discuss how they should be characterized in terms of morphologically, pluripotent stem cell behavior, and

  4. Generation of Induced Pluripotent Stem Cells from Hair Follicle Bulge Neural Crest Stem Cells

    NARCIS (Netherlands)

    Ma, Ming-San; Czepiel, Marcin; Krause, Tina; Schaefer, Karl-Herbert; Boddeke, Erik; Copray, Sjef

    2014-01-01

    Induced pluripotent stem cells (iPSCs) are promising candidates for the study of disease models as well as for tissue engineering purposes. Part of a strategy to develop safe reprogramming technique is reducing the number of exogenous reprogramming factors. Some cells types are more prone to

  5. Hematopoietic stem cell mobilization therapy accelerates recovery of renal function independent of stem cell contribution

    NARCIS (Netherlands)

    Stokman, Geurt; Leemans, Jaklien C.; Claessen, Nike; Weening, Jan J.; Florquin, Sandrine

    2005-01-01

    Acute renal failure and tubular cell loss as a result of ischemia constitute major challenges in renal pathophysiology. Increasing evidence suggests important roles for bone marrow stem cells in the regeneration of renal tissue after injury. This study investigated whether the enhanced availability

  6. Mesenchymal Stem Cells in Cardiology

    Science.gov (United States)

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

    2017-01-01

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

  7. Differentiation of isolated human umbilical cord mesenchymal stem cells into neural stem cells

    Science.gov (United States)

    Chen, Song; Zhang, Wei; Wang, Ji-Ming; Duan, Hong-Tao; Kong, Jia-Hui; Wang, Yue-Xin; Dong, Meng; Bi, Xue; Song, Jian

    2016-01-01

    AIM To investigate whether umbilical cord human mesenchymal stem cell (UC-MSC) was able to differentiate into neural stem cell and neuron in vitro. METHODS The umbilical cords were obtained from pregnant women with their written consent and the approval of the Clinic Ethnics Committee. UC-MSC were isolated by adherent culture in the medium contains 20% fetal bovine serum (FBS), then they were maintained in the medium contain 10% FBS and induced to neural cells in neural differentiation medium. We investigated whether UC-MSC was able to differentiate into neural stem cell and neuron in vitro by using flow cytometry, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunofluorescence (IF) analyzes. RESULTS A substantial number of UC-MSC was harvested using the tissue explants adherent method at about 2wk. Flow cytometric study revealed that these cells expressed common markers of MSCs, such as CD105 (SH2), CD73 (SH3) and CD90. After induction of differentiation of neural stem cells, the cells began to form clusters; RT-PCR and IF showed that the neuron specific enolase (NSE) and neurogenic differentiation 1-positive cells reached 87.3%±14.7% and 72.6%±11.8%, respectively. Cells showed neuronal cell differentiation after induced, including neuron-like protrusions, plump cell body, obviously and stronger refraction. RT-PCR and IF analysis showed that microtubule-associated protein 2 (MAP2) and nuclear factor-M-positive cells reached 43.1%±10.3% and 69.4%±19.5%, respectively. CONCLUSION Human umbilical cord derived MSCs can be cultured and proliferated in vitro and differentiate into neural stem cells, which may be a valuable source for cell therapy of neurodegenerative eye diseases. PMID:26949608

  8. Differentiation of isolated human umbilical cord mesenchymal stem cells into neural stem cells

    Directory of Open Access Journals (Sweden)

    Song Chen

    2016-01-01

    Full Text Available AIM: To investigate whether umbilical cord human mesenchymal stem cell (UC-MSC was able to differentiate into neural stem cell and neuron in vitro. METHODS: The umbilical cords were obtained from pregnant women with their written consent and the approval of the Clinic Ethnics Committee. UC-MSC were isolated by adherent culture in the medium contains 20% fetal bovine serum (FBS, then they were maintained in the medium contain 10% FBS and induced to neural cells in neural differentiation medium. We investigated whether UC-MSC was able to differentiate into neural stem cell and neuron in vitro by using flow cytometry, reverse transcriptase-polymerase chain reaction (RT-PCR and immunofluorescence (IF analyzes. RESULTS: A substantial number of UC-MSC was harvested using the tissue explants adherent method at about 2wk. Flow cytometric study revealed that these cells expressed common markers of MSCs, such as CD105 (SH2, CD73 (SH3 and CD90. After induction of differentiation of neural stem cells, the cells began to form clusters; RT-PCR and IF showed that the neuron specific enolase (NSE and neurogenic differentiation 1-positive cells reached 87.3%±14.7% and 72.6%±11.8%, respectively. Cells showed neuronal cell differentiation after induced, including neuron-like protrusions, plump cell body, obviously and stronger refraction. RT-PCR and IF analysis showed that microtubule-associated protein 2 (MAP2 and nuclear factor-M-positive cells reached 43.1%±10.3% and 69.4%±19.5%, respectively. CONCLUSION: Human umbilical cord derived MSCs can be cultured and proliferated in vitro and differentiate into neural stem cells, which may be a valuable source for cell therapy of neurodegenerative eye diseases.

  9. Adipose stem cells for bone tissue repair

    OpenAIRE

    Ciuffi, Simone; Zonefrati, Roberto; Brandi, Maria Luisa

    2017-01-01

    Adipose-derived stem/stromal cells (ASCs), together with adipocytes, vascular endothelial cells, and vascular smooth muscle cells, are contained in fat tissue. ASCs, like the human bone marrow stromal/stem cells (BMSCs), can differentiate into several lineages (adipose cells, fibroblast, chondrocytes, osteoblasts, neuronal cells, endothelial cells, myocytes, and cardiomyocytes). They have also been shown to be immunoprivileged, and genetically stable in long-term cultures. Nevertheless, unlik...

  10. Curcumin increased the differentiation rate of neurons in neural stem cells via wnt signaling in vitro study.

    Science.gov (United States)

    Chen, Fei; Wang, Haoxiang; Xiang, Xin; Yuan, Jichao; Chu, Weihua; Xue, Xingsen; Zhu, Haitao; Ge, Hongfei; Zou, Mingming; Feng, Hua; Lin, Jiangkai

    2014-12-01

    The objective of the present study was to clarify the relationship between the neuroprotective effects of curcumin and the classical wnt signaling pathway. Using Sprague-Dawley rats at a gestational age of 14.5 d, we isolated neural stem cells from the anterior two-thirds of the fetal rat brain. The neural stem cells were passaged three times using the half media replacement method and identified using cellular immunofluorescence. After passaging for three generations, we cultured cells in media without basic fibroblast growth factor and epidermal growth factor. Then we treated cells in five different ways, including a blank control group, a group treated with IWR1 (10 μmol/L), a group treated with curcumin (500 nmol/L), a group treated with IWR1 + curcumin, and a group treated with dimethyl sulfoxide (10 μmol/L). We then measured the protein and RNA expression levels for wnt3a and β-catenin using Western blotting and Reverse transcription-polymerase chain reaction (RT-PCR). Western-blotting: after the third generation of cells had been treated for 72 h, we observed that wnt3a and β-catenin expression was significantly increased in the group receiving 500 nmol/L curcumin but not in the other groups. Furthermore, cells in the IWR1-treated group showed decreased wnt3a and β-catenin expression, and wnt3a and β-catenin was also decreased in the IWR1 + 500 nmol/L curcumin group. No obvious change was observed in the dimethyl sulfoxide group. RT-PCR showed similar changes to those observed with the Western blotting experiments. Our study suggests that curcumin can activate the wnt signaling pathway, which provides evidence that curcumin exhibits a neuroprotective effect through the classical wnt signaling pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Age-related Deterioration of Hematopoietic Stem Cells.

    Science.gov (United States)

    Kim, Mi Jung; Kim, Min Hwan; Kim, Seung Ah; Chang, Jae Suk

    2008-11-01

    Aging is the process of system deterioration over time in the whole body. Stem cells are self-renewing and therefore have been considered exempt from the aging process. Earlier studies by Hayflick showed that there is an intrinsic limit to the number of divisions that mammalian somatic cells can undergo, and cycling kinetics and ontogeny-related studies strongly suggest that even the most primitive stem cell functions exhibit a certain degree of aging. Despite these findings, studies on the effects of aging on stem cell functions are inconclusive. Here we review the age-related properties of hematopoietic stem cells in terms of intrinsic and extrinsic alterations, proliferative potential, signaling molecules, telomere and telomerase, senescence and cancer issues, regenerative potential and other indications of stem cell aging are discussed in detail.

  12. Differential number of CD34+, CD133+ and CD34+/CD133+ cells in peripheral blood of patients with congestive heart failure

    Directory of Open Access Journals (Sweden)

    Fritzenwanger M

    2009-03-01

    Full Text Available Abstract Background Endothelial progenitor cells (EPC which are characterised by the simulateous expression of CD34, CD133 and vascular endothelial growth receptor 2 (VEGF 2 are involved in the pathophysiology of congestive heart failure (CHF and their number and function is reduced in CHF. But so far our knowledge about the number of circulating hematopoietic stem/progenitor cells (CPC expressing the early hematopoietic marker CD133 and CD34 in CHF is spares and therefore we determined their number and correlated them with New York Heart Association (NYHA functional class. Methods CD34 and CD133 surface expression was quantified by flow cytometry in the peripheral venous blood of 41 healthy adults and 101 patients with various degrees of CHF. Results CD34+, CD133+ and CD34+/CD133+ cells correlated inversely with age. Both the number of CD34+ and of CD34+/CD133+ cells inversely correlated with NYHA functional class. The number of CD133+ cells was not affected by NYHA class. Furthermore the number of CD133+ cells did not differ between control and CHF patients. Conclusion In CHF the release of CD34+, CD133+ and CD34+/CD133+ cells from the bone marrow seems to be regulated differently. Modulating the releasing process in CHF may be a tool in CHF treatment.

  13. Comparison of survival outcome between donor types or stem cell sources for childhood acute myeloid leukemia after allogenic hematopoietic stem cell transplantation: A multicenter retrospective study of Study Alliance of Yeungnam Pediatric Hematology-oncology.

    Science.gov (United States)

    Shim, Ye Jee; Lee, Jae Min; Kim, Heung Sik; Jung, Nani; Lim, Young Tak; Yang, Eu Jeen; Hah, Jeong Ok; Lee, Young-Ho; Chueh, Hee Won; Lim, Jae Young; Park, Eun Sil; Park, Jeong A; Park, Ji Kyoung; Park, Sang Kyu

    2018-06-19

    We compared transplant outcomes between donor types and stem cell sources for childhood acute myeloid leukemia (AML). The medical records of children with AML in the Yeungnam region of Korea from January 2000 to June 2017 were reviewed. In all, 76 children with AML (male-to-female ratio = 46:30) received allogenic hematopoietic stem cell transplantation (allo-HSCT). In total, 29 patients received HSCT from either a matched-related donor or a mismatched-related donor, 32 patients received an unrelated donor, and 15 patients received umbilical cord blood. In term of stem cell sources, bone marrow was used in 15 patients and peripheral blood in 46 patients. For all HSCT cases, the 5-year overall survival (OS) was 73.1% (95% CI: 62.7-83.5) and the 5-year event-free survival (EFS) was 66.1% (95% CI: 54.5-77.7). There was no statistical difference in 5-year OS according to the donor types or stem cell sources (P = .869 and P = .911). There was no statistical difference in 5-year EFS between donor types or stem cell sources (P = .526 and P = .478). For all HSCT cases, the 5-year relapse rate was 16.1% (95% CI: 7.3-24.9) and the 5-year non-relapse mortality (NRM) was 13.3% (95% CI: 5.1-21.5). There was no statistical difference in the 5-year relapse rate according to the donor types or stem cell sources (P = .971 and P = .965). There was no statistical difference in the 5-year NRM between donor types or stem cell sources (P = .461 and P = .470). © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Advanced research on separating prostate cancer stem cells

    International Nuclear Information System (INIS)

    Hao Yumei; He Xin; Song Naling

    2013-01-01

    Prostate cancer is a common malignant tumor in male urinary system,and may easily develop into the hormone refractory prostate cancer which can hardly be cured. Recent studies had found that the prostate cancer stem cells may be the source of the prostate cancer's occurrence,development, metastasis and recurrence. The therapy targeting the prostate cancer stem cells may be the effective way to cure prostate cancer. But these cells is too low to be detected. The difficulty lies in the low separation efficiency of prostate cancer stem cell, so the effectively separating prostate cancer stem cells occupied the main position for the more in-depth research of prostate cancer stem cells. This paper reviews the research progress and existing problems on the several main separating methods of prostate cancer stem cells, includes the fluorescence activated cells sorting and magnetic activated cells sorting based on prostate cancer stem cell surface markers, the side-population sorting and serum-free medium sphere forming sorting based on prostate cancer stem cell's biology. (authors)

  15. Stem Cells: New Hope For Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Gazdic Marina

    2015-03-01

    Full Text Available Stem cell therapy offers several attractive strategies for spinal cord repair. The regenerative potential of pluripotent stem cells was confirmed in an animal model of Spinal Cord Injury (SCI; nevertheless, optimized growth and differentiation protocols along with reliable safety assays should be established prior to the clinical application of hESCs and iPSCs. Th e therapeutic effects of mesenchymal stem cells (MSCs in SCI result from neurotrophin secretion, angiogenesis, and antiinflammatory actions. Several preclinical SCI studies have reported that the occurrence of axonal extension, remyelination and neuroprotection occur after the transplantation of olfactory ensheathing cells (OECs. The transplantation of neural stem cells NSCs (NSCs promotes partial functional improvement after SCI because of their potential to differentiate into neurons, oligodendrocytes, and astrocytes. The ideal source of stem cells for safe and efficient cell-based therapy for SCI remains a challenging issue that requires further investigation.

  16. Viscoelastic and dynamic properties of embryonic stem cells

    DEFF Research Database (Denmark)

    Ritter, Christine

    Stem cells are often referred to as the ‘holy grail’ of regenerative medicine, because they possessthe ability to develop into any cell type. The use of stem cells within medicine is currently limited bythe effectivity of differentiation and cell reprogramming protocols, making it therefore...... imperative tounderstand stem cells’ differentiation mechanisms better. Studies have shown that mechanical cuescan have an influence on stem cell fate decision. However, in order to understand the reaction of stemcells to mechanical input, one should first investigate and understand the mechanical properties...... ofthe cells themselves. In this thesis, the viscoelastic properties of mouse embryonic stem cells primedeither toward the epiblast (Epi) or the primitive endoderm (PrE) lineage were investigated.Optical tweezers were used to measure the fluctuations of endogenous lipid granules and therebydraw...

  17. Stimulation and support of haemopoietic stem cell proliferation by irradiated stroma cell colonies in bone marrow cell culture in vitro

    International Nuclear Information System (INIS)

    Mori, K.J.; Izumi, Hiroko; Seto, Akira

    1981-01-01

    A culture system was established in which haemopoietic stem cells can undergo a recovery proliferation after a depletion of the stem cells, completely in vitro. To elucidate the source of the stimulatory factors, normal bone marrow cells were overlayed on top of the irradiated adherent 'stromal' cell colonies in the bone marrow cell culture. This stimulated the proliferation of haemopoietic stem cells in the cultured cells in suspension. The present results indicate that the stromal cells produce factors which stimulate stem cell proliferation. Whether the stimulation is evoked by direct cell-cell interactions or by humoral factors is as yet to be studied. (author)

  18. Differentiation of Bovine Spermatogonial Stem Cells into Osteoblasts

    OpenAIRE

    Qasemi-Panahi, Babak; Tajik, Parviz; Movahedin, Mansoureh; Moghaddam, Gholamali; Barzgar, Younes; Heidari-Vala, Hamed

    2011-01-01

    Spermatogonial Stem Cell (SSC) technologies provide multiple opportunities for research in the field of biotechnology and regenerative medicine. The therapeutic use of Embryonic Stem Cells (ESCs) is restricted due to severe ethical and immunological concerns. Therefore, we need a new pluripotent cell type. Despite well-known role of germ cells in the gametogenesis, some facts apparently show their multipotentiality. In the present study, bovine SSCs were co-cultured with Sertoli cell for 7 da...

  19. [Bioethical challenges of stem cell tourism].

    Science.gov (United States)

    Ventura-Juncá, Patricio; Erices, Alejandro; Santos, Manuel J

    2013-08-01

    Stem cells have drawn extraordinary attention from scientists and the general public due to their potential to generate effective therapies for incurable diseases. At the same time, the production of embryonic stem cells involves a serious ethical issue concerning the destruction of human embryos. Although adult stem cells and induced pluripotential cells do not pose this ethical objection, there are other bioethical challenges common to all types of stem cells related particularly to the clinical use of stem cells. Their clinical use should be based on clinical trials, and in special situations, medical innovation, both of which have particular ethical dimensions. The media has raised unfounded expectations in patients and the public about the real clinical benefits of stem cells. At the same time, the number of unregulated clinics is increasing around the world, making direct offers through Internet of unproven stem cell therapies that attract desperate patients that have not found solutions in standard medicine. This is what is called stem cells tourism. This article reviews this situation, its consequences and the need for international cooperation to establish effective regulations to prevent the exploitation of patients and to endanger the prestige of legitimate stem cell research.

  20. Chitosan-hyaluronan based 3D co-culture platform for studying the crosstalk of lung cancer cells and mesenchymal stem cells.

    Science.gov (United States)

    Han, Hao-Wei; Hsu, Shan-Hui

    2016-09-15

    The controversial roles of mesenchymal stem cells (MSCs) in lung cancer development are not yet resolved because of the lack of an extracellular environment that mimics the tumor microenvironment. Three-dimensional (3D) culture system is an emerging research tool for biomedical applications such as drug screening. In this study, MSCs and human non-small cell lung carcinoma cells (A549) were co-cultured on a thin biomaterial-based substratum (hyaluronan-grafted chitosan, CS-HA; ∼2μm), and they were self-organized into the 3D tumor co-spheroids with core-shell structure. The gene expression levels of tumorigenicity markers in cancer cells associated with cancer stemness, epithelial-mesenchymal transition (EMT) property, and cell mobility were up-regulated for more than twofold in the MSC-tumor co-spheroids, through the promoted expression of certain tumor enhancers and the direct cell-cell interaction. To verify the different extents of tumorigenicity, A549 cells or those co-cultured with MSCs were transplanted into zebrafish embryos for evaluation in vivo. The tumorigenicity obtained from the zebrafish xenotransplantation model was consistent with that observed in vitro. These evidences suggest that the CS-HA substrate-based 3D co-culture platform for cancer cells and MSCs may be a convenient tool for studying the cell-cell interaction in a tumor-like microenvironment and potentially for cancer drug testing. Mesenchymal stem cells (MSCs) have been found in several types of tumor tissues. However, the controversial roles of MSCs in cancer development are still unsolved. Chitosan and hyaluronan are commonly used materials in the biomedical field. In the current study, we co-cultured lung cancer cells and MSCs on the planar hyaluronan-grafted chitosan (CS-HA) hybrid substrates, and discovered that lung cancer cells and MSCs were rapidly self-assembled into 3D tumor spheroids with core-shell structure on the substrates after only two days in culture. Therefore, CS

  1. Nanotopography Promotes Pancreatic Differentiation of Human Embryonic Stem Cells and Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Kim, Jong Hyun; Kim, Hyung Woo; Cha, Kyoung Je; Han, Jiyou; Jang, Yu Jin; Kim, Dong Sung; Kim, Jong-Hoon

    2016-03-22

    Although previous studies suggest that nanotopographical features influence properties and behaviors of stem cells, only a few studies have attempted to derive clinically useful somatic cells from human pluripotent stem cells using nanopatterned surfaces. In the present study, we report that polystyrene nanopore-patterned surfaces significantly promote the pancreatic differentiation of human embryonic and induced pluripotent stem cells. We compared different diameters of nanopores and showed that 200 nm nanopore-patterned surfaces highly upregulated the expression of PDX1, a critical transcription factor for pancreatic development, leading to an approximately 3-fold increase in the percentage of differentiating PDX1(+) pancreatic progenitors compared with control flat surfaces. Furthermore, in the presence of biochemical factors, 200 nm nanopore-patterned surfaces profoundly enhanced the derivation of pancreatic endocrine cells producing insulin, glucagon, or somatostatin. We also demonstrate that nanopore-patterned surface-induced upregulation of PDX1 is associated with downregulation of TAZ, suggesting the potential role of TAZ in nanopore-patterned surface-mediated mechanotransduction. Our study suggests that appropriate cytokine treatments combined with nanotopographical stimulation could be a powerful tool for deriving a high purity of desired cells from human pluripotent stem cells.

  2. Cellular Components, Including Stem-Like Cells, of Preterm Mother's Mature Milk as Compared with Those in Her Colostrum: A Pilot Study.

    Science.gov (United States)

    Kaingade, Pankaj; Somasundaram, Indumathi; Sharma, Akshita; Patel, Darshan; Marappagounder, Dhanasekaran

    2017-09-01

    Whether the preterm mothers' mature milk retains the same cellular components as those in colostrum including stem-like cell, cell adhesion molecules, and immune cells. A total of five preterm mothers were recruited for the study having an average age of 30.2 years and gestational age of 29.8 weeks from the Pristine Women's Hospital, Kolhapur. Colostrum milk was collected within 2-5 days and matured milk was collected 20-30 days after delivery from the same mothers. Integral cellular components of 22 markers including stem cells, immune cells, and cell adhesion molecules were measured using flowcytometry. Preterm mature milk was found to possess higher expressions of hematopoietic stem cells, mesenchymal stem-like cells, immune cells, few cell adhesion molecules, and side population cells than colostrum. The increased level of these different cell components in mature milk may be important in the long-term preterm baby's health growth. Further similar research in a larger population of various gestational ages and lactation stages of preterm mothers is warranted to support these pilot findings.

  3. Dormancy activation mechanism of oral cavity cancer stem cells.

    Science.gov (United States)

    Chen, Xiang; Li, Xin; Zhao, Baohong; Shang, Dehao; Zhong, Ming; Deng, Chunfu; Jia, Xinshan

    2015-07-01

    Radiotherapy and chemotherapy are targeted primarily at rapidly proliferating cancer cells and are unable to eliminate cancer stem cells in the G0 phase. Thus, these treatments cannot prevent the recurrence and metastasis of cancer. Understanding the mechanisms by which cancer stem cells are maintained in the dormant G0 phase, and how they become active is key to developing new cancer therapies. The current study found that the anti-cancer drug 5-fluorouracil, acting on the oral squamous cell carcinoma KB cell line, selectively killed proliferating cells while sparing cells in the G0 phase. Bisulfite sequencing PCR showed that demethylation of the Sox2 promoter led to the expression of Sox2. This then resulted in the transformation of cancer stem cells from the G0 phase to the division stage and suggested that the transformation of cancer stem cells from the G0 phase to the division stage is closely related to an epigenetic modification of the cell.

  4. Skin Stem Cells in Silence, Action, and Cancer

    Directory of Open Access Journals (Sweden)

    Elaine Fuchs

    2018-05-01

    Full Text Available In studying how stem cells make and maintain tissues, nearly every chapter of a cell biology textbook takes on special interest. The field even allows us to venture where no chapters have yet been written. In studying this basic problem, we are continually bombarded by nature's surprises and challenges. Stem cell biology has captured my interest for nearly my entire scientific career. Below, I focus on my laboratory's contributions to this fascinating field, to which so many friends and colleagues have made seminal discoveries equally deserving of this award. : In this Perspective, Elaine Fuchs describes her laboratory's contributions to the field of skin stem cells, giving a historical overview of their first isolation and characterization, the discovery of extrinsic and intrinsic factors regulating skin stem cell states, and their role in skin disease. Keywords: stem cells, skin, hair follicle, cancer, wound healing, epidermis

  5. Update on small intestinal stem cells

    OpenAIRE

    Tesori, Valentina; Puglisi, Maria Ausiliatrice; Lattanzi, Wanda; Gasbarrini, Giovanni Battista; Gasbarrini, Antonio

    2013-01-01

    Among somatic stem cells, those residing in the intestine represent a fascinating and poorly explored research field. Particularly, somatic stem cells reside in the small intestine at the level of the crypt base, in a constant balance between self-renewal and differentiation. Aim of the present review is to delve into the mechanisms that regulate the delicate equilibrium through which intestinal stem cells orchestrate intestinal architecture. To this aim, special focus will be addressed to id...

  6. Ethical Issues in Stem Cell Research

    OpenAIRE

    Lo, Bernard; Parham, Lindsay

    2009-01-01

    Stem cell research offers great promise for understanding basic mechanisms of human development and differentiation, as well as the hope for new treatments for diseases such as diabetes, spinal cord injury, Parkinson’s disease, and myocardial infarction. However, human stem cell (hSC) research also raises sharp ethical and political controversies. The derivation of pluripotent stem cell lines from oocytes and embryos is fraught with disputes about the onset of human personhood. The reprogramm...

  7. Stem cell aging: Survival of the laziest?

    OpenAIRE

    Muller-Sieburg, Christa; Sieburg, Hans B.

    2008-01-01

    The question whether stem cells age remains an enigma. Traditionally, aging was thought to change the properties of hematopoietic stem cells (HSC). We discuss here a new model of stem cell aging that challenges this view. It is now well-established that the HSC compartment is heterogeneous, consisting of epigenetically fixed subpopulations of HSC that differ in self-renewal and differentiation capacity. New data show that the representation of these HSC subsets changes during aging. HSC that ...

  8. Directional differentiation of chicken embryonic stem cells into ...

    African Journals Online (AJOL)

    Jane

    2011-08-01

    Aug 1, 2011 ... In this study, the differentiation potential of chicken ES cells was investigated ... Key words: Chicken embryonic stem cells, in vitro, directional differentiation, .... synthesized by using the Revert Aid first strand cDNA synthesis kit.

  9. Monitoring stem cells in phase contrast imaging

    Science.gov (United States)

    Lam, K. P.; Dempsey, K. P.; Collins, D. J.; Richardson, J. B.

    2016-04-01

    Understanding the mechanisms behind the proliferation of Mesenchymal Stem cells (MSCs) can offer a greater insight into the behaviour of these cells throughout their life cycles. Traditional methods of determining the rate of MSC differentiation rely on population based studies over an extended time period. However, such methods can be inadequate as they are unable to track cells as they interact; for example, in autologous cell therapies for osteoarthritis, the development of biological assays that could predict in vivo functional activity and biological action are particularly challenging. Here further research is required to determine non-histochemical biomarkers which provide correlations between cell survival and predictive functional outcome. This paper proposes using a (previously developed) advanced texture-based analysis algorithm to facilitate in vitro cells tracking using time-lapsed microscopy. The technique was adopted to monitor stem cells in the context of unlabelled, phase contrast imaging, with the goal of examining the cell to cell interactions in both monoculture and co-culture systems. The results obtained are analysed using established exploratory procedures developed for time series data and compared with the typical fluorescent-based approach of cell labelling. A review of the progress and the lessons learned are also presented.

  10. Therapeutic potential of stem cells in veterinary practice

    Directory of Open Access Journals (Sweden)

    Nitin E Gade

    Full Text Available Stem cell research acquired great attention during last decade inspite of incredible therapeutic potential of these cells the ethical controversies exists. Stem cells have enormous uses in animal cloning, drug discovery, gene targeting, transgenic production and regenerative therapy. Stem cells are the naïve cells of body which can self-renew and differentiate into other cell types to carry out multiple functions, these properties have been utilized in therapeutic application of stem cells in human and veterinary medicine. The application of stem cells in human medicine is well established and it is commonly used for chronic and accidental injuries. In Veterinary sciences previous studies mostly focused on establishing protocols for isolation and their characterization but with advancement in array of techniques for in vitro studies, stem cells rapidly became a viable tool for regenerative therapy of chronic, debilitating and various unresponsive clinical diseases and disorders. Multipotent adult stem cells have certain advantages over embryonic stem cells like easy isolation and expansion from numerous sources, less immunogenicity and no risk of teratoma formation hence their use is preferred in therapeutics. Adult stem cells have been utilized for treatment of spinal injuries, tendonitis, cartilage defects, osteoarthritis and ligament defects, liver diseases, wounds, cardiac and bone defects in animals. The multi-potential capability of these cells can be better utilized in near future to overcome the challenges faced by the clinicians. This review will emphasize on the therapeutic utilization and success of stem cell therapies in animals. [Vet. World 2012; 5(8.000: 499-507

  11. Study on the protective effect of MgSO4 on the radiation-induced neural stem cell injury

    International Nuclear Information System (INIS)

    Liu Ping; Tu Yu

    2010-01-01

    Objective: To explore the neuroprotective effect of magnesium sulfate on radiation induced neural stem cell injury. Methods: Brain tissue was obtained from new-born sprague-dawley rats within 24 hours, and the cerebral hemisphere was dissociated to culture the neural stem cells. After being identified by immunofluorescence method, the neural stem cells were randomly divided into 3 groups as blank control group, experimental control group and experimental group. The neural stem cells of experimental control group and experimental group were irradiated with 2 or 4 Gy of gamma rays. The proliferation and the cell cycle of neural stem cells were detected at different time-points ranging from 24 h,48 h, 72 h after irradiation with CCK-8 and FCM. Results: Compared with the blank control group, the proliferation rate of experimental control group was significantly reduced (t=5.33-8.44, P<0.05 ), and the G 1 phase arrest of experimental control group was significantly enhanced (t=30.60-71.22, P<0.05).Compared with the experimental control group, the proliferation of experimental group significantly increased excluding that of 24 h (t=2.45-4.71, P<0.05), the apoptosis rate of experimental group significantly decreased (t=6.73-41.12, P<0.05), which was closer to the blank control group.Conclusion: Magnesium sulfate can alleviate the injury of proliferation and decrease the cell apoptosis in the early stage after irradiation. (authors)

  12. Stem cell treatment of degenerative eye disease

    Directory of Open Access Journals (Sweden)

    Ben Mead

    2015-05-01

    Full Text Available Stem cell therapies are being explored extensively as treatments for degenerative eye disease, either for replacing lost neurons, restoring neural circuits or, based on more recent evidence, as paracrine-mediated therapies in which stem cell-derived trophic factors protect compromised endogenous retinal neurons from death and induce the growth of new connections. Retinal progenitor phenotypes induced from embryonic stem cells/induced pluripotent stem cells (ESCs/iPSCs and endogenous retinal stem cells may replace lost photoreceptors and retinal pigment epithelial (RPE cells and restore vision in the diseased eye, whereas treatment of injured retinal ganglion cells (RGCs has so far been reliant on mesenchymal stem cells (MSC. Here, we review the properties of non-retinal-derived adult stem cells, in particular neural stem cells (NSCs, MSC derived from bone marrow (BMSC, adipose tissues (ADSC and dental pulp (DPSC, together with ESC/iPSC and discuss and compare their potential advantages as therapies designed to provide trophic support, repair and replacement of retinal neurons, RPE and glia in degenerative retinal diseases. We conclude that ESCs/iPSCs have the potential to replace lost retinal cells, whereas MSC may be a useful source of paracrine factors that protect RGC and stimulate regeneration of their axons in the optic nerve in degenerate eye disease. NSC may have potential as both a source of replacement cells and also as mediators of paracrine treatment.

  13. Hematopoietic stem cell expansion : challenges and opportunities

    NARCIS (Netherlands)

    Walasek, Marta A.; van Os, Ronald; de Haan, Gerald; Kanz, L; Fibbe, WE; Lengerke, C; Dick, JE

    2012-01-01

    Attempts to improve hematopoietic reconstitution and engraftment potential of ex vivo-expanded hematopoietic stem and progenitor cells (HSPCs) have been largely unsuccessful due to the inability to generate sufficient stem cell numbers and to excessive differentiation of the starting cell

  14. Stem cell treatment of degenerative eye disease.

    Science.gov (United States)

    Mead, Ben; Berry, Martin; Logan, Ann; Scott, Robert A H; Leadbeater, Wendy; Scheven, Ben A

    2015-05-01

    Stem cell therapies are being explored extensively as treatments for degenerative eye disease, either for replacing lost neurons, restoring neural circuits or, based on more recent evidence, as paracrine-mediated therapies in which stem cell-derived trophic factors protect compromised endogenous retinal neurons from death and induce the growth of new connections. Retinal progenitor phenotypes induced from embryonic stem cells/induced pluripotent stem cells (ESCs/iPSCs) and endogenous retinal stem cells may replace lost photoreceptors and retinal pigment epithelial (RPE) cells and restore vision in the diseased eye, whereas treatment of injured retinal ganglion cells (RGCs) has so far been reliant on mesenchymal stem cells (MSC). Here, we review the properties of non-retinal-derived adult stem cells, in particular neural stem cells (NSCs), MSC derived from bone marrow (BMSC), adipose tissues (ADSC) and dental pulp (DPSC), together with ESC/iPSC and discuss and compare their potential advantages as therapies designed to provide trophic support, repair and replacement of retinal neurons, RPE and glia in degenerative retinal diseases. We conclude that ESCs/iPSCs have the potential to replace lost retinal cells, whereas MSC may be a useful source of paracrine factors that protect RGC and stimulate regeneration of their axons in the optic nerve in degenerate eye disease. NSC may have potential as both a source of replacement cells and also as mediators of paracrine treatment. Copyright © 2015. Published by Elsevier B.V.

  15. Pilot social feasibility study for the establishment of a public human umbilical cord blood stem cell bank in South Africa.

    Science.gov (United States)

    Meissner-Roloff, Madelein; Young, Wendy; Rangaka, Isabella; Lombaard, Hennie; Dhai, Ames; Tsotsi, Norma; Pepper, Michael S

    2012-12-01

    There is a large unmet need in South Africa for bone marrow transplantation. Umbilical cord blood (UCB) is an important source of stem cells for the treatment of haematological and non-haematological diseases. Access to the two existing private umbilical cord blood stem cell banks (UCB SCBs) in South Africa is limited to individuals that can afford it, which further aggravates the ever increasing divide between families from different socio-economic classes. The problem is compounded by a severe global shortage of genetically compatible samples, representative of the South African demographics. Establishing a public human UCB SCB in South Africa would provide more South Africans with access to previously unavailable treatment in the form of affordable, genetically compatible stem cells for bone marrow transplantation. A public UCB SCB has many facets to consider, one of which is public preparedness and support for the bank. This was assessed in a social feasibility pilot study which is reported here. In addition to the findings of this social feasibility study, other important considerations for establishing a public human UCB SCB in SA include; (a) testing the samples for HIV and other infectious diseases (required for compliance with international regulatory standards); (b) flow cytometric analysis for enumeration of CD34+ UCB stem cells; (c) mapping of HLA genotypes/alleles; and (d) a study of the economic feasibility of this endeavour.The social feasibility study was conducted to gauge public preparedness and support for a public SCB through patient interviews and questionnaires. The process was dynamic due to its novel nature for interviewers and interviewees alike. Many obstacles were met and dealt with which lead to the compilation of results discussed here in the form of a pilot social feasibility study.In the South African context, we are faced with unique and rich challenges relating to cultural and religious differences that are further augmented by

  16. Single-cell sequencing in stem cell biology.

    Science.gov (United States)

    Wen, Lu; Tang, Fuchou

    2016-04-15

    Cell-to-cell variation and heterogeneity are fundamental and intrinsic characteristics of stem cell populations, but these differences are masked when bulk cells are used for omic analysis. Single-cell sequencing technologies serve as powerful tools to dissect cellular heterogeneity comprehensively and to identify distinct phenotypic cell types, even within a 'homogeneous' stem cell population. These technologies, including single-cell genome, epigenome, and transcriptome sequencing technologies, have been developing rapidly in recent years. The application of these methods to different types of stem cells, including pluripotent stem cells and tissue-specific stem cells, has led to exciting new findings in the stem cell field. In this review, we discuss the recent progress as well as future perspectives in the methodologies and applications of single-cell omic sequencing technologies.

  17. Hardwiring Stem Cell Communication through Tissue Structure.

    Science.gov (United States)

    Xin, Tianchi; Greco, Valentina; Myung, Peggy

    2016-03-10

    Adult stem cells across diverse organs self-renew and differentiate to maintain tissue homeostasis. How stem cells receive input to preserve tissue structure and function largely relies on their communication with surrounding cellular and non-cellular elements. As such, how tissues are organized and patterned not only reflects organ function, but also inherently hardwires networks of communication between stem cells and their environment to direct tissue homeostasis and injury repair. This review highlights how different methods of stem cell communication reflect the unique organization and function of diverse tissues. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Nanomaterials for Engineering Stem Cell Responses.

    Science.gov (United States)

    Kerativitayanan, Punyavee; Carrow, James K; Gaharwar, Akhilesh K

    2015-08-05

    Recent progress in nanotechnology has stimulated the development of multifunctional biomaterials for tissue engineering applications. Synergistic interactions between nanomaterials and stem cell engineering offer numerous possibilities to address some of the daunting challenges in regenerative medicine, such as controlling trigger differentiation, immune reactions, limited supply of stem cells, and engineering complex tissue structures. Specifically, the interactions between stem cells and their microenvironment play key roles in controlling stem cell fate, which underlines therapeutic success. However, the interactions between nanomaterials and stem cells are not well understood, and the effects of the nanomaterials shape, surface morphology, and chemical functionality on cellular processes need critical evaluation. In this Review, focus is put on recent development in nanomaterial-stem cell interactions, with specific emphasis on their application in regenerative medicine. Further, the emerging technologies based on nanomaterials developed over the past decade for stem cell engineering are reviewed, as well as the potential applications of these nanomaterials in tissue regeneration, stem cell isolation, and drug/gene delivery. It is anticipated that the enhanced understanding of nanomaterial-stem cell interactions will facilitate improved biomaterial design for a range of biomedical and biotechnological applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. The Patentability of Stem Cells in Australia.

    Science.gov (United States)

    Petering, Jenny; Cowin, Prue

    2015-07-01

    The potential therapeutic applications of stem cells are unlimited. However, the ongoing political and social debate surrounding the intellectual property and patenting considerations of stem cell research has led to the implementation of strict legislative regulations. In Australia the patent landscape surrounding stem cells has evolved considerably over the past 20 years. The Australian Patents Act 1990 includes a specific exclusion to the patentability of human beings and of biological processes for their generation. However, this exclusion has received no judicial consideration to date, and so its scope and potential impact on stem cell patents is unclear. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  20. Hardwiring stem cell communication through tissue structure

    Science.gov (United States)

    Xin, Tianchi; Greco, Valentina; Myung, Peggy

    2016-01-01

    Adult stem cells across diverse organs self-renew and differentiate to maintain tissue homeostasis. How stem cells receive input to preserve tissue structure and function largely relies on their communication with surrounding cellular and non-cellular elements. As such, how tissues are organized and patterned not only reflects organ function but also inherently hardwires networks of communication between stem cells and their environment to direct tissue homeostasis and injury repair. This review highlights how different methods of stem cell communication reflect the unique organization and function of diverse tissues. PMID:26967287

  1. Role of Abcg2 During Mouse Embroyonic Stem Cell Diffferentiation

    Science.gov (United States)

    Role of Abcg2 During Mouse Embryonic Stem Cell Differentiation. Abcg2 is a multidrug resistance ATP-binding cassette (ABC) transporter whose activity may be considered a hallmark of stem cell plasticity. The role of Abcg2 during early embryogenesis, however, is unclear. Studies...

  2. Stem Cell Therapy for Myocardial Infarction: Are We Missing Time?

    NARCIS (Netherlands)

    ter Horst, Kasper W.

    2010-01-01

    The success of stem cell therapy in myocardial infarction (MI) is modest, and for stem cell therapy to be clinically effective fine-tuning in regard to timing, dosing, and the route of administration is required. Experimental studies suggest the existence of a temporal window of opportunity bound by

  3. Transcriptional profiling of putative human epithelial stem cells

    Directory of Open Access Journals (Sweden)

    Koçer Salih S

    2008-07-01

    Full Text Available Abstract Background Human interfollicular epidermis is sustained by the proliferation of stem cells and their progeny, transient amplifying cells. Molecular characterization of these two cell populations is essential for better understanding of self renewal, differentiation and mechanisms of skin pathogenesis. The purpose of this study was to obtain gene expression profiles of alpha 6+/MHCI+, transient amplifying cells and alpha 6+/MHCI-, putative stem cells, and to compare them with existing data bases of gene expression profiles of hair follicle stem cells. The expression of Major Histocompatibility Complex (MHC class I, previously shown to be absent in stem cells in several tissues, and alpha 6 integrin were used to isolate MHCI positive basal cells, and MHCI low/negative basal cells. Results Transcriptional profiles of the two cell populations were determined and comparisons made with published data for hair follicle stem cell gene expression profiles. We demonstrate that presumptive interfollicular stem cells, alpha 6+/MHCI- cells, are enriched in messenger RNAs encoding surface receptors, cell adhesion molecules, extracellular matrix proteins, transcripts encoding members of IFN-alpha family proteins and components of IFN signaling, but contain lower levels of transcripts encoding proteins which take part in energy metabolism, cell cycle, ribosome biosynthesis, splicing, protein translation, degradation, DNA replication, repair, and chromosome remodeling. Furthermore, our data indicate that the cell signaling pathways Notch1 and NF-κB are downregulated/inhibited in MHC negative basal cells. Conclusion This study demonstrates that alpha 6+/MHCI- cells have additional characteristics attributed to stem cells. Moreover, the transcription profile of alpha 6+/MHCI- cells shows similarities to transcription profiles of mouse hair follicle bulge cells known to be enriched for stem cells. Collectively, our data suggests that alpha 6+/MHCI- cells

  4. Targeting cancer stem cells in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    He AR

    2014-12-01

    Full Text Available Aiwu Ruth He,1 Daniel C Smith,1 Lopa Mishra2 1Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, 2Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: The poor outcome of patients with hepatocellular carcinoma (HCC is attributed to recurrence of the disease after curative treatment and the resistance of HCC cells to conventional chemotherapy, which may be explained partly by the function of liver cancer stem cells (CSCs. Liver CSCs have emerged as an important therapeutic target against HCC. Numerous surface markers for liver CSCs have been identified, and include CD133, CD90, CD44, CD13, and epithelial cell adhesion molecules. These surface markers serve not only as tools for identifying and isolating liver CSCs but also as therapeutic targets for eradicating these cells. In studies of animal models and large-scale genomic analyses of human HCC samples, many signaling pathways observed in normal stem cells have been found to be altered in liver CSCs, which accounts for the stemness and aggressive behavior of these cells. Antibodies and small molecule inhibitors targeting the signaling pathways have been evaluated at different levels of preclinical and clinical development. Another strategy is to promote the differentiation of liver CSCs to less aggressive HCC that is sensitive to conventional chemotherapy. Disruption of the tumor niche essential for liver CSC homeostasis has become a novel strategy in cancer treatment. To overcome the challenges in developing treatment for liver CSCs, more research into the genetic makeup of patient tumors that respond to treatment may lead to more effective therapy. Standardization of HCC CSC tumor markers would be helpful for measuring the CSC response to these agents. Herein, we review the current strategies for developing treatment to eradicate liver CSCs and to improve the outcome for patients with

  5. Regeneration of irradiated salivary glands with stem cell marker expressing cells

    DEFF Research Database (Denmark)

    Nanduri, Lalitha S Y; Maimets, Martti; Pringle, Sarah A

    2011-01-01

    BACKGROUND: Stem cell therapy could be a potential way for reducing radiation-induced hyposalivation and improving the patient's quality of life. However, the identification and purification of salivary gland stem cells have not been accomplished. This study aims to better characterize the stem/p...

  6. Framework for Traffic Congestion Management

    Directory of Open Access Journals (Sweden)

    Mahmud Hassan TALUKDAR

    2013-06-01

    Full Text Available Traffic Congestion is one of many serious global problems in all great cities resulted from rapid urbanization which always exert negative externalities upon society. The solution of traffic congestion is highly geocentric and due to its heterogeneous nature, curbing congestion is one of the hard tasks for transport planners. It is not possible to suggest unique traffic congestion management framework which could be absolutely applied for every great cities. Conversely, it is quite feasible to develop a framework which could be used with or without minor adjustment to deal with congestion problem. So, the main aim of this paper is to prepare a traffic congestion mitigation framework which will be useful for urban planners, transport planners, civil engineers, transport policy makers, congestion management researchers who are directly or indirectly involved or willing to involve in the task of traffic congestion management. Literature review is the main source of information of this study. In this paper, firstly, traffic congestion is defined on the theoretical point of view and then the causes of traffic congestion are briefly described. After describing the causes, common management measures, using world- wide, are described and framework for supply side and demand side congestion management measures are prepared.

  7. Immune reconstitution after allogeneic hematopoietic stem cell transplantation in children: a single institution study of 59 patients

    Directory of Open Access Journals (Sweden)

    Hyun O Kim

    2013-01-01

    Full Text Available &lt;b&gt;Purpose:&lt;/b&gt; Lymphocyte subset recovery is an important factor that determines the success of hematopoietic stem cell transplantation (HSCT. Temporal differences in the recovery of lymphocyte subsets and the factors influencing this recovery are important variables that affect a patient's posttransplant immune reconstitution, and therefore require investigation. &lt;b&gt;Methods:&lt;/b&gt; The time taken to achieve lymphocyte subset recovery and the factors influencing this recovery were investigated in 59 children who had undergone HSCT at the Department of Pediatrics, The Catholic University of Korea Seoul St. Mary's Hospital, and who had an uneventful follow-up period of at least 1 year. Analyses were carried out at 3 and 12 months post-transplant. An additional study was performed 1 month post-transplant to evaluate natural killer (NK cell recovery. The impact of preand post-transplant variables, including diagnosis of Epstein-Barr virus (EBV DNAemia posttransplant,on lymphocyte recovery was evaluated. &lt;b&gt;Results:&lt;/b&gt; The lymphocyte subsets recovered in the following order: NK cells, cytotoxic T cells, B cells,and helper T cells. At 1 month post-transplant, acute graft-versus-host disease was found to contribute significantly to the delay of CD16+/56+ cell recovery. Younger patients showed delayed recovery of both CD3+/CD8+ and CD19+ cells. EBV DNAemia had a deleterious impact on the recovery of both CD3+ and CD3+/CD4+ lymphocytes at 1 year post-transplant. &lt;b&gt;Conclusion:&lt;/b&gt; In our pediatric allogeneic HSCT cohort, helper T cells were the last subset to recover. Younger age and EBV DNAemia had a negative impact on the post-transplant recovery of T cells and B cells.

  8. Stem cells in the human breast

    DEFF Research Database (Denmark)

    Petersen, Ole William; Polyak, Kornelia

    2010-01-01

    The origins of the epithelial cells participating in the development, tissue homeostasis, and cancer of the human breast are poorly understood. However, emerging evidence suggests a role for adult tissue-specific stem cells in these processes. In a hierarchical manner, these generate the two main...... mammary cell lineages, producing an increasing number of cells with distinct properties. Understanding the biological characteristics of human breast stem cells and their progeny is crucial in attempts to compare the features of normal stem cells and cancer precursor cells and distinguish these from...... nonprecursor cells and cells from the bulk of a tumor. A historical overview of research on human breast stem cells in primary tissue and in culture reveals the progress that has been made in this area, whereas a focus on the cell-of-origin and reprogramming that occurs during neoplastic conversion provides...

  9. Pluripotent stem cell-derived neural stem cells: From basic research to applications

    OpenAIRE

    Otsu, Masahiro; Nakayama, Takashi; Inoue, Nobuo

    2014-01-01

    Basic research on pluripotent stem cells is designed to enhance understanding of embryogenesis, whereas applied research is designed to develop novel therapies and prevent diseases. Attainment of these goals has been enhanced by the establishment of embryonic stem cell lines, the technological development of genomic reprogramming to generate induced-pluripotent stem cells, and improvements in vitro techniques to manipulate stem cells. This review summarizes the techniques required to generate...

  10. Stem cells in bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Jeong Min [Department of Preventive and Social Dentistry and Institute of Oral Biology, College of Dentistry, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Kim, Byung-Chul; Park, Jae-Hong; Kwon, Il Keun; Hwang, Yu-Shik [Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, College of Dentistry, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Mantalaris, Anathathios, E-mail: yshwang@khu.ac.k [Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ (United Kingdom)

    2010-12-15

    Bone tissue engineering has been one of the most promising areas of research, providing a potential clinical application to cure bone defects. Recently, various stem cells including embryonic stem cells (ESCs), bone marrow-derived mesenchymal stem cells (BM-MSCs), umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs), adipose tissue-derived stem cells (ADSCs), muscle-derived stem cells (MDSCs) and dental pulp stem cells (DPSCs) have received extensive attention in the field of bone tissue engineering due to their distinct biological capability to differentiate into osteogenic lineages. The application of these stem cells to bone tissue engineering requires inducing in vitro differentiation of these cells into bone forming cells, osteoblasts. For this purpose, efficient in vitro differentiation towards osteogenic lineage requires the development of well-defined and proficient protocols. This would reduce the likelihood of spontaneous differentiation into divergent lineages and increase the available cell source for application to bone tissue engineering therapies. This review provides a critical examination of the various experimental strategies that could be used to direct the differentiation of ESC, BM-MSC, UCB-MSC, ADSC, MDSC and DPSC towards osteogenic lineages and their potential applications in tissue engineering, particularly in the regeneration of bone. (topical review)

  11. Stem cells in bone tissue engineering

    International Nuclear Information System (INIS)

    Seong, Jeong Min; Kim, Byung-Chul; Park, Jae-Hong; Kwon, Il Keun; Hwang, Yu-Shik; Mantalaris, Anathathios

    2010-01-01

    Bone tissue engineering has been one of the most promising areas of research, providing a potential clinical application to cure bone defects. Recently, various stem cells including embryonic stem cells (ESCs), bone marrow-derived mesenchymal stem cells (BM-MSCs), umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs), adipose tissue-derived stem cells (ADSCs), muscle-derived stem cells (MDSCs) and dental pulp stem cells (DPSCs) have received extensive attention in the field of bone tissue engineering due to their distinct biological capability to differentiate into osteogenic lineages. The application of these stem cells to bone tissue engineering requires inducing in vitro differentiation of these cells into bone forming cells, osteoblasts. For this purpose, efficient in vitro differentiation towards osteogenic lineage requires the development of well-defined and proficient protocols. This would reduce the likelihood of spontaneous differentiation into divergent lineages and increase the available cell source for application to bone tissue engineering therapies. This review provides a critical examination of the various experimental strategies that could be used to direct the differentiation of ESC, BM-MSC, UCB-MSC, ADSC, MDSC and DPSC towards osteogenic lineages and their potential applications in tissue engineering, particularly in the regeneration of bone. (topical review)

  12. Epidermal stem cells response to radiative genotoxic stress

    International Nuclear Information System (INIS)

    Marie, Melanie

    2013-01-01

    Human skin is the first organ exposed to various environmental stresses, which requires the development by skin stem cells of specific mechanisms to protect themselves and to ensure tissue homeostasis. As stem cells are responsible for the maintenance of epidermis during individual lifetime, the preservation of genomic integrity in these cells is essential. My PhD aimed at exploring the mechanisms set up by epidermal stem cells in order to protect themselves from two genotoxic stresses, ionizing radiation (Gamma Rays) and ultraviolet radiation (UVB). To begin my PhD, I have taken part of the demonstration of protective mechanisms used by keratinocyte stem cells after ionizing radiation. It has been shown that these cells are able to rapidly repair most types of radiation-induced DNA damage. Furthermore, we demonstrated that this repair is activated by the fibroblast growth factor 2 (FGF2). In order to know if this protective mechanism is also operating in cutaneous carcinoma stem cells, we investigated the response to gamma Rays of carcinoma stem cells isolated from a human carcinoma cell line. As in normal keratinocyte stem cells, we demonstrated that cancer stem cells could rapidly repair radio-induced DNA damage. Furthermore, fibroblast growth factor 2 also mediates this repair, notably thanks to its nuclear isoforms. The second project of my PhD was to study human epidermal stem cells and progenitors responses to UVB radiation. Once cytometry and irradiation conditions were set up, the toxicity of UVB radiation has been evaluate in the primary cell model. We then characterized UVB photons effects on cell viability, proliferation and repair of DNA damage. This study allowed us to bring out that responses of stem cells and their progeny to UVB are different, notably at the level of part of their repair activity of DNA damage. Moreover, progenitors and stem cells transcriptomic responses after UVB irradiation have been study in order to analyze the global

  13. Clinical potentials of human pluripotent stem cells.

    Science.gov (United States)

    Mora, Cristina; Serzanti, Marialaura; Consiglio, Antonella; Memo, Maurizio; Dell'Era, Patrizia

    2017-08-01

    Aging, injuries, and diseases can be considered as the result of malfunctioning or damaged cells. Regenerative medicine aims to restore tissue homeostasis by repairing or replacing cells, tissues, or damaged organs, by linking and combining different disciplines including engineering, technology, biology, and medicine. To pursue these goals, the discipline is taking advantage of pluripotent stem cells (PSCs), a peculiar type of cell possessing the ability to differentiate into every cell type of the body. Human PSCs can be isolated from the blastocysts and maintained in culture indefinitely, giving rise to the so-called embryonic stem cells (ESCs). However, since 2006, it is possible to restore in an adult cell a pluripotent ESC-like condition by forcing the expression of four transcription factors with the rejuvenating reprogramming technology invented by Yamanaka. Then the two types of PSC can be differentiated, using standardized protocols, towards the cell type necessary for the regeneration. Although the use of these derivatives for therapeutic transplantation is still in the preliminary phase of safety and efficacy studies, a lot of efforts are presently taking place to discover the biological mechanisms underlying genetic pathologies, by differentiating induced PSCs derived from patients, and new therapies by challenging PSC-derived cells in drug screening.

  14. Economics and Outcome After Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study.

    Science.gov (United States)

    Gratwohl, Alois; Sureda, Anna; Baldomero, Helen; Gratwohl, Michael; Dreger, Peter; Kröger, Nicolaus; Ljungman, Per; McGrath, Eoin; Mohty, Mohamad; Nagler, Arnon; Rambaldi, Alessandro; de Elvira, Carmen Ruiz; Snowden, John A; Passweg, Jakob; Apperley, Jane; Niederwieser, Dietger; Stijnen, Theo; Brand, Ronald

    2015-12-01

    Hematopoietic stem cell transplantation (HSCT) is a lifesaving expensive medical procedure. Hence, more transplants are performed in more affluent countries. The impact of economic factors on patient outcome is less defined. We analyzed retrospectively a defined cohort of 102,549 patients treated with an allogeneic (N = 37,542; 37%) or autologous (N = 65,007; 63%) HSCT. They were transplanted by one of 404 HSCT centers in 25 European countries between 1999 and 2006. We searched for associations between center-specific microeconomic or country-specific macroeconomic factors and outcome. Center patient-volume and center program-duration were significantly and systematically associated with improved survival after allogeneic HSCT (HR 0·87; 0·84-0·91 per 10 patients; p < 0·0001; HR 0·90;0·85-0·90 per 10 years; p < 0·001) and autologous HSCT (HR 0·91;0·87-0·96 per 10 patients; p < 0·001; HR 0·93;0·87-0·99 per 10 years; p = 0·02). The product of Health Care Expenditures by Gross National Income/capita was significantly associated in multivariate analysis with all endpoints (R(2) = 18%; for relapse free survival) after allogeneic HSCT. Data indicate that country- and center-specific economic factors are associated with distinct, significant, systematic, and clinically relevant effects on survival after HSCT. They impact on center expertise in long-term disease and complication management. It is likely that these findings apply to other forms of complex treatments.

  15. Economics and Outcome After Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Alois Gratwohl

    2015-12-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is a lifesaving expensive medical procedure. Hence, more transplants are performed in more affluent countries. The impact of economic factors on patient outcome is less defined. We analyzed retrospectively a defined cohort of 102,549 patients treated with an allogeneic (N = 37,542; 37% or autologous (N = 65,007; 63% HSCT. They were transplanted by one of 404 HSCT centers in 25 European countries between 1999 and 2006. We searched for associations between center-specific microeconomic or country-specific macroeconomic factors and outcome. Center patient-volume and center program-duration were significantly and systematically associated with improved survival after allogeneic HSCT (HR 0·87; 0·84–0·91 per 10 patients; p < 0·0001; HR 0·90;0·85–0·90 per 10 years; p < 0·001 and autologous HSCT (HR 0·91;0·87–0·96 per 10 patients; p < 0·001; HR 0·93;0·87–0·99 per 10 years; p = 0·02. The product of Health Care Expenditures by Gross National Income/capita was significantly associated in multivariate analysis with all endpoints (R2 = 18%; for relapse free survival after allogeneic HSCT. Data indicate that country- and center-specific economic factors are associated with distinct, significant, systematic, and clinically relevant effects on survival after HSCT. They impact on center expertise in long-term disease and complication management. It is likely that these findings apply to other forms of complex treatments.

  16. Experimental study on therapy of acute radiation sickness with transplantation of allogeneic peripheral blood hemopoietic stem cells

    International Nuclear Information System (INIS)

    Ma Enpu; Bi Jianjin; Zhan Aiqin

    1995-01-01

    In the study, 10 beagles were used. All the dogs were irradiated with 6.5 Gy of γ-rays from a 60 Co source (dose rate, 95.6-107.9 R/min) and divided into three groups. All the three dogs in the control group died, having survived 7.5 days on the average after irradiation. In the second group, four dogs were transplanted with allogeneic peripheral blood hemopoietic stem cells (PBHSC) without removing T lymphocytes. The results of sex chromosome tests after irradiation and transplantation showed that the cells were of donor type. All the four dogs died of severe graft versus-host disease (GVHD) and survived 41.6 days on the average after irradiation. In the third group, three dogs received transplantation of allogeneic PBHSC without T lymphocytes. Two of them died, and the third developed mild GVHD and survived over 4 years

  17. Generation of Cardiomyocytes from Pluripotent Stem Cells.

    Science.gov (United States)

    Nakahama, Hiroko; Di Pasquale, Elisa

    2016-01-01

    The advent of pluripotent stem cells (PSCs) enabled a multitude of studies for modeling the development of diseases and testing pharmaceutical therapeutic potential in vitro. These PSCs have been differentiated to multiple cell types to demonstrate its pluripotent potential, including cardiomyocytes (CMs). However, the efficiency and efficacy of differentiation vary greatly between different cell lines and methods. Here, we describe two different methods for acquiring CMs from human pluripotent lines. One method involves the generation of embryoid bodies, which emulates the natural developmental process, while the other method chemically activates the canonical Wnt signaling pathway to induce a monolayer of cardiac differentiation.

  18. Embryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells

    NARCIS (Netherlands)

    D. ten Berge (Derk); D. Kurek (Dorota); T. Blauwkamp (Tim); W. Koole (Wouter); A. Maas (Alex); E. Eroglu (Elif); R.K. Siu (Ronald); R. Nusse (Roel)

    2011-01-01

    textabstractPluripotent stem cells exist in naive and primed states, epitomized by mouse embryonic stem cells (ESCs) and the developmentally more advanced epiblast stem cells (EpiSCs; ref.). In the naive state of ESCs, the genome has an unusual open conformation and possesses a minimum of repressive

  19. Derivation of porcine pluripotent stem cells for biomedical research.

    Science.gov (United States)

    Shiue, Yow-Ling; Yang, Jenn-Rong; Liao, Yu-Jing; Kuo, Ting-Yung; Liao, Chia-Hsin; Kang, Ching-Hsun; Tai, Chein; Anderson, Gary B; Chen, Lih-Ren

    2016-07-01

    Pluripotent stem cells including embryonic stem cells (ESCs), embryonic germ cells (EGCs), and induced pluripotent stem cells (iPSCs) are capable of self-renew and limitlessly proliferating in vitro with undifferentiated characteristics. They are able to differentiate in vitro, spontaneously or responding to suitable signals, into cells of all three primary germ layers. Consequently, these pluripotent stem cells will be valuable sources for cell replacement therapy in numerous disorders. However, the promise of human ESCs and EGCs is cramped by the ethical argument about destroying embryos and fetuses for cell line creation. Moreover, there are still carcinogenic risks existing toward the goal of clinical application for human ESCs, EGCs, and iPSCs. Therefore, a suitable animal model for stem cell research will benefit the further development of human stem cell technology. The pigs, on the basis of their similarity in anatomy, immunology, physiology, and biochemical properties, have been wide used as model animals in the study of various human diseases. The development of porcine pluripotent stem cell lines will hold the opportunity to provide an excellent material for human counterpart to the transplantation in biomedical research and further development of cell-based therapeutic strategy. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Maintenance and Neuronal Differentiation of Chicken Induced Pluripotent Stem-Like Cells

    OpenAIRE

    Dai, Rui; Rossello, Ricardo; Chen, Chun-chun; Kessler, Joeran; Davison, Ian; Hochgeschwender, Ute; Jarvis, Erich D.

    2014-01-01

    Pluripotent stem cells have the potential to become any cell in the adult body, including neurons and glia. Avian stem cells could be used to study questions, like vocal learning, that would be difficult to examine with traditional mouse models. Induced pluripotent stem cells (iPSCs) are differentiated cells that have been reprogrammed to a pluripotent stem cell state, usually using inducing genes or other molecules. We recently succeeded in generating avian iPSC-like cells using mammalian ge...

  1. Mesenchymal stem cell-conditioned medium accelerates skin wound healing: An in vitro study of fibroblast and keratinocyte scratch assays

    International Nuclear Information System (INIS)

    Walter, M.N.M.; Wright, K.T.; Fuller, H.R.; MacNeil, S.; Johnson, W.E.B.

    2010-01-01

    We have used in vitro scratch assays to examine the relative contribution of dermal fibroblasts and keratinocytes in the wound repair process and to test the influence of mesenchymal stem cell (MSC) secreted factors on both skin cell types. Scratch assays were established using single cell and co-cultures of L929 fibroblasts and HaCaT keratinocytes, with wound closure monitored via time-lapse microscopy. Both in serum supplemented and serum free conditions, wound closure was faster in L929 fibroblast than HaCaT keratinocyte scratch assays, and in co-culture the L929 fibroblasts lead the way in closing the scratches. MSC-CM generated under serum free conditions significantly enhanced the wound closure rate of both skin cell types separately and in co-culture, whereas conditioned medium from L929 or HaCaT cultures had no significant effect. This enhancement of wound closure in the presence of MSC-CM was due to accelerated cell migration rather than increased cell proliferation. A number of wound healing mediators were identified in MSC-CM, including TGF-β1, the chemokines IL-6, IL-8, MCP-1 and RANTES, and collagen type I, fibronectin, SPARC and IGFBP-7. This study suggests that the trophic activity of MSC may play a role in skin wound closure by affecting both dermal fibroblast and keratinocyte migration, along with a contribution to the formation of extracellular matrix.

  2. Role of adipose-derived stem cells in wound healing.

    Science.gov (United States)

    Hassan, Waqar Ul; Greiser, Udo; Wang, Wenxin

    2014-01-01

    Impaired wound healing remains a challenge to date and causes debilitating effects with tremendous suffering. Recent advances in tissue engineering approaches in the area of cell therapy have provided promising treatment options to meet the challenges of impaired skin wound healing such as diabetic foot ulcers. Over the last few years, stem cell therapy has emerged as a novel therapeutic approach for various diseases including wound repair and tissue regeneration. Several different types of stem cells have been studied in both preclinical and clinical settings such as bone marrow-derived stem cells, adipose-derived stem cells (ASCs), circulating angiogenic cells (e.g., endothelial progenitor cells), human dermal fibroblasts, and keratinocytes for wound healing. Adipose tissue is an abundant source of mesenchymal stem cells, which have shown an improved outcome in wound healing studies. ASCs are pluripotent stem cells with the ability to differentiate into different lineages and to secrete paracrine factors initiating tissue regeneration process. The abundant supply of fat tissue, ease of isolation, extensive proliferative capacities ex vivo, and their ability to secrete pro-angiogenic growth factors make them an ideal cell type to use in therapies for the treatment of nonhealing wounds. In this review, we look at the pathogenesis of chronic wounds, role of stem cells in wound healing, and more specifically look at the role of ASCs, their mechanism of action and their safety profile in wound repair and tissue regeneration. © 2014 by the Wound Healing Society.

  3. Isolation, characterization, and differentiation of stem cells for cartilage regeneration.

    Science.gov (United States)

    Beane, Olivia S; Darling, Eric M

    2012-10-01

    The goal of tissue engineering is to create a functional replacement for tissues damaged by injury or disease. In many cases, impaired tissues cannot provide viable cells, leading to the investigation of stem cells as a possible alternative. Cartilage, in particular, may benefit from the use of stem cells since the tissue has low cellularity and cannot effectively repair itself. To address this need, researchers are investigating the chondrogenic capabilities of several multipotent stem cell sources, including adult and extra-embryonic mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). Comparative studies indicate that each cell type has advantages and disadvantages, and while direct comparisons are difficult to make, published data suggest some sources may be more promising for cartilage regeneration than others. In this review, we identify current approaches for isolating and chondrogenically differentiating MSCs from bone marrow, fat, synovium, muscle, and peripheral blood, as well as cells from extra-embryonic tissues, ESCs, and iPSCs. Additionally, we assess chondrogenic induction with growth factors, identifying standard cocktails used for each stem cell type. Cell-only (pellet) and scaffold-based studies are also included, as is a discussion of in vivo results.

  4. The New Federalism: State Policies Regarding Embryonic Stem Cell Research.

    Science.gov (United States)

    Acosta, Nefi D; Golub, Sidney H

    2016-09-01

    Stem cell policy in the United States is an amalgam of federal and state policies. The scientific development of human pluripotent embryonic stem cells (ESCs) triggered a contentious national stem cell policy debate during the administration of President George W. Bush. The Bush "compromise" that allowed federal funding to study only a very limited number of ESC derived cell lines did not satisfy either the researchers or the patient advocates who saw great medical potential being stifled. Neither more restrictive legislation nor expansion of federal funding proved politically possible and the federal impasse opened the door for a variety of state-based experiments. In 2004, California became the largest and most influential state venture into stem cell research by passing "Prop 71," a voter initiative that created a new stem cell agency and funded it with $3 billion. Several states followed suit with similar programs to protect the right of investigators to do stem cell research and in some cases to invest state funding in such projects. Other states devised legislation to restrict stem cell research and in five states, criminal penalties were included. Thus, the US stem cell policy is a patchwork of multiple, often conflicting, state and federal policies. © 2016 American Society of Law, Medicine & Ethics.

  5. Training stem cells for treatment of malignant brain tumors

    Institute of Scientific and Technical Information of China (English)

    Shengwen; Calvin; Li; Mustafa; H; Kabeer; Long; T; Vu; Vic; Keschrumrus; Hong; Zhen; Yin; Brent; A; Dethlefs; Jiang; F; Zhong; John; H; Weiss; William; G; Loudon

    2014-01-01

    The treatment of malignant brain tumors remains a challenge. Stem cell technology has been applied in the treatment of brain tumors largely because of the ability of some stem cells to infiltrate into regions within the brain where tumor cells migrate as shown in preclinical studies. However, not all of these efforts can translate in the effective treatment that improves the quality of life for pa-tients. Here, we perform a literature review to identify the problems in the field. Given the lack of efficacy of most stem cell-based agents used in the treatment of malignant brain tumors, we found that stem cell distribution(i.e., only a fraction of stem cells applied capable of targeting tumors) are among the limiting factors. We provide guidelines for potential improvements in stem cell distribution. Specifically, we use an engineered tissue graft platform that replicates the in vivo microenvironment, and provide our data to validate that this culture platform is viable for producing stem cells that have better stem cell distribution than with the Petri dish culture system.

  6. 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.

  7. Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0644 TITLE: Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells PRINCIPAL INVESTIGATOR: Chun-Ju...Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0644 5c. PROGRAM ELEMENT...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Cancer stem cells (CSCs), a cell population with acquired perpetuating self-renewal properties which

  8. Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-14-1-0115 TITLE: Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas PRINCIPAL INVESTIGATOR: Kyuson Yun...CA130273 - Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0115 5c. PROGRAM...hypothesis, we originally proposed to transform neural stem cells (NSCs) and neural progenitor cells (NPCs) in vivo by expressing an activated form

  9. Rejuvenating Strategies for Stem Cell-based Therapies in Aging

    Science.gov (United States)

    Neves, Joana; Sousa-Victor, Pedro; Jasper, Heinrich

    2017-01-01

    SUMMARY Recent advances in our understanding of tissue regeneration and the development of efficient approaches to induce and differentiate pluripotent stem cells for cell replacement therapies promise exciting avenues for treating degenerative age-related diseases. However, clinical studies and insights from model organisms have identified major roadblocks that normal aging processes impose on tissue regeneration. These new insights suggest that specific targeting of environmental niche components, including growth factors, ECM and immune cells, and intrinsic stem cell properties that are affected by aging will be critical for development of new strategies to improve stem cell function and optimize tissue repair processes. PMID:28157498

  10. Different Effects of BORIS/CTCFL on Stemness Gene Expression, Sphere Formation and Cell Survival in Epithelial Cancer Stem Cells.

    Directory of Open Access Journals (Sweden)

    Loredana Alberti

    Full Text Available Cancer stem cells are cancer cells characterized by stem cell properties and represent a small population of tumor cells that drives tumor development, progression, metastasis and drug resistance. To date, the molecular mechanisms that generate and regulate cancer stem cells are not well defined. BORIS (Brother of Regulator of Imprinted Sites or CTCFL (CTCF-like is a DNA-binding protein that is expressed in normal tissues only in germ cells and is re-activated in tumors. Recent evidences have highlighted the correlation of BORIS/CTCFL expression with poor overall survival of different cancer patients. We have previously shown an association of BORIS-expressing cells with stemness gene expression in embryonic cancer cells. Here, we studied the role of BORIS in epithelial tumor cells. Using BORIS-molecular beacon that was already validated, we were able to show the presence of BORIS mRNA in cancer stem cell-enriched populations (side population and spheres of cervical, colon and breast tumor cells. BORIS silencing studies showed a decrease of sphere formation capacity in breast and colon tumor cells. Importantly, BORIS-silencing led to down-regulation of hTERT, stem cell (NANOG, OCT4, SOX2 and BMI1 and cancer stem cell markers (ABCG2, CD44 and ALDH1 genes. Conversely, BORIS-induction led to up-regulation of the same genes. These phenotypes were observed in cervical, colon and invasive breast tumor cells. However, a completely different behavior was observed in the non-invasive breast tumor cells (MCF7. Indeed, these cells acquired an epithelial mesenchymal transition phenotype after BORIS silencing. Our results demonstrate that BORIS is associated with cancer stem cell-enriched populations of several epithelial tumor cells and the different phenotypes depend on the origin of tumor cells.

  11. Evaluation of early healing events around mesenchymal stem cell-seeded collagen-glycosaminoglycan scaffold. An experimental study in Wistar rats.

    LENUS (Irish Health Repository)

    Alhag, Mohamed

    2011-03-01

    Tissue engineering using cell-seeded biodegradable scaffolds offers a new bone regenerative approach that might circumvent many of the limitations of current therapeutic modalities. The aim of this experiment was to study the early healing events around mesenchymal stem cell-seeded collagen-glycosaminoglycan scaffolds.

  12. Nanoscale Mechanical Stimulation of Human Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    H Nikukar

    2014-05-01

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

  13. Stem Cells for Cardiac Regeneration by Cell Therapy and Myocardial Tissue Engineering

    Science.gov (United States)

    Wu, Jun; Zeng, Faquan; Weisel, Richard D.; Li, Ren-Ke

    Congestive heart failure, which often occurs progressively following a myocardial infarction, is characterized by impaired myocardial perfusion, ventricular dilatation, and cardiac dysfunction. Novel treatments are required to reverse these effects - especially in older patients whose endogenous regenerative responses to currently available therapies are limited by age. This review explores the current state of research for two related approaches to cardiac regeneration: cell therapy and tissue engineering. First, to evaluate cell therapy, we review the effectiveness of various cell types for their ability to limit ventricular dilatation and promote functional recovery following implantation into a damaged heart. Next, to assess tissue engineering, we discuss the characteristics of several biomaterials for their potential to physically support the infarcted myocardium and promote implanted cell survival following cardiac injury. Finally, looking ahead, we present recent findings suggesting that hybrid constructs combining a biomaterial with stem and supporting cells may be the most effective approaches to cardiac regeneration.

  14. Induced Pluripotent Stem Cells for Regenerative Medicine

    OpenAIRE

    Hirschi, Karen K.; Li, Song; Roy, Krishnendu

    2014-01-01

    With the discovery of induced pluripotent stem (iPS) cells, it is now possible to convert differentiated somatic cells into multipotent stem cells that have the capacity to generate all cell types of adult tissues. Thus, there is a wide variety of applications for this technology, including regenerative medicine, in vitro disease modeling, and drug screening/discovery. Although biological and biochemical techniques have been well established for cell reprogramming, bioengineering technologies...

  15. Stem cell factor enhances the survival of murine intestinal stem cells after photon irradiation

    International Nuclear Information System (INIS)

    Leigh, B.R.; Khan, W.; Hancock, S.L.

    1995-01-01

    Recombinant rat stem cell factor (SCF) has been shown to decrease lethality in mice exposed to total-body irradiation (TBI) in the lower range of lethality through radioprotection of hematopoietic stem cells and acceleration of bone marrow repopulation. This study evaluates the effect of SCF on the survival of the intestinal mucosal stem cell after TBI. This non-hematopoietic cell is clinically relevant. Gastrointestinal toxicity is common during and after abdominal and pelvic radiation therapy and limits the radiation dose in these regions. As observed with bone marrow, the administration of SCF to mice prior to TBI enhanced the survival of mouse duodenal crypt stem cells. The maximum enhancement of survival was seen when 100 μ/kg of SCF was given intraperitoneally 8 h before irradiation. This regimen increased the survival of duodenal crypt stem cells after 12.0 Gy TBI from 22.5 ± 0.7 per duodenal cross section for controls to 30.0 ± 1.7 after treatment with SCF (P=0.03). The TBI dose producing 50% mortality of 6 days (LD 50/6 ) was increased from 14.9 Gy for control mice to 19.0 Gy for mice treated with SCF (dose modification factor = 1.28). These findings demonstrate that SCF (dose modification factor = 1.28). These findings demonstrate that SCF has radioprotective effects on a non-hematopoietic stem cell population and suggest that SCF may be of clinical value in preventing radiation injury to the intestine. 29 refs., 4 figs

  16. Stem cells and cancer of the stomach and intestine.

    Science.gov (United States)

    Vries, Robert G J; Huch, Meritxell; Clevers, Hans

    2010-10-01

    Cancer in the 21st century has become the number one cause of death in developed countries. Although much progress has been made in improving patient survival, tumour relapse is one of the important causes of cancer treatment failure. An early observation in the study of cancer was the heterogeneity of tumours. Traditionally, this was explained by a combination of genomic instability of tumours and micro environmental factors leading to diverse phenotypical characteristics. It was assumed that cells in a tumour have an equal capacity to propagate the cancer. This model is currently known as the stochastic model. Recently, the Cancer stem cell model has been proposed to explain the heterogeneity of a tumour and its progression. According to this model, the heterogeneity of tumours is the result of aberrant differentiation of tumour cells into the cells of the tissue the tumour originated from. Tumours were suggested to contain stem cell-like cells, the cancer stem cells or tumour-initiating cells, which are uniquely capable of propagating a tumour much like normal stem cells fuel proliferation and differentiation in normal tissue. In this review we discuss the normal stem cell biology of the stomach and intestine followed by both the stochastic and cancer stem cell models in light of recent findings in the gastric and intestinal systems. The molecular pathways underlying normal and tumourigenic growth have been well studied, and recently the stem cells of the stomach and intestine have been identified. Furthermore, intestinal stem cells were identified as the cells-of-origin of colon cancer upon loss of the tumour suppressor APC. Lastly, several studies have proposed the positive identification of a cancer stem cell of human colon cancer. At the end we compare the cancer stem cell model and the stochastic model. We conclude that clonal evolution of tumour cells resulting from genetic mutations underlies tumour initiation and progression in both cancer models. This

  17. The continuum of stem cell transdifferentiation: possibility of hematopoietic stem cell plasticity with concurrent CD45 expression.

    Science.gov (United States)

    Udani, V M

    2006-02-01

    Recent years have seen a surge of scientific research examining adult stem cell plasticity. For example, the hematopoietic stem cell has been shown to give rise to skin, respiratory epithelium, intestinal epithelium, renal epithelium, liver parenchyma, pancreas, skeletal muscle, vascular endothelium, myocardium, and central nervous system (CNS) neurons. The potential for such stem cell plasticity seems to be enhanced by stressors such as injury and neoplasia. Interestingly, recent studies have demonstrated that hematopoietic stem cells may be able to adopt certain nonhematopoietic phenotypes, such as endothelial, neural, or skeletal muscle phenotypes, without entirely losing their initial hematopoietic identity. We propose that transdifferentiation can, in certain conditions, be a partial rather than a complete event, and we encourage further investigation into the phenomenon of a stem cell simultaneously expressing phenotypic features of two distinct cell fates.

  18. Non-Random Chromosome Segregation in Stem Cells

    OpenAIRE

    Conboy, Michael J; Karasov, Ariela O; Rando, Thomas A

    2007-01-01

    Decades ago, the "immortal strand hypothesis" was proposed as a means by which stem cells might limit acquiring mutations that could give rise to cancer, while continuing to proliferate for the life of an organism. Originally based on observations in embryonic cells, and later studied in terms of stem cell self-renewal, this hypothesis has remained largely unaccepted because of few additional reports, the rarity of the cells displaying template strand segregation, and alternative interpretati...

  19. Stem cell homing-based tissue engineering using bioactive materials

    Science.gov (United States)

    Yu, Yinxian; Sun, Binbin; Yi, Chengqing; Mo, Xiumei

    2017-06-01

    Tissue engineering focuses on repairing tissue and restoring tissue functions by employing three elements: scaffolds, cells and biochemical signals. In tissue engineering, bioactive material scaffolds have been used to cure tissue and organ defects with stem cell-based therapies being one of the best documented approaches. In the review, different biomaterials which are used in several methods to fabricate tissue engineering scaffolds were explained and show good properties (biocompatibility, biodegradability, and mechanical properties etc.) for cell migration and infiltration. Stem cell homing is a recruitment process for inducing the migration of the systemically transplanted cells, or host cells, to defect sites. The mechanisms and modes of stem cell homing-based tissue engineering can be divided into two types depending on the source of the stem cells: endogenous and exogenous. Exogenous stem cell-based bioactive scaffolds have the challenge of long-term culturing in vitro and for endogenous stem cells the biochemical signal homing recruitment mechanism is not clear yet. Although the stem cell homing-based bioactive scaffolds are attractive candidates for tissue defect therapies, based on in vitro studies and animal tests, there is still a long way before clinical application.

  20. Cancer stem cells of the digestive system.

    Science.gov (United States)

    Colvin, Hugh S; Nishida, Naohiro; Koseki, Jun; Konno, Masamitsu; Kawamoto, Koichi; Tsunekuni, Kenta; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi

    2014-12-01

    Stem cells of the digestive system are ideal in many ways for research, given they are abundant, highly proliferative and have a uniform structural arrangement. This in turn has enormously aided the research of cancer stem cells of the digestive system, which is now shaping our understanding of cancer stem cells. In this review, the recent advances in the understanding of cancer stem cells of the digestive system have been summarized, including aspects such as their identification, origin, cell-cycle dormancy, relationship with epithelial-mesenchymal transition, cellular metabolism and the underlying molecular mechanisms. Newly acquired knowledge concerning cancer stem cells have led to the development of novel cancer therapeutics with provisional yet encouraging results. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Isolation and functional interrogation of adult human prostate epithelial stem cells at single cell resolution.

    Science.gov (United States)

    Hu, Wen-Yang; Hu, Dan-Ping; Xie, Lishi; Li, Ye; Majumdar, Shyama; Nonn, Larisa; Hu, Hong; Shioda, Toshi; Prins, Gail S

    2017-08-01

    Using primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was corroborated using in vitro and in vivo regenerative assays and documentation of symmetric/asymmetric division. Robust WNT10B and KRT13 levels without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to isolate label-retaining stem cells from label-free progenitors, RNA-seq identified unique gene signatures for the separate populations which may serve as useful biomarkers. Knockdown of KRT13 or PRAC1 reduced sphere formation and symmetric self-renewal highlighting their role in stem cell maintenance. Pathways analysis identified ribosome biogenesis and membrane estrogen-receptor signaling enriched in stem cells with NF-ĸB signaling enriched in progenitors; activities that were biologically confirmed. Further, bioassays identified heightened autophagy flux and reduced metabolism in stem cells relative to progenitors. These approaches similarly identified stem-like cells from prostate cancer specimens and prostate, breast and colon cancer cell lines suggesting wide applicability. Together, the present studies isolate and identify unique characteristics of normal human prostate stem cells and uncover processes that maintain stem cell homeostasis in the prostate gland. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Isolation and functional interrogation of adult human prostate epithelial stem cells at single cell resolution

    Directory of Open Access Journals (Sweden)

    Wen-Yang Hu

    2017-08-01

    Full Text Available Using primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was corroborated using in vitro and in vivo regenerative assays and documentation of symmetric/asymmetric division. Robust WNT10B and KRT13 levels without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to isolate label-retaining stem cells from label-free progenitors, RNA-seq identified unique gene signatures for the separate populations which may serve as useful biomarkers. Knockdown of KRT13 or PRAC1 reduced sphere formation and symmetric self-renewal highlighting their role in stem cell maintenance. Pathways analysis identified ribosome biogenesis and membrane estrogen-receptor signaling enriched in stem cells with NF-ĸB signaling enriched in progenitors; activities that were biologically confirmed. Further, bioassays identified heightened autophagy flux and reduced metabolism in stem cells relative to progenitors. These approaches similarly identified stem-like cells from prostate cancer specimens and prostate, breast and colon cancer cell lines suggesting wide applicability. Together, the present studies isolate and identify unique characteristics of normal human prostate stem cells and uncover processes that maintain stem cell homeostasis in the prostate gland.

  3. Symmetric vs. asymmetric stem cell divisions: an adaptation against cancer?

    Directory of Open Access Journals (Sweden)

    Leili Shahriyari

    Full Text Available Traditionally, it has been held that a central characteristic of stem cells is their ability to divide asymmetrically. Recent advances in inducible genetic labeling provided ample evidence that symmetric stem cell divisions play an important role in adult mammalian homeostasis. It is well understood that the two types of cell divisions differ in terms of the stem cells' flexibility to expand when needed. On the contrary, the implications of symmetric and asymmetric divisions for mutation accumulation are still poorly understood. In this paper we study a stochastic model of a renewing tissue, and address the optimization problem of tissue architecture in the context of mutant production. Specifically, we study the process of tumor suppressor gene inactivation which usually takes place as a consequence of two "hits", and which is one of the most common patterns in carcinogenesis. We compare and contrast symmetric and asymmetric (and mixed stem cell divisions, and focus on the rate at which double-hit mutants are generated. It turns out that symmetrically-dividing cells generate such mutants at a rate which is significantly lower than that of asymmetrically-dividing cells. This result holds whether single-hit (intermediate mutants are disadvantageous, neutral, or advantageous. It is also independent on whether the carcinogenic double-hit mutants are produced only among the stem cells or also among more specialized cells. We argue that symmetric stem cell divisions in mammals could be an adaptation which helps delay the onset of cancers. We further investigate the question of the optimal fraction of stem cells in the tissue, and quantify the contribution of non-stem cells in mutant production. Our work provides a hypothesis to explain the observation that in mammalian cells, symmetric patterns of stem cell division seem to be very common.

  4. The potential application of stem cell in dentistry

    Directory of Open Access Journals (Sweden)

    Ketut Suardita

    2006-12-01

    Full Text Available Stem cells are generally defined as cells that have the capacity to self-renewal and differentiate to specialize cell. There are two kinds of stem cell, embryonic stem cell and adult stem cells. Stem cell therapy has been used to treat diseases including Parkinson’s and Alzheimer’s diseases, spinal cord injury, stroke, burns, heart diseases, diabetes, osteoarthritis, and rheumatoid arthritis. Stem cells were found in dental pulp, periodontal ligament, and alveolar bone marrow. Because of their potential in medical therapy, stem cells were used to regenerate lost or damage teeth and periodontal structures. This article discusses the potential application of stem cells for dental field.

  5. 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.

  6. Scientists' perspectives on the ethical issues of stem cell research.

    Science.gov (United States)

    Longstaff, Holly; Schuppli, Catherine A; Preto, Nina; Lafrenière, Darquise; McDonald, Michael

    2009-06-01

    This paper describes findings from an ethics education project funded by the Canadian Stem Cell Network (SCN). The project is part of a larger research initiative entitled "The Stem Cell Research Environment: Drawing the Evidence and Experience Together". The ethics education study began with a series of focus groups with SCN researchers and trainees as part of a "needs assessment" effort. The purpose of these discussions was to identify the main ethical issues associated with stem cell (SC) research from the perspective of the stem cell community. This paper will focus on five prominent themes that emerged from the focus group data including: (1) the source of stem cells; (2) the power of stem cells; (3) working within a charged research environment; (4) the regulatory context; and (5) ethics training for scientists. Additional discussions are planned with others involved in Canadian stem cell research (e.g., research ethics board members, policy makers) to supplement initial findings. These assessment results combined with existing bioethics literature will ultimately inform a web-based ethics education module for the SCN. We believe that our efforts are important for those analyzing the ethical, legal, and social issues (ELSI) in this area because our in depth understanding of stem cell researcher perspectives will enable us to develop more relevant and effective education material, which in turn should help SC researchers address the important ethical challenges in their area.

  7. Aqp 9 and Brain Tumour Stem Cells

    Directory of Open Access Journals (Sweden)

    Guri Fossdal

    2012-01-01

    Full Text Available Several studies have implicated the aquaporins (aqp 1, 4, and 9 in the pathogenesis of malignant brain tumours, suggesting that they contribute to motility, invasiveness, and oedema formation and facilitate metabolism in tumour cells under hypoxic conditions. We have studied the expression of aqp1, 4, and 9 in biopsies from glioblastomas, isolated tumour stem cells grown in a tumoursphere assay and analyzed the progenitor and differentiated cells from these cultures. We have compared these to the situation in normal rat brain, its stem cells, and differentiated cells derived thereof. In short, qPCR in tumour tissue showed presence of aqp1, 4, and 9. In the tumour progenitor population, aqp9 was markedly more highly expressed, whilst in tumour-derived differentiated cells, aqp4 was downregulated. However, immunostaining did not reveal increased protein expression of aqp9 in the tumourspheres containing progenitor cells; in contrast, its expression (both mRNA and protein was high in differentiated cultures. We, therefore, propose that aquaporin 9 may have a central role in the tumorigenesis of glioblastoma.

  8. Immunohistochemical characterisation of the hepatic stem cell niche in feline hepatic lipidosis: a preliminary morphological study.

    Science.gov (United States)

    Valtolina, Chiara; Robben, Joris H; Favier, Robert P; Rothuizen, Jan; Grinwis, Guy Cm; Schotanus, Baukje A; Penning, Louis C

    2018-05-01

    Objectives The aim of this study was to describe the cellular and stromal components of the hepatic progenitor cell niche in feline hepatic lipidosis (FHL). Methods Immunohistochemical staining for the progenitor/bile duct marker (K19), activated Kupffer cells (MAC387), myofibroblasts (alpha-smooth muscle actin [α-SMA]) and the extracellular matrix component laminin were used on seven liver biopsies of cats with FHL and three healthy cats. Double immunofluorescence stainings were performed to investigate co-localisation of different cell types in the hepatic progenitor cell (HPC) niche. Results HPCs, Kupffer cells, myofibroblasts and laminin deposition were observed in the liver samples of FHL, although with variability in the expression and positivity of the different immunostainings between different samples. When compared with the unaffected cats where K19 positivity and minimal α-SMA and laminin positivity were seen mainly in the portal area, in the majority of FHL samples K19 and α-SMA-positive cells and laminin positivity were seen also in the periportal and parenchymatous area. MAC387-positive cells were present throughout the parenchyma. Conclusions and relevance This is a preliminary morphological study to describe the activation and co-localisation of components of the HPC niche in FHL. Although the HPC niche in FHL resembles that described in hepatopathies in dogs and in feline lymphocytic cholangitis, the expression of K19, α-SMA, MAC387 and lamin is more variable in FHL, and a common pattern of activation could not be established. Nevertheless, when HPCs were activated, a spatial association between HPCs and their niche could be demonstrated.

  9. Accelerating stem cell trials for Alzheimer's disease.

    Science.gov (United States)

    Hunsberger, Joshua G; Rao, Mahendra; Kurtzberg, Joanne; Bulte, Jeff W M; Atala, Anthony; LaFerla, Frank M; Greely, Henry T; Sawa, Akira; Gandy, Sam; Schneider, Lon S; Doraiswamy, P Murali

    2016-02-01

    At present, no effective cure or prophylaxis exists for Alzheimer's disease. Symptomatic treatments are modestly effective and offer only temporary benefit. Advances in induced pluripotent stem cell (iPSC) technology have the potential to enable development of so-called disease-in-a-dish personalised models to study disease mechanisms and reveal new therapeutic approaches, and large panels of iPSCs enable rapid screening of potential drug candidates. Different cell types can also be produced for therapeutic use. In 2015, the US Food and Drug Administration granted investigational new drug approval for the first phase 2A clinical trial of ischaemia-tolerant mesenchymal stem cells to treat Alzheimer's disease in the USA. Similar trials are either underway or being planned in Europe and Asia. Although safety and ethical concerns remain, we call for the acceleration of human stem cell-based translational research into the causes and potential treatments of Alzheimer's disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Exposure Setup and Dosimetry for a Study on Effects of Mobile Communication Signals on Human Hematopoietic Stem Cells in vitro

    Directory of Open Access Journals (Sweden)

    M. Rohland

    2017-09-01

    Full Text Available In this paper we describe the design of an exposure setup used to study possible non-thermal effects due to the exposure of human hematopoietic stem cells to GSM, UMTS and LTE mobile communication signals. The experiments are performed under fully blinded conditions in a TEM waveguide located inside an incubator to achieve defined environmental conditions as required for the living cells. Chamber slides containing the cells in culture medium are placed on the septum of the waveguide. The environmental and exposure parameters such as signal power, temperatures, relative humidity and CO2 content of the surrounding atmosphere are monitored permanently during the exposure experiment. The power of the exposure signals required to achieve specific absorption rates of 0.5, 1, 2 and 4 W kg−1 are determined by numerical calculation of the field distribution inside the cell culture medium at 900 MHz (GSM, 1950 MHz (UMTS and 2535 MHz (LTE. The dosimetry is verified both with scattering parameter measurements on the waveguide with and without containers filled with cell culture medium and with temperature measurements with non-metallic probes in separate heating experiments.

  11. The effect of simulated microgravity on human mesenchymal stem cells cultured in an osteogenic differentiation system: a bioinformatics study.

    Science.gov (United States)

    Sheyn, Dima; Pelled, Gadi; Netanely, Dvir; Domany, Eytan; Gazit, Dan

    2010-11-01

    One proposed strategy for bone regeneration involves ex vivo tissue engineering, accomplished using bone-forming cells, biodegradable scaffolds, and dynamic culture systems, with the goal of three-dimensional tissue formation. Rotating wall vessel bioreactors generate simulated microgravity conditions ex vivo, which lead to cell aggregation. Human mesenchymal stem cells (hMSCs) have been extensively investigated and shown to possess the potential to differentiate into several cell lineages. The goal of the present study was to evaluate the effect of simulated microgravity on all genes expressed in hMSCs, with the underlying hypothesis that many important pathways are affected during culture within a rotating wall vessel system. Gene expression was analyzed using a whole genome microarray and clustering with the aid of the National Institutes of Health's Database for Annotation, Visualization and Integrated Discovery database and gene ontology analysis. Our analysis showed 882 genes that were downregulated and 505 genes that were upregulated after exposure to simulated microgravity. Gene ontology clustering revealed a wide variety of affected genes with respect to cell compartment, biological process, and signaling pathway clusters. The data sets showed significant decreases in osteogenic and chondrogenic gene expression and an increase in adipogenic gene expression, indicating that ex vivo adipose tissue engineering may benefit from simulated microgravity. This finding was supported by an adipogenic differentiation assay. These data are essential for further understanding of ex vivo tissue engineering using hMSCs.

  12. Stem Cell Therapy: A Promising Therapeutic Method for Intracerebral Hemorrhage.

    Science.gov (United States)

    Gao, Liansheng; Xu, Weilin; Li, Tao; Chen, Jingyin; Shao, Anwen; Yan, Feng; Chen, Gao

    2018-01-01

    Spontaneous intracerebral hemorrhage (ICH) is one type of the most devastating cerebrovascular diseases worldwide, which causes high morbidity and mortality. However, efficient treatment is still lacking. Stem cell therapy has shown good neuroprotective and neurorestorative effect in ICH and is a promising treatment. In this study, our aim was to review the therapeutic effects, strategies, related mechanisms and safety issues of various types of stem cell for ICH treatment. Numerous studies had demonstrated the therapeutic effects of diverse stem cell types in ICH. The potential mechanisms include tissue repair and replacement, neurotrophy, promotion of neurogenesis and angiogenesis, anti-apoptosis, immunoregulation and anti-inflammation and so forth. The microenvironment of the central nervous system (CNS) can also influence the effects of stem cell therapy. The detailed therapeutic strategies for ICH treatment such as cell type, the number of cells, time window, and the routes of medication delivery, varied greatly among different studies and had not been determined. Moreover, the safety issues of stem cell therapy for ICH should not be ignored. Stem cell therapy showed good therapeutic effect in ICH, making it a promising treatment. However, safety should be carefully evaluated, and more clinical trials are required before stem cell therapy can be extensively applied to clinical use.

  13. DNA repair in murine embryonic stem cells and differentiated cells

    International Nuclear Information System (INIS)

    Tichy, Elisia D.; Stambrook, Peter J.

    2008-01-01

    Embryonic stem (ES) cells are rapidly proliferating, self-renewing cells that have the capacity to differentiate into all three germ layers to form the embryo proper. Since these cells are critical for embryo formation, they must have robust prophylactic mechanisms to ensure that their genomic integrity is preserved. Indeed, several studies have suggested that ES cells are hypersensitive to DNA damaging agents and readily undergo apoptosis to eliminate damaged cells from the population. Other evidence suggests that DNA damage can cause premature differentiation in these cells. Several laboratories have also begun to investigate the role of DNA repair in the maintenance of ES cell genomic integrity. It does appear that ES cells differ in their capacity to repair damaged DNA compared to differentiated cells. This minireview focuses on repair mechanisms ES cells may use to help preserve genomic integrity and compares available data regarding these mechanisms with those utilized by differentiated cells

  14. Physiology of stem cell-derived cardiomyocytes

    NARCIS (Netherlands)

    Boer, T.P. de

    2007-01-01

    All chapters in this thesis revolve around the general theme, stem cells and their electrophysiological characteristics and capacity to induce pro-arrhythmia. The first part of this thesis focusses on key aspects that are relevant to possible pro-arrhythmic effects of stem cell transplantation. An

  15. Stem Cell Research and Health Education

    Science.gov (United States)

    Eve, David J.; Marty, Phillip J.; McDermott, Robert J.; Klasko, Stephen K.; Sanberg, Paul R.

    2008-01-01

    Stem cells are being touted as the greatest discovery for the potential treatment of a myriad of diseases in the new millennium, but there is still much research to be done before it will be known whether they can live up to this description. There is also an ethical debate over the production of one of the most valuable types of stem cell: the…

  16. Cerebral toxoplasmosis after haematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Agnieszka Zaucha-Prażmo

    2017-05-01

    Full Text Available Toxoplasmosis is an opportunistic infection caused by the parasite Toxoplasma gondii. The infection is severe and difficult to diagnose in patients receiving allogeneic haematopoietic stem cell transplantation (HSCT. It frequently involves the central nervous system. The case is presented of cerebral toxoplasmosis in a 17-year-old youth with Fanconi anaemia treated with haematopoietic stem cell transplantation (HSCT

  17. Pathological modifications of plant stem cell destiny

    Science.gov (United States)

    In higher plants, the shoot apex contains undifferentiated stem cells that give rise to various tissues and organs. The fate of these stem cells determines the pattern of plant growth as well as reproduction; and such fate is genetically preprogrammed. We found that a bacterial infection can derai...

  18. 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.

  19. Representations of stem cell clinics on Twitter.

    Science.gov (United States)

    Kamenova, Kalina; Reshef, Amir; Caulfield, Timothy

    2014-12-01

    The practice of travelling abroad to receive unproven and unregulated stem cell treatments has become an increasingly problematic global phenomenon known as 'stem cell tourism'. In this paper, we examine representations of nine major clinics and providers of such treatments on the microblogging network Twitter. We collected and conducted a content analysis of Twitter posts (n = 363) by these establishments and by other users mentioning them, focusing specifically on marketing claims about treatment procedures and outcomes, discussions of safety and efficacy of stem cell transplants, and specific representations of patients' experiences. Our analysis has shown that there were explicit claims or suggestions of benefits associated with unproven stem cell treatments in approximately one third of the tweets and that patients' experiences, whenever referenced, were presented as invariably positive and as testimonials about the efficacy of stem cell transplants. Furthermore, the