http://stemcellres.com The most accessed research articles published by Stem Cell Research & Therapy 2010-07-07T00:00:00Z This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ Mesenchymal stem cells (MSCs) are multipotential nonhematopoietic progenitor cells that are isolated from many adult tissues, in particular from the bone marrow and adipose tissue. Along with their capacity for differentiating into cells of mesodermal lineage, such as adipocytes, osteoblasts and chondrocytes, these cells have also generated great interest for their ability to display immunomodulatory capacities. Indeed, a major breakthrough came with the finding that they are able to induce peripheral tolerance, suggesting they may be used as therapeutic tools in immune-mediated disorders. The present review aims at discussing the current knowledge on the targets and mechanisms of MSC-mediated immunosuppression as well as the potential use of MSCs as modulators of immune responses in a variety of diseases related to alloreactive immunity or autoimmunity http://stemcellres.com/content/1/1/2 Soufiane Ghannam Carine Bouffi Farida Djouad Christian Jorgensen Daniele Noel Stem Cell Research & Therapy 2010, 1:2 2010-03-15T00:00:00Z doi:10.1186/scrt2 Stem Cell Research & Therapy 1757-6512 1 2 2010-03-15T00:00:00Z XML IntroductionHuman multipotent mesenchymal stem cell (MSC) therapies are being tested clinically for a variety of disorders, including Crohn's disease, multiple sclerosis, graft-versus-host disease, type 1 diabetes, bone fractures, and cartilage defects. However, despite the remarkable clinical advancements in this field, most applications still use traditional culture media containing fetal bovine serum. The ill-defined and highly variable nature of traditional culture media remains a challenge, hampering both the basic and clinical human MSC research fields. To date, no reliable serum-free medium for human MSCs has been available. Methods: In this study, we developed and tested a serum-free growth medium on human bone marrow-derived MSCs through the investigation of multiple parameters including primary cell isolation, multipassage expansion, mesoderm differentiation, cellular phenotype, and gene-expression analysis. Results: Similar to that achieved with traditional culture medium, human MSCs expanded in serum-free medium supplemented with recombinant human platelet-derived growth factor-BB (PDGF-BB), basic fibroblast growth factor (bFGF), and transforming growth factor (TGF)-β1 showed extensive propagation with retained phenotypic, differentiation, and colony-forming unit potential. To monitor global gene expression, the transcriptomes of bone marrow-derived MSCs expanded under serum-free and serum-containing conditions were compared, revealing similar expression profiles. In addition, the described serum-free culture medium supported the isolation of human MSCs from primary human marrow aspirate with continual propagation. Conclusions: Although the described serum-free MSC culture medium is not free of xenogeneic components, this medium provides a substitute for serum-containing medium for research applications, setting the stage for future clinical applications. http://stemcellres.com/content/1/1/8 Lucas Chase Uma Lakshmipathy Luis Solchaga Mahendra Rao Mohan Vemuri Stem Cell Research & Therapy 2010, 1:8 2010-04-02T00:00:00Z doi:10.1186/scrt8 Stem Cell Research & Therapy 1757-6512 1 8 2010-04-02T00:00:00Z XML Treatment of extensive bone defects requires autologous bone grafting or implantation of bone substitute materials. An attractive alternative has been to engineer fully viable, biological bone grafts in vitro by culturing osteogenic cells within three-dimensional scaffolds, under conditions supporting bone formation. Such grafts could be used for implantation, but also as physiologically relevant models in basic and translational studies of bone development, disease and drug discovery. A source of human cells that can be derived in large numbers from a small initial harvest and predictably differentiated into bone forming cells is critically important for engineering human bone grafts. We discuss the characteristics and limitations of various types of human embryonic and adult stem cells, and their utility for bone tissue engineering. http://stemcellres.com/content/1/2/10 Darja Marolt Miomir Knezevic Gordana Vunjak-Novakovic Stem Cell Research & Therapy 2010, 1:10 2010-05-04T00:00:00Z doi:10.1186/scrt10 Stem Cell Research & Therapy 1757-6512 1 10 2010-05-04T00:00:00Z XML Adipose tissue is now recognized as an accessible, abundant, and reliable site for the isolation of adult stem cells suitable for tissue engineering and regenerative medicine applications. The past decade has witnessed an explosion of preclinical data relating to the isolation, characterization, cryopreservation, differentiation, and transplantation of freshly isolated stromal vascular fraction cells and adherent, culture-expanded, adipose-derived stromal/stem cells in vitro and in animal models. This body of work has provided evidence supporting clinical translational applications of adipose-derived cells in safety and efficacy trials. The present article reviews the case reports and phase I-III clinical evidence using autologous adipose-derived cells that have been published, to date, in the fields of gastroenterology, neurology, orthopedics, reconstructive surgery, and related clinical disciplines. Future directions and challenges facing the field are discussed and evaluated. http://stemcellres.com/content/1/2/19 Jeffrey Gimble Farshid Guilak Bruce Bunnell Stem Cell Research & Therapy 2010, 1:19 2010-06-29T00:00:00Z doi:10.1186/scrt19 Stem Cell Research & Therapy 1757-6512 1 19 2010-06-29T00:00:00Z XML Stem cells maintain homeostasis in adult tissues via self-renewal and generation of terminally differentiated cells. Alterations in this intricate balance can result in disease. It has become increasingly evident that cancer can be initiated at the level of stem cells. Therefore, understanding what causes stem cells to become cancerous may lead to new therapeutic approaches. Multiple signaling pathways ultimately affect stem cell survival and proliferation, thus maintaining homeostasis in the gut. Changes in these pathways could perturb normal stem cell behavior, leading to cancerous stem cells. In addition, cancerous stem cells show resistance to current therapies and may lead to a dangerous selection process resulting in recurrence and metastasis. Genomic instability, the driving force of mutation and resistance, may give cancerous stem cells an adaptive advantage, especially when subjected to cancer therapies. Targeting the unique characteristics of cancerous stem cells to promote either terminal differentiation or destruction would effectively eradicate cancer and improve patient care and survival. http://stemcellres.com/content/1/2/13 Julie Chandler Eric Lagasse Stem Cell Research & Therapy 2010, 1:13 2010-05-20T00:00:00Z doi:10.1186/scrt13 Stem Cell Research & Therapy 1757-6512 1 13 2010-05-20T00:00:00Z XML Induction of pluripotency from somatic cells by exogenous transcription factors is made possible by a variety of epigenetic changes that take place during the reprogramming process. The derivation of fully reprogrammed induced pluripotent stem (iPS) cells is achieved through establishment of embryonic stem cell (ESC)-like epigenetic architecture permitting the reactivation of key endogenous pluripotency-related genes, establishment of appropriate bivalent chromatin domains and DNA hypomethylation of genomic heterochromatic regions. Restructuring of the epigenetic landscape, however, is a very inefficient process and the vast majority of the induced cells fail to complete the reprogramming process. Optimal ESC-like epigenetic reorganization is necessary for all reliable downstream uses of iPS cells, including in vitro modeling of disease and clinical applications. Here, we discuss the key advancements in the understanding of dynamic epigenetic changes taking place over the course of the reprogramming process and how aberrant epigenetic remodeling may impact downstream applications of iPS cell technology. http://stemcellres.com/content/1/1/3 Ugljesa Djuric James Ellis Stem Cell Research & Therapy 2010, 1:3 2010-03-15T00:00:00Z doi:10.1186/scrt3 Stem Cell Research & Therapy 1757-6512 1 3 2010-03-15T00:00:00Z XML Based on their capacity to suppress immune responses, multipotent mesenchymal stromal cells (MSCs) are intensively studied for regenerative medicine. Moreover, MSCs have paracrine effects, including immunomodulation that occurs through the secretion of soluble mediators, including nitric oxide or interleukin-6, transforming growth factor-beta, human leukocyte antigen G5, and prostaglandin E2. MSCs in the bone marrow are in close contact with T and B cells and regulate immunological memory by organizing defined numbers of dedicated survival niches for plasma cells and memory T cells in the bone marrow. All of these biological effects are probably shared by all stromal cells, including fibroblasts and stem cells isolated from exfoliated deciduous teeth. The therapeutical implications are discussed. http://stemcellres.com/content/1/2/15 Christian Jorgensen Stem Cell Research & Therapy 2010, 1:15 2010-06-08T00:00:00Z doi:10.1186/scrt15 Stem Cell Research & Therapy 1757-6512 1 15 2010-06-08T00:00:00Z XML IntroductionMesenchymal stem cells (MSCs) offer promise for intervertebral disc (IVD) repair and regeneration because they are easily isolated and expanded, and can differentiate into several mesenchymal tissues. Notochordal (NC) cells contribute to IVD development, incorporate into the nucleus pulposus (NP), and stimulate mature disc cells. However, there have been no studies investigating the effects of NC cells on adult stem cell differentiation. The premise of this study is that IVD regeneration is more similar to IVD development than to IVD maintenance, and we hypothesize that soluble factors from NC cells differentiate MSCs to a phenotype characteristic of nucleus pulposus (NP) cells during development. The eventual clinical goal would be to isolate or chemically/recombinantly produce the active agent to induce the therapeutic effects, and to use it as either an injectable therapy for early intervention on disc disease, or in developing appropriately pre-differentiated MSC cells in a tissue engineered NP construct. Methods: Human MSCs from bone marrow were expanded and pelleted to form high-density cultures. MSC pellets were exposed to either control medium (CM), chondrogenic medium (CM with dexamethasone and transforming growth factor, (TGF)-β3) or notochordal cell conditioned medium (NCCM). NCCM was prepared from NC cells maintained in serum free medium for four days. After seven days culture, MSC pellets were analyzed for appearance, biochemical composition (glycosaminoglycans and DNA), and gene expression profile (sox-9, collagen types-II and III, laminin-β1 and TIMP1(tissue inhibitor of metalloproteinases-1)). Results: Significantly higher glycosaminoglycan accumulation was seen in NCCM treated pellets than in CM or TGFβ groups. With NCCM treatment, increased gene expression of collagen III, and a trend of increasing expression of laminin-β1 and decreased expression of sox-9 and collagen II relative to the TGFβ group was observed. Conclusions: Together, results suggest NCCM stimulates mesenchymal stem cell differentiation toward a potentially NP-like phenotype with some characteristics of the developing IVD. http://stemcellres.com/content/1/2/18 Casey Korecki Juan Taboas Rocky Tuan James Iatridis Stem Cell Research & Therapy 2010, 1:18 2010-06-16T00:00:00Z doi:10.1186/scrt18 Stem Cell Research & Therapy 1757-6512 1 18 2010-06-16T00:00:00Z XML IntroductionAmniotic fluid harbors cells indicative of all three germ layers and pluripotent fetal amniotic fluid stem cells (AFS) are considered as potentially valuable for applications in cellular therapy and tissue engineering. We investigated if it is possible to direct the cell fate of AFS in vivo by transplantation experiments into a particular microenvironment, the mammary fat pad. This microenvironment provides the prerequisites to study stem cell function and the communication between mesenchymal and epithelial cells. Upon clearance of the endogenous epithelium, the ductal tree can be reconstituted by the transfer of exogenously provided mammary stem cells. Analogously, exogenously provided stem cells from other tissues can be investigated for their potential to contribute to mammary gland regeneration. Methods: We derived pluripotent murine AFS, measured the expression of stem cell markers and confirmed their in vitro differentiation potential. AFS were transplanted into cleared and non cleared fat pads of immunocompromised mice to evaluate their ability to assume particular cell fates under the instructive conditions of the fat pad microenvironment and the hormonal stimulation during pregnancy. Results: Transplantation of AFS into cleared fat pads alone or in the presence of exogenous mammary epithelial cells caused their differentiation into stroma and adipocytes and replaced endogenous mesenchymal components surrounding the ducts in co-transplantation experiments. Similarly, transplantation of AFS into fat pads which had not been previously cleared, led to AFS derived stromal cells surrounding the elongating endogenous ducts. AFS expressed the marker protein -SMA, but did not integrate into the myoepithelial cell layer of the ducts in virgin mice. Upon pregnancy a small number of AFS derived cells were present in acinar structures. Conclusions: Our data demonstrate that the microenvironmental cues of the mammary fat pad cause AFS to participate in mammary gland regeneration by providing mesenchymal components to emerging glandular structures, but do not incorporate or differentiate into ductal epithelial cells. http://stemcellres.com/content/1/3/20 Petra Klemmt Vida Vafaizadeh Bernd Groner Stem Cell Research & Therapy 2010, 1:20 2010-07-07T00:00:00Z doi:10.1186/scrt20 Stem Cell Research & Therapy 1757-6512 1 20 2010-07-07T00:00:00Z PDF IntroductionBone marrow (BM) stroma currently represents the most common and investigated source of mesenchymal progenitor cells (MPCs); however, comparable adult progenitor or stem cells have also been isolated from a wide variety of tissues. This study aims to assess the functional similarities of MPCs from different tissues and to identify specific factor(s) related to their multipotency. Methods: For this purpose, we directly compared MPCs isolated from different adult tissues, including bone marrow, tonsil, muscle, and dental pulp. We first examined and compared proliferation rates, immunomodulatory properties, and multidifferentiation potential of these MPCs in vitro. Next, we specifically evaluated activin A expression profile and activin A:follistatin ratio in MPCs from the four sources. Results: The multidifferentiation potential of the MPCs is correlated with activin A level and/or the activin A:follistatin ratio. Interestingly, by siRNA-mediated activin A knockdown, activin A was shown to be required for the chondrogenic and osteogenic differentiation of MPCs. These findings strongly suggest that activin A has a pivotal differentiation-related role in the early stages of chondrogenesis and osteogenesis while inhibiting adipogenesis of MPCs. Conclusions: This comparative analysis of MPCs from different tissue sources also identifies bone marrow-derived MPCs as the most potent MPCs in terms of multilineage differentiation and immunosuppression, two key requirements in cell-based regenerative medicine. In addition, this study implicates the significance of activin A as a functional marker of MPC identity. http://stemcellres.com/content/1/2/11 Farida Djouad Wesley Jackson Brent Bobick Sasa Janjanin Yingjie Song George Huang Rocky Tuan Stem Cell Research & Therapy 2010, 1:11 2010-05-04T00:00:00Z doi:10.1186/scrt11 Stem Cell Research & Therapy 1757-6512 1 11 2010-05-04T00:00:00Z XML