http://stemcellres.com The latest research articles published by Stem Cell Research & Therapy 2012-01-26T00:00:00Z Stem cells are currently seen as a treatment for tissue regeneration in neurological diseases such as multiple sclerosis, anticipating that they integrate and differentiate into neural cells. Mesenchymal stem cells (MSCs), a subset of adult progenitor cells, differentiate into cells of the mesodermal lineage but also, under certain experimental circumstances, into cells of the neuronal and glial lineage. Their clinical development, however, has been significantly boosted by the demonstration that MSCs display significant therapeutic plasticity mainly occurring through bystander mechanisms. These features have been exploited in the effective treatment of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis where the inhibition of the autoimmune response resulted in a significant amelioration of disease and decrease of demyelination, immune infiltrates and axonal loss. Surprisingly, these effects do not require MSCs to engraft in the central nervous system but depend on the cells' ability to inhibit pathogenic immune responses both in the periphery and inside the central nervous system and to release neuroprotective and pro-oligodendrogenic molecules favoring tissue repair. These results paved the road for the utilization of MSCs for the treatment of multiple sclerosis. http://stemcellres.com/content/3/1/3 Sara Morando Tiziana Vigo Marianna Esposito Simona Casazza Giovanni Novi Maria Cristina Principato Roberto Furlan Antonio Uccelli Stem Cell Research & Therapy 2012, null:3 2012-01-26T00:00:00Z doi:10.1186/scrt94 Mesenchymal stem cells in EAE Many studies have demonstrated that mesenchymal stem cells are effective in the treatment of experimental autoimmune encephalomyelitis (EAE) and may have potential as a therapeutic option in multiple sclerosis. /content/figures/scrt94-toc.gif Stem Cell Research & Therapy 1757-6512 ${item.volume} 3 2012-01-26T00:00:00Z XML Stem cell transplantation is emerging as a potential therapy to treat heart diseases. Promising results from early animal studies led to an explosion of small, non-controlled clinical trials that created even further excitement by showing that stem cell transplantation improved left ventricular systolic function and enhanced remodelling. However, the specific mechanisms by which these cells improve heart function remain largely unknown. A large variety of cell types have been considered to possess the regenerative ability needed to repair the damaged heart. One of the most studied cell types is the bone marrow-derived mononuclear cells and these form the focus of this review. This review article aims to provide an overview of their use in the setting of acute myocardial infarction, the challenges it faces and the future of stem cell therapy in heart disease. http://stemcellres.com/content/3/1/2 Samer Arnous Abdul Mozid John Martin Anthony Mathur Stem Cell Research & Therapy 2012, null:2 2012-01-17T00:00:00Z doi:10.1186/scrt93 Stem cell therapy in heart disease The use of bone-marrow derived mononuclear cells in cardiac repair after acute myocardial infarction, a leading cause of death and disability, is reviewed by Anthony Mathur and colleagues. /content/figures/scrt93-toc.gif Stem Cell Research & Therapy 1757-6512 ${item.volume} 2 2012-01-17T00:00:00Z XML For many years, the hematopoietic stem cell (HSC) has been well characterized in mice as a cell that can singly reconstitute the whole hematopoietic system of primary recipient animals as well as that of secondary hosts. That clinical bone marrow transplantation is a successful treatment strategy is indirect evidence that such a cell exists in humans. To date, similar criteria have not been applied to human HSCs. However, using a humanized mouse model of xenotransplantation, a recent paper shows that single human cells can fully reconstitute the lymphomyeloid system of primary recipient animals and, in some cases, that of secondary hosts. http://stemcellres.com/content/3/1/1 Rhodri Ceredig Stem Cell Research & Therapy 2012, null:1 2012-01-13T00:00:00Z doi:10.1186/scrt92 Identifying human hematopoietic stem cells Rhodri Ceredig discusses a significant advance in our understanding of human hematopoiesis. /content/figures/scrt92-toc.gif Stem Cell Research & Therapy 1757-6512 ${item.volume} 1 2012-01-13T00:00:00Z XML Distinct stem cell types have been established from embryos and identified in the fetal tissues and umbilical cord blood as well as in specific niches in many adult mammalian tissues and organs such as bone marrow, brain, skin, eyes, heart, kidneys, lungs, gastrointestinal tract, pancreas, liver, breast, ovaries, and prostate. All stem cells are undifferentiated cells that exhibit unlimited self-renewal and can generate multiple cell lineages or more restricted progenitor populations that can contribute to tissue homeostasis by replenishing the cells or to tissue regeneration after injury. The remarkable progress of regenerative medicine in the last few years indicates promise for the use of stem cells in the treatment of ophthalmic disorders. Experimental and human studies with intravitreal bone marrow-derived stem cells have begun. This paper reviews recent advances and potential sources of stem cells for cell therapy in retinal diseases. http://stemcellres.com/content/2/6/50 Rubens Siqueira Stem Cell Research & Therapy 2011, null:50 2011-12-29T00:00:00Z doi:10.1186/scrt91 /content/figures/scrt91-toc.gif Stem Cell Research & Therapy 1757-6512 ${item.volume} 50 2011-12-29T00:00:00Z XML IntroductionMesenchymal stem cells (MSCs) play a central role in mediating endogenous repair of cell and tissue damage. Biological aging is a universal process that results in changes at the cellular and molecular levels. In the present study, the role of microRNA (miRNA) in age-induced molecular changes in MSCs derived from adipose tissue (ASCs) and bone marrow (BMSCs) from young and old human donors were investigated using an unbiased genome-wide approach. Methods: Human ASCs and BMSCs from young and old donors were cultured and total RNA was isolated. The miRNA fraction was enriched and used to determine the expression profile of miRNA in young and old donor MSCs. Based on miRNA expression, differences in donor MSCs were further investigate utilizing differentiation assays, Western blot, immunocytochemistry, and bioinformatics. Results: Biological aging demonstrated reduced osteogenic and adipogenic potential in ASCs isolated from older donors, while cell size, complexity and cell surface markers remained intact with aging. Analysis of miRNA profiles revealed that small subsets of active miRNAs changed secondary to aging. Evaluation of miRNA showed significantly decreased levels of gene expression of inhibitory kappa B kinase (IkappaB), interleukin-1alpha, inducible nitric oxide synthase (iNOS), mitogen-activated protein kinase/p38, ERK1/2, c-fos, and c-jun in MSCs from older donors by both bioinformatics and Western blot analysis. Nuclear factor kappa B (NF-kappaB), myc, and interleukin-4 receptor mRNA levels were significantly elevated in aged cells from both the adipose and bone marrow depots. Immunocytochemistry showed nuclear localization in young donors, however, a cytosolic predominance of phosphorylated NF-kappaB in ASCs from older donors. Western blot demonstrated significantly elevated levels of NF-kappaB subunits, p65 and p50, and AKT. Conclusions: These findings suggest that differential expression of miRNA is an integral component of biological aging in MSCs. http://stemcellres.com/content/2/6/49 Amitabh Pandey Julie Semon Deepak Kaushal Regina O'Sullivan Julie Glowacki Jeffery Gimble Bruce Bunnell Stem Cell Research & Therapy 2011, null:49 2011-12-14T00:00:00Z doi:10.1186/scrt90 MicroRNAs in stem cell aging Differential expression of microRNAs is an integral component of biological aging in mesenchymal stem cells, regulating gene expression related to a variety of functions including cellular proliferation and inflammation. /content/figures/scrt90-toc.gif Stem Cell Research & Therapy 1757-6512 ${item.volume} 49 2011-12-14T00:00:00Z PDF A clinical trial using human embryonic stem cell (hESC) therapy for an inherited retinal degenerative disease is about to commence. The Advanced Cell Technology (ACT) trial will treat patients with Stargardt's macular dystrophy using transplanted retinal pigment epithelium derived from hESCs. Currently, no effective treatment is available for Stargardt's disease so a stem cell-based therapy that can slow progression of this blinding condition could represent a significant breakthrough. While there are some hurdles to clear, the ACT trial is a fine example of translational research that could eventually pave the way for a range of stem cell therapies for the retina and other tissues. http://stemcellres.com/content/2/6/47 Reinhold Medina Desmond Archer Alan Stitt Stem Cell Research & Therapy 2011, null:47 2011-12-07T00:00:00Z doi:10.1186/scrt88 /content/figures/scrt88-toc.gif Stem Cell Research & Therapy 1757-6512 ${item.volume} 47 2011-12-07T00:00:00Z XML IntroductionEnd-stage renal disease (ESRD) is a major public health problem. Although kidney transplantation is a viable therapeutic option, this therapy is associated with significant limitations, including a shortage of donor organs. Induced pluripotent stem (iPS) cell technology, which allows derivation of patient-specific pluripotent stem cells, could provide a possible alternative modality for kidney replacement therapy for patients with ESRD. Methods: The feasibility of iPS cell generation from patients with a history of ESRD was investigated using lentiviral vectors expressing pluripotency-associated factors. Results: In the present article we report, for the first time, generation of iPS cells from kidney transplant recipients with a history of autosomal-dominant polycystic kidney disease (ADPKD), systemic lupus erythematosus, or Wilms tumor and ESRD. Lentiviral transduction of OCT4, SOX2, KLF4 and c-MYC, under feeder-free conditions, resulted in reprogramming of skin-derived keratinocytes. Keratinocyte-derived iPS cells exhibited properties of human embryonic stem cells, including morphology, growth properties, expression of pluripotency genes and surface markers, spontaneous differentiation and teratoma formation. All iPS cell clones from the ADPKD patient retained the conserved W3842X mutation in exon 41 of the PKD1 gene. Conclusions: Our results demonstrate successful iPS cell generation from patients with a history of ESRD, PKD1 gene mutation, or chronic immunosuppression. iPS cells from autosomal kidney diseases, such as ADPKD, would provide unique opportunities to study patient-specific disease pathogenesis in vitro. http://stemcellres.com/content/2/6/48 Tayaramma Thatava Adam Armstrong Josep Genebriera De Lamo Ramakrishna Edukulla Yulia Krotova Khan Toshie Sakuma Seiga Ohmine Jamie Sundsbak Peter Harris Yogish Kudva Yasuhiro Ikeda Stem Cell Research & Therapy 2011, null:48 2011-12-06T00:00:00Z doi:10.1186/scrt89 iPSCs generated after kidney transplantation Disease-specific induced pluripotent stem cells (iPSCs) have been generated from kidney transplant recipients, providing opportunities to study patient-specific disease pathogenesis in vitro and demonstrating potential for autologous kidney replacement therapy. /content/figures/scrt89-toc.gif Stem Cell Research & Therapy 1757-6512 ${item.volume} 48 2011-12-06T00:00:00Z XML Specialized microenvironments called niches help maintain stem cells in an undifferentiated and self-renewing state. The existence of niches has long been predicted from mammalian studies, but identifying stem cells in their native environments in vivo has remained a challenge in most vertebrates. Many of the mechanistic insights into how niches regulate stem cell maintenance have been obtained using invertebrate models such as Drosophila. Here, we focus on the Drosophila ovarian germline stem cell niche and review recent studies that have begun to reveal how intricate crosstalk between various signaling pathways regulates stem cell maintenance, how the extracellular matrix modulates the signaling output of the niche and how epigenetic programming influences cell development and function both inside and outside the niche to ensure proper tissue homeostasis. These insights will probably inform the study of mammalian niches and how their malfunction contributes to human disease. http://stemcellres.com/content/2/6/45 Susan Eliazer Michael Buszczak Stem Cell Research & Therapy 2011, null:45 2011-11-25T00:00:00Z doi:10.1186/scrt86 /content/figures/scrt86-toc.gif Stem Cell Research & Therapy 1757-6512 ${item.volume} 45 2011-11-25T00:00:00Z XML In this review, we will describe the cardiac differentiation from ES cells, iPS cells, and the current progress of using iPS cell derived cardiomyocyte for heart disease modeling and for the development of therapeutic strategies. In addition, we will summarize the recent direct reprogramming of cardiomyocyte from fibroblast cells, which provides another method for potential heart disease therapy. http://stemcellres.com/content/2/6/44 Tung-Ying Lu Lei Yang Stem Cell Research & Therapy 2011, null:44 2011-11-18T00:00:00Z doi:10.1186/scrt85 /content/figures/scrt85-toc.gif Stem Cell Research & Therapy 1757-6512 ${item.volume} 44 2011-11-18T00:00:00Z XML IntroductionThe induced pluripotent stem cell (iPSC) technology allows generation of patient-specific pluripotent stem cells, thereby providing a novel cell-therapy platform for severe degenerative diseases. One of the key issues for clinical-grade iPSC derivation is the accessibility of donor cells used for reprogramming. Methods: We examined the feasibility of reprogramming mobilized GMP-grade hematopoietic progenitor cells (HPCs) and peripheral blood mononuclear cells (PBMCs) and tested the pluripotency of derived iPS clones. Results: Ectopic expression of OCT4, SOX2, KLF4, and c-MYC in HPCs and PBMCs resulted in rapid iPSC derivation. Long-term time-lapse imaging revealed efficient iPSC growth under serum- and feeder-free conditions with frequent mitotic events. HPC- and PBMC-derived iPS cells expressed pluripotency-associated markers, including SSEA-4, TRA-1-60, and NANOG. The global gene-expression profiles demonstrated the induction of endogenous pluripotent genes, such as LIN28, TERT, DPPA4, and PODXL, in derived iPSCs. iPSC clones from blood and other cell sources showed similar ultrastructural morphologies and genome-wide gene-expression profiles. On spontaneous and guided differentiation, HPC- and PBMC-derived iPSCs were differentiated into cells of three germ layers, including insulin-producing cells through endodermal lineage, verifying the pluripotency of the blood-derived iPSC clones. Conclusions: Because the use of blood cells allows minimally invasive tissue procurement under GMP conditions and rapid cellular reprogramming, mobilized HPCs and unmobilized PBMCs would be ideal somatic cell sources for clinical-grade iPSC derivation, especially from diabetes patients complicated by slow-healing wounds. http://stemcellres.com/content/2/6/46 Seiga Ohmine Allan Dietz Michael Deeds Katherine Hartjes David Miller Tayaramma Thatava Toshie Sakuma Yogish Kudva Yasuhiro Ikeda Stem Cell Research & Therapy 2011, null:46 2011-11-16T00:00:00Z doi:10.1186/scrt87 iPSCs from blood cells Hematopoietic progenitor cells and peripheral blood mononuclear cells could be ideal somatic cell sources for clinical-grade induced pluripotent stem cell (iPSC) derivation, allowing minimally invasive tissue procurement and rapid cellular reprogramming. /content/figures/scrt87-toc.gif Stem Cell Research & Therapy 1757-6512 ${item.volume} 46 2011-11-16T00:00:00Z XML