http://stemcellres.com The latest research articles published by Stem Cell Research & Therapy 2012-05-10T00:00:00Z Human embryonic stem cells have the capacity for self-renewal and pluripotency and thus are a primary candidate for tissue engineering and regenerative therapies. These cells also provide an opportunity to study the development of human tissues ex vivo. To date, numerous human embryonic stem cell lines have been derived and characterized. In this review, we will detail the strategies used to direct tissue-specific differentiation of embryonic stem cells. We also will discuss how these strategies have produced new sources of tissue-specific progenitor cells. Finally, we will describe the next generation of methods being developed to identify and select stem cell-derived tissue precursors for experimental study and clinical use. http://stemcellres.com/content/3/3/17 Harold Bernstein William Hyun Stem Cell Research & Therapy 2012, null:17 2012-05-10T00:00:00Z doi:10.1186/scrt108 Tissue-specific differentiation of ESCs Bernstein and Hyun review strategies used to direct tissue-specific differentiation of embryonic stem cells (ESCs), and methods for the identification and selection of tissue-specific precursors for scientific study and clinical use. /content/figures/scrt108-toc.gif Stem Cell Research & Therapy 1757-6512 ${item.volume} 17 2012-05-10T00:00:00Z XML IntroductionIt is hypothesized that administration of stromal/stem cells isolated from the adipose tissue (ASCs) and umbilical cord (HUCPVCs) can ameliorate the injured central nervous system (CNS). However it is still not clear whether they have similar or opposite effects on primary cultures of neuronal populations. The objective of the present work was to determine if ASCs and HUCPVCs preferentially act, or not, on specific cell populations within the CNS. Methods: Primary cultures of hippocampal neurons were exposed to ASCs and HUCPVCs conditioned media (CM) (obtained 24, 48, 72 and 96 hours after 3 days of culture) for 1 week. Results: Cell viability experiments (MTS test) revealed that CM obtained from both cell populations at all time points did not cause any deleterious effects on neuronal cells. In fact, it was determined that whenever the ASCs CM were supplemented with basic fibroblast growth factor (bFGF) and B27, there was a significant increase on the metabolic viability and neuronal cell density of the cultures. On the other hand in the absence of CM supplementation, it was the HUCPVCs secretome that had the highest impact on the metabolic viability and cell density. In an attempt to unveil which factors could be involved in the observed effects, a screening for the presence of bFGF, nerve growth factor (NGF), stem cell factor (SCF), hepatocyte growth factors (HGF) and vascular endothelial growth factor (VEGF) in the CM was performed. Results revealed the presence of all these factors in ASCs CM, except bFGF; in contrast, in HUCPVCs CM it was only possible to detect robust NGF expression. Conclusions: Overall the results herein confirm important differences on the secretome of ASCs and HUCPVCs, which leads to distinct effects on the metabolic viability and neuronal cell densities in primary cultures of hippocampal neurons; however, the factor(s) that promote the stronger effect of the HUCPVCs CM in neuronal survival is(are) still to be identified. http://stemcellres.com/content/3/3/18 Carlos Ribeiro Joana Fraga Mario Graos Nuno Neves Rui Reis Jeffrey Gimble Nuno Sousa Antonio Salgado Stem Cell Research & Therapy 2012, null:18 2012-05-02T00:00:00Z doi:10.1186/scrt109 Differences in stem cell secretomes The secretome of human umbilical cord perivascular cells (HUPVCs) and adipose tissue-derived stem cells differ, with HUPVC conditioned media able to promote neuronal survival and differentiation without exogenous supplement. /content/figures/scrt109-toc.gif Stem Cell Research & Therapy 1757-6512 ${item.volume} 18 2012-05-02T00:00:00Z PDF No abstract http://stemcellres.com/content/3/2/16 Philippa Locke Rocky Tuan Timothy O'Brien Stem Cell Research & Therapy 2012, null:16 2012-04-30T00:00:00Z doi:10.1186/scrt107 /content/figures/scrt107-toc.gif Stem Cell Research & Therapy 1757-6512 ${item.volume} 16 2012-04-30T00:00:00Z XML The clinical use of stem cells, such as bone marrow-derived and, more recently, resident cardiac stem cells, offers great promise for treatment of myocardial infarction and heart failure. The epicardium-derived cells have also attracted attention for their angiogenic paracrine actions and ability to differentiate into cardiomyocytes and vascular cells when activated during cardiac injury. In a recent study, Chong and colleagues have described a distinct population of epicardium-derived mesenchymal stem cells that reside in a perivascular niche of the heart and have a broad multilineage potential. Exploring the therapeutic capacity of these cells will be an exciting future endeavor. http://stemcellres.com/content/3/2/15 Nenad Bursac Stem Cell Research & Therapy 2012, null:15 2012-04-30T00:00:00Z doi:10.1186/scrt106 From the heart: epicardial stem cells Nenad Bursac comments on recent research describing a distinct population of epicardium-derived mesenchymal stem cells residing in a perivascular niche of the heart with a broad multilineage potential, and considers future applications. /content/figures/scrt106-toc.gif Stem Cell Research & Therapy 1757-6512 ${item.volume} 15 2012-04-30T00:00:00Z XML Stem cells have tremendous applications in the field of regenerative medicine and tissue engineering. These are pioneering fields that aim to create new treatments for disease that currently have limited therapies or cures. A particularly popular avenue of research has been the regeneration of bone and cartilage to combat various orthopaedic diseases. Magnetic nanoparticles (MNPs) have been applied to aid the development and translation of these therapies from research to the clinic. This review highlights contemporary research for the applications of iron-oxide-based MNPs for the therapeutic implementation of stem cells in orthopaedics. These MNPs comprise of an iron oxide core, coated with a choice of biological polymers that can facilitate the uptake of MNPs by cells through improving endocytic activity. The combined use of these oxides and the biological polymer coatings meet biological requirements, effectively encouraging the use of MNPs in regenerative medicine. The association of MNPs with stem cells can be achieved via the process of endocytosis resulting in the internalisation of these particles or the attachment to cell surface receptors. This allows for the investigation of migratory patterns through various tracking studies, the targeting of particle-labelled cells to desired locations via the application of an external magnetic field and, finally, for activation stem cells to initiate various cellular responses to induce the differentiation. Characterisation of cell localisation and associated tissue regeneration can therefore be enhanced, particularly for in vivo applications. MNPs have been shown to have the potential to stimulate differentiation of stem cells for orthopaedic applications, without limiting proliferation. However, careful consideration of the use of active agents associated with the MNP is suggested, for differentiation towards specific lineages. This review aims to broaden the knowledge of current applications, paving the way to translate the in vitro and in vivo work into further orthopaedic clinical studies. http://stemcellres.com/content/3/2/13 Ian Wimpenny Hareklea Markides Alicia El Haj Stem Cell Research & Therapy 2012, null:13 2012-04-19T00:00:00Z doi:10.1186/scrt104 Nanoparticles and stem cells in orthopaedics Alicia El Haj and colleagues review recent research on the applications of iron-oxide-based magnetic nanoparticles to improve how stem cells are controlled, monitored and targeted to sites of repair. /content/figures/scrt104-toc.gif Stem Cell Research & Therapy 1757-6512 ${item.volume} 13 2012-04-19T00:00:00Z XML IntroductionDown syndrome (DS), a major cause of mental retardation, is caused by trisomy of some or all of human chromosome 21 and includes three basic karyotypes: trisomy 21, translocation, and mosaicism. The derivation of DS-specific induced pluripotent stem cells (iPSCs) provides us novel DS models that can be used to determine the DS mechanism and to devise therapeutic approaches for DS patients. Methods: In the present study, fibroblasts from patients with DS of various karyotypes were reprogrammed into iPSCs via the overexpression of four factors: OCT4, SOX2, KLF4, and c-MYC, by using lentiviral vectors. The abilities of the iPSC-DS in the self-renewal and pluripotency in vitro and in vivo were then examined. Results: The iPSC-DS showed characteristics similar to those of human embryonic stem cells, particularly the morphology, surface marker (SSEA4, TRA-1-60, and TRA-1-81) expression, pluripotent-specific transcription-factor expression levels, and methylation status of the OCT4 promoter. The pluripotency of iPSC-DS was also tested in vitro and in vivo. Embryoid bodies were formed and showed the expression of differentiated markers for three germ layers. Furthermore, iPSC-DS formed classic teratomas when injected into nonobese diabetic-severe combined immunodeficient (NOD-SCID) mice. Conclusions: iPSCs were generated from patients with DS. The iPSCs derived from different types of DS may be used in DS modeling, patient-care optimization, drug discovery, and eventually, autologous cell-replacement therapies. http://stemcellres.com/content/3/2/14 Xiaoning Mou Yuanbo Wu Henghua Cao Qingzhang Meng Qihui Wang Chengchao Sun Shengshou Hu Yue Ma Hao Zhang Stem Cell Research & Therapy 2012, null:14 2012-04-18T00:00:00Z doi:10.1186/scrt105 Down syndrome-specific iPSCs The derivation of induced pluripotent stem cells (iPSCs) from two patients with different karyotypes of Down syndrome offers opportunities for disease modeling, drug discovery and potential future cell replacement therapies. /content/figures/scrt105-toc.gif Stem Cell Research & Therapy 1757-6512 ${item.volume} 14 2012-04-18T00:00:00Z XML Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive accumulation of Lewy body inclusions along with selective destruction of dopaminergic (DA) neurons in the nigrostriatal tract of the brain. Genetic studies have revealed much about the pathophysiology of PD, enabling the identification of both biomarkers for diagnosis and genetic targets for therapeutic treatment, which are evolved in tandem with the development of stem cell technologies. The discovery of induced pluripotent stem (iPS) cells facilitates the derivation of stem cells from adult somatic cells for personalized treatment and thus overcomes not only the limited availability of human embryonic stem cells but also ethical concerns surrounding their use. Non-viral, non-integration, or non-DNA-mediated reprogramming technologies are being developed. Protocols for generating midbrain DA neurons are undergoing constant refinement. The iPS cell-derived DA neurons provide cellular models for investigating disease progression in vitro and for screening molecules of novel therapeutic potential and have beneficial effects on improving the behavior of parkinsonian animals. Further progress in the development of safer non-viral/non-biased reprogramming strategies and the subsequent generation of homogenous midbrain DA neurons shall pave the way for clinical trials. A combined approach of drugs, cell replacement, and gene therapy to stop disease progression and to improve treatment may soon be within our reach. http://stemcellres.com/content/3/2/11 Stuart Gibson Guo-dong Gao Sanbing Shen Stem Cell Research & Therapy 2012, null:11 2012-04-03T00:00:00Z doi:10.1186/scrt102 Progress on Parkinson's Sanbing Shen and colleagues provide an overview of recent progress towards a combined approach of drugs, cell replacement, and gene therapy to halt disease progression and improve treatment of Parkinson's disease. /content/figures/scrt102-toc.gif Stem Cell Research & Therapy 1757-6512 ${item.volume} 11 2012-04-03T00:00:00Z XML IntroductionThe development of reproducible methods for deriving human embryonic stem cell (hESC) lines in compliance with good manufacturing practice (GMP) is essential for the development of hESC-based therapies. Although significant progress has been made toward the development of chemically defined conditions for the maintenance and differentiation of hESCs, efficient derivation of new hESCs requires the use of fibroblast feeder cells. However, GMP-grade feeder cell lines validated for hESC derivation are not readily available. Methods: We derived a fibroblast cell line (NclFed1A) from human foreskin in compliance with GMP standards. Consent was obtained to use the cells for the production of hESCs and to generate induced pluripotent stem cells (iPSCs). We compared the line with a variety of other cell lines for its ability to support derivation and self-renewal of hESCs. Results: NclFed1A supports efficient rates (33%) of hESC colony formation after explantation of the inner cell mass (ICM) of human blastocysts. This compared favorably with two mouse embryonic fibroblast (MEF) cell lines. NclFed1A also compared favorably with commercially available foreskin fibroblasts and MEFs in promoting proliferation and pluripotency of a number of existing and widely used hESCs. The ability of NclFed1A to maintain self-renewal remained undiminished for up to 28 population doublings from the master cell bank. Conclusions: The human fibroblast line Ncl1Fed1A, produced in compliance with GMP standards and qualified for derivation and maintenance of hESCs, is a useful resource for the advancement of progress toward hESC-based therapies in regenerative medicine. http://stemcellres.com/content/3/2/12 Nilendran Prathalingam Linda Ferguson Lesley Young Georg Lietz Rachel Oldershaw Lyn Healy Albert Craig Helen Lister Rakesh Binaykia Radhika Sheth Alison Murdoch Mary Herbert Stem Cell Research & Therapy 2012, null:12 2012-03-28T00:00:00Z doi:10.1186/scrt103 GMP fibroblast line for hESC derivation The human fibroblast line Ncl1Fed1A, produced in compliance with good manufacturing practice (GMP) standards, has been qualified for derivation and maintenance of human embryonic stem cells (hESCs). /content/figures/scrt103-toc.gif Stem Cell Research & Therapy 1757-6512 ${item.volume} 12 2012-03-28T00:00:00Z XML Tissues characterized by constant turnover contain post-mitotic, terminally differentiated cells originating from highly proliferative progenitors, which in turn derive from a relatively small population of stem cells. At the population level, self-renewal and differentiation are the possible outcomes of stem cell proliferation; overall, however, stem cells are quiescent if compared with their direct progeny. The recent discovery of a particularly quiescent, or dormant, subpopulation of hematopoietic stem cells (HSCs) raises a number of fundamental questions. As stem cell fate is influenced by the signals integrated by the stem cell niche, will dormant HSCs reside in specific dormant niches? Is the mechanism of dormancy common to multiple regenerating tissues or specific to the hematopoietic system? If cancer is maintained by a few cancer stem cells, do they also contain a subpopulation of dormant cells, and could this be exploited for therapeutic purposes? http://stemcellres.com/content/3/2/10 Roberta Sottocornola Cristina Lo Celso Stem Cell Research & Therapy 2012, null:10 2012-03-19T00:00:00Z doi:10.1186/scrt101 Sleeping beauties? Sottocornola and Lo Celso review recent findings on dormant hematopoietic stem cells, examining whether the mechanism of dormancy is common amongst regenerating tissues, and discuss implications for cancer therapy. /content/figures/scrt101-toc.gif Stem Cell Research & Therapy 1757-6512 ${item.volume} 10 2012-03-19T00:00:00Z XML Induced pluripotent stem (iPS) cells, obtained from reprogramming somatic cells by ectopic expression of a defined set of transcription factors or chemicals, are expected to be used as differentiated cells for drug screening or evaluations of drug toxicity and cell replacement therapies. As pluripotent stem cells, iPS cells are similar to embryonic stem (ES) cells in morphology and marker expression. Several types of iPS cells have been generated using combinations of reprogramming molecules and/or small chemical compounds from different types of tissues. A comprehensive approach, such as global gene or microRNA expression analysis and whole genomic DNA methylation profiling, has demonstrated that iPS cells are similar to their embryonic counterparts. Considering the substantial variation among iPS cell lines reported to date, the safety and therapeutic implications of these differences should be thoroughly evaluated before they are used in cell therapies. Here, we review recent research defining the concept of standardization for iPS cells, their ability to differentiate and the identity of the differentiated cells. http://stemcellres.com/content/3/2/8 Tohru Sugawara Koichiro Nishino Akihiro Umezawa Hidenori Akutsu Stem Cell Research & Therapy 2012, null:8 2012-03-08T00:00:00Z doi:10.1186/scrt99 iPS cells, identity and fate Hide Akutsu and colleagues review recent research on variation in induced pluripotent stem (iPS) cells, their ability to differentiate and the identity of the differentiated cells. /content/figures/scrt99-toc.gif Stem Cell Research & Therapy 1757-6512 ${item.volume} 8 2012-03-08T00:00:00Z XML