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Stem Cells Translational Medicine

Stuart P Atkinson
No abstract text is available yet for this article.
October 15, 2018: Stem Cells Translational Medicine
Lingling Yang, Songmei Zhang, Haoyun Duan, Muchen Dong, Xiaoli Hu, Zhaohua Zhang, Yao Wang, Xiaoping Zhang, Weiyun Shi, Qingjun Zhou
Chronic inflammation and severe dry eye are two important adverse factors for the successful transplant of cultured limbal stem cells. The aim of this study was to investigate the effects of inflammation and hyperosmotic stress (a key pathological factor in dry eye) on corneal epithelial stem cells (CESCs) and corneal epithelial wound healing. We observed that the CESCs exhibited significant morphological changes when treated with either interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), or hyperosmotic stress...
October 9, 2018: Stem Cells Translational Medicine
Martijn F Hoes, Nils Bomer, Peter van der Meer
Until recently, in vivo and ex vivo experiments were the only means to determine factors and pathways involved in disease pathophysiology. After the generation of characterized human embryonic stem cell lines, human diseases could readily be studied in an extensively controllable setting. The introduction of human-induced pluripotent stem cells, a decade ago, allowed the investigation of hereditary diseases in vitro. In the field of cardiology, diseases linked to known genes have successfully been studied, revealing novel disease mechanisms...
October 9, 2018: Stem Cells Translational Medicine
Julia Marcheque, Benedetta Bussolati, Marie Csete, Laura Perin
Significant progress has been made to advance stem cell products as potential therapies for kidney diseases: various kinds of stem cells can restore renal function in preclinical models of acute and chronic kidney injury. Nonetheless this literature contains contradictory results, and for this reason, we focus this review on reasons for apparent discrepancies in the literature, because they contribute to difficulty in translating renal regenerative therapies. Differences in methodologies used to derive and culture stem cells, even those from the same source, in addition to the lack of standardized renal disease animal models (both acute and chronic), are important considerations underlying contradictory results in the literature...
October 9, 2018: Stem Cells Translational Medicine
Himanshu Arora, Marilia Sanches Santos Rizzo Zuttion, Bruno Nahar, Dolores Lamb, Joshua M Hare, Ranjith Ramasamy
Exogenous testosterone therapy can be used to treat testosterone deficiency; however, it has several adverse effects including infertility due to negative feedback on the hypothalamic-pituitary--gonadal (HPG) axis. Leydig stem cell (LSC) transplantation could provide a new strategy for treating testosterone deficiency, but clinical translatability of injecting stem cells inside the testis is not feasible. Here, we explore the feasibility of subcutaneously autografting LSCs in combination with Sertoli and myoid cells to increase testosterone...
October 2, 2018: Stem Cells Translational Medicine
Yijun Liu, Xuegang Yuan, Nathalie Muñoz, Timothy M Logan, Teng Ma
Human mesenchymal stem cells (hMSCs) promote endogenous tissue repair in part by coordinating multiple components of the host immune system in response to environmental stimuli. Recent studies have shown that hMSCs are metabolically heterogeneous and actively reconfigure metabolism to support the biochemical demands of tissue repair. However, how hMSCs regulate their energy metabolism to support their immunomodulatory properties is largely unknown. This study investigates hMSC metabolic reconfiguration during immune activation and provides evidence that the hMSC metabolic state significantly influences their immunomodulatory properties...
October 1, 2018: Stem Cells Translational Medicine
Jeremy A Antonyshyn, Meghan J McFadden, Anthony O Gramolini, Stefan O P Hofer, J Paul Santerre
Considerable effort has been directed toward deriving endothelial cells (ECs) from adipose-derived mesenchymal stem cells (ASCs) since 2004, when it was first suggested that ECs and adipocytes share a common progenitor. While the capacity of ASCs to express endothelial markers has been repeatedly demonstrated, none constitute conclusive evidence of an endothelial phenotype as all reported markers have been detected in other, non-endothelial cell types. In this study, quantitative phenotypic comparisons to representative EC controls were used to determine the extent of endothelial differentiation being achieved with ASCs...
September 30, 2018: Stem Cells Translational Medicine
Ken Yoshida, Ayumu Nakashima, Shigehiro Doi, Toshinori Ueno, Tomoe Okubo, Ki-Ichiro Kawano, Masami Kanawa, Yukio Kato, Yukihito Higashi, Takao Masaki
Serum used in culture medium brings risks of immune reactions or infections and thus may hinder using ex vivo expanded mesenchymal stem cells (MSCs) for medical treatment. Here, we cultured MSCs in a serum-free medium (SF-MSCs) and in a medium containing 10% fetal bovine serum (10%MSCs) and investigated their effects on inflammation and fibrosis. MSC-conditioned medium suppressed transforming growth factor-β1-induced phosphorylation of Smad2 in HK-2 cells, with no significant difference between the two MSCs...
September 30, 2018: Stem Cells Translational Medicine
Manoj M Lalu, Sasha Mazzarello, Jennifer Zlepnig, Yuan Yi Ryan Dong, Joshua Montroy, Lauralyn McIntyre, P J Devereaux, Duncan J Stewart, C David Mazer, Carly C Barron, Daniel I McIsaac, Dean A Fergusson
Preclinical and clinical evidence suggests that mesenchymal stem cells (MSCs) may be beneficial in treating both acute myocardial infarction (AMI) and ischemic heart failure (IHF). However, the safety profile and efficacy of MSC therapy is not well-known. We conducted a systematic review of clinical trials that evaluated the safety or efficacy of MSCs for AMI or IHF. Embase, PubMed/Medline, and Cochrane Central Register of Controlled Trials were searched from inception to September 27, 2017. Studies that examined the use of MSCs administered to adults with AMI or IHF were eligible...
September 26, 2018: Stem Cells Translational Medicine
Bianca Vezzani, Isaac Shaw, Hanna Lesme, Li Yong, Nusrat Khan, Carlo Tremolada, Bruno Péault
Autologous adipose tissue is used for tissue repletion and/or regeneration as an intact lipoaspirate or as enzymatically derived stromal vascular fraction (SVF), which may be first cultured into mesenchymal stem cells (MSCs). Alternatively, transplant of autologous adipose tissue mechanically fragmented into submillimeter clusters has recently showed remarkable efficacy in diverse therapeutic indications. To document the biologic basis of the regenerative potential of microfragmented adipose tissue, we first analyzed the distribution of perivascular presumptive MSCs in adipose tissue processed with the Lipogems technology, observing a significant enrichment in pericytes, at the expense of adventitial cells, as compared to isogenic enzymatically processed lipoaspirates...
September 26, 2018: Stem Cells Translational Medicine
Arnold I Caplan
Cell-based therapies have come of age and several phase III trials are now being conducted. Cell-based therapies, especially involving mesenchymal stem cells (MSCs), have substantial nonresponder rates as have been reported in some current clinical trials. This high rate is expected as the MSCs are neither tuned for each of the diseases that are being treated nor for the huge variance in the genetics and response characteristics of the individual patients being treated. Such nonresponders might be used as a control group, and thus eliminating the need for placebo controls...
September 25, 2018: Stem Cells Translational Medicine
Morgan M Stanton, Evangeline Tzatzalos, Matthew Donne, Nikola Kolundzic, Ingvar Helgason, Dusko Ilic
Stem cells are unique cell populations able to copy themselves exactly as well as specialize into new cell types. Stem cells isolated from early stages of embryo development are pluripotent, i.e., can be differentiated into multiple different cell types. In addition, scientists have found a way of reverting specialized cells from an adult into an embryonic-like state. These cells, that are as effective as cells isolated from early embryos, are termed induced pluripotent stem cells (iPSCs). The potency of iPSC technology is recently being employed by researchers aimed at helping wildlife and environmental conservation efforts...
September 24, 2018: Stem Cells Translational Medicine
Hua-Tao Xie, David A Sullivan, Di Chen, Mark P Hatton, Wendy R Kam, Yang Liu
The meibomian gland (MG) is a sebaceous gland that secretes through a holocrine process. Because such secretion requires the destruction of MG acinar epithelial cells, they need constant renewal and differentiation. The processes that promote these regenerative events in the human MG are unknown, nor is it known how to distinguish MG progenitor and differentiated cells. We discovered that Lrig1 and DNase2 serve as biomarkers for human MG progenitor and differentiated cells, respectively. Lrig1 is expressed in MG basal epithelial cells in the acinar periphery, a location where progenitor cells originate in sebaceous glands...
September 24, 2018: Stem Cells Translational Medicine
Bárbara Mendes-Pinheiro, Fábio G Teixeira, Sandra I Anjo, Bruno Manadas, Leo A Behie, António J Salgado
Parkinson's disease (PD) is a progressive neurodegenerative movement disorder that results from the death of dopamine (DA) neurons. Over recent years, differentiated or undifferentiated neural stem cells (NSCs) transplantation has been widely used as a means of cell replacement therapy. However, compelling evidence has brought attention to the array of bioactive molecules produced by stem cells, defined as secretome. As described in the literature, other cell populations have a high-neurotrophic activity, but little is known about NSCs...
September 20, 2018: Stem Cells Translational Medicine
Leili Rohani, Adiv A Johnson, Pooyan Naghsh, Derrick E Rancourt, Henning Ulrich, Heidrun Holland
Now that induced pluripotent stem cell (iPSC)-based transplants have been performed in humans and organizations have begun producing clinical-grade iPSCs, it is imperative that strict quality control standards are agreed upon. This is essential as both ESCs and iPSCs have been shown to accumulate genomic aberrations during long-term culturing. These aberrations can include copy number variations, trisomy, amplifications of chromosomal regions, deletions of chromosomal regions, loss of heterozygosity, and epigenetic abnormalities...
September 14, 2018: Stem Cells Translational Medicine
Hongling Li, Li Zhu, Huimin Chen, Tangping Li, Qin Han, Shihua Wang, Xinglei Yao, Hongli Feng, Linyuan Fan, Shaorong Gao, Richard Boyd, Xu Cao, Ping Zhu, Jing Li, Armand Keating, Xiaodong Su, Robert Chunhua Zhao
Cell transplantation holds considerable promise for end-stage liver diseases but identifying a suitable, transplantable cell type has been problematic. Here, we describe a novel type of mesenchymal stem cells (MSCs) from human adipose tissue. These cells are different from previously reported MSCs, they are in the euchromatin state with epigenetic multipotency, and express pluripotent markers MYC, KLF4, and GMNN. Most of the genes associated with germ layer specification are modified by H3K4me3 or co-modified by H3K4me3 and H3K27me3...
September 11, 2018: Stem Cells Translational Medicine
Alejandro Navas, Fátima Sofía Magaña-Guerrero, Alfredo Domínguez-López, César Chávez-García, Graciela Partido, Enrique O Graue-Hernández, Francisco Javier Sánchez-García, Yonathan Garfias
Acute ocular chemical burns are ophthalmic emergencies requiring immediate diagnosis and treatment as they may lead to permanent impairment of vision. The clinical manifestations of such burns are produced by exacerbated innate immune response via the infiltration of inflammatory cells and activation of stromal fibroblasts. New therapies are emerging that are dedicated to repair mechanisms that improve the ocular surface after damage; for example, transplantation of stem cells (SC) has been successfully reported for this purpose...
September 10, 2018: Stem Cells Translational Medicine
Ciro Menale, Elisabetta Campodoni, Eleonora Palagano, Stefano Mantero, Marco Erreni, Antonio Inforzato, Elena Fontana, Francesca Schena, Rob Van't Hof, Monica Sandri, Anna Tampieri, Anna Villa, Cristina Sobacchi
Biomimetic scaffolds are extremely versatile in terms of chemical composition and physical properties, which can be defined to accomplish specific applications. One property that can be added is the production/release of bioactive soluble factors, either directly from the biomaterial, or from cells embedded within the biomaterial. We reasoned that pursuing this strategy would be appropriate to setup a cell-based therapy for RANKL-deficient Autosomal Recessive Osteopetrosis, a very rare skeletal genetic disease in which lack of the essential osteoclastogenic factor RANKL impedes osteoclast formation...
September 5, 2018: Stem Cells Translational Medicine
Jie Fang, Yang Guo, Sheng Tan, Zhanhui Li, HuiFang Xie, Pingyan Chen, Kai Wang, Zhicong He, Peng He, Yiquan Ke, Xiaodan Jiang, Zhenzhou Chen
Transplantation of endothelial progenitor cells (EPCs) is a proven safe and effective method for treatment of cerebral ischemia in animal experiments. However, safety and efficacy need to be determined in clinical trials. We performed a two-center, randomized, placebo-controlled phase I/IIa trial with blinded outcome assessment on 18 patients with acute cerebral infarct within the middle cerebral artery territory, and followed for up to 4 years. Autologous ex vivo expanded EPCs were injected intravenously in the EPC group, and patients who received saline or autologous bone marrow stromal cells served as control groups...
August 29, 2018: Stem Cells Translational Medicine
So Yoon Ahn, Yun Sil Chang, Se In Sung, Won Soon Park
We previously demonstrated that transplanting mesenchymal stem cells (MSCs) improved recovery from brain injury induced by severe intraventricular hemorrhage (IVH) in newborn rats. To assess the safety and feasibility of MSCs in preterm infants with severe IVH, we performed a phase I dose-escalation clinical trial. The first three patients received a low dose of MSCs (5 × 106 cells/kg), and the next six received a high dose (1 × 107 cells/kg). We assessed adverse outcomes, including mortality and the progress of posthemorrhagic hydrocephalus...
August 21, 2018: Stem Cells Translational Medicine
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