The activation of fibroblasts and their reprogramming into a neural cell-like state following wounding supports the regrowth of axons from local nerves
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Summaries of the most recent articles published in STEM CELLS and STEM CELLS Translational Medicine.
This study represents the first description of a robust, scalable, and cost-effective method for generating immunomodulatory human iPSC-MSCs
The safe and tolerable intramuscular administration of stempeucel may represent an effective alternative treatment in Buerger's disease patients
A new review discusses the central role of BRD4 in stem cell identity and potential applications of BRD4 inhibitors in stem cell-based therapeutics
A newly discovered mechanism overrides reprogramming-induced senescence, thereby increasing the number of cells amenable to becoming iPSCs
PUFAs effectively suppress the self-renewal and growth of breast cancer stem cells by downregulating the expression of lipogenic enzymes
Researchers compare extracellular vesicles isolated from differing MSC types with regards to their ability to influence angiogenesis and chondrogenesis
A new review describes the interplay between cardiac ECM and stem and progenitor cells during the response to ischemic heart diseases
Human mesenchymal stem cell (MSC) therapy represents a potentially exciting treatment choice for disorders resulting from an inflammatory/heightened immune response. In a new STEM CELLS Translational Medicine study from the labs of Carl A. Gregory and Roland Kaunas (Texas A&M Health Science Center, Bryan, TX, USA), researchers report on their studies regarding the therapeutic development of induced pluripotent stem cell-derived MSCs (iPSC-MSCs) Rogers et al. established procedures for the manufacture of iPSC-MSCs attached to novel digestible microcarriers in scalable bioreactors that permitted rapid harvest at high yields and viability. Overall, this study represents the first description of a robust, scalable, and cost-effective method for generating human iPSC-MSCs, which represents a significant contribution to their translational potential. Image - Osteogenic and adipogenic differentiation potential after RWVB expansion on GelMA microcarriers.
A recent STEM CELLS Translational Medicine article from researchers led by Pawan Kumar Gupta (Stempeutics Research Pvt. Ltd, Bangalore, India) reports on their continued study of the safety and efficacy of Stempeucel®, an ex-vivo cultured, pooled, human bone marrow-derived adult allogeneic mesenchymal stromal cell product, in critical limb ischemia associated with Buerger's disease. The authors report continued long-term efficacy over a period of twelve months follow-up, corroborating the result obtained in earlier phase II studies, with significant improvements observed in rest pain, systolic ankle pressure, and ankle-brachial pressure index with accelerated ulcer healing. Overall, the safe and tolerable intramuscular administration of Stempeucel® may represent an effective alternative treatment in patients with Buerger's disease.
Epigenetic regulation and transcriptional reprogramming both play critical roles during stem cell differentiation and lineage commitment. The therapeutic application of stem cells requires the elucidation of how epigenetic factors control lineage commitment. BRD4, an epigenetic regulator and transcription factor, binds to acetylated histones in super-enhancer regions and regulates the expression of essential pluripotency genes. As a druggable target, BRD4 represents an attractive candidate for potential applications in therapeutics. In their recent STEM CELLS review article, researchers led by Sheetal Uppal (Bhabha Atomic Research Centre (BARC), Mumbai, India) discuss the central role of BRD4 in stem cell identity and potential applications of BRD4 inhibitors in stem cell-based therapeutics.
A new STEM CELLS article from Lisa Porter (University of Windsor, Ontario, Canada) reveals an epigenetic mechanism involving the cell cycle regulator SPY1 used by normal fibroblasts to override reprogramming-induced senescence, thereby increasing the number of cells amenable to becoming induced pluripotent stem cells (iPSCs). Lubanska et al. note that improving reprogramming efficiencies will support ongoing iPSC-related regenerative approaches and may reveal mechanisms important to normal development and disease states.
Dysregulated lipid metabolism associates with the growth of cancer stem cells (CSC); however, potential interventions targeting this pathway remain relatively unexplored. A new STEM CELLS article from researchers led by Jing Xuan Kang (Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA) demonstrates that breast CSCs have a distinct fatty acid profile due to the aberrant expression of lipogenic enzymes, which influence self-renewal and proliferative capabilities. Furthermore, Luo et al. report that omega-3 polyunsaturated fatty acids (PUFAs) effectively suppress the self-renewal and growth of breast CSC by downregulating lipogenic enzyme expression. These findings provide a potential therapeutic application of omega-3 PUFAs by targeting fatty acid metabolism in breast CSCs.
Mesenchymal stem cells (MSCs) represent an exciting source for regenerative medicine applications. MSCs derived from different tissues might have distinctive characteristics, while related studies suggest a critical therapeutic role for extracellular vesicles secreted by MSCs. In a recent STEM CELLS Translational Medicine article, researchers led by Roberta Tasso and Chiara Gentili (University of Genova, Genoa, Italy) compared extracellular vesicles isolated from bone marrow and adipose tissue MSCs. Gorgun et al. observed different functional effects of MSC-derived exosomes on the differentiation and maturation of cartilage tissue and angiogenesis; therefore, a deeper investigation of biological effects may aid the specific selection of optimal extracellular vesicle-cell sources for use in specific therapeutic settings.
A new STEM CELLS review article from researchers led by Michael E. Davis (Emory University School of Medicine/Georgia Institute of Technology, Atlanta, Georgia, USA) describes the interplay between cardiac extracellular matrix (ECM) and cardiac-related stem and progenitor cells during the response to ischemic heart diseases (IHD). Park et al. report a bi-directional relationship where both the effect of cells on the new matrix and the effect of the matrix on the cells must be considered.
Reactive oxygen species (ROS) participate in the regulation of almost all intracellular processes; however, the number of studies devoted to redox signaling in pluripotent cells (PSCs) remains limited. In a new STEM CELLS article, researchers led by Julia Ivanova (Institute of Cytology of the Russian Academy of Sciences, Russia) discovered that proliferation and accurate DNA synthesis in PSCs require the maintenance of physiological levels of ROS. A decrease in ROS levels leads to the disturbance of S-phase regulation, loss of DNA integrity, and apoptosis. Overall, this article provides new insight into the redox homeostasis of PSCs, which may represent a powerful tool for research in developmental biology and biomedical applications.
Improved treatments for diseased or degenerated tissues and organs are greatly needed; now, researchers led by Dan S. Kaufman (University of California, San Diego, La Jolla, California, USA) demonstrate the ability to efficiently derive macrophages from human induced pluripotent stem cells (iPSCs) with the ability to improve liver fibrosis in a mouse xenograft model. This new STEM CELLS study from Pouyanfard et al. supports the clinical translation of iPSC-derived cells to treat diverse fibrotic diseases.
A new STEM CELLS review article stresses the importance of implementing complex 3D brain organoids derived from human induced pluripotent stem cells. Researchers led by Kristine K. Freude (University of Copenhagen, Denmark) note that brain organoids should contain contributions from various brain regions, such as the assembloids formed by the fusion of cortical and thalamic organoids. Chandrasekaran et al. also underscore the relevance of protein and post-translational modifications of proteins to disease development and progression, as illustrated by schizophrenia, a neurodevelopmental disease with highly diverse risk gene contribution. Overall, the authors hope that their insight will contribute to a better understanding of complex neurological diseases.