A new study using an equine model provides further support to the value of mesenchymal stem cell secretome-based treatments for infected wounds
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Summaries of the most recent articles published in STEM CELLS and STEM CELLS Translational Medicine.
A new review summarizes current research concerning intranasally-administered MSC-EVs administrated and their potential as a therapeutic approach
ELF3 induces the differentiation of mesenchymal stem cells into carcinoma-associated fibroblasts exhibiting an inflammatory phenotype
Researchers describe how to counteract the decline in neurogenesis observed in the V-SVZ in animal models of Parkinson's disease
The activation of fibroblasts and their reprogramming into a neural cell-like state following wounding supports the regrowth of axons from local nerves
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
Treating neurological disorders remains a challenge due to the implication of multifactorial, complex etiologies. In recent years, the therapeutic benefits of the intranasal administration of extracellular vesicles isolated from mesenchymal stem cells (MSC-EVs) have gained attention. Extracellular vesicles retain the advantages of their parental cells, while intranasal administration provides a non-invasive method to bypass the blood-brain barrier and target specific pathological regions. In a recent STEM CELLS review article, researchers led by Daniel Offen (Tel Aviv University, Israel) summarize the current status of research into MSC-EVs administrated via the intranasal pathways and the potential of this promising therapeutic approach.
The mechanisms determining the heterogeneity of stromal populations in the tumor microenvironment remain poorly understood. A recent STEM CELLS study from the lab of David R. Rowley (Baylor College of Medicine, Houston, TX, USA) identifies ELF3 (E74 Like ETS Transcription Factor 3) as an essential transcription factor regulating the differentiation of a critical pro-inflammatory stromal cell type (carcinoma-associated fibroblasts exhibiting an inflammatory phenotype or iCAFs) and provides evidence for mesenchymal stem cells (MSCs) as iCAF progenitors cells.
Parkinson's disease is a major neurodegenerative disease and how the lack of dopamine affects neurogenesis in the ventricular-subventricular zone (V-SVZ) remains unclear. In a new STEM CELLS article, researchers led by José Luis Labandeira-Garcia and Jannette Rodríguez-Pallares (Universidade de Santiago de Compostela, Spain) show that dopamine increases proliferation and generation of neuroblasts in the V-SVZ and that the blockade of angiotensin AT2 receptors suppresses these effects, showing a functional dependence between dopamine and the renin-angiotensin system (RAS). More importantly, Garcia-Garrote et al. establish that the blockade of angiotensin AT1 receptors or stimulation of angiotensin AT2 receptors can counteract the decline in neurogenesis observed in the V-SVZ in animal models of Parkinson's disease.
A new STEM CELLS Translational Medicine article from researchers led by Chunmeng Shi and Yu Wang (Army Medical University, Chongqing, China) reports on the activation and reprogramming of fibroblasts into a neural cell-like state following wounding and how their direct contact with local nerves promotes axon regrowth through the ID1/ID3-Itga6 pathway. Chen et al. also established that the transplantation of ID1/ID3 fibroblasts significantly improved local nerve regeneration following wounding. The results of the present study increase our current understanding of the pathophysiology of local nerve injury and may aid the challenge of treating peripheral nerve disorders and peripheral neuropathies in relatively chronic refractory wounds.
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.