Human perivascular progenitor cells reduce osteoclast formation, thereby preventing bone graft resorption and yielding better outcomes in a preclinical xenograft model
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Summaries of the most recent articles published in STEM CELLS and STEM CELLS Translational Medicine.
A proof‐of‐principle study reports on the sensitive in vivo tracking of iPSC‐CMs in a clinically relevant model of myocardial infarction
A new review article provides a balanced view of the potential of MSC therapy for COVID-19, with concerns regarding clinics offering unproven stem cell treatments in mind
A fascinating article succinctly provides readers with a working knowledge of SCI and cell therapies at the leading edge of research.
A new review summarizes past progress, the present state, and the future potential of endothelial‐colony forming cell therapy as a stem cell therapy for vascular repair.
Osteocyte‐derived mechanically-activated extracellular vesicles hold great potential as a novel cell‐free therapy to enhance bone regeneration
Researchers now describe the improved design and in vitro and in vivo testing of a novel inducible “suicide switch” safety system for iPSC‐derived cell‐based therapies
A curative immunotherapy for AML remains undescribed, possibly due to the resistance of the LSCs
In vivo imaging techniques can help to guide the clinical translation of cell‐based therapeutics; however, immunogenicity and potential genotoxicity currently limited related strategies. In a proof‐of‐principle study published in STEM CELLS Translational Medicine, researchers led by Cynthia E. Dunbar and So Gun Hong (National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA) report how the site‐specific delivery of the sodium/iodide symporter (NIS) gene via CRISPR/Cas9 gene-editing technology enabled the sensitive in vivo tracking of induced pluripotent stem cell‐derived cardiomyocytes (iPSC‐CM) in a clinically relevant model of myocardial infarction. Furthermore, Ostrominski and Yada et al. established that NIS‐positive iPSC‐CMs retained electrophysiological characteristics when compared to controls. Featuring a superior safety profile, this approach offers broader applications in both the preclinical and clinical development of cardiac cell therapies.
Although mesenchymal stem cell (MSC) administration is an unproven stem cell therapy-based approach for the treatment of COVID‐19 patients, there exists a growing demand for new therapies among patients and healthcare workers. As highlighted by preclinical and clinical findings, MSCs possess remarkable immunomodulatory features and thus have the potential to modulate the pulmonary microenvironment, inhibit pulmonary fibrosis, and treat lung dysfunction in COVID‐19 induced pneumonia and respiratory distress syndrome. Now, a new STEM CELLS Translational Medicine review article from Alp Can (Ankara University, Turkey) and Hakan Coskun (Harvard Medical School, Boston, Massachusetts, USA) provides a balanced view on the potential of MSC therapy for COVID-19, with concerns regarding clinics offering unproven stem cell treatments in mind.
Traumatic spinal cord injuries (SCIs) result in lifelong disability and financial burden for millions of patients and caregivers worldwide. Cell‐based therapies have emerged as a neuroprotective and neuroregenerative strategy for SCI, and now, a new STEM CELLS Translational Medicine article from the lab of Michael G. Fehlings (University of Toronto, Toronto, Ontario, Canada) highlights critical preclinical and clinical data in cell therapy with an emphasis on the pathobiology and mechanisms of recovery. Ahuja et al. also discusses adjunct treatments to maximize the efficacy of the grafts and important translational considerations such as clinical‐grade scale‐up and delivery techniques. This fascinating article succinctly provides readers with a working knowledge of SCI and cell therapies at the leading edge of research.
A new STEM CELLS Translational Medicine review from the laboratory of David S. Allan (University of Ottawa, Ottawa, Ontario, Canada) summarizes past progress, the present state, and the future potential of endothelial‐colony forming cell therapy as a stem cell therapy for vascular repair. Liao et al. report on studies identified through a systematic search, with a focus on preclinical data from animal studies. Overall, they highlight both the drawbacks and the novel findings that may lead to the progress of said stem cell therapies into the clinic.
Bone regeneration requires the osteogenesis of mesenchymal stem cells, with physical loading a potent stimulus driving this process. While osteocytes are mechanosensitive cells that play fundamental roles in coordinating bone mechanoadaptation, the exact mechanisms involved remain poorly understood. Now, a new study from the laboratory of David A. Hoey (Trinity College Dublin, Ireland) demonstrates that osteocytes subjected to fluid shear secrete a distinct collection of factors that enhance stem cell recruitment and osteogenesis. Eichholz et al. identified that these factors are delivered via extracellular vesicles (EVs), demonstrating a novel mechanism of osteocyte‐stem cell communication; therefore, osteocyte‐derived mechanically-activated EVs hold great potential as a novel cell‐free therapy to enhance bone regeneration. For more, see STEM CELLS Translational Medicine now!
The growth of human induced pluripotent stem cell (iPSC)‐derived cell therapies has prompted the need for effective safety measures; however, there currently exists but a few inducible cell “suicide” systems. In a new STEM CELLS Translational Medicine study, researchers led by Aaron J. Carman (InVitro Cell Research LLC, Greater New York Metropolitan Area, NY, USA) now describe the improved design and in vitro and in vivo testing of a novel inducible “suicide switch” safety system for iPSC‐derived cell‐based therapies.
Antibody‐ and cell‐based immunotherapies have emerged as encouraging therapeutic approaches in applied hematology; however, a curative immunotherapy for acute myeloid leukemia (AML) remains undescribed, possibly due to the resistance of the leukemic stem cells (LSCs) that reside in several different fractions of the AML clone. In a recent STEM CELLS Translational Medicine concise review, researchers led by Peter Valent (Medical University of Vienna, Austria) discuss novel markers and targets expressed on LSCs in AML with an emphasis on the potential value of these antigens in the context of antibody‐based and/or cell‐based therapies. The authors also discuss various limitations and the possible pitfalls associated with such therapies.
A new STEM CELLS article from the lab of Anthony P. Hollander (University of Liverpool, UK) has shown that mesenchymal stem cell (MSC) chondrogenesis represents a transient property that is lost as cells age in vitro, whereas trophic repair potency is maintained until MSCs cease to grow. Salerno et al. note that their findings highlight the importance of defining the intended mode of action when preparing MSCs for injection into osteoarthritic joints and demonstrate that the development of injectable MSC therapies for osteoarthritis must take into account the transient nature of chondrogenic potency relative to their sustained trophic potency with increasing passages. Overall, specific strategies should be adopted to exploit one or other of these mechanisms of action.
A new study from the laboratory of Judith Staerk (University of Oslo, Norway) has revealed a novel link between DNA methyltransferase (DNMT) 3B and metabolic flux in human embryonic stem cells (hESCs). In their new STEM CELLS study, Cieslar‐Pobuda et al. discovered that the loss of DNMT3B disrupted mitochondrial fusion and fission balance, reduced mitochondrial DNA levels, and elicited a switch from glycolysis to oxidative phosphorylation. Furthermore, DNMT3B loss led to the overexpression and hyperactivity of isocitrate dehydrogenases and buildup of α‐ketoglutarate and the significant upregulation of transcription factors during early neural differentiation.
A new STEM CELLS Translational Medicine study from Patrizia Ferretti (UCL Institute of Child Health, London, UK) and Amel Ibrahim (NYU College of Dentistry, New York, NY, USA) tested the hypothesis that by reproducing the physical and biochemical bone microenvironment through the use of three‐dimensional (3D) culture and vascularization, one can enhance osteogenic maturation in human adipose‐derived stem cells (hASCs). The authors' findings demonstrate the critical role of vascularization and 3D culture in driving osteogenic maturation of cells readily available but constitutively less committed to this lineage. Furthermore, they suggest a crucial avenue for recreating the bone microenvironment for tissue engineering of mature craniofacial bone tissues from pediatric hASCs, as well as bone marrow-derived mesenchymal stem cells and osteoprogenitor cells.