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Summaries of the most recent articles published in STEM CELLS and STEM CELLS Translational Medicine.

January 14, 2020

Stem cell‐based therapy using neural stem/progenitor cells (NS/PCs) derived from human‐induced pluripotent cells (hiPSCs) represents a promising approach for the treatment of neurodegenerative diseases and neurotrauma.

January 14, 2020

The function of the sphingosine‐1‐phosphate (S1P) signaling pathway in embryonic stem cells (ESCs) remains unclear; therefore, researchers led by Todd Evans

January 14, 2020

Mesenchymal stem cells (MSCs) have direct effects on islet β‐cells that improve their insulin secretory function, and studies have highlighted the essential nature of the generation of ATP and other metabolic coupling factors by mitochondrial metabolism for nutrient‐induced insulin secretion.

January 14, 2020

Cell therapy in bone tissue engineering has considerable translational potential; however, the limited harvest of osteoblasts and mesenchymal stem cells, and a poor osteogenic potential of isolated patient fibroblasts constrain current approaches.

January 10, 2020

While various stem cell-based therapeutics are currently under investigation as a treatment option following trauma, such as brain or lung injury, stem cells readily express tissue factor (TF), which causes rapid blood clotting.

January 10, 2020

Mesenchymal stem cells (MSC) have been subcultured from various tissue, leading to a spectrum of MSCs displaying properties reflective of tissue microenvironment or developmental origin. As a result, MSCs possess a diverse range of therapeutic effects, including immunomodulatory, angiogenic, and tissue regenerative properties.

January 10, 2020

While mesenchymal stem cells (MSCs) have been reported to prevent renal injuries via immune regulation in diabetic models, the mechanisms at play remain to be fully elucidated.

January 10, 2020

The biological properties and functional activities of c‐Kit+ adult cardiac interstitial cells, or cCICs, continue to elude researchers despite decades of investigation; however, researchers led by

Past Buzz

January 14,2020 Sphingosine Levels Key for Maintaining Stem Cell Fate

The function of the sphingosine‐1‐phosphate (S1P) signaling pathway in embryonic stem cells (ESCs) remains unclear; therefore, researchers led by Todd Evans (Weill Cornell Medicine, New York, New York, USA) recently employed a genetic approach to eliminate S1P from murine ESCs by deleting both sphingosine kinase orthologs. Reporting in STEM CELLS, Pandey et al. discovered that loss of both kinases inhibited ESC proliferation, with cells arresting at the G2/M checkpoint. However, as synthase expression reversed this phenotype, the accumulation of sphingosine caused the defect rather than the lack of S1P. The authors note that these data agree with previous results from early zebrafish embryos, suggesting a critical conserved role for limiting sphingosine levels in stem and progenitor cells.

January 14,2020 Mitochondrial Transfer from MSCs to Islet β-cells

Mesenchymal stem cells (MSCs) have direct effects on islet β‐cells that improve their insulin secretory function, and studies have highlighted the essential nature of the generation of ATP and other metabolic coupling factors by mitochondrial metabolism for nutrient‐induced insulin secretion. Additionally, impaired mitochondrial function, and thus reduced oxygen consumption rate, results in defective insulin secretion and reduced islet β‐cell survival. Writing in a STEM CELLS article, researchers led by Chloe L Rackham (King's College London, UK) report, for the first time, that human MSCs transfer their mitochondria to cocultured human islet β‐cells. The findings of this fascinating new study suggest that the mitochondrial donation capacity of MSCs should be harnessed to ensure the functional longevity of transplanted human islets in clinical protocols.

January 14,2020 Direct Osteoblastic Reprogramming by IGFBP7

Cell therapy in bone tissue engineering has considerable translational potential; however, the limited harvest of osteoblasts and mesenchymal stem cells, and a poor osteogenic potential of isolated patient fibroblasts constrain current approaches. Now, a new study led by Zufu Lu and Hala Zreiqat (University of Sydney, Camperdown, NSW, Australia) and published in STEM CELLS Translational Medicine reports an innovative approach that promotes the trans‐differentiation of human fibroblasts into functional osteoblasts using a single naturally bioactive protein, insulin growth factor binding protein‐7 (IGFBP7). The authors of this new study believe that this approach exhibits significant advantages over other commonly used cell sources and will potentially lead to a shift in the current paradigm of bone regenerative medicine.

January 10,2020 Stem Cell Therapies Affect Clotting following Trauma

While various stem cell-based therapeutics are currently under investigation as a treatment option following trauma, such as brain or lung injury, stem cells readily express tissue factor (TF), which causes rapid blood clotting. Now, new research from the laboratory of Mitchell J. George (McGovern Medical School at The University of Texas Health Science Center, Houston, Texas, USA) provides evidence for the acceleration of clot formation in trauma patients as TF load of a given stem cell treatment increases. Furthermore, the team demonstrates heparin as a potential reversal agent in response to this procoagulatory effect. For all the details, see STEM CELLS Translational Medicine now!

January 10,2020 Regenerative Potential of Pancreatic MSC Secretome

Mesenchymal stem cells (MSC) have been subcultured from various tissue, leading to a spectrum of MSCs displaying properties reflective of tissue microenvironment or developmental origin. As a result, MSCs possess a diverse range of therapeutic effects, including immunomodulatory, angiogenic, and tissue regenerative properties. In a new STEM CELLS study, researchers led by David A. Hess (Western University, London, ON, Canada) utilized label‐free mass spectrometry and functional analyses to characterize the proteome and secretome of MSC populations established from human pancreas tissue. Cooper et al. reported that pancreatic MSCs demonstrated a unique Vimentinhigh/Nestinhigh proteome restricted from adipogenesis, yet pancreatic MSCs secreted proteomic effectors associated with endothelial cell chemotaxis, angiogenesis, and islet regeneration. Overall, the authors believe that their findings will help to fully elucidate the secretory functions of pancreatic MSCs as a possible therapeutic agent for regenerative medicine applications.

January 10,2020 MSC-polarized Macrophages Alleviate Diabetic Nephropathy

While mesenchymal stem cells (MSCs) have been reported to prevent renal injuries via immune regulation in diabetic models, the mechanisms at play remain to be fully elucidated. Reporting in a new STEM CELLS article, researchers led by Yanrong Lu and Younan Chen (West China Hospital, Chengdu, China) establish that the depletion of macrophages abolishes the renal protective role of MSCs. Furthermore, Yuan et al. demonstrate that the adoptive transfer of MSC‐educated macrophages confers renal protection in diabetic nephropathy model mice, while TFEB knockdown in macrophages abolishes these effects. Overall, this exciting study provides both novel insights into MSC‐based immune regulation and scientific evidence for clinical application of MSCs in diabetic nephropathy.

January 10,2020 Environmental Adaptation of Cardiac Interstitial Cells

The biological properties and functional activities of c‐Kit+ adult cardiac interstitial cells, or cCICs, continue to elude researchers despite decades of investigation; however, researchers led by Mark A. Sussman (San Diego State University, San Diego, CA, USA) recently discovered that developmental environmental cues influence their phenotypic properties. Reporting in a new STEM CELLS Translational Medicine article, Wang et al. discovered that while the delivery of cCICs into early embryonic blastocysts leads to trophectoderm integration with exclusion from the inner cell mass, the introduction of cCICs into the developing myocardium of late fetal or early postnatal hearts resulted in extended persistence and acquisition of phenotypic traits consistent with fibroblasts. Overall, the authors believe that their findings support the rationale for cCIC therapy in the context of congenital and pediatric cardiomyopathic conditions.

January 7,2020 Phase III Trial of Autologous MSCs for Perianal Fistula

A recent STEM CELLS Translational Medicine article from researchers led by Mariano García‐Arranz (Universidad Autónoma de Madrid, Spain) provides evidence of the safety of autologous adipose-derived mesenchymal stem cell (MSC) therapy for complex perianal fistula in a phase III multicenter, randomized, single‐blind clinical trial. Furthermore, the authors suggest that this approach also provides an advantage over a good surgical protocol at two years after treatment; however, following this time, results stay similar to those shown with allogenic MSCs in previous clinical trials.

 

January 7,2020 MSC-Induced Kidney Transplant Tolerance

A case report published in STEM CELLS Translational Medicine provides the first evidence that autologous bone marrow‐derived mesenchymal stromal cells (MSC) infusion associates with safe, complete discontinuation of maintenance antirejection drugs late after living‐donor kidney transplantation, eventually allowing a state of operational tolerance. Researchers led by Giuseppe Remuzzi (Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy) believe that this case may provide a basis for future studies assessing whether a panel of non-invasive immunomonitoring tools, in addition to clinical criteria, could identify a pro‐tolerogenic signature after MSC therapy that could eventually help to identify patients who are amenable to safe immunosuppressive drug discontinuation. Casiraghi et al. note the requirement of further investigations building on this approach in living‐donor as well as in deceased-donor kidney transplantation.

January 7,2020 Hair Follicle Regeneration - A Review

 While hair loss affects a growing number of people worldwide, the limited efficacy and side effects suffered following current treatment approaches have fostered the search for alternative therapeutic solutions. Much hope lies in hair follicle bioengineering (the development of functional hair follicles from an expanded population of hair‐inductive cells); however, human follicle neogenesis with patient-derived cells remains unreported. In the hope of driving this field forward, researchers led by Ana Rita Castro and Elsa Logarinho (Universidade do Porto, Porto, Portugal) provide a review on cell‐based hair follicle tissue engineering that systematically compiles emerging strategies and disclosing those obstacles that limit translation into the clinics. For all the details, see STEM CELLS Translational Medicine now!