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

January 21, 2020

The promotion of blood vessel growth for therapeutic purposes remains a challenge both for the treatment of ischemia and the generation of functional tissue‐engineered grafts, as physiological angiogenesis represents an extraordinarily complex process.

January 21, 2020

Pulp stem cells can be readily harvested from dental pulp tissue of extracted permanent teeth and exfoliated deciduous teeth; however, we currently lack a systematic and comprehensive review of pulp stem cells in terms of biological attributes and therapeutic applications.

January 21, 2020

Mesenchymal stem cells (MSCs) have vast therapeutic potential for the treatment for neurological diseases and damage, with many of their effects mediated by components of the stem cell secretome.

January 21, 2020

A new article from researchers led by Eran Zimran (Hadassah University Center, Jerusalem, Israel) recently described how the transplantation of

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.

Past Buzz

January 21,2020 Human Dental Pulp Stem Cells – A Review

Pulp stem cells can be readily harvested from dental pulp tissue of extracted permanent teeth and exfoliated deciduous teeth; however, we currently lack a systematic and comprehensive review of pulp stem cells in terms of biological attributes and therapeutic applications. To fill this knowledge gap, researchers led by Jing Mao (Huazhong University of Science and Technology, Wuhan, China) and Yan Liu (Peking University, Beijing, China) now provide a concise review of the area in STEM CELLS Translational Medicine. Shi et al. concentrate on pulp stem cells to emphasize their updated biological characteristics such as cell markers, multipotency and origin, and promising therapeutic applications, including endodontic regeneration and extraoral tissue repair and regeneration.

January 21,2020 Exosomal CNP Promotes Recovery of Damaged Brain

Mesenchymal stem cells (MSCs) have vast therapeutic potential for the treatment for neurological diseases and damage, with many of their effects mediated by components of the stem cell secretome. Researchers led by Hua‐Jung Li (National Health Research Institutes, Zhunan, Taiwan) found that prostaglandin E2 receptor 4 (EP4)-induced MSC extracellular vesicles/exosomes has an elevated ability to rescue damaged brain functions and established the requirement of elevated 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase (CNP) levels for this effect. Overall, this new STEM CELLS Translational Medicine article from Chen et al. suggests that CNP modulation represents a potential target for treating brain damage and neural degeneration diseases and further underscore the power of MSC-derived paracrine-acting factors.

January 21,2020 Ex Vivo Expansion of Adult HSCs With Valproic Acid

A new article from researchers led by Eran Zimran (Hadassah University Center, Jerusalem, Israel) recently described how the transplantation of ex vivo valproic acid (VPA)-treated adult mobilized peripheral blood and bone marrow hematopoietic stem cells (HSCs) into immune‐deficient mice led to non-biased long‐term multilineage hematopoietic cell engraftment, including T cells. The authors believe that their findings support the use of VPA, a histone deacetylase inhibitor, in ex vivo HSC expansion for future gene modification strategies. For all the details, see STEM CELLS Translational Medicine now!

January 14,2020 Visualization of Undifferentiated Neural Stem/Progenitor Cells

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. However, not all transplanted cells fully differentiate into mature neurons and glial cells, even following the application of clinically “safe” clones, undifferentiated cells can trigger tumorigenic overgrowth. Now, researchers led by Masaya Nakamura and Hideyuki Okano (Keio University School of Medicine, Shinjuku‐ku, Tokyo, Japan) have taken advantage of the expression of the 18 kDa translocator protein (TSPO) to visualize residual immature neural cells after NS/PC transplantation in the central nervous system with positron emission tomography using a TSPO ligand. For more on how these new findings from Tanimoto et al. may have critical importance in regenerative medicine, see STEM CELLS Translational Medicine now!

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.