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Summaries of the most recent articles published in STEM CELLS and STEM CELLS Translational Medicine.
Researchers from the laboratory of Catherine Ovitt (University of Rochester, New York, USA) realized that several diverse and non‐overlapping cell
Previous research from the lab of Björn Behr (University Hospital Bergmannsheil Bochu
While the stem cell secretome presents itself as an efficient and safe means to treat a range of disease and disorders, solubilized growth factors can undergo rapid degradation following administration, thereby requiring efficient delivery and controlled release for enhanced tissue regeneration.
In the hope of developing more efficient stem cell-treatments for ischemic heart diseases, researchers led by Masaaki Ii (Osaka Medical College, Japan) recently assessed the outcomes of a combinatorial strategy on the ischemic myocardium. In brief, Yokoyama et al.
A recent STEM CELLS article from the laboratories of Xuemei Fu and Yang Xu (Sun Yat‐sen University, Shenzhen, Guangdong, China) aims to describe the mechanisms controlling the switch from glycolysis in self-renewing human embryonic stem cells (hESCs) to oxidative phosphorylation upon differentiation. Liu et al. established that Indoleamine 2,3‐dioxygenase 1 (IDO1) expression in hESCs maintains pluripotency by suppressing mitochondrial activity and promoting glycolysis through an increase in the NAD+/NADH ratio. However, during differentiation of hESCs, IDO1 significantly decreases as the cells switch to oxidative phosphorylation. The authors hope that their new findings will also shed light on the link between pluripotency and cancer, as cancer cells have a similar metabolic profile to stem cells.
Researchers from the laboratory of Catherine Ovitt (University of Rochester, New York, USA) realized that several diverse and non‐overlapping cell populations had been designated as adult stem cells in the mammalian salivary gland. In a new STEM CELLS review, Weng et al. focus on the criteria used to define these cell populations and highlight the limitations associated with each. The authors hope that this critical re‐evaluation of the characterization of these cell populations may serve to highlight those cells of interest to the development of salivary gland-based regenerative therapies.
Previous research from the lab of Björn Behr (University Hospital Bergmannsheil Bochum, Germany) demonstrated diminished healing capacity following bone infections, mainly due to reduced osteoblastogenesis, increased osteoclastogenesis, and elevated B‐cell activity. In their new STEM CELLS Translational Medicine article, the team evaluated bone regeneration following treatment with adipose‐derived stem cells (ASCs) in an established murine animal model of bone infection. Interestingly, Wagner et al. discovered that ASC treatment prompted the restoration of bone healing via the elevation of osteoblastogenesis and downregulation of both osteoclastogenesis and B‐cell number. Could ASC therapy represent a novel treatment approach?
A recent review article from the labs of Raleigh Jonscher (University of Colorado School of Medicine, USA) and Jaime Belkind‐Gerson (Children's Hospital Colorado, USA) offers a concise but wide‐ranging survey on the current state of progress in research related to adult enteric neurogenesis in response to injury, specifically regarding glial cell‐derived neurotrophic factor, serotonin, endocannabinoids, and lipopolysaccharide signaling. The authors describe the current understanding of adult enteric neurogenesis and the systems involved and go on to highlight promising avenues for potential clinical development. Overall, targeting the neurogenic pathways presents a promising avenue toward the development of new and innovative treatments for acquired damage to the enteric nervous system. For more, see STEM CELLS now!
To investigate how Hedgehog signaling regulates the epithelial stem cell niche and controls stem cell differentiation within the cervical loop (a specific epithelial structure at the apical side of the tooth germ), researchers from the lab of Anamaria Balic (University of Helsinki, Finland) employed pharmacological attenuation of Hedgehog signaling during in vitro organ and cell culture. Binder at al. now report that the simultaneous Hedgehog pathway-mediated regulation of stem cells, cell adhesion, and differentiation in the tooth epithelium relates to functional differences between the Ptch1 and Ptch2 receptors, which are additionally potentiated by the activity of the Dhh Hedgehog ligand. See STEM CELLS now for more on a study that may impact the understanding of the outcomes of Hedgehog signaling in other tissues/organs and the development of novel treatments strategies for a range of disease/disorders.
While the stem cell secretome presents itself as an efficient and safe means to treat a range of disease and disorders, solubilized growth factors can undergo rapid degradation following administration, thereby requiring efficient delivery and controlled release for enhanced tissue regeneration. A recent STEM CELLS Translational Medicine article details recent research from the lab of James J. Yoo (Wake Forest School of Medicine, Winston‐Salem, NC, USA) and their application of a gel‐based delivery system for controlled delivery of the secretome of human placental stem cells in a rat model of renal regeneration. Excitingly, Yim et al. report that their new approach leads to the effective functional and structural restoration of the injured kidney, thereby suggesting that delivery of the stem cell‐derived secretome can help to efficiently repair renal tissue injury safely and without the risk of possible side effects such as immune rejection.
In the hope of developing more efficient stem cell-treatments for ischemic heart diseases, researchers led by Masaaki Ii (Osaka Medical College, Japan) recently assessed the outcomes of a combinatorial strategy on the ischemic myocardium. In brief, Yokoyama et al. established that treatment with statin (Simvastatin) loaded poly(lactic‐co‐glycolic) acid nanoparticles synergized with adipose stem cell (ASC) therapy and led to an increased level of functional recovery in the damaged heart by inducing myocardial regeneration with increased vascularity and pericardium‐derived de novo cardiomyocytes. The authors hope that their new STEM CELLS Translational Medicine will permit the development of innovative therapies for myocardial infarction without requiring pluripotent stem cell‐derived cardiomyocytes.
To explore the role of proNGF, the precursor of nerve growth factor (NGF), on the biology of adult neural stem cells (NSCs), researchers from the labs of Antonino Cattaneo (European Brain Research Institute) and Raffaella Scardigli (National Council of Research – Institute of Translational Pharmacology, Rome, Italy) analyzed adult hippocampal neurogenesis in AD11 transgenic mice. This model exhibits the constitutive expression of an anti‐NGF antibody, thereby leading to an imbalance of proNGF over mature NGF. Reporting in STEM CELLS, Corvaglia et al. now identify proNGF as a specific mitogenic factor for the proliferation of adult hippocampal NSCs and also in induced neural stem cells (iNS), a result which may foster the development of future therapeutic approaches based on the stimulation of endogenous adult neurogenesis or cell‐reprogramming protocols.
Exciting new research from the laboratory of Marita Bosticardo (IRCCS San Raffaele Scientific Institute, Milan, Italy) provides proof‐of‐principle for a new approach toward thymic regeneration. Bortolomai et al. generated thymic organoids by seeding gene‐modified postnatal murine thymic epithelial cells (TECs) into three‐dimensional (3D) collagen type I scaffolds mimicking the thymic ultrastructure. The in vivo results found that thymic organoids transplanted subcutaneously in athymic nude mice became vascularized but ultimately failed to support thymopoiesis because of limited persistence in vivo. See STEM CELLS Translational Medicine now for what could represent a launching off point for the development of new thymic regeneration strategies.
Recent research from the laboratory of Jizhou Yan (Shanghai Ocean University, Shanghai, China) sought to delineate the regulatory networks controlling gonadal stem cell renewal in zebrafish. Reporting in STEM CELLS, Guo et al. employed genome‐wide transcriptome mining and gonadal microinjections to demonstrate the importance of two GPCR‐regulatory circuits: miR430a‐Sox9a increased the testis spermatogonia reserve and miR218a‐Sox9b increased the ovarian follicle reserve. The team hopes that their new research will aid in the development of novel therapeutic interventions for aging‐related ovarian failure and testicular regression in humans.