Nanofat and NFG synergize to promote sensory recovery of anterolateral thigh free flaps
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Summaries of the most recent articles published in STEM CELLS and STEM CELLS Translational Medicine.
An inhibitor of dihydroorotate dehydrogenase specifically induces elevated levels of cytotoxicity in mouse PSCs
A report identifies the main technical procedures currently used by public cord blood banks worldwide
New research reveals superior bone formation in bone marrow MSC‐laden composites in rat tibial defects
Osteoblastic Wls deletion impairs the bone marrow microenvironment and bone mass accrual, while also inducing age‐independent senescence of MSCs
New research identifies two different stem cell populations that can differentiate into cementoblasts in the periodontium
Researchers use three-dimensional rabbit neurospheres to model the neurodevelopmental effects of intrauterine growth restriction
Multipotent stem cells can alter the immune response to injury, limit the damage due to inflammation and thereby promote repair
The success of regenerative medicine approaches that employ pluripotent stem cells (PSCs) requires the exclusion of self-renewing undifferentiated cells from the differentiated cell population. Now, a new study from Toru Kondo (Hokkaido University, Japan) describes how brequinar (BRQ), the most potent available inhibitor of dihydroorotate dehydrogenase (DHODH), specifically induces elevated levels of cytotoxicity in mouse PSCs and not lineage‐committed progenitor cells and differentiated functional cells. Furthermore, BRQ prevents teratoma formation in vivo without any visible unwanted side effects in mice. For all the details, see STEM CELLS now!
In a STEM CELLS Translational Medicine brief report, a team led by Monique Jöris (World Marrow Donor Association, Leiden, The Netherlands) aims to identify and understand the main technical procedures currently used by public cord blood banks worldwide. This World Marrow Donor Association data, generated by surveying cord blood banks directly, represents a dedicated global effort to serve the cord blood banking community. Furthermore, the article identifies areas for the improvement of cord blood banks that will facilitate access to this therapeutic approach.
Researchers led by Bikramjit Basu (Indian Institute of Science, Bangalore) and Sujata Mohanty (All India Institute of Medical Sciences, New Delhi, India) recently developed an easy and economical method to generate a porous, multi-material composite that mirrors the stochastic geometry of bone. Subsequently, the team evaluated three clinically relevant mesenchymal stem cell (MSC) populations (derived from the umbilical cord, the adipose tissue, and the bone marrow) within said composites for early osseointegration and revealed superior bone formation in bone marrow MSC‐laden composites in rat tibial defects. For more information, see Midha et al. in STEM CELLS Translational Medicine.
Mechanisms by which osteoblastic Wntless deletion regulates the fate and functions of bone marrow-resident mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) in relation to age remain incompletely understood. Now, a STEM CELLS article from the lab of Jeong‐Chae Lee (Jeonbuk National University, Jeonju, South Korea) describes how osteoblastic Wls deletion impairs the bone marrow microenvironment and bone mass accrual while also inducing age‐independent senescence of MSCs in a mouse model. However, Poudel et al. also discovered that osteoblastic Wls ablation induces senescence of HSCs with the impaired production of progeny and hematopoietic development only at advanced ages.
A recent STEM CELLS article from the lab of Paul Sharpe (Kings College London, UK) has identified two different stem cell populations that can differentiate into cementoblasts in the periodontium. Zhao et al. demonstrated that while both Axin2+ and CD90+ stem cell populations give rise to cementoblasts at development stages, only the Axin2+ stem cell population continues to form cementoblasts in the adult. The CD90+ stem cells that normally remain in a quiescent state in adults can respond during periodontal disease and form cementoblasts; however, bacterial metabolites can inhibit this regenerative ability. Overall, these exciting findings have profound implications for the use of exogenous cells and the mobilization of resident cells as therapies to restore tissue following periodontal disease.
New research from the lab of Marta Barenys (University of Barcelona, Spain) describes an entirely novel methodology for the generation of three-dimensional rabbit neurospheres that can differentiate into neurons, astrocytes, and oligodendrocytes. In their new STEM CELLS Translational Medicine article, the authors report the implementation of this method to model the neurodevelopmental effects of intrauterine growth restriction (IUGR) and for toxicity testing and efficacy testing of new pharmaceuticals. Interestingly, they encountered differences in basic neurogenic processes induced by IUGR, established that neurospheres obtained from IUGR brains display significantly impaired oligodendrocyte differentiation, and demonstrated that the in vitro exposure of IUGR neurospheres to thyroid hormone could revert this impairment.
While cell therapies hold remarkable promise in replacing injured cells and repairing damaged tissues, cell replacement represents just one part of the therapeutic effect. Treatment approaches employing a range of adult stem cells can improve patients' outcomes with neurological conditions such as traumatic brain injury and hearing loss without directly replacing damaged or lost cells. As the immune system plays a central role in injury response and tissue repair, researchers led by James E. Baumgartner (Advent Health for Children/University of Central Florida College of Medicine, Orlando, Florida, USA) suggest that multipotent stem cell therapies can achieve a therapeutic effect by altering the immune response to injury, thereby limiting damage due to inflammation and possibly promoting repair. These findings, reported recently in STEM CELLS Translational Medicine, argue for a broader understanding of the mechanisms by which cell therapies can benefit patients.
A new STEM CELLS Translational Medicine article from the lab of Antonio del Sol Mesa (University of Luxembourg, Belvaux, Luxembourg) reports on the TransSynW computational web application, which can identify cell conversion transcription factors for any cell population in single‐cell RNA‐sequencing data. Ribeiro et al. note that TransSynW does not require prior biological information, computer programming, or computational resources from the users. TransSynW also prioritizes pioneer factors among predicted conversion transcription factors to facilitate the chromatin opening process often required for cell conversion and predicts marker genes to assess cell conversion experiments. Overall, the authors establish TransSynW as a fundamental tool to guide the design of novel cell conversion protocols in stem cell research and regenerative medicine.
The neural crest, a remarkable embryonic stem cell population, contributes to the generation of a wide variety of derivatives, including neurons, glia, cartilage, bone, pigment cells, and endocrine cells. As the list of derivatives has expanded since the identification of the neural crest over 150 years ago, the neural crest's clinical significance has become more evident. Furthermore, central questions regarding stemness formation and maintenance remain poorly understood. Now, in a new Concise Review from STEM CELLS, researchers led by Surangi N. Perera and Laura Kerosuo (National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, USA) discuss those studies related to how this post‐gastrulation cell population maintains its stem cell potential from embryonic to adult stages.
A new STEM CELLS Translational Medicine article from researchers led by Annamaria Cimini (University of L'Aquila, L'Aquila) and Liborio Stuppia (D'Annunzio University, Chieti‐Pescara, Italy) reports on the potential of the secretome derived from human amniotic fluid stem cells (hAFSCs) as a therapeutic approach to ischemia/reperfusion injury. Castelli and Antonucci et al. found that the hAFSC secretome activated pro‐survival and anti‐apoptotic pathways in an in vitro model, while subsequent analysis of the exosomal microRNA component of the secretome revealed the presence of microRNAs involved in neurotrophin signaling and those related to neuroprotection and neuronal cell death. Overall, the authors highlight the AFSC secretome as a potential means to stimulate neuronal plasticity and ameliorate cognitive loss and neural replacement, and thereby represent a suitable treatment for ischemia/reperfusion injury.