A new Perspective article from a team led by Geoffrey P. Lomax (California Institute for Regenerative Medicine, Oakland, CA, USA) aims to build consensus for the stem cell field to ensure proper conduct of clinical research and the regulation of the practice of medicine involving cell‐based treatments.
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Summaries of the most recent articles published in STEM CELLS and STEM CELLS Translational Medicine.
Modeling human neurodevelopmental disease using stem cell biology techniques requires significant expertise to allow for the discovery of cell phenotypes.
Cerebral adrenoleukodystrophy (CALD), characterized by imaging findings of demyelination, inflammation, and contrast enhancement on magnetic resonance imaging, suffers from a lack of accepted therapies for patients with advanced forms of the disease.
A new STEM CELLS Translational Medicine article led by Naoya Uchida (National Insti
The liver is an essential organ in the body that performs crucial functions such as metabolism, and recently, researchers have invested enormous resources to generate liver cells from induced pluripotent stem cells and to develop robust three-dimensional liver organoids that faithfully resemble the liver. Now, a team led by Setjie W.
The transplantation of gene-edited stem cells represents a promising strategy for the treatment of neurodegenerative diseases.
Nicotinamide adenine dinucleotide (NAD+) induces an intermediate state of naivety in human embryonic stem cells (hESCs) characterized by a shift from glycolytic to oxidative metabolism, increased self‐renewal, and epigenetic alterations. Conversely, inhibition of the malate aspartate shuttle (MAS), which recycles NAD+, causes a dramatic loss of oxidative metabolism and pluripotency marker expression.
Modeling human neurodevelopmental disease using stem cell biology techniques requires significant expertise to allow for the discovery of cell phenotypes. Now, a new Review Article from (Carl Ernst, McGill University and Douglas Hospital Research Institute, Montreal, Quebec, Canada) provides a roadmap for experimental planning for those less familiar with the use of induced pluripotent stem cells to model human neurodevelopmental disease. For all the details, see STEM CELLS Translational Medicine now!
Cerebral adrenoleukodystrophy (CALD), characterized by imaging findings of demyelination, inflammation, and contrast enhancement on magnetic resonance imaging, suffers from a lack of accepted therapies for patients with advanced forms of the disease. In a recent STEM CELLS Translational Medicine article, researchers led by Troy Lund (University of Minnesota, USA) report on their attempts to deliver mesenchymal stem cells (MSCs) via the intrathecal route in two boys with rapidly advancing CALD in hopes of utilizing their anti‐inflammatory ability to halt disease progression. Gupta et al. noted the feasibility and ease of this administration route; however, subsequent follow‐up showed progressive demyelination in both patients, perhaps due to the advanced nature of the disease in the patients or an inadequate cell dose.
A new STEM CELLS Translational Medicine article led by Naoya Uchida (National Institutes of Health, Bethesda, MD, USA) describes the successful correction of the sickle mutation in induced pluripotent stem cells derived from a patient with sickle cell disease (SCD). Haro‐Mora et al. employed an improved serum‐free technique that included the generation of induced pluripotent stem cell‐sacs, a hemangioblast‐like structure containing hematopoietic stem and progenitor cells that can be differentiated into erythroid cells containing mostly definitive globins.
The liver is an essential organ in the body that performs crucial functions such as metabolism, and recently, researchers have invested enormous resources to generate liver cells from induced pluripotent stem cells and to develop robust three-dimensional liver organoids that faithfully resemble the liver. Now, a team led by Setjie W. Maepa and Hlumani Ndlovu (University of Cape Town, South Africa) review in detail those advances that have been achieved towards the development of protocols to generate hepatocytes, cholangiocytes, and Kupffer cells, and discuss the application of these tools to model liver disease with a specific focus on hepatic steatosis, acute liver failure, and drug-induced liver injury. For all this, and more, see STEM CELLS now!
A recent STEM CELLS article from researchers led by Yogita K. Adlakha (National Brain Research Centre, Manesar, India) describes the derivation of human neural stem cells (hNSCs) from human induced pluripotent stem cells (hiPSCs) that faithfully display immunoreactivity towards NSC markers and serve as a model to study neurological diseases. Using this model, Channakkar et al. show that a brain enriched small non‐coding RNA (miR‐137) enhances neuronal differentiation by inducing mitochondrial biogenesis, fusion, fission, and oxidative phosphorylation. The authors hope that this newly described pathway may facilitate the design of treatments for aging‐associated neurodegenerative diseases.
The transplantation of gene-edited stem cells represents a promising strategy for the treatment of neurodegenerative diseases. Huntington's disease (HD) is one such neurodegenerative diseases in which this strategy has been studied; however, the transfer of mutant huntingtin (HTT) protein aggregates from HD cells to transplanted stem cells in the host brain by a “prion‐like” mechanism represents a recently-identified issue and brings into a question to what extent stem cell/gene‐corrected cell transplants are viable for the treatment of HD. For more on this fascinating topic, see the recent STEM CELLS Translational Medicine Concise Review article from the laboratory of Julien Rossignol (Central Michigan University, Mount Pleasant, Michigan USA).
Nicotinamide adenine dinucleotide (NAD+) induces an intermediate state of naivety in human embryonic stem cells (hESCs) characterized by a shift from glycolytic to oxidative metabolism, increased self‐renewal, and epigenetic alterations. Conversely, inhibition of the malate aspartate shuttle (MAS), which recycles NAD+, causes a dramatic loss of oxidative metabolism and pluripotency marker expression. Now, a new study from the laboratory of David K. Gardner (University of Melbourne, Parkville, VIC, Australia) reveals a vital role for MAS in regulating the metabolic state of hESCs. Collectively, the findings reported recently in STEM CELLS indicate that NAD+ availability is not only regulated by MAS but also that NAD+ is critical to the maintenance of self‐renewal in hESCs and a potential regulator of the pluripotent state.
Successful pre‐clinical studies in animal models heralded the increasing clinical interest of cord blood in regenerative therapy. Controlled clinical trials in patients with cerebral palsy and type I diabetes, amongst other conditions, provided results highlighting that heterogeneity in the cellular product, patients, study design, and the timing of outcome measurements remain as barriers to metanalysis and a clearer understanding of efficacy. Controlled studies of modest size have been reported for a range of additional conditions. The conduct of controlled clinical trials to evaluate potential new uses of cord blood for regenerative therapy remains essential, and consistency in outcome reporting in terms of the instruments used and the time points for assessment after therapy are needed, including longer follow up of study participants. Frequent and careful evaluation of the evidence will allow cord blood banks, health care providers, and patients to assess potential new options in the use of cord blood for regenerative therapy. For more on this subject, see a recent STEM CELLS article from David Allan (Ottawa Hospital Research Institute, University of Ottawa and Canadian Blood Services).
Hematopoietic stem cell transplantation (HSCT) is commonly used to treat leukemias and severe disorders of the blood and immune system; however, the extension of HSCT to many patients in need of transplant, or into various new areas of disease that might benefit, remains problematic. This vast, untapped potential results from inadequate sources of healthy, immune‐compatible stem cells for transplant, technological barriers to efficient engraftment, and the significant health risks associated with the HSCT procedure itself. Now, a new Perspective article published in STEM CELLS Translational Medicine elaborates on current limitations of HSCT and describes novel strategies to overcome them, including key innovations developed with support from the California Institute for Regenerative Medicine. The authors, from the labs of Sohel Talib and Kelly A. Shepard (California Institute for Regenerative Medicine, Oakland, California, USA) believe that addressing these challenges could greatly expand the feasibility and accessibility of HSCT to all who might benefit, and enable HSCT to serve as a leading paradigm for developing new stem cell-based therapies in the future.
A new study published in STEM CELLS Translational Medicine reveals the transcriptional identities of human fetal mesoangioblasts derived from the aorta and cardiac and skeletal muscle tissues, with specific gene signatures correlating with the myogenic differentiation properties inherent to their derivative tissues. Gene network analysis carried out by researchers from the lab of Marisa E. Jaconi (University of Geneva, Switzerland) identified four major superclusters of differentially expressed genes and uncovered a global set of upregulated and downregulated genes between skeletal and cardiac muscle mesoangioblasts, with those from the aorta exhibiting an intermediate profile. Collectively, Ronzoni et al. provide a set of critical genes accounting for, and possibly predicting, lineage‐specific differentiation commitment during development, which may help to improve the future management of muscle regeneration.