Current Stem Cell Reports最新文献

Purpose of review: Organoids are an emerging technology utilizing three-dimensional (3D), multi-cellular in vitro models to represent the function and physiological responses of tissues and organs. By using physiologically relevant models, more accurate tissue responses to viral infection can be observed, and effective treatments and preventive strategies can be identified. Animals and two-dimensional (2D) cell culture models occasionally result in inaccurate disease modeling outcomes. Organoids have been developed to better represent human organ and tissue systems, and accurately model tissue function and disease responses. By using organoids to study SARS-Cov-2 infection, researchers have now evaluated the viral effects on different organs and evaluate efficacy of potential treatments. The purpose of this review is to highlight organoid technologies and their ability to model SARS-Cov-2 infection and tissue responses.

Recent findings: Lung, cardiac, kidney, and small intestine organoids have been examined as potential models of SARS-CoV-2 infection. Lung organoid research has highlighted that SARS-CoV-2 shows preferential infection of club cells and have shown value for the rapid screening and evaluations of multiple anti-viral drugs. Kidney organoid research suggests human recombinant soluble ACE2 as a preventative measure during early-stage infection. Using small intestine organoids, fecal to oral transmission has been evaluated as a transmission route for the virus. Lastly in cardiac organoids drug evaluation studies have found that drugs such as bromodomain, external family inhibitors, BETi, and apabetalone may be effective treatments for SARs-CoV-2 cardiac injury.

Summary: Organoids are an effective tool to study the effects of viral infections and for drug screening and evaluation studies. By using organoids, more accurate disease modeling can be performed, and physiological effects of infection and treatment can be better understood.

Purpose of review: Cryopreservation and its associated freezing and thawing procedures-short "freeze-thawing"-are among the final steps in economically viable manufacturing and clinical application of diverse cellular therapeutics. Translation from preclinical proof-of-concept studies to larger clinical trials has indicated that these processes may potentially present an Achilles heel to optimal cell product safety and particularly efficacy in clinical trials and routine use.

Recent findings: We review the current state of the literature on how cryopreservation of cellular therapies has evolved and how the application of this technique to different cell types is interlinked with their ability to engraft and function upon transfer in vivo, in particular for hematopoietic stem and progenitor cells (HSPCs), their progeny, and therapeutic cell products derived thereof. We also discuss pros and cons how this may differ for non-hematopoietic mesenchymal stromal/stem cell (MSC) therapeutics. We present different avenues that may be crucial for cell therapy optimization, both, for hematopoietic (e.g., effector, regulatory, and chimeric antigen receptor (CAR)-modified T and NK cell based products) and for non-hematopoietic products, such as MSCs and induced pluripotent stem cells (iPSCs), to achieve optimal viability, recovery, effective cell dose, and functionality of the cryorecovered cells.

Summary: Targeted research into optimizing the cryopreservation and freeze-thawing routines and the adjunct manufacturing process design may provide crucial advantages to increase both the safety and efficacy of cellular therapeutics in clinical use and to enable effective market deployment strategies to become economically viable and sustainable medicines.

Purpose of review: Human pluripotent stem cells have the potential to revolutionize the treatment of inborn and degenerative diseases, including aging and autoimmunity. A major barrier to their wider adoption in cell therapies is immune rejection. Genome editing allows for tinkering of the human genome in stem and progenitor cells and raises the prospect for overcoming the immune barriers to transplantation.

Recent findings: Initial attempts have focused primarily on the major histocompatibility barrier that is formed by the human leukocyte antigens (HLA). More recently, immune checkpoint inhibitors, such as PD-L1, CD47, or HLA-G, are being explored both, in the presence or absence of HLA, to mitigate immune rejection by the various cellular components of the immune system.

Summary: In this review, we discuss progress in surmounting immune barriers to cell transplantation, with a particular focus on genetic engineering of human pluripotent stem and progenitor cells and the therapeutic cell types derived from them.

Purpose of review: Cell and tissue products do not just reflect their present conditions; they are the culmination of all they have encountered over time. Currently, routine cell culture practices subject cell and tissue products to highly variable and non-physiologic conditions. This article defines five cytocentric principles that place the conditions for cells at the core of what we do for better reproducibility in Regenerative Medicine.

Recent findings: There is a rising awareness of the cell environment as a neglected, but critical variable. Recent publications have called for controlling culture conditions for better, more reproducible cell products.

Summary: Every industry has basic quality principles for reproducibility. Cytocentric principles focus on the fundamental needs of cells: protection from contamination, physiologic simulation, and full-time conditions for cultures that are optimal, individualized, and dynamic. Here, we outline the physiologic needs, the technologies, the education, and the regulatory support for the cytocentric principles in regenerative medicine.

Purpose of review: How stem cells balance proliferation with differentiation, giving rise to specific daughter cells during development to build an embryo or tissue, remains an open question. Here, we discuss recent evidence that cytokinetic abscission regulation in stem cells, particularly neural stem cells (NSCs), is part of the answer. Abscission is a multi-step process mediated by the midbody, a microtubule-based structure formed in the intercellular bridge between daughter cells after mitosis.

Recent findings: Human mutations and mouse knockouts in abscission genes reveal that subtle disruptions of NSC abscission can cause brain malformations. Experiments in several epithelial systems have shown that midbodies serve as scaffolds for apical junction proteins and are positioned near apical membrane fate determinants. Abscission timing is tightly controlled and developmentally regulated in stem cells, with delayed abscission in early embryos and faster abscission later. Midbody remnants (MBRs) contain over 400 proteins and may influence polarity, fate, and ciliogenesis.

Summary: As NSCs and other stem cells build tissues, they tightly regulate three aspects of abscission: midbody positioning, duration, and MBR handling. Midbody positioning and remnants establish or maintain cell polarity. MBRs are deposited on the apical membranes of epithelia, can be released or internalized by surrounding cells, and may sequester fate determinants or transfer information between cells. Work in cell lines and simpler systems has shown multiple roles for abscission regulation influencing stem cell polarity, potency, and daughter fates during development. Elucidating how the abscission process influences cell fate and tissue growth is important for our continued understanding of brain development and stem cell biology.