Cell Regeneration最新文献

Knee osteoarthritis is the most common joint disease. It causes pain and suffering for affected patients and is the source of major economic costs for healthcare systems. Despite ongoing research, there is a lack of knowledge regarding disease mechanisms, biomarkers, and possible cures. Current treatments do not fulfill patients' long-term needs, and it often requires invasive surgical procedures with subsequent long periods of rehabilitation. Researchers and companies worldwide are working to find a suitable cell source to engineer or regenerate a functional and healthy articular cartilage tissue to implant in the damaged area. Potential cell sources to accomplish this goal include embryonic stem cells, mesenchymal stem cells, or induced pluripotent stem cells. The differentiation of stem cells into different tissue types is complex, and a suitable concentration range of specific growth factors is vital. The cellular microenvironment during early embryonic development provides crucial information regarding concentrations of signaling molecules and morphogen gradients as these are essential inducers for tissue development. Thus, morphogen gradients implemented in developmental protocols aimed to engineer functional cartilage tissue can potentially generate cells comparable to those within native cartilage. In this review, we have summarized the problems with current treatments, potential cell sources for cell therapy, reviewed the progress of new treatments within the regenerative cartilage field, and highlighted the importance of cell quality, characterization assays, and chemically defined protocols.

Cell metabolism plays vital roles in organismal development, but it has been much less studied than transcriptional and epigenetic control of developmental programs. The difficulty might be largely attributed to the lack of in situ metabolite assays. Genetically encoded fluorescent sensors are powerful tools for noninvasive metabolic monitoring in living cells and in vivo by highly spatiotemporal visualization. Among all living organisms, the NAD(H) and NADP(H) pools are essential for maintaining redox homeostasis and for modulating cellular metabolism. Here, we introduce NAD(H) and NADP(H) biosensors, present example assays in developing organisms, and describe promising prospects for how sensors contribute to developmental biology research.

Cellular reprogramming has rapidly become a promising methodology to generate new cardiomyocytes from non-cardiomyocyte cell types. Using the transient expression of OSKM factors, Chen et al. demonstrate a unique reprogramming strategy involving the modulation of the resident adult cardiomyocyte identity to an immature proliferative state (Science 373:1537-40, 2021). This OSKM-mediated reversion results in the adoption by adult murine cardiomyocytes of a transcriptional profile similar to cardiomyocytes found in developing hearts, as well as increased proliferative capacity of these reprogrammed cardiomyocytes compared to mature cardiomyocytes. Furthermore, this novel approach enhances the regeneration of adult murine hearts post-myocardial injury. Although concerns and questions remain, the encouraging results of this study advance the field of cardiac regeneration by providing a new technique to generate cardiomyocytes as well as insights into cardiomyocyte dedifferentiation and its relation to proliferation.

Stem cell-based embryo models present new opportunities to study early embryonic development. In a recent study, Kagawa et al. identified an approach to create human pluripotent stem cell-based blastoids that resemble the human blastocysts. These blastoids efficiently generated analogs of the EPI, TE, PrE lineages with transcriptomes highly similar to those found in vivo. Furthermore, the formation of these lineages followed the same sequence and pace of blastocyst development, and was also dependent on the same pathways required for lineage specification. Finally, the blastoids were capable of attaching to stimulated endometrial cells to mimic the process of implantation. While more comprehensive analysis is needed to confirm its validity and usefulness, this new blastoid system presents the latest development in the attempt to model early human embryogenesis in vitro.