Cellular reprogramming最新文献

Blastoids are stem cell-based cellular models that resemble preimplantation embryos and have the potential to ease the investigation of developmental processes and associated diseases. Despite the fast-paced progress of blastoid technology in mice and humans, there was limited evidence of its potential for nonhuman primates. Wu et al. developed a highly efficient protocol for blastoid production in rhesus monkeys and performed standard assays for blastoid characterization at the cellular and molecular levels. By applying cellular reprogramming, Wu et al. generated blastoids from young and aged monkeys. The integration of blastoid protocol with microfluidics allowed their production at scale. If follow-up reports describe blastoid differentiation to peri- and post-implantation stages, it may place rhesus monkeys as an attractive model species for exploring mammalian development ex vivo.

The global prevalence of obesity continues to rise with no signs of slowing. Because obesity is a risk factor for numerous diseases, it diminishes both quality of life and life expectancy. Hence, developing effective strategies for obesity prevention and treatment is an urgent priority. Brown and beige adipocytes dissipate energy as heat via nonshivering thermogenesis, making them promising targets for treating metabolic disorders such as obesity. Since the 2009 discovery of metabolically active brown adipose tissue in adult humans, significant progress has been made in elucidating the developmental origins and physiological roles of brown and beige adipocytes. However, many aspects of their intrinsic biology remain poorly understood. In vitro analyses are indispensable for overcoming the limitations of in vivo studies, but isolating human brown adipocytes for culture is ethically and technically challenging. Therefore, just as in vitro models of white adipocytes have been invaluable for understanding adipose biology, establishing reliable in vitro systems for brown and beige adipocytes is crucial. This review summarizes current methodologies for generating brown and beige adipocytes in vitro-including cellular reprogramming approaches-a technological advance poised to accelerate future research on these thermogenic adipocytes.

The aim of this study is to investigate the effects of a peptide mixture composed of arginine (Arg), aspartic acid (Asp), and phenylalanine (Phe) on the proliferation and neural differentiation of human dermal mesenchymal stem cells (HDMSCs). HDMSCs were isolated from residual skin tissue following circumcision and purified using a combination of long-term trypsin stress and suspension culture. The impact of the peptide mixture on HDMSC proliferation was assessed at various concentrations using a Cell Counting Kit-8 (CCK-8) assay. Based on preliminary screening of proliferative activity, an optimal peptide mixture concentration for promoting proliferation was selected for further HDMSCs culture. During this culture, morphological changes were observed. Differentiation efficiency was evaluated using immunofluorescence staining for the neural markers Nestin and Neurofilament-L (NF-L) at weeks 3 and 6 of culture, respectively. Primary adherent HDMSCs exhibited a long spindle morphology and formed spherical cell clusters in suspension culture. A peptide mixture at concentrations of 5 ng/mL Arg, 20 ng/mL Asp, and 40 ng/mL Phe significantly promoted HDMSC proliferation (p < 0.05). During the induction period, the cells gradually acquired neuronal morphological characteristics, including cell body contraction and process extension. Immunofluorescence results showed that the cells expressed Nestin by week 3, shifting to NF-L positivity by week 6. This indicates that the peptide mixture induced the differentiation of HDMSCs into neural cells. A peptide mixture containing Arg, Asp, and Phe has been shown to effectively induce the differentiation of HDMSCs into neural cells. This provides a novel and safe strategy for the regeneration of neural tissue.

Reproductive disorders affect millions of women worldwide, playing a crucial role in determining female fertility health and quality of life. Conventional methods such as surgery, hormone therapy, and assisted reproductive technologies can be successful in some cases, but are limited by adverse effects, and limited effectiveness. In recent years, cell therapy has provided new possibilities for treating various infertility disorders. The articles extracted from PubMed and Scopus databases were based on cell therapy premature ovarian failure (POF), intrauterine adhesions, Asherman syndrome (AS), recurrent implantation failure (RIF), repeat implantation failure, polycystic ovary syndrome (PCOS), endometriosis, preeclampsia, and clinical trials. The collected articles were added to EndNote X7, and review articles along with duplicate studies were eliminated. Several studies have indicated that peripheral blood mononuclear cells, autologous platelet-rich plasma, mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs), adipose-derived stromal vascular fraction, and umbilical cord stem cells can be used to treat reproductive diseases, including POF, AS, and RIF. PCOS, endometriosis, and preeclampsia were deleted from the study, because there were no clinical cell therapy studies for these diseases. Among the 210 studies, 28 were selected as eligible for further evaluation. Various clinical trials have supported the role of cell therapy in treating reproductive disorders. Although the information from this systematic review is promising, further studies are needed to evaluate the efficacy and safety of these and other cells in treating infertility.

Sahu et al. (2024) demonstrate that targeted partial reprogramming with Oct4, Sox2, and Klf4 (OSK) delivered via adeno-associated virus (AAV) to Cdkn2a-positive cells rejuvenates senescent cells while maintaining cellular identity. In a progeroid and naturally aged mouse model, a single AAV injection improved lifespan, reduced inflammation, restored tissue integrity, and enhanced wound healing. Complementary results in human fibroblasts confirmed Cdkn2a-driven OSK expression attenuated inflammation-associated genes during replicative senescence and treatments inducing DNA damage. These encouraging results highlight its potential as a safer alternative to systemic senolytic therapies for age-associated disorders.

Stem cells may be manipulated in vitro to induce hepatic differentiation. We investigated the effect of hypoxia and photobiomodulation therapy (PBMT) on the hepatogenic differentiation of human adipose-derived stem cells (hASCs). hASCs were exposed to different carbon dioxide concentrations with photobiomodulation (PBM) using low-level light. Cell survival and secretion of hepatocyte growth factor (HGF) of the hASCs were evaluated by immunostaining and Western blot analyses. Hepatic differentiation was assessed via immunocytochemical staining, fluorescence-activated cell sorting, and Western blot analysis for liver-specific genes and proteins, including albumin (ALB), cytokeratins 8/18, and alpha-fetoprotein (AFP). PBM therapy has been shown to enhance proliferation and cytokine secretion of a number of cells. The expression profiles of ALB, AFP, and cytokeratin 8/18 demonstrated that when HGF, hypoxia, or PBMT were treated individually, incomplete hepatocyte differentiation was achieved. In contrast, quantitative analysis of ALB, cytokeratins 8/18, and AFP showed that HGF was enhanced significantly by hypoxia+PBM treatment. The obtained cell populations contained progenitors that expressed both hepatic ALB and cytokeratin 8/18 markers, as well as AFP. These data suggest that PBMT and hypoxia are effective biostimulators of hASCs in hepatogenic differentiation, which enhances the survival of hASCs and stimulates the secretion of growth factors.