Stem Cell Reviews and Reports最新文献

Demyelinating diseases, such as multiple sclerosis, damage the protective myelin sheaths of the central nervous system. The development of effective therapies has been hampered by the lack of models that accurately replicate human myelin biology. Here we present a novel method to generate human myelin spheres (MyS) by coculturing of hPSC-derived neuronal and oligodendrocyte precursor cells, to create myelinated neurons. Using multimodal analyses including confocal and (electron)microscopy, single-nuclei transcriptomics, lipidomics, and electrophysiology, we demonstrate myelination in MyS as early as six weeks into coculture. These myelinated structures mature over time into multilamellar and compacted myelin sheaths with lipid compositions and transcriptomic profiles mirror the temporal dynamics of in vivo human oligodendrocyte development and neuronal myelination, resembling those of late fetal oligodendrocytes. By employing lysolecithin-induced demyelination and Rabies virus infection experiments, we demonstrate the potential of MyS as an innovative, physiologically relevant platform for studying myelin-related neurodegeneration and neuroinfection.

Despite recent novel drug approvals and numerous treatment options, the steroid-refractory chronic graft-versus-host disease (SR-cGvHD) remains a significant clinical problem. We aimed to evaluate the efficacy and safety of available therapies in adult patients, based on a systematic review and meta-analysis. The analyzed treatment options included: axatilimab, belumosudil, extracorporeal photopheresis (ECP), ibrutinib, imatinib, rovadicitinib, and ruxolitinib. The endpoints included: best overall response rate (ORR), 12-month failure-free survival (FFS), the ratio of patients who discontinued therapy due to unacceptable toxicity, and the ratio of patients who experienced grade 3-5 adverse events. Rovadicitinib was the most effective treatment option, with manageable safety profile. Axatilimab produced a high response rate, yet worse 12-month FFS. It was a very safe option in SR-cGvHD. Despite promising efficacy, belumosudil produced the highest incidence of adverse events of all drugs. Ruxolitinib was proven to be an efficient and safe drug. Ibrutinib produced poor results in terms of both efficacy and safety. ECP was proven to be a very safe therapy, without spectacular efficacy. The analysis of imatinib yielded inconsistent results. As cGvHD is a disease with a heterogeneous clinical image, clinical experience remains an important factor that affects treatment choice for patients with certain disease manifestations.

Regenerative medicine promises the possibility of custom-made, ready-to-use human organs without the risk of immune rejection. Human pluripotent stem cells (hPSCs) are the workhorses of stem cell-based tissue engineering. With inherent capabilities to adopt nearly any cellular form, they are supposed to solve the soaring demand for transplantable organs. Technically, PSCs are converted into cells of interest using a stepwise approach (differentiation) mimicking embryonic development. Animal models have been crucial in advancing our understanding of human embryology, mainly due to the widespread conservation of the mammalian regulome. Differentiation protocols have evolved with time from two-dimensional (2D) monocultures, which are relatively easy to maintain, to more complex three-dimensional (3D) organoids that enhance the capacity for staging multilineage assemblies. The appeal of 3D systems lies in their operational resemblance to the actual morphology of tissues. While each platform has pros and cons, its specific strengths can be leveraged to tell a more compelling story of development and how complex pathologies take root. Here, we reviewed key methodologies for the in vitro production of human functional cell lineages from hPSCs. We have connected the most recent science to the work that came before and analyzed where the trends we see now might lead. We examined the shift from 2D cell monolayers to 3D organoids. Additionally, we highlighted hybrid approaches and innovative discoveries that support the reliable generation of physiologically mature cells, enabling the study of development and disease at new depths.

Estrogen deficiency-induced uterine atrophy is a major cause of menstrual disorders and infertility in postmenopausal women and patients with premature ovarian failure. However, current hormone replacement therapies carry long-term risks and fail to achieve physiological endometrial regeneration. It has been demonstrated that dimethyloxalylglycine (DMOG) can augment the therapeutic effects of mesenchymal stem cells (MSCs), but the effects of DMOG-pretreated MSCs on Estrogen deficiency-induced uterine atrophy remain unclear. This study aimed to explore whether DMOG-pretreated human umbilical cord MSCs (hUC-MSCs) could repair estrogen deficiency-induced uterine atrophy. The results showed that compared with the MSCs group, the DM group significantly improved the disordered estrous cycle of ovariectomy (OVX) mice, increased serum estradiol (E2) levels, and restored uterine morphology and index, and facilitated the recovery of endometrial thickness and gland number. Masson staining confirmed that the DM group had a more significant reduction in endometrial fibrosis. Immunofluorescence demonstrated enhanced expression of Oct-4 and Nanog in the DM group, which suggests that DMOG-pretreated hUC-MSCs may exert paracrine effects to promote the formation of VSELs, thereby facilitating the remodeling of endometrial epithelial structure. This provides a novel and effective strategy for the treatment of estrogen deficiency-related uterine atrophy.