Project description:As a key factor for differentiation and development, IGF-1 has attracted scientists’ attention gradually in recent years. However, its exact effects in human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are still unclear. In this study, we mainly investigated whether IGF-1 could affect some biological functions of UC-MSCs.
Project description:This study revealed the heterogeneity of UC-MSCs using single-cell sequencing technology (10x Genomics). Through in vitro and in vivo experiments, it was determined that the LRP1high UC-MSCs subpopulation has therapeutic effects in improving ovarian function. This finding provides theoretical support for the screening of stem cell preparations for use in POF, aiming to reduce the impact of other interfering cell components on ovarian tissue and provide precise, safe, and effective clinical strategies for stem cell therapy in POF. Mechanistic exploration further revealed that the LRP1high UC-MSCs subpopulation primarily improves mitochondrial function of granulosa cells by modulating DNA damage pathways, extracellular matrix-related signals, and cellular metabolism. Consequently, it more effectively enhances the quality of aging mouse oocytes, offering new insights into targeting LRP1high UC-MSCs for precise treatment of premature ovarian failure.
Project description:This study revealed the heterogeneity of UC-MSCs using single-cell sequencing technology (10x Genomics). Through in vitro and in vivo experiments, it was determined that the LRP1high UC-MSCs subpopulation has therapeutic effects in improving ovarian function. This finding provides theoretical support for the screening of stem cell preparations for use in POF, aiming to reduce the impact of other interfering cell components on ovarian tissue and provide precise, safe, and effective clinical strategies for stem cell therapy in POF. Mechanistic exploration further revealed that the LRP1high UC-MSCs subpopulation primarily improves mitochondrial function of granulosa cells by modulating DNA damage pathways, extracellular matrix-related signals, and cellular metabolism. Consequently, it more effectively enhances the quality of aging mouse oocytes, offering new insights into targeting LRP1high UC-MSCs for precise treatment of premature ovarian failure.
Project description:Cells sense the biophysical properties of the surrounding microenvironment. In particular, the stiffness of the extracellular milieu can be interrogated by cells and integrated through mechanotransduction. Many cellular processes (like proliferation, migration, or differentiation) depend on the mechanical status of the cell (being largely dictated by actomyosin-dependent intracellular contractility), which in turn is influenced by the mechanical properties of the microenvironment. In this study, we explored the influence of substrate stiffness on the proteome of undifferentiated human umbilical cord matrix mesenchymal stem/stromal cells (hUCM-MSCs). The relative abundance of several identified proteins suffered significant changes when comparing between substrates. Interestingly, many of such proteins are related to the regulation of the actin cytoskeleton, a main player of mechanotransduction and cell physiology in response to mechanical cues.
Project description:Human umbilical cord matrix-mesenchymal stromal cells (hUCM-MSC) have demonstrated beneficial effects in experimental acute myocardial infarction (AMI). In this study, we investigated the outcome of the delivery of hUCM-MSC after reperfusion in a translational model of AMI in swine. We have found that intracoronary injection of the cell product was associated with improved systolic function and that improvement in mechanical performance. This did not depend on the reduction of morphological infarct size alone, despite treated animals showing signs of less adverse remodeling.
Project description:Mesenchymal stem cells (MSCs) have been shown to exert therapeutic effects on various autoimmune diseases. However, such therapeutic effect is not always achieved. Among many reasons, MSC culture methodologies may account for the these differences. It is known that oxygen concentration could profoundly affect the properties of MSCs. Therefore, we compared human umbilical cord derived MSCs cultured under hypoxic and normoxic conditions. We used microarrays to profile the gene expression of human umbilical cord derived MSCs under 10% oxygen and normoxia conditions.
Project description:Mesenchymal stem cells (MSCs) are a population of multipotent cells with an attractive ability to promote tissue repair by regulating regeneration and inflammation. Ironically, the immune regulatory capacity of MSCs, regardless of their tissue origin, is endowed by inflammatory cytokines (e.g., IFNg plus TNFa). Effective application of MSCs relies on the production of relatively homogeneous MSCs. However, the cellular heterogeneity, and the differentiation trajectories of in vitro expanded MSCs remains unclear. We profiled the transcriptomes of 361 single MSCs derived from two umbilical cords (UC-MSCs). The MSCs are from different passages and culture conditions with or without inflammatory cytokine stimulation. Weighted gene correlation network analysis for the expression of their highly variable genes revealed that UC-MSCs surprisingly possess only limited heterogeneity. Cell cycle based principal component analysis showed that the limited heterogeneity identified in these UC-MSCs was strongly associated with their entrance into the G2/M phase. This was further proven by the observation that one featured gene CD168 was expressed in a cell-cycle dependent manner. When CD168high UC-MSCs were sorted and cultured in vitro, they repopulated into a new community that is similar to the original status. Our results demonstrated that in vitro expanded UC-MSCs is a well-organized population with limited heterogeneity dominated by cell cycle status. Thus, our studies argues that standardization of MSCs for disease treatment is possible.
Project description:This study reports a case of a 4-year-old boy patient with abnormalities of muscle tone, movement and motor skills, as well as unstable gait leading to frequent falls. The results of the electroencephalogram (EEG) indicate moderately abnormal EEG, accompanied by irregular seizures. Based on these clinical characteristics, the patient was diagnosed with cerebral palsy (CP) in our hospital. In this study, the patient was treated with umbilical cord mesenchymal stem cell (UC-MSC) transplantation therapy. This patient received UC-MSC transplantation 3 times (5.3*107) in total. After three successive cell transplantations, the patient recovered well and showed obvious improvements in EEG and limb strength, motor function, and language expression. However, the improvement in intelligence quotient (IQ) was less obvious. These results indicate that UC-MSC transplantation is a promising treatment for cerebral palsy.
Project description:A non-controversial and non-invasive source of adult stem cells (ASCs), particularly hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) is human umbilical cord blood. HSCs derived from cord blood have been used for treating leukemia and other blood disorders for the last 30 years. While the presence of MSCs in cord blood is limited, umbilical cord has been found to be promising source of MSCs. However, the cord is an anatomically complex organ and potential isolation of MSCs from its various parts has not been fully explored. In this study we dissected the cord into cord placenta junction (CPJ), cord tissue (CT), and Wharton’s jelly (WJ) and isolated stem cells. These cells exhibited fibroid morphology, expressed MSC-specific markers including CD90, CD73, CD105, CD44, and CD29 and differentiated into chondrogenic, osteogenic, myogenic and neurogenic lineages. In addition, they all expressed pluripotency genes, OCT4, Nanog, Sox2 and KLF4 but expression of these markers was highest in CPJ followed by WJ and CT. CPJ-MSCs also had higher rate of proliferation compared to WJ- and CT-MSCs. Proliferation of WJ- and CT-MSCs was markedly decreased upon passaging with concomitant decrease in expression of MSC and pluripotency markers. Based on their greater self-renewal potential, CPJ-MSCs could be superior to WJ- and CT-MSCs for the applications in therapeutic and regenerative medicine.
Project description:Mesenchymal stem cell (MSC) transplantation may serve as an important treatment modality in chronic kidney disease (CKD); however, the underlying mechanisms remain unclear. Advanced oxidation protein products (AOPP) have been demonstrated to induce renal tubular epithelial cell (RTEC) injury via autophagy inhibition. Therefore, the present study was performed to investigate the role of human umbilical cord-derived MSCs (hUC-MSCs) in RTEC autophagy. AOPP-treated HK-2 cells were co-cultured with hUC-MSCs or treated with recombinant humanized hepatocyte growth factor (HGF). Western blotting was used to detect the levels of autophagy-and PI3K/AKT/mTOR signaling pathway-related proteins, and immunofluorescence staining was used to detect the levels of autophagy-related proteins. The HGF protein levels in HK-2 cells and the hUC-MSC co-culture system were measured. The cells were subsequently treated with tivantinib, an HGF competitive inhibitor, and the levels of autophagy-related proteins were detected. Microtubule-associated protein 1 light chain 3B (LC3B) II/LC3B I (LC3II/LC3I) and beclin 1 protein levels were increased, while p62, PI3K, phosphorylated (p)-AKT and the p-mTOR protein levels were decreased in AOPP-treated HK-2 cells co-cultured with hUC-MSC, compared with the group treated with AOPP only. Furthermore, HGF expression was increased in AOPP-treated HK-2 cells co-cultured with hUC-MSC, compared with the group treated with AOPP alone. When HGF activity was inhibited using tivantinib, these effects on LC3II/LC3I, beclin 1, p62, PI3K, p-AKT, and p-mTOR expression were partially reversed. Furthermore, the effects of tivantinib were reversed by Ly294002. In conclusion, the present study revealed that hUC-MSCs partially reversed AOPP-mediated inhibition of autophagy in HK-2 cells via secretion of HGF, indicating that hUC-MSCs may serve as a potential therapy for preventing the progression of CKD.