| Mesenchymal stem cells(MSC)is a kind of adult multipotent stem cells originated from the mesoderm,which has the ability of self-renewal,proliferation and differentiation Currently,MSC has been widely used in clinical trials for the treatment of different diseases and is expected to become the main force of cell therapy in the future.MSC can be isolated from a lot of tissues,such as adipose,umbilical cord,placenta,dental pulp However,how to choose the type of MSC according to the disease is still a difficult problem.Adipose-derived stem cells(ADSC)and bone marrow mesenchymal stem cells(BMSC)are both used in clinical studies to treat osteoarthritis,but it is not known which one is more suitable?Here,we use the evidence of single-cell altas to answer the question In the first chapter,the characteristics and clinical efficacy of ADSC and BMSC were compared by combining single cell RNA sequencing(scRNA-seq)analysis,bulk cell level verification,and meta-analysis of clinical trials.In the second chapter,based on the conclusions of the first chapter,we compared the characteristics of adipose tissues of different depots and age,as well as the MSC isolated from these adipose tissuesChapter 1 scRNA-seq analysis of ADSC and BMSC showed that ADSC had higher transcriptome homogeneity,higher immunosuppression capacity and lower immunogenicity.In addition,the results of meta-analysis revealed that ADSC was more stable than BMSC in clinical trials of cellular therapy for osteoarthritis.These results suggest that ADSC may be superior to BMSC in the treatment of osteoarthritisChapter 2 After initially identifying the potential advantages of ADSC for inflammatory regulation and treatment of osteoarthritis,this study further explored the differences in adipose tissues at different depots and age,and how these differences affect the function of ADSC.To answer the above questions,this study performed scRNA-seq to analyze the cell composition of adipose tissues in different depots,and found that the proportion of anti-inflammatory M2 macrophage in gluteofemoral subcutaneous adipose tissue(GSAT)was significantly higher than that in abdominal subcutaneous adipose tissue(ASAT),which contained more collagen;GSAT and ASAT took different ways to response to aging,and AS AT was characterized by the proliferation of T cells and the apoptosis of adipose progenitor cells during aging,while the endothelial cells of GSAT underwent severe remodeling;In vitro differentiation experiments of ADSC showed that ADSC derived from young GSAT had the optimal adipogenic and osteogenic differentiation potential.What's more,ADSC derived from GSAT could better resist the loss of differentiation potential caused by aging.These results suggest that GSAT may be a better source of ADSC than ASAT.To sum up,this study analyzed the biological and clinical characteristics of ADSC and BMSC from multiple perspectives,revealing the advantages of ADSC in inflammation regulation and osteoarthritis treatment.The unique advantage of GSAT and the good state of GSAT derived ADSC was identified through the analysis of adipose tissue cell atlas of different depots and different age as well as ADSC in vitro functional verification.This work provides a new strategy for the biological study of MSC,provides a theoretical basis for the source selection of MSC therapy,and lays a foundation for the development of MSC-based precision medicine. |
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