Title : IPSC-MSCs for cell and gene therapy in cartilage repair
Abstract:
Human mesenchymal stem cells (MSCs) represent the most used stem cells for clinical application, which have been used in over 1500 clinical trials to treat over 30 diseases due to multilineage differentiation potential, secretome and immunosuppression. The clinical application of MSCs is greatly hampered by limited life span of primary MSCs, resulting in insufficient cells. To overcome this problem, we established a step-wise, chemically defined and highly efficient iPSC-MSC platform, which will provide an alternative source of MSCs. iPSC-MSCs displayed similar surface antigen profile, trilineage differentiation potential, gene expression profile and epigenetic profile to primary MSCs. During defining differentiation protocol, we found ascorbate promoted specification and chondrogenesis of iPSC-MSCs through ion-dependent dioxygenase. Most importantly, iPSC-MSCs can repair cartilage similar to bone marrow-derived MSCs. Using our unique iPSC-MSC platform, we screened one novel gene regulating MSC stemness. So far, little is known about key transcription factors to MSC stemness. Knockdown of this gene abolished MSC proliferation and colony formation (CFU-F). Moreover, accelerated MSC senescence and a decrease in the expression of cell surface antigens linked to the MSC phenotype was observed, multi-linage differentiation was greatly impaired. Notably, overexpression resulted in improved multi-lineage differentiation, including chondrogenesis of MSCs. The identification of the novel genes regulating stemness will provide novel strategies for gene therapy in cartilage repair.
Audience Take Away:
- Human mesenchymal stem cells (MSCs) represent the most used stem cells for clinical application.
- iPSC-MSCs will provide an unlimited alternative to primary MSCs.
- iPSC-MSCs are similar to primary MSCs in surface antigen profile, trilineage differentiation potential in vitro, gene expression profile and epigenetic profile.
- iPSC-MSCs repaired cartilage defects similar to primary MSCs
- Identification of novel genes regulating stemness improves MSC quality, which not only provides insight into molecular basis of MSC biology, but also represents promising strategies of gene therapy in cartilage repair.
