P1336: longterm ex vivo expansion of functional murine and human hematopoietic stem cells using bone-lining stromal cells
HemaSphere(2023)
摘要
Topic: 23. Hematopoiesis, stem cells and microenvironment Background: Hematopoietic stem cells (HSCs) have the potential to treat various hematological disorders, but the limited availability of HSCs for transplantation remains a significant clinical challenge. Ex vivo expansion of HSCs is a promising approach to overcome this shortcoming, but current methods have limitations, such as reduced self-renewal capacity and differentiation potential. While there have been recent attempts to expand HSCs using optimized media, stable ex vivo expansion of HSCs remains limited. Given the substantial clinical importance of HSCs for bone marrow transplantation, robustly functioning systems with preservation of HSC self-renewal ex vivo are urgently needed. Aims: The aim of this study is to investigate the potential of functionally defined bone lining reinvigorated mesenchymal stem cells (rMSCs) to facilitate ex vivo expansion of both murine and human hematopoietic stem cells (HSCs) with importance to clinical hematology. Methods: Using bone digestion followed by flow cytometry, bone-lining mesenchymal stromal cells were successfully isolated, cultured and expanded, and subsequently long-term co-cultured with HSCs. The isolation process established in mice was successfully implemented in the human system using human femur bones for the isolation of the stromal cells. Results: We have established a reproducible and robust protocol for the isolation and subsequent expansion of bone-lining rMSCs, functionally defined by their capability to ex vivo maintain and expand HSCs. During long-term in vitro expansion together with rMSCs, HSCs retained their phenotypic stem cell state with functional bone marrow reconstitution capacity. Additionally, the co-culture system allowed for clonal expansion of single HSCs, which could have exciting applications in rare diseases and may significantly reduce the number of experimental animals required for HSC analysis. The isolation process for rMSCs established in mice was successfully implemented in the human system, and initial co-culture experiments of human rMSCs and human HSCs suggest similar maintenance and expansion of human HSCs ex vivo. Summary/Conclusion We could show that growth-promoting, functionally defined rMSCs can be used in a co-culture with HSCs to effectively ex vivo maintain and expand functional HSCs. The results suggest exciting new research and therapeutic opportunities for gene therapy and personalized medicine Keywords: Bone Marrow, Hematopoietic stem cell, Mesenchymal stem cell, Ex vivo expansion
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关键词
stem cells,stromal cells,longterm ex vivo expansion,human hematopoietic,vivo expansion,bone-lining
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