State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China.
Cell Prolif. 2023 May;56(5):e13472. doi: 10.1111/cpr.13472. Epub 2023 May 17.
Haematopoietic stem cell transplantation (HSCT) is widely used in regenerative medicine. HSCT can be used not only to treat certain types of blood cancer and immune disorders but also to induce immune tolerance in organ transplantation. However, the inadequacy of HSCs available for transplantation is still a major hurdle for clinical applications. Here, we established a novel inducible haematopoietic cell-depleting mouse model and tested the feasibility of using chimeric complementation to regenerate HSCs and their progeny cells. Large populations of syngeneic and major histocompatibility-mismatched haematopoietic cells were successfully regenerated by this model. The stable allogeneic chimeric mice maintained a substantial population of donor HSCs and Tregs, which indicated that the donor allogeneic HSCs successfully repopulated the recipient blood system, and the regenerated donor Tregs played essential roles in establishing immune tolerance in the allogeneic recipients. In addition, rat blood cells were detected in this model after xenotransplantation of rat whole bone marrow (BM) or Lin BM cells. This mouse model holds promise for regenerating xenogeneic blood cells, including human haematopoietic cells.
造血干细胞移植（HSCT）广泛应用于再生医学。HSCT 不仅可用于治疗某些类型的血液癌症和免疫性疾病，还可诱导器官移植中的免疫耐受。然而，可供移植的 HSCs 不足仍然是临床应用的主要障碍。在这里，我们建立了一种新型的诱导性造血细胞耗竭小鼠模型，并测试了利用嵌合互补来再生 HSCs 及其祖细胞的可行性。该模型成功地再生了大量的同基因和主要组织相容性不合的造血细胞。稳定的同种异体嵌合小鼠保持了大量的供体 HSCs 和 Tregs，这表明供体同种异体 HSCs 成功地重新填充了受者的血液系统，而再生的供体 Tregs 在同种异体受者中建立免疫耐受方面发挥了重要作用。此外，在大鼠骨髓（BM）或 Lin BM 细胞异种移植后，该模型中检测到了大鼠的血细胞。这种小鼠模型有望再生异种血细胞，包括人类造血细胞。
