移植后饮食限制对造血重建和造血干细胞重建能力维持的影响。
Effect of Post-transplant Dietary Restriction on Hematopoietic Reconstitution and Maintenance of Reconstitution Capacity of Hematopoietic Stem Cells.
发表日期:2024 Jul 05
作者:
Si Tao, Xingxing Qiu, Yiting Wang, Rongrong Qiu, Chenghui Yu, Man Sun, Lulu Liu, Zhendong Tao, Liu Zhang, Duozhuang Tang
来源:
Stem Cell Reviews and Reports
摘要:
造血细胞移植(HCT)是许多血液恶性肿瘤以及一些非恶性疾病的重要治疗方法。移植后造血受多种因素影响,移植后造血延迟的机制仍知之甚少。由于预处理治疗引起的并发症,接受 HCT 的患者常常会出现食物摄入量显着减少的情况。在这里,我们使用饮食限制(DR)小鼠模型来研究移植后饮食减少对造血和造血干细胞(HSC)的影响。我们发现移植后 DR 显着抑制原代受体小鼠的淋巴细胞生成和骨髓生成。然而,当将来自初级受体小鼠的骨髓细胞(BMC)连续移植到二级和三级受体小鼠中时,来自暴露于移植后DR的初级受体小鼠的HSC表现出更高的重建能力。纯化的 HSC 移植实验表明,移植后 DR 极大地抑制了造血干细胞 (HSC) 的扩增。此外,移植后 DR 重塑了受体小鼠的肠道微生物群,抑制了炎症反应,因此可能有助于维持 HSC 功能。我们的研究结果可能对临床工作具有重要意义,因为接受 HCT 的患者食物摄入量减少以及消化和吸收问题很常见。© 2024。作者。
Hematopoietic cell transplantation (HCT) is an important therapy for many hematological malignancies as well as some non-malignant diseases. Post-transplant hematopoiesis is affected by multiple factors, and the mechanisms of delayed post-transplant hematopoiesis remain poorly understood. Patients undergoing HCT often suffer from significantly reduced food intake due to complications induced by preconditioning treatments. Here, we used a dietary restriction (DR) mouse model to study the effect of post-transplant dietary reduction on hematopoiesis and hematopoietic stem cells (HSCs). We found that post-transplant DR significantly inhibited both lymphopoiesis and myelopoiesis in the primary recipient mice. However, when bone marrow cells (BMCs) from the primary recipient mice were serially transplanted into secondary and tertiary recipient mice, the HSCs derived from the primary recipient mice, which were exposed to post-transplant DR, exhibited a much higher reconstitution capacity. Transplantation experiments with purified HSCs showed that post-transplant DR greatly inhibited hematopoietic stem cell (HSC) expansion. Additionally, post-transplant DR reshaped the gut microbiotas of the recipient mice, which inhibited inflammatory responses and thus may have contributed to maintaining HSC function. Our findings may have important implications for clinical work because reduced food intake and problems with digestion and absorption are common in patients undergoing HCT.© 2024. The Author(s).