Hematopoietic stem cells under pressure.
Hematopoietic stem cells under pressure.
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DOI：
10.1097/moh.0000000000000347
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发表时间：
2017-07
影响因子：
3.2
通讯作者：
McKinney-Freeman S
中科院分区：
文献类型：
--
作者：
Ganuza M;McKinney-Freeman S
造血干细胞（hsc）和祖细胞的任务是在面对各种损伤和挑战时维持造血稳态，包括感染、炎症和出血。造血干细胞具有重建自身造血系统被破坏的生物体的整个造血系统的非凡能力。这种能力在临床上通过造血干细胞移植（HSCT）被常规利用。在这里，我们关注造血干细胞在移植过程中克服的生理和分子瓶颈。移植后，造血干细胞需要遇到受损的骨髓（BM）生态位，其分子特征是氧浓度增加和细胞因子环境改变。最近在造血干细胞移植过程中涉及了新的机制和途径，包括移植的造血干细胞依赖于调节分子的分泌，促进移植和保护造血干细胞免受细胞器稳态干扰的途径。更好地了解造血干细胞耐受移植应激的分子过程，将为进一步改善造血干细胞移植过程中的调节方案和移植提供新的靶点。
Hematopoietic stem cells (HSCs) and progenitors are tasked with maintaining hematopoietic homeostasis in the face of numerous insults and challenges, including infection, inflammation and exsanguination. HSCs possess the remarkable ability to reconstitute the entire hematopoietic system of an organism whose own hematopoietic system has been ablated. This ability is exploited routinely in the clinic via HSC transplantation (HSCT). Here, we focus on the physiological and molecular bottlenecks overcome by HSCs during transplantation. Upon transplantation, HSCs need to encounter a damaged bone marrow (BM) niche, characterized molecularly by increases in oxygen concentrations and an altered cytokine milieu. New mechanisms and pathways have been recently implicated during HSCT, including transplanted HSC-dependent secretion of conditioning molecules that facilitate engraftment and pathways that protect HSCs from perturbed organelle homeostasis. Better understanding the molecular processes HSCs employ to withstand the stress of transplant will illuminate novel targets for further improving conditioning regimens and engraftment during HSCT.