Cytoreductive protocols are integral both as conditioning regimens for bone marrow (BM) transplantation and as part of therapies for malignancies, but their associated comorbidities represent a long-standing clinical problem. In particular, they cause myeloablation that debilitates the physiological role of mesenchymal stem and precursor cells (MSPCs) in sustaining hematopoiesis. This review addresses the damaging impact of cytoreductive regimens on MSPCs. In addition, it discusses prospects for alleviating the resulting iatrogenic comorbidities. New insights into the structural and functional dynamics of hematopoietic stem cell (HSC) niches reveal the existence of “empty” niches and the ability of the donor-derived healthy HSCs to outcompete the defective HSCs in occupying these niches. These findings support the notion that conditioning regimens, conventionally used to ablate the recipient hematopoiesis to create space for engraftment of the donor-derived HSCs, may not be a necessity for allogeneic BM transplantation. In addition, the capacity of the MSPCs to cross-talk with HSCs, despite major histocompatibility complex disparity, and suppress graft versus host disease indicates the possibility for development of a conditioning-free, MSPCs-enhanced protocol for BM transplantation. The clinical advantage of supplementing cytoreductive protocols with MSPCs to improve autologous hematopoiesis reconstitution and alleviate cytopenia associated with chemo and radiation therapies for cancer is also discussed.

中文翻译：

---

间充质-造血干细胞轴在自体和异体造血中的作用的新见解

细胞减灭方案作为骨髓 (BM) 移植的预处理方案和恶性肿瘤治疗的一部分都是不可或缺的，但它们相关的合并症代表了一个长期存在的临床问题。特别是，它们会导致骨髓消融，从而削弱间充质干细胞和前体细胞 (MSPC) 在维持造血过程中的生理作用。本综述讨论了细胞减灭方案对 MSPC 的破坏性影响。此外，它还讨论了减轻由此产生的医源性合并症的前景。对造血干细胞 (HSC) 壁龛结构和功能动力学的新见解揭示了“空”壁龛的存在以及供体来源的健康 HSCs 在占据这些壁龛方面胜过有缺陷的 HSCs 的能力。这些发现支持了这样一种观点，即调理方案，传统上用于消融受体造血为供体来源的 HSC 植入创造空间，可能不是同种异体 BM 移植的必要条件。此外，尽管存在主要的组织相容性复合体差异，但 MSPC 与 HSC 交互的能力以及抑制移植物抗宿主病的能力表明，有可能开发出一种无条件的、MSPC 增强的 BM 移植方案。还讨论了用 MSPC 补充细胞减灭方案以改善自体造血重建和减轻与癌症化疗和放疗相关的血细胞减少症的临床优势。尽管存在主要的组织相容性复合体差异，但 MSPC 与 HSC 交互的能力以及抑制移植物抗宿主病的能力表明开发无条件的、MSPC 增强的 BM 移植方案的可能性。还讨论了用 MSPC 补充细胞减灭方案以改善自体造血重建和减轻与癌症化疗和放疗相关的血细胞减少症的临床优势。尽管存在主要的组织相容性复合体差异，但 MSPC 与 HSC 交互的能力以及抑制移植物抗宿主病的能力表明开发无条件的、MSPC 增强的 BM 移植方案的可能性。还讨论了用 MSPC 补充细胞减灭方案以改善自体造血重建和减轻与癌症化疗和放疗相关的血细胞减少症的临床优势。