Table 1 Causes and consequences of pre-HCT conditioning on the BM niche.
Cell type | Factors produced | Role in the normal HSC niche | Impact of HCT conditioning | Consequences on hematopoietic recovery | Model system | Ref. |
|---|---|---|---|---|---|---|
Endothelial cells | CXCL12, SCF, Angiopoietin | Maintenance of quiescent HSCs (AECs), HSC migration and proliferation(SECs) | Loss of ECs in a IR dose-dependent manner; increased risk of EC-related disorders in human | Engraftment depends on recovery of SECs through activation of VEGFR2; signaling inhibition results in delayed hematopoietic recovery | Mice, human | |
Mesenchymal stromal cells | CXCL12, SCF, Angiopoietin | HSC homeostasis | MSCs are not fully eradicated but do accumulate DNA damage | Unclear, hematopoietic recovery might be delayed. | Human, in vitro | |
Osteolineage cells | CXCL12, SCF, Angiopoietin, Thrombopoietin, Osteopontin | Regulation of more committed hematopoietic progenitor cells; HSC maintenance by osteoblasts is subject of debate. | Bone-related complications; compromised osteoblast number and function. | Unclear. The supportive effect of osteolineage cells on HSCs may be less evident than previously thought. | Mice and human (in vitro) | |
Adipocytes | Adiponectin, Lectin, SCF | HSC proliferation | Increased BM adipocyte content | Controversial. Potentially contributing to (transient) hematopoietic aplasia. However, others report on their promotive role in hematopoietic regeneration. | Mice and human (in vitro) | |
Sympathetic neurons | Noradrenalin | HSPCs proliferation, differentiation, and migration | Transient or persistent sympathetic neuropathy; loss of sympathetic fibers | Impaired bone marrow regeneration | Mice | [10] |
Nociceptive neurons | CGRP | HSC homing and migration | Unknown | Unknown | NA | NA |
