Table 2 Niche-directed therapeutic strategies.
Niche cell type | Therapeutic strategy | Model system | Effect | Ref. |
|---|---|---|---|---|
Endothelial cells | Co-infusion of ECs with hematopoietic stem cells; Administration of PEDF, defibrotide, and NAC. | Mice and humans (phase I/II and III) | Improved HSC repopulating activity, engraftment, and survival after irradiation; Protection of recipient ECs from chemotherapy-induced damage; Prophylactic oral NAC was safe and effective in preventing poor hematopoietic reconstitution by improving BM EC function in allo-HCT recipients; Effect will further be identified in phase III clinical trial. | [35,36,37,38,39] Trial no. NCT03967665 (currently recruiting) |
Mesenchymal stromal cells | Co-infusion of MSCs with hematopoietic cells | Humans (phase I/II clinical trials) | Prompt engraftment of donor HSCs | Trials are reviewed in ref. [53], Trial no. NCT04247945 (currently recruiting) |
Osteolineage cells | Parathyroid hormone (PTH) injection | Mice and Humans (halted at phase II) | Increases the number of osteoblasts and HSCs in the BM and improves post-HCT survival in mice. No beneficial effect on hematopoietic engraftment was observed in human HCT recipients. | [73] |
Adipocytes | Simvastatin treatment | Mice | Prevents radiotherapy-induced BM adipogenesis and improves HSC engraftment | [82] |
Sympathetic nervous system | Administration of hematopoietic growth factors, such as G-CSF and GM-CSF; Neuroprotection by administration of 4-methylcatechol | Mice | Increased expression of neuronal receptors on HSPCs, enhancing their proliferation and repopulation capacity; Accelerates BM regeneration | [86] |
Nociceptive neurons | Unknown | NA | NA | NA |
