Therapeutic targeting of a stem cell niche.
The specialized microenvironment or niche where stem cells reside provides regulatory input governing stem cell function. We tested the hypothesis that targeting the niche might improve stem cell-based therapies using three mouse models that are relevant to clinical uses of hematopoietic stem (HS) cells. We and others previously identified the osteoblast as a component of the adult HS cell niche and established that activation of the parathyroid hormone (PTH) receptor on osteoblasts increases stem cell number. Here we show that pharmacologic use of PTH increases the number of HS cells mobilized into the peripheral blood for stem cell harvests, protects stem cells from repeated exposure to cytotoxic chemotherapy and expands stem cells in transplant recipients. These data provide evidence that the niche may be an attractive target for drug-based stem cell therapeutics.
Adams
Gregor B
GB
Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
Martin
Roderick P
RP
Alley
Ian R
IR
Chabner
Karissa T
KT
Cohen
Kenneth S
KS
Calvi
Laura M
LM
Kronenberg
Henry M
HM
Scadden
David T
DT
D053687:Adult Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology / Q000637:transplantation; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008810:Mice, Inbred C57BL; D010281:Parathyroid Hormone / Q000008:administration & dosage*; D033581:Stem Cell Transplantation / Q000379:methods*
D010281:Parathyroid Hormone