Letter abstract
Nature Biotechnology 25, 238 - 243 (2007)
Published online: 21 January 2007 | doi:10.1038/nbt1281
There is a Corrigendum (August 2007) associated with this Letter.
There is a Corrigendum (February 2008) associated with this Letter.
Therapeutic targeting of a stem cell niche
Gregor B Adams1,4, Roderick P Martin1,4, Ian R Alley1,4, Karissa T Chabner1,4, Kenneth S Cohen1,4, Laura M Calvi3, Henry M Kronenberg2 & David T Scadden1,4
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 number1, 2, 3. 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.
- Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
- Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Massachusetts 02114, USA.
- Endocrine Unit, Department of Medicine, University of Rochester School of Medicine, 601 Elmwood Avenue, Rochester, New York 14642, USA.
- Harvard Stem Cell Institute, Harvard University, 42 Church Street, Cambridge, Massachusetts 02138, USA.
Correspondence to: David T Scadden1,4 e-mail: scadden.david@mgh.harvard.edu
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