Bajaj, M.S. and Ghode, S.S. and Rohan , S. and Kulkarni , R.S. and Limaye , L.S. and Kale , V.P. (2015) Simvastatin improves hematopoietic stem cell engraftment by preventing irradiation-induced marrow adipogenesis and radio-protecting the niche cells. Hematologica, 100 (8). pp. 323-327.

Text 53. Dr. Kale (Haematologica) paid open access.pdf Restricted to Repository staff only Download (2348Kb) | Request a copy

Abstract

Pre-transplant myeloablation increases marrow adipogenesis and destroys the niche cells, adversely affecting the hematopoietic stem cell (HSC) engraftment. This becomes a serious issue when donor HSCs are few or possess compromised functionality. Therapeutic targeting of the niche1 to increase HSC engraftment became popular after it was demonstrated that an increase in osteoblast numbers leads to an increase in HSC number.2,3 Statins, the drugs used to treat hypercholesterolemia, have several clinically useful pleiotropic effects including inhibition of adipogenesis in marrow-derived mesenchymal cells in vitro and prevention of irradiationinduced tissue and cell damage.4,5 Therefore, we hypothesized that Simvastatin-treatment of stem cell transplant (SCT) recipients might improve HSC engraftment by preventing irradiationinduced adipogenesis and by radio-protecting the niche cells. We found that Simvastatintreatment of recipient mice positively affects engraftment and expansion of donor HSCs by inhibiting marrow adipogenesis and radio-protecting niche cells. Simvastatin-treatment of nonirradiated mice boosts the HSC numbers by remodeling the niche. These data provide evidence that Simvastatin can be an effective niche-targeting agent to improve HSC engraftment by treating both recipients as well as donors. As Simvastatin is already widely used, clinical application of this approach might be relatively straightforward.

Item Type:	Article
Additional Information:	This is Open Access article for full text click on web link
Subjects:	Stem Cell Biology
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	04 Dec 2015 08:07
Last Modified:	18 Dec 2021 13:23
URI:	http://nccs.sciencecentral.in/id/eprint/207

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