Induced Pluripotent Stem Cell Derived Mesenchymal Stem Cells for Attenuating Age-Related Bone Loss
Annual rept. 1 Jul 2011-30 Jun 2012
MILTON S HERSHEY MEDICAL CENTER PA
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Osteoporosis, both age-related and post-menopausal, is a huge health problem in the United States and indeed worldwide. Despite extensive research there remain few therapeutic approaches, with the exception of parathyroid hormone, that actually increase bone formation in osteoporotic patients. There are several limitations to the use of parathyroid hormone suggesting the need for continued research into anabolic therapies for osteoporosis. Mesenchymal stem cell MSC differentiation towards the bone forming osteoblastic lineage decreases as a function of age and may contribute to age-related bone loss. Therefore, MSC therapy may be beneficial in treating age-related bone loss. However, MSC availability decreases with age. To overcome the problem of age-related reduced availability of MSC we propose to examine the bone anabolic potential of induced pluripotent stem cell iPS derived MSC in age-related bone loss. Unfortunately deriving MSC from iPS can require extended in vitro culture, which decreases the differentiation potential of MSC. Since biomaterial surface characteristics, including stiffness and topography, can control MSC differentiation in vitro, including toward the osteoblastic lineage, the goal of this project is to identify biomaterial surface characteristics that enhance differentiation of iPS toward MSC and MSC toward osteoblastic cells. Our hypothesis is that culturing iPS on nanotopographic surfaces results in enrichment of a population of cells exhibiting MSC characteristics. Continued culture of these iPS derived MSC on nanotopographies results in increased osteoblastic differentiation and increased potential to induce bone formation in senescent accelerated mice SAMP6, a murine model of age-induced bone loss. Successful completion of the specific aims would suggest a novel and highly innovative therapeutic approach to age-related osteoporosis.
- Anatomy and Physiology
- Medicine and Medical Research