970: Tissue Regeneration Using Canine Mesenchymal Stem Cells: Effects of Donor Characteristics and ex vivo Expansion on Cell Pluripotency

Grant Status: Closed

Grant Amount: $165,348
Dr. Susan W. Volk, VMD PhD, University of Pennsylvania
January 1, 2008 - June 30, 2010
Sponsor(s): American Cavalier King Charles Spaniel Club Charitable Trust, American Whippet Club, Friends of Norfolk Terrier, Greyhound Club of America, Japanese Chin Club of America, Keeshond Club of America, National American Pit Bull Terrier Association, Norfolk Terrier Club, Saluki Health Research, Inc., Yorkshire Terrier Club of America
Breed(s): -All Dogs
Research Program Area: Treatment

Project Summary

Mesenchymal stem cells (MSCs) are attractive candidates for cell-based therapies because of their relative ease of isolation, broad differentiation potential, and ability to be expanded in vitro. Regenerative medicine strategies using MSCs aim to restore function to damaged tissues, particularly for orthopedic, cardiovascular and neurologic diseases. Although tremendous potential for stem cell therapies exists for canine patients, an understanding of the basic biology of canine MSCs is lacking and must be established prior to initiating responsible clinical trials in patients. Importantly, multiple studies have shown that extrapolation of biologic properties of MSCs between species is unreliable. In our Canine Health Foundation sponsored research project, we have investigated the effect of donor age, harvest site and in vitro passage on the ability of the cells to directly contribute to bone, fat, and cartilage. We identified differences in the ability of MSCs to become bone depending on the age of the dog the cells were harvested from as well as the site from which they were obtained. These findings may help direct future clinical trials by choosing to use MSCs which are most effective for therapy. Because expansion of cell numbers is an important part of the process to generate adequate quantities for therapies, understanding how this process affects the capacity of those cells to differentiate into target cells is vital for therapeutic success. Our studies suggest that expansion of cell numbers has a significant effect on these cells and that those who use these cells for clinical applications need to be aware of such effects. Additional studies are on going to further define as well as limit these effects so that efficacy and safety are maximally preserved. A thorough, systematic understanding of the basic biology of canine MSCs will have a significant impact on the design of future stem cell clinical trials. Clinical trials using MSCs in humans are currently underway and provide a basis for exciting new therapies for many of the most common ailments of dogs: heart failure, neurologic conditions, osteoarthritis, kidney and liver diseases and diabetes. MSC-based therapies could have significant positive effects on quality of life for dogs that are affected by a variety of degenerative, genetic and traumatic conditions, their owners, and the veterinarians who treat them.

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