ZWEIG BANNER  

The Harry M. Zweig Memorial Fund for Equine Research


Identification of the Optimal Biologic to Enhance Endogenous Stem Cell Recruitment and Homing for Facilitated Musculoskeletal Tissue Regeneration

Principal Investigator: Lisa Fortier
Contact Information: Email: laf4@cornell.edu; Phone: 607-253-3102
Project Costs: $92,885
Project Period: 1/1/2012-12/31/2013

Fortier
Dr. Lisa Fortier

Stem cell therapies are commonly applied in horses to enhance repair of musculoskeletal tissues and return the animal to athletic function. Stem cells from bone marrow and fat have been isolated, cultured, and re-injected into injured tendon or cartilage/joints.  Although it is presently unclear if the stem cells function to replace the injured tissue, or if they impart anti-inflammatory or immunomodulatory properties, both experimental and clinical evidence supports their use for return to function in horses following musculoskeletal injury.  One disadvantage to this type of direct-injection stem cell therapy is the need for two procedures, one to remove the tissue from which the stem cells will be isolated, and a second procedure to administer the stem cells. Two-step procedures would naturally be more expensive than one-step techniques, but another pitfall with this type of approach is that it delays the time from diagnosis to treatment by as much as 2 months because of the lengthy culture period required to propagate the stem cells. A more contemporary approach to stem cell therapy is to find a means to recruit the body’s natural reserve of stem cells that reside in all tissues. Our collaborator Dr. Mao used such a technique to take advantage of the ability of growth factors to recruit stem cells in a rabbit model of shoulder replacement.

Our hypothesis for this proposal is that biologics will provide a physiologically balanced concentration of growth factors that will enhance stem cell recruitment to the site of injury. The natural biologics that we will test include those that have demonstrated to enhance musculoskeletal repair in horses such as platelet rich plasma (PRP), bone marrow aspirate, bone marrow aspirate concentrate, and fibrinogen. We will aim to use fluorescent based migration assays to quantify which biologic is best for recruitment of stem cells of musculoskeletal origin including those derived from cartilage, tendon, bone marrow and adipose-derived stem cells. If our hypothesis is correct that one or more of the biologics enhance stem cell recruitment, then a simple administration of an autogenous biologic could eliminate the need for stem cell extraction and propagation.

Harnessing the body’s natural ability to repair through the use of biologics as a method to enhance stem cell recruitment to the site of injury would provide a more time and cost efficient means to treat horses with musculoskeletal injuries and facilitate their return to athletic performance. Beyond the scope of this proposal, our long term goals would be to gain a more mechanistic understanding of stem cell recruitment and to apply the biologics in vivo to determine how the recruited stem cells are functioning to enhance tissue regeneration.