NEW YORK R & D CENTER FOR TRANSLATIONAL MEDICINE & THERAPEUTICS INC — Department of Health and Human Services STTR Phase I: NIA

Description

Project Summary This study aims to prove the concept and feasibility that TendonCure extracellular vesicles that contain signaling molecules i e exosomes secreted by mesenchymal stem cells i e tendon stem progenitor cells TSPCs or adipose derived stem cells ADSCs from individual patients donors cultured on a novel scaffold exert therapeutic efficacy on tendinopathy when injected into the diseased tendon of the same donor Tendinopathy is a common chronic tendon disorder that affects of individuals over years old It is characterized by pain swelling loss of function and impaired performance There is currently no cure for tendinopathy Spontaneous repair or treatment typically leads to scar formation resulting in a weakened tissue with reduced function and mechanical properties that may ultimately rupture with further use Our previous and preliminary studies show that MSCs grown on the TendonCure scaffold are modulated towards tenocyte differentiation with enhanced tenogenesis related gene expression Furthermore TSPCs cultured with exogenous TendonCure T or TendonCure A TendonCure derived from TSPCs or ADSCs respectively exhibited tenogenesis related gene expression profile changes with increased expression of tenogenic markers and decreased expression of gene markers for the adipo and chondrogenic lineages Importantly local injection of TendonCure showed therapeutic efficacy in an overuse induced supraspinatus tendinopathy rat model in vivo While the results are promising the suggested efficacy of TendonCure was based on statistically significant results in TendonCure from MSCs of a young to middle aged group However whether TendonCure derived from MSCs of aged individuals exerts such therapeutic effects is unknown We therefore hypothesize that TendonCure from MSCs of aged individuals exerts therapeutic efficacy on tendinopathy TendonCure T and TendonCure A will be harvested from TSPCs and ADSCs respectively which are isolated from aged patients at y o and cultured on TendonCure scaffolds Control exosomes will be derived from TSPCs and ADSCs from the same patients as the TendonCure groups and grown in regular D culture Adult nude rats subjected to decline treadmill at two weeks with expected mild tendinopathy will be injected weekly in the supraspinatus tendons with TendonCure or control exosomes or placebo phosphate buffered saline or kept for normal cage activity control Four weeks after injection animals will be evaluated for efficacy on pain behaviors and supraspinatus tendons will be dissected for efficacy evaluation with assays for histology and mechanical properties testing Upon successful completion of Phase I and II studies we will carry out clinical trials focusing on common sites of tendinopathy TendonCure will be marketed as a biologic for treating tendinopathy and other tendon disorders Project Narrative Tendinopathy is a common chronic tendon disorder especially in the aged population characterized by pain and impaired performance and currently has no cure or effective treatments Our preliminary studies show exosomes extracellular vesicles secreted by mesenchymal stem cells MSCs from young donors when grown on a novel scaffold exert therapeutic efficacy in healing diseased tendon tissue by carrying specific signaling molecules as active ingredients The proposed study will determine whether exosomes from MSCs of aged donors grown on this novel scaffold also have therapeutic efficacy in treating tendinopathy