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 30-50% of individuals over 60 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 65-80 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 2D 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. 1
|Effective start/end date||9/15/17 → 8/31/19|
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