Theranostics 2019; 9(14):4241-4254. doi:10.7150/thno.35285

Research Paper

A Combination of Oxo-M and 4-PPBP as a potential regenerative therapeutics for tendon injury

Solaiman Tarafder, Christopher Ricupero, Sumeet Minhas, Rebecca J. Yu, Ashleigh D. Alex, Chang H. Lee

Columbia University College of Dental Medicine, 630 W. 168th street, Vanderbilt Clinic 12-210, New York, NY 10032

Abstract

Tendons injuries frequently result in scar-like tissue with poor biochemical structure and mechanical properties. We have recently reported that CD146+ perivascular originated tendon stem/progenitor cells (TSCs), playing critical roles in tendon healing. Here, we identified highly efficient small molecules that selectively activate endogenous TSCs for tendon regeneration.

Methods: From a pool of ERK1/2 and FAK agonists, Oxo-M and 4-PPBP were identified, and their roles in tenogenic differentiation of TSCs and in vivo tendon healing were investigated. Controlled delivery of Oxo-M and 4-PPBP was applied via PLGA µS. Signaling studies were conducted to determine the mechanism for specificity of Oxo-M and 4-PPBP to CD146+ TSCs.

Results: A combination of Oxo-M and 4-PPBP synergistically increased the expressions of tendon-related gene markers in TSCs. In vivo, delivery of Oxo-M and 4-PPBP significantly enhanced healing of fully transected rat patellar tendons (PT), with functional restoration and reorganization of collagen fibrous structure. Our signaling study suggested that Oxo-M and 4-PPBP specifically targets CD146+ TSCs via non-neuronal muscarinic acetylcholine receptors (AChR) and σ1 receptor (σ1) signaling.

Principal conclusions: Our findings demonstrate a significant potential of Oxo-M and 4-PPBP as a regenerative therapeutics for tendon injuries.

Keywords: Tendon, Regenerative Medicine, Endogenous stem/progenitor cells, Small molecules

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How to cite this article:
Tarafder S, Ricupero C, Minhas S, Yu RJ, Alex AD, Lee CH. A Combination of Oxo-M and 4-PPBP as a potential regenerative therapeutics for tendon injury. Theranostics 2019; 9(14):4241-4254. doi:10.7150/thno.35285. Available from http://www.thno.org/v09p4241.htm