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

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

✉ Corresponding author: Chang H. Lee, PhD., Associate Professor, Regenerative Engineering Laboratory, Associate Director, Center for Advanced Regenerative Technologies, Columbia University Irving Medical Center, 630 W. 168 St. VC12-230, New York, NY 1 More

Citation:
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. https://www.thno.org/v09p4241.htm
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Abstract

Graphic 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

Citation styles

APA
Tarafder, S., Ricupero, C., Minhas, S., Yu, R.J., Alex, A.D., Lee, C.H. (2019). A Combination of Oxo-M and 4-PPBP as a potential regenerative therapeutics for tendon injury. Theranostics, 9(14), 4241-4254. https://doi.org/10.7150/thno.35285.

ACS
Tarafder, S.; Ricupero, C.; Minhas, S.; Yu, R.J.; Alex, A.D.; Lee, C.H. 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.

NLM
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. https://www.thno.org/v09p4241.htm

CSE
Tarafder S, Ricupero C, Minhas S, Yu RJ, Alex AD, Lee CH. 2019. A Combination of Oxo-M and 4-PPBP as a potential regenerative therapeutics for tendon injury. Theranostics. 9(14):4241-4254.

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