Platelet like cells differentiated from human adipose derived mesenchymal stem cells promote healing of tendinopathy in rats

Tendon and ligament disorders, such as tendinopathy, cause pain and limit levels of activities of daily living. Thus, devising methods to heal them is crucial. Although treatment with autologous platelet rich plasma (PRP) is reportedly useful against tendon injury, PRP requires blood sampling and its quality varies. Here we show that platelet-like cells (ASCL-PLCs) derived from a heterologous human adipose-derived mesenchymal stem cell line (ASCL) promote significant tendon repair in a collagenase-induced injury model in rat Achilles tendons. Single administration of human ASCL-PLCs to rat Achilles tendon after 2 weeks of collagenase treatment significantly increased tendon strength and improved semi-quantitative histological evaluation scores in 4 weeks relative to PBS-treated controls. Moreover, xeno-graft reactions were not evident in ASCL-PLC-administered rats. In vitro, ASCL-PLC treatment significantly upregulated Col1a1, Lox and Mkx gene expression in NIH3T3 fibroblasts and activated ERK signaling. Overall, ASCL-PLCs could serve as a useful tool to repair injured tendons and treat tendinopathy. This approach eliminates the need for blood sampling, ensures consistent quality, supports xeno-transplantation, and increases injured tendon strength.