Tenomodulin highly expressing MSCs as a better cell source for tendon injury healing

// Yonghui Hou 1, 2, * , Ming Ni 3, * , Sien Lin 2 , Yuxin Sun 2 , Weiping Lin 2 , Yamei Liu 4 , Haibin Wang 1 , Wei He 1 , Gang Li 2, 5 and Liangliang Xu 1, 6 1 Key Laboratory of Orthopaedics & Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, P.R. China 2 Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, P.R. China 3 Department of Orthopaedics, PLA General Hospital, Beijing, P.R. China 4 Department of Diagnostics of Traditional Chinese Medicine, Guangzhou University of Traditional Chinese Medicine, Guangzhou, P.R. China 5 Stem Cells and Regenerative Medicine Laboratory, Lui Che Woo Institute of Innovative Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, P.R. China 6 Laboratory of Orthopaedics & Traumatology, Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, P.R. China * These authors have contributed equally to this work Correspondence to: Liangliang Xu, email: xull-2016@gzucm.edu.cn Gang Li, email: gangli@cuhk.edu.hk Wei He, email: hewei1123@gzucm.edu.cn Keywords: mesenchymal stem cells, tenogenic differentiation, tendon, tenomodulin Received: June 07, 2017 Accepted: July 13, 2017 Published: August 24, 2017 ABSTRACT Tendon injuries are common orthopedic problems which may cause severe morbidity. MSCs (mesenchymal stem cells) have shown promising effect on tissue engineering and have been used for the treatment of tendon injury. But the low tenogenic differentiation capacity of MSCs have hindered their application. In the present study, we have constructed the Tenomodulin (Tnmd) promoter-driven GFP expression lentiviral plasmid. After transduced into BMSCs, the expression of GFP was used to select BMSCs highly expressing Tnmd by flow cytometry. We found that MSCs with higher level of Tnmd expression had stronger tenogenic differentiation ability. Furthermore, RNA sequencing was performed to identify the molecular difference between BMSCs expressing higher and lower levels of Tnmd. And finally we demonstrated that GDF7 was upregulated in BMSCs highly expressing Tnmd and played an vital role in promoting tenogenic differentiation of BMSCs. GDF7 was mainly accounted for the elevated tenogenic differentiation ability of BMSCs with higher Tnmd expression as silencing the endogenous GDF7 significantly inhibited tenogenesis in BMSCs. In addition, the effect of BMSCs with higher Tnmd level on tendon healing was evaluated by a rat patellar tendon injury model. Taken together, our study showed that Tnmd could be used as an ideal cell surface marker to select cells with higher tenogenic differentiation ability from BMSCs, and GDF7 was indispensable for tenogenesis of MSCs.