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

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.

SUBMITTER: Hou Y

PROVIDER: S-EPMC5652790 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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

Hou Yonghui Y Ni Ming M Lin Sien S Sun Yuxin Y Lin Weiping W Liu Yamei Y Wang Haibin H He Wei W Li Gang G Xu Liangliang L

Oncotarget 20170824 44

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 high ...[more]

PMID: 29100398

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Project description:Background:A new trend in the treatment for alveolar clefts in patients with cleft lip and palate involves the use of bone tissue engineering strategies to reduce or eliminate the morbidity associated with autologous bone grafting. The use of mesenchymal stem cells-autologous cells obtained from tissues such as bone marrow and fat-combined with various biomaterials has been proposed as a viable option for use in cleft patients. However, invasive procedures are necessary to obtain the mesenchymal stem cells from these two sources. To eliminate donor site morbidity, noninvasive stem cell sources such as the umbilical cord, orbicularis oris muscle, and deciduous dental pulp have been studied for use in alveolar cleft bone tissue engineering. In this study, we evaluate the osteogenic potential of these various stem cell types. Methods:Ten cellular strains obtained from each different source (umbilical cord, orbicularis oris muscle, or deciduous dental pulp) were induced to osteogenic differentiation in vitro, and the bone matrix deposition of each primary culture was quantified. To evaluate whether greater osteogenic potential of the established mesenchymal stem cell strains was associated with an increase in the expression profile of neural crest genes, real-time qPCR was performed on the following genes: SRY-box 9, SRY-box 10, nerve growth factor receptor, transcription factor AP-2 alpha, and paired box 3. Results:The mesenchymal stem cells obtained from deciduous dental pulp and orbicularis oris muscle demonstrated increased osteogenic potential with significantly more extracellular bone matrix deposition when compared to primary cultures obtained from the umbilical cord after twenty-one days in culture (p = 0.007 and p = 0.005, respectively). The paired box 3 gene was more highly expressed in the MSCs obtained from deciduous dental pulp and orbicularis oris muscle than in those obtained from the umbilical cord. Conclusion:These results suggest that deciduous dental pulp and orbicularis oris muscle stem cells demonstrate superior osteogenic differentiation potential relative to umbilical cord-derived stem cells and that this increased potential is related to their neural crest origins. Based on these observations, and the distinct translational advantage of incorporating stem cells from noninvasive tissue sources into tissue engineering protocols, greater study of these specific cell lines in the setting of alveolar cleft repair is indicated.

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

Publications

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

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