Enhancement of Tendon Repair Using Tendon-Derived Stem Cells in Small Intestinal Submucosa via M2 Macrophage Polarization

Xufeng Mao; Liwei Yao; Mei Li; Xiqian Zhang; Bowen Weng; Weilai Zhu; Renhao Ni; Kanan Chen; Linhua Yi; Jiyuan Zhao; Haijiao Mao

doi:10.3390/cells11172770

Enhancement of Tendon Repair Using Tendon-Derived Stem Cells in Small Intestinal Submucosa via M2 Macrophage Polarization

Cells. 2022 Sep 5;11(17):2770. doi: 10.3390/cells11172770.

Authors

Xufeng Mao¹, Liwei Yao¹, Mei Li^{2

3}, Xiqian Zhang¹, Bowen Weng², Weilai Zhu², Renhao Ni², Kanan Chen², Linhua Yi¹, Jiyuan Zhao², Haijiao Mao¹

Affiliations

¹ Department of Orthopaedic Surgery, The Affiliated Hospital of Medical School, Ningbo University, Ningbo 315020, China.
² Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China.
³ Ningbo Medical Science Research Institute, Ningbo 315020, China.

Abstract

(1) Background: Reconstruction of Achilles tendon defects and prevention of postoperative tendon adhesions were two serious clinical problems. In the treatment of Achilles tendon defects, decellularized matrix materials and mesenchymal stem cells (MSCs) were thought to address both problems. (2) Methods: In vitro, cell adhesion, proliferation, and tenogenic differentiation of tendon-derived stem cells (TDSCs) on small intestinal submucosa (SIS) were evaluated. RAW264.7 was induced by culture medium of TDSCs and TDSCs-SIS scaffold groups. A rat Achilles tendon defect model was used to assess effects on tendon regeneration and antiadhesion in vivo. (3) Results: SIS scaffold facilitated cell adhesion and tenogenic differentiation of TDSCs, while SIS hydrogel coating promoted proliferation of TDSCs. The expression of TGF-β and ARG-1 in the TDSCs-SIS scaffold group were higher than that in the TDSCs group on day 3 and 7. In vivo, the tendon regeneration and antiadhesion capacity of the implanted TDSCs-SIS scaffold was significantly enhanced. The expression of CD163 was significantly highest in the TDSCs-SIS scaffold group; meanwhile, the expression of CD68 decreased more significantly in the TDSCs-SIS scaffold group than the other two groups. (4) Conclusion: This study showed that biologically prepared SIS scaffolds synergistically promote tendon regeneration with TDSCs and achieve antiadhesion through M2 polarization of macrophages.

Keywords: Achilles tendon defects; small intestinal submucosa (SIS); tendon adhesion; tendon regeneration; tendon-derived stem cells (TDSCs); treatment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Achilles Tendon*
Animals
Cell Differentiation
Macrophages
Rats
Rats, Sprague-Dawley
Stem Cells*

Grants and funding

This research was funded by the Medical health Project of Health Department of Zhejiang Province, grant number 2019KY614 and 2021KY1045; Ningbo public welfare science and technology project, grant number 2021S104; Ningbo major science and technology project, grant number 2022Z133; and Open Fund of Institute of Human Biomechanics, Ningbo University, grant number CJ-HBIO202109.