Combination Effect of Rotator Cuff Repair with Secretome-hypoxia MSCs Ameliorates TNMD, RUNX2, and Healing Histology Score in Rotator Cuff Tear Rats

Document Type : RESEARCH PAPER

Authors

1 Doctoral Study Program, Faculty of Medicine, Padjadjaran University, Bandung, West Java, Indonesia

2 Division of Oncology, Department of Orthopedic Surgery, Faculty of Medicine, Padjadjaran University, Bandung, Indonesia

3 Department of Orthopedics and Traumatology, Faculty of Medicine, Padjadjaran University, Indonesia

4 Department of Physiology, Faculty of Medicine, Padjadjaran University, Bandung Indonesia

5 Stem Cell and Cancer Research, Semarang, Indonesia

Abstract

Objectives: In order to treat a rat model of rotator cuff rupture, this work concentrated on the expression 
of TNMD and RUNX2, followed by rotator cuff repair and secretome-hMSCs.
Methods: A total of thirty 10-weeks-old male Sprague–Dawley rats were separated into five groups randomly, RC 
on week 0, lesion treated with a rotator cuff repair and saline (RC + NaCl group, n = 6) for 2 and 8 weeks, and lesion 
treated with a rotator cuff repair and secretome-hMSCs (RC + secretome-hMSC group, n = 6) for 2 and 8 weeks. 
The supraspinatus and infraspinatus muscle–tendon units were obtained for histological and biomechanical 
investigation at 0, 2 and 8 weeks following injury.
Results: The findings showed that, in comparison with the RC + NaCl group, secretome-hMSCs significantly 
improved tendon repair by upregulating TNMD and RUNX2 expression and histology score.
Conclusion: Combining Secretome-hypoxia MSCs with RC healing may help rats with rotator cuff tears.
 Level of evidence: IV

Keywords

Main Subjects


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5.                Saremi H, Amini M, Seifrabiei M. Comparison of Anterior and Posterior Transfer of Latissimus Dorsi Tendon to Humeral Head in Patients with Massive and Irreparable Rotator Cuff Tear. Arch Bone Jt Surg. 2023; 11(4):236-240. 

doi:10.22038/ABJS.2023.68222.3226.

  1. Cobb TE, Dimock RAC, Memon SD, et al. Rotator Cuff Repair With Patch Augmentation: What Do We Know? Arch Bone Jt Surg. 2022; 10(10):833-846. doi:10.22038/ABJS.2022.61345.3012.
  2. Stone MA, Henry TW, Gutman MJ, Ho JC, Namdari S, Orthopaedic R. Surgical Treatment of Shoulder Infection Following Rotator Cuff Repair. Arch Bone Jt Surg. 2023;11(2):111-116. doi:10.22038/ABJS.2022.52089.2572.
  3. Barry F. MSC Therapy for Osteoarthritis: An Unfinished Story. J Orthop Res. 2019; 37(6):1229-1235. doi:10.1002/JOR.24343.
  4. Lotfinia M, Lak S, Ghahhari NM, et al. Hypoxia pre-conditioned embryonic mesenchymal stem cell secretome reduces IL-10 production by peripheral blood mononuclear cells. Iran Biomed J. 2017; 21(1):24-31. doi:10.18869/acadpub.ibj.21.1.24.
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  9. Yonemitsu R, Tokunaga T, Shukunami C, et al. Fibroblast Growth Factor 2 Enhances Tendon-to-Bone Healing in a Rat Rotator Cuff Repair of Chronic Tears. Am J Sports Med. 2019; 47(7):1701-1712. doi: 10.1177/0363546519836959.
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  2. Wang C, Hu Q, Song W, Yu W, He Y. Adipose Stem Cell–Derived Exosomes Decrease Fatty Infiltration and Enhance Rotator Cuff Healing in a Rabbit Model of Chronic Tears. Am J Sports Med. 2020;48(6):1456-1464. doi: 10.1177/0363546520908847.
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31.              Rahimi B, Panahi M, Saraygord-Afshari N, et al. The secretome of mesenchymal stem cells and oxidative stress: challenges and opportunities in cell-free regenerative medicine. Mol Biol Reports. 2021; 48(7):5607-5619. doi: 10.1007/S11033-021-

  1. Sevivas N, Teixeira FG, Portugal R, et al. Mesenchymal Stem Cell Secretome Improves Tendon Cell Viability In Vitro and Tendon-Bone Healing In Vivo When a Tissue Engineering Strategy Is Used in a Rat Model of Chronic Massive Rotator Cuff Tear. Am J Sports Med. 2018; 46(2):449-459. doi: 10.1177/0363546517735850.
  2. Fu G, Lu L, Pan Z, Fan A, Yin F. Adipose-derived stem cell exosomes facilitate rotator cuff repair by mediating tendon-derived stem cells. Regen Med. 2021; 16(4):359-372. doi: 10.2217/RME-2021-0004.
  3. He J, Ping S, Yu F, Yuan X, Wang J, Qi J. Mesenchymal stem cell-derived exosomes: therapeutic implications for rotator cuff injury. Regen Med. 2021; 16(08):803-15. doi: 10.2217/rme-2020-0183.
  4. Xu T, Xu M, Bai J, et al. Tenocyte-derived exosomes induce the tenogenic differentiation of mesenchymal stem cells through TGF-β. Cytotechnology. 2019; 71(1):57-65. doi:10.1007/S10616-018-0264-Y/FIGURES/5.
  5. Saremi H, Amini M, Seifrabiei M. Comparison of Anterior and Posterior Transfer of Latissimus Dorsi Tendon to Humeral Head in Patients with Massive and Irreparable Rotator Cuff Tear. Arch Bone Jt Surg. 2023; 11(4):236-240. doi:10.22038/ABJS.2023.68222.3226.
  6. Cobb TE, Dimock RAC, Memon SD, et al. Rotator Cuff Repair With Patch Augmentation: What Do We Know? Arch Bone Jt Surg. 2022; 10(10):833-846. doi:10.22038/ABJS.2022.61345.3012.
  7. Stone MA, Henry TW, Gutman MJ, Ho JC, Namdari S, Orthopaedic R. Surgical Treatment of Shoulder Infection Following Rotator Cuff Repair. Arch Bone Jt Surg. 2023;11(2):111-116. doi:10.22038/ABJS.2022.52089.2572.
  8. Barry F. MSC Therapy for Osteoarthritis: An Unfinished Story. J Orthop Res. 2019; 37(6):1229-1235. doi:10.1002/JOR.24343.
  9. Lotfinia M, Lak S, Ghahhari NM, et al. Hypoxia pre-conditioned embryonic mesenchymal stem cell secretome reduces IL-10 production by peripheral blood mononuclear cells. Iran Biomed J. 2017; 21(1):24-31. doi:10.18869/acadpub.ibj.21.1.24.
  10. Putra A, Pertiwi D, Milla MN, et al. Hypoxia-preconditioned MSCs have superior effect in ameliorating renal function on acute renal failure animal model. Open Access Maced J Med Sci. 2019; 7(3):305-310. doi:10.3889/oamjms.2019.049.
  11. Putra A, Widyatmoko A, Ibrahim S, et al. Case series of the first three severe COVID-19 patients treated with the secretome of hypoxia-mesenchymal stem cells in Indonesia. F1000Res. 2021; 10:228. doi:10.12688/f1000research.51191.3.
  12. Rahimi B, Panahi M, Saraygord-Afshari N, et al. The secretome of mesenchymal stem cells and oxidative stress: challenges and opportunities in cell-free regenerative medicine. Mol Biol Rep. 2021;48(7):5607-5619. doi:10.1007/s11033-021-06360-7.
  13. Eleuteri S, Fierabracci A. Insights into the Secretome of Mesenchymal Stem Cells and Its Potential Applications. Int J Mol Sci. 2019; 20(18):4597. doi: 10.3390/IJMS20184597.
  14. Yonemitsu R, Tokunaga T, Shukunami C, et al. Fibroblast Growth Factor 2 Enhances Tendon-to-Bone Healing in a Rat Rotator Cuff Repair of Chronic Tears. Am J Sports Med. 2019; 47(7):1701-1712. doi: 10.1177/0363546519836959.
  15. Valenti MT, Carbonare LD, Mottes M. Ectopic expression of the osteogenic master gene RUNX2 in melanoma. World J Stem Cells. 2018; 10(7):78. doi:10.4252/WJSC.V10.I7.78.
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  3. Sevivas N, Teixeira FG, Portugal R, et al. Mesenchymal Stem Cell Secretome Improves Tendon Cell Viability In Vitro and Tendon-Bone Healing In Vivo When a Tissue Engineering Strategy Is Used in a Rat Model of Chronic Massive Rotator Cuff Tear. Am J Sports Med. 2018; 46(2):449-459. doi: 10.1177/0363546517735850.
  4. Zhen G, Wen C, Jia X, et al. Inhibition of TGF–β signaling in subchondral bone mesenchymal stem cells attenuates osteoarthritis HHS Public Access. Nat Med. 2013; 19(6):704-712. doi:10.1038/nm.3143.
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