Skip to main content

Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study



The purpose of this study was to evaluate the efficiency of biologic augmentation of rotator cuff repair with iliac crest bone marrow-derived mesenchymal stem cells (MSCs). The prevalence of healing and prevention of re-tears were correlated with the number of MSCs received at the tendon-to-bone interface.


Forty-five patients in the study group received concentrated bone marrow-derived MSCs as an adjunct to single-row rotator cuff repair at the time of arthroscopy. The average number of MSCs returned to the patient was 51,000 ± 25,000. Outcomes of patients receiving MSCs during their repair were compared to those of a matched control group of 45 patients who did not receive MSCs. All patients underwent imaging studies of the shoulder with iterative ultrasound performed every month from the first postoperative month to the 24th month. The rotator cuff healing or re-tear was confirmed with MRI postoperatively at three and six months, one and two years and at the most recent follow up MRI (minimum ten-year follow-up).


Bone marrow-derived MSC injection as an adjunctive therapy during rotator cuff repair enhanced the healing rate and improved the quality of the repaired surface as determined by ultrasound and MRI. Forty-five (100 %) of the 45 repairs with MSC augmentation had healed by six months, versus 30 (67 %) of the 45 repairs without MSC treatment by six months. Bone marrow concentrate (BMC) injection also prevented further ruptures during the next ten years. At the most recent follow-up of ten years, intact rotator cuffs were found in 39 (87 %) of the 45 patients in the MSC-treated group, but just 20 (44 %) of the 45 patients in the control group. The number of transplanted MSCs was determined to be the most relevant to the outcome in the study group, since patients with a loss of tendon integrity at any time up to the ten-year follow-up milestone received fewer MSCs as compared with those who had maintained a successful repair during the same interval.


This study showed that significant improvement in healing outcomes could be achieved by the use of BMC containing MSC as an adjunct therapy in standard of care rotator cuff repair. Furthermore, our study showed a substantial improvement in the level of tendon integrity present at the ten-year milestone between the MSC-treated group and the control patients. These results support the use of bone marrow-derived MSC augmentation in rotator cuff repair, especially due to the enhanced rate of healing and the reduced number of re-tears observed over time in the MSC-treated patients.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2


  1. Awad HA, Butler DL, Boivin GP, Smith FN, Malaviya P, Huibregtse B et al (1999) Autologous mesenchymal stem cell-mediated repair of tendon. Tissue Eng 5:267–77

    CAS  PubMed  Article  Google Scholar 

  2. Barber FA, Coons DA, Ruiz-Suarez M (2007) Cyclic load testing of biodegradable suture anchors containing 2 high-strength sutures. Arthroscopy 23:355–360

    PubMed  Article  Google Scholar 

  3. Boileau P, Brassart N, Watkinson DJ, Carles M, Hatzidakis AM, Krishnan SG (2005) Arthroscopic repair of full-thickness tears of the supraspinatus: Does the tendon really heal? J Bone Joint Surg Am 87:1229–1240

    PubMed  Article  Google Scholar 

  4. Bigliani LU, Cordasco FA, McIlveen SJ, Musso ES (1992) Operative treatment of failed repairs of the rotator cuff. J Bone Joint Surg Am 74:1505–1515

    CAS  PubMed  Google Scholar 

  5. Caplan AI (2005) Review: mesenchymal stem cells: cell-based reconstructive therapy in orthopedics. Tissue Eng 11:1198–1211

    CAS  PubMed  Article  Google Scholar 

  6. Chang CH, Chen C, Su C, Liu H, Yu C (2009) Rotator cuff repair with periosteum for enhancing tendon-bone healing: a biomechanical and histological study in rabbits. Knee Surg Sports Traumatol Arthrosc 17:1447–1453

    PubMed  Article  Google Scholar 

  7. Castro-Malaspina H, Gay RE, Resnick G, Kapoor N, Meyers P, Chiarieri D et al (1980) Characterization of human bone marrow fibroblast colony-forming cells (CFU-F) and their progeny. Blood 56:289–301

    CAS  PubMed  Google Scholar 

  8. Chen JM, Willers C, Xu J, Wang A, Zheng MH (2007) Autologous tenocyte therapy using porcine-derived bioscaffolds for massive rotator cuff defect in rabbits. Tissue Eng 13:1479–91

    CAS  PubMed  Article  Google Scholar 

  9. Chong AK, Ang AD, Goh JC, Hui JH, Lim AY, Lee EH et al (2007) Bone marrow-derived mesenchymal stem cells influence early tendon healing in a rabbit Achilles tendon model. J Bone Joint Surg Am 89:74–81

    PubMed  Article  Google Scholar 

  10. Cohen S, Leshansky L, Zussman E, Burman M, Srouji S, Livne E et al (2010) Repair of full-thickness tendon injury using connective tissue progenitors efficiently derived from human embryonic stem cells and fetal tissues. Tissue Eng Part A 16:3119–37

    PubMed  Article  Google Scholar 

  11. Ellera Gomes JL, da Silva RC, Silla LM, Abreu MR, Pellanda R (2012) Conventional rotator cuff repair complemented by the aid of mononuclear autologous stem cells. Knee Surg Sports Traumatol Arthrosc 20(2):373–377

  12. Funakoshi T, Majima T, Iwasaki N, Suenaga N, Sawaguchi N, Shimode K et al (2005) Application of tissue engineering techniques for rotator cuff regeneration using a chitosan-based hyaluronan hybrid fiber scaffold. Am J Sports Med 33:1193–201

    PubMed  Article  Google Scholar 

  13. Galatz LM, Ball CM, Teefey SA, Middleton WD, Yamaguchi K (2004) The outcome and repair integrity of completely arthroscopically repaired large and massive rotator cuff tears. J Bone Joint Surg Am 86-A:219–224

    PubMed  Google Scholar 

  14. Gerber C, Fuchs B, Hodler J (2000) The results of repair of massive tears of the rotator cuff. J Bone Joint Surg Am 82:505–515

    CAS  PubMed  Google Scholar 

  15. Geuze RE, Kruyt MC, Verbout AJ, Alblas J, Dhert WJ (2008) Comparing various off-the-shelf methods for bone tissue engineering in a large-animal ectopic implantation model: bone marrow, allogeneic bone marrow stromal cells, and platelet gel. Tissue Eng Part A 14:1435–1443

    CAS  PubMed  Article  Google Scholar 

  16. Goble EM, Somers WK, Clark R, Olsen RE (1994) The development of suture anchors for use in soft tissue fixation to bone. Am J Sports Med 22:236–239

    CAS  PubMed  Article  Google Scholar 

  17. Goutallier D, Bernageau J, Patte D (1989) L’evaluation par le scanner de la trophicite des muscles de la coiffe des rotateurs ayant une rupture tendineuse. Rev Chir Orthop Reparatrice Appar Mot 75(suppl 1):126–127

    Google Scholar 

  18. Hernigou P, Beaujean F (2002) Treatment of osteonecrosis with autologous bone marrow grafting. Clin Orthop Relat Res 405:14–23

    PubMed  Article  Google Scholar 

  19. Hernigou P, Poignard A, Beaujean F, Rouard H (2005) Percutaneous autologous bone-marrow grafting for nonunions. Influence of the number and concentration of progenitor cells. J Bone Joint Surg Am 87:1430–7

    PubMed  Article  Google Scholar 

  20. Hernigou P, Homma Y, Flouzat-Lachaniette CH, Poignard A, Chevallier N, Rouard H (2013) Cancer risk is not increased in patients treated for orthopaedic diseases with autologous bone marrow cell concentrate. J Bone Joint Surg Am 95(24):2215–2221

  21. Hoffmann A, Gross G (2006) Tendon and ligament engineering: from cell biology to in vivo application. Regen Med 1:563–574

    CAS  PubMed  Article  Google Scholar 

  22. Karas EH, Iannotti JP (1998) Failed repair of the rotator cuff: evaluation and treatment of complications. Instr Course Lect 47:87–95

    CAS  PubMed  Google Scholar 

  23. Kobayashi M, Itoi E, Minagawa H, Miyakoshi N, Takahashi S, Tuoheti Y et al (2006) Expression of growth factors in the early phase of supraspinatus tendon healing in rabbits. J Shoulder Elbow Surg 15:371–7

    PubMed  Article  Google Scholar 

  24. Kovacevic D, Rodeo S (2008) Biological augmentation of rotator cuff tendon repair. Clin Orthop Relat Res 466:622–633

    PubMed Central  PubMed  Article  Google Scholar 

  25. Murphy MB, Moncivais K, Caplan AI (2013) Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Exp Mol Med 45:e54. doi:10.1038/emm.2013.94

    PubMed Central  PubMed  Article  Google Scholar 

  26. Murray DH, Kubiak EN, Jazrawi LM, Araghi A, Kummer F, Loebenberg MI et al (2007) The effect of cartilage-derived morphogenetic protein 2 on initial healing of a rotator cuff defect in a rat model. J Shoulder Elbow Surg 16:251–254

  27. Okamoto N, Kushida T, Oe K, Umeda M, Ikehara S, Iida H (2010) Treating Achilles tendon rupture in rats with bone-marrow-cell transplantation therapy. J Bone Joint Surg Am 92:2776–2784

  28. Riley G (2004) The pathogenesis of tendinopathy. A molecular perspective. Rheumatology (Oxford) 43:131–42

    CAS  Article  Google Scholar 

  29. Rodeo SA, Potter HG, Kawamura S, Turner AS, Kim HJ, Atkinson BL (2007) Biologic augmentation of rotator cuff tendon-healing with use of a mixture of osteoinductive growth factors. J Bone Joint Surg Am 89:2485–97. doi:10.2106/JBJS.C.01627

    PubMed  Article  Google Scholar 

  30. Rui YF, Lui PP, Li G, Fu SC, Lee YW, Chan KM (2010) Isolation and characterization of multipotent rat tendon-derived stem cells. Tissue Eng Part A 16:1549–1558

  31. Salingcarnboriboon R, Yoshitake H, Tsuji K, Obinata M, Amagasa T, Nifuji A et al (2003) Establishment of tendon-derived cell lines exhibiting pluripotent mesenchymal stem cell-like property. Exp Cell Res 287:289–300

    CAS  PubMed  Article  Google Scholar 

  32. Schneider PR, Buhrmann C, Mobasheri A, Matis U, Shakibaei M (2011) Three-dimensional high-density co-culture with primary tenocytes induces tenogenic differentiation in mesenchymal stem cells. J Orthop Res 29:1351–60. doi:10.1002/jor.21400

    CAS  PubMed  Article  Google Scholar 

  33. Seeherman HJ, Archambault JM, Rodeo SA, Turner AS, Zekas L, D’Augusta D et al (2008) rhBMP-12 accelerates healing of rotator cuff repairs in a sheep model. J Bone Joint Surg Am 90:2206–2219

Download references


We thank Ted Sand and Richard Suzuki and the other members of Celling Biosciences for reviewing the final manuscript and for their help in translation.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Philippe Hernigou.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hernigou, P., Flouzat Lachaniette, C.H., Delambre, J. et al. Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study. International Orthopaedics (SICOT) 38, 1811–1818 (2014).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • Rotator cuff
  • Shoulder arthroscopy
  • Mesenchymal stem cell
  • Rotator cuff re-tear
  • Rotator cuff repair