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.
KeywordsRotator cuff Shoulder arthroscopy Mesenchymal stem cell Rotator cuff re-tear Rotator cuff repair
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.
- 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):373–377Google 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):126–127Google 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):2215–2221Google 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 16:251–254Google Scholar
- 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 92:2776–2784Google 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 16:1549–1558Google 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 90:2206–2219Google Scholar