Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study.
Purpose 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 retears were correlated with the number of MSCs received atthe tendon-to-bone interface. Methods Forty-five patients in the study group received concentrated bone marrow-derived MSCs as an adjunct to singlerow 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). Results 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.
Conclusion 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.
For patients who received MSCs of the footprint there was a negative correlation between the time to obtain total healing of a same surface and the concentration of MSCs in the graft (Rs= –0.4; p=0.04). Size of the tear also had a significant relation (p=0.03) with time to healing, i.e. patients in the MSC-treatment group with tears larger than 2 cm needed a longer time to reach total healing (average six months) compared to the patients with tears smaller than 2 cm (average three months). Regardless of the size of the tear, patients in the control group took two months longer to reach total healing when matched for tear size compared to the patients in the MSC-treatment group.
From a schematic point of view, patients who received more than 30,000 MSCs had healed 2 cm² or more over the footprint at three months, while those who received fewer than 30,000 MSCs needed at least four months or more to achieve the same degree of surface healing. For control group patients, none had achieved healing of 2 cm² at three months, but required on average six months for surface healing to reach 2 cm.
Note: The authors used colony forming units (10 days of culture) to determine the number of mesenchymal stem cells, not simple counting of cells on flow cytometer.