In the previous post, I started reviewing a classic paper published by Dr. Philippe Hernigou and co-workers, entitled “Biological augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study.” I will continue in this post by reporting on clinical outcomes from the study. Most importantly, Dr. Hernigou assessed whether or not there was an intact tendon present at 10-year follow up, which is an objective clinical outcome that greatly diminishes any potential influence of a placebo effect. It also is hard to imagine a placebo effect lasting 10 years! See the previous post for study parameters, patient selection and my views on the utility of case-controlled clinical studies versus Level I clinical study formats.
Patients were followed by ultrasound (US) on at least a monthly basis, and MRI at major intervals, including a 10-year follow up. Any abnormality detected by US was confirmed by MRI. One advantage of using both types of imaging is that the surgical repair used during the treatment can complicate the interpretation of MRIs, but won’t create artifacts on US. A unique feature reported in the paper was the use of a rubric for assessing footprint healing based on US imaging. Their subjective scoring system had a value of “0” for no evidence of healing up to “4” for total healing, as assessed by US, reflecting the degree of bonding of the tendon to the bony surface in the footprint.
The following clinical observations were reported by Hernigou and co-workers:
- 87% of the BMC-treated patients were assessed by blinded readers to have intact tendons at the 10-year follow up compared to just 44% of the control patients.
- There were no rotator cuff failures for the BMC group during the first 6 months following repair (100% intact).
- The control group experienced 8 failures by 3 months and an additional 7 failures by 6 months (67% intact).
- The rate of footprint healing using the group’s rubric was slower for the control group, taking 2 months longer for total healing at the footprint, compared to the BMC group.
- Within the BMC-treated group those patients receiving >30,000 MSCs (determined by performing a tissue culture-based assessment yielding an estimate of MSC content) reached 2 cm2 of healing surface at 3 months, but for those receiving <30,000 MSCs that milestone of healing wasn’t reached until 4 months.
- Control patients needed an average of 6 months to reach 2 cm2.
- Within the BMC-treated group, the patients with intact tendons at 10-year follow up had received an average of 54,000 MSCs, while the patients with non-intact tendons had received just 14,000 MSCs. The difference is statistically significant.
Of all of the interesting clinical data reported in the paper, if you look just at the long-term outcome of intact or non-intact tendon at 10-year follow up (Item 1), the data shows that you are nearly twice as likely to have an intact tendon if you had received BMC augmentation compared to the standard of care surgical repair. So, the BMC augmentation didn’t result in just a little improvement, say 15-20%, but a whopping 100% increase in the number of patients with an intact tendon after 10-years compared to the control group. Keep in mind, none of these patients were restricted in the use of their repaired shoulders, so this is as real-world as you can get.
One criticism I have heard is that the failure rate of the control group might have been lower with a more current surgical protocol, like using a double row of sutures. But I am not aware of data demonstrating superiority of a 2-row versus 1-row of sutures for rotator cuff repair at a 10-year milestone. Furthermore, focusing just on the surgical technique misses the point Dr. Hernigou’s data makes about the kinetics of healing in this type of injury. As reported, patients in the control group suffered a much higher frequency of failure during the first 6-months compared to the BMC-augmented group, with no failures in the latter group and a 33% failure rate in the former. Given that the two groups of patients received the same surgical procedure, the dramatic difference in failure rates during the first six months highlights a significant benefit of BMC augmentation.
In addition, within the BMC-treated group, patients receiving more than 30,000 MSCs took less time to reach 2 cm2 of healing in the footprint compared to those receiving fewer than 30,000 MSCs. The authors suggest that the improved healing during the first 6-month period demonstrated by the BMC-treated group probably improved the odds of a patient having an intact tendon after 10-years.
It also is worth mentioning that one of the issues with surgeries like rotator cuff repair is compliance of the patient with post-treatment rehab protocols. In this case, Dr. Hernigou clearly stated that the rehab program for the patients was not aggressive, but took a slower approach than currently is the fashion. Given the fairly high revision rates for this type of surgery in general, it would seem that the faster the healing within the first 6-month period the more robust the recovery could be even for less-compliant patients. If the injury heals more quickly, it becomes less important when a patient disregard’s their physician’s instruction and starts using their shoulder more aggressively.
One of the important refinements of the practice of regenerative medicine using BMC demonstrated in the study is that Dr. Hernigou treated both the repaired tendon, as well as the subchondral bone marrow depot zone below the footprint. The reason for treating the subchondral compartment is that he found that patients with rotator cuff tears had a subchondral bone marrow depot with fewer MSCs present in the compartment compared to the number of MSCs in a healthy shoulder. He published this result in 2015.
Thus, it would seem that by injecting both the tendon and the zone beneath the footprint, it was possible to dramatically improve the recovery and functionality of torn rotator cuff tendons over an extended period of time. By focusing on the objective clinical outcome of intact or non-intact status of the repaired rotator cuff tendon at 10-years, Dr. Hernigou in my opinion has made a compelling case to augment rotator cuff repairs with BMC. There also are implications for partial tears—a far more frequent clinical pathology.
Although Dr. Hernigou didn’t comment directly in the paper about adverse events, I will provide the following:
- No one died as a result of their bone marrow aspiration.
- The degree of fatty infiltration continued to increase in patients who had received the standard of care surgical procedure, but not in patients receiving BMC-augmentation.
- Control patients suffered re-tears at a substantially higher rate compared to the BMC-treated group and the control group’s re-tears frequently were more complex (i.e., involving more than one tendon upon re-tear).
So, all in all, BMC augmentation of rotator cuff tears seems like a safe procedure with a significant therapeutic benefit as reported by Hernigou and co-workers.