Study finds MSCs accelerate healing, improve tendon integrity
Although arthroscopic rotator cuff repair has become a fairly common surgical procedure, retears can occur. Researchers from Henri Mondor Hospital, Paris University, have found that the use of bone-marrow-derived mesenchymal stem cells (MSCs) during arthroscopy enhances tendon healing and decreases the likelihood of retears.
"The frequency of retears following rotator cuff repair is greater than 25 percent,"said Philippe Hernigou, MD, PhD, during the recent AAOS/Orthopaedic Research Society (ORS) Biologic Treatments for Orthopaedic Injuries Research Symposium. "Moreover, revision surgery can be technically demanding and the healing of recurrent tears is not always predictable. We hypothesized that biologic augmentation with MSCs during arthroscopic rotator cuff surgery would result in improved healing at the tendon-to-bone interface."
Dr. Hernigou and his colleagues have studied the use of bone marrow-derived MSCs harvested from the iliac crest for more than 25 years. They believe this is the first study to evaluate the long-term effectiveness of MSC augmentation for rotator cuff repair.
To test their hypothesis, the researchers compared outcomes between two groups of arthroscopic rotator cuff repair patients; one group was treated with MSCs and the other was not. The MSC group involved 45 patients with full-thickness supraspinatus tendon tears, ranging in size from 1.5 cm to 3.5 cm. All underwent single-row arthroscopic rotator cuff repair and adjunct therapy using bone marrow-derived MSCs between 2000 and 2005. Patients with the following conditions were excluded:
- tears that appeared irreparable by arthroscopy
- tears that extended to either the subscapularis tendon or the infraspinatus tendon
- degenerative arthritis of the glenohumeral joint
- previous biceps tenotomy, biceps tenodesis, or shoulder surgeries
The control group included 45 patients (28 males, 25 females; mean age = 61 years) matched on tear size and tendon rupture location who had undergone single-row arthroscopic rotator cuff repair without MSC implantation before 2000. Age, sex, and dominant shoulder were similar between the two groups.
MSCs were harvested from the iliac crest and injected during arthroscopy into the junction between the bone and tendon and in the bone at the site of the footprint. An average 51,000 MSCs were injected per patient.
All patients underwent the same rehabilitation program following surgery and were evaluated with ultrasound monthly for 24 months, and with magnetic resonance imaging (MRI) at 3 months, 6 months, and 1, 2, and 10 years.
Short-, long-term results
As expected, tears smaller than 2 cm healed faster than larger tears. In the group treated with MSCs, the mean healing time for smaller tears was 3 months, while tears larger than 2 cm required of mean healing time of 6 months (P = 0.03). When comparing tears of the same size, control group patients took 2 months longer to heal than patients treated with MSCs. At 6 months after surgery, 100 percent of the tears in the MSC treatment group had healed versus 67 percent in the control group.
The researchers also observed that the number of MSCs transplanted had a direct correlation with outcomes. "When we injected more than 30,000 MSCs, surface healing on the footprint was greater than 2 cm2 at 3 months. When we injected less than 30,000 MSCs, the same amount of healing did not occur until at least 4 months,"Dr. Hernigou explained. "Control group patients required an average of 6 months for surface healing to reach 2 cm2."
At 10-year follow-up, 87 percent of the repairs in the MSC-treated group and 44 percent of those in the control group were still intact (P< 0.05). "Patients in the control group were approximately four times more likely to have experienced a poor outcome, including deficient or no healing or frank rupture, compared to the MSC group,"Dr. Hernigou said.
AAOS Research Symposia and Scientific Meetings
For more than 20 years, AAOS research symposia have brought together outstanding researchers in the development and presentation of information on the "cutting edge"of orthopaedics. The AAOS research symposia (formerly the AAOS/National Institutes of Health workshops) represent a long history of collaboration among the Academy, governmental agencies, industry, specialty societies, the Orthopaedic Research and Education Foundation, the Orthopaedic Research Society, leading researchers, and clinicians.
The annual workshops are designed to define the knowledge base in a chosen topic area based on scientific evidence, to identify gaps in the knowledge base, and to outline future research opportunities. The workshops provide an opportunity for experts and new investigators to exchange information and develop collaborative endeavors through scientific presentations and active discussion groups.
Previous topics have ranged from engineering technology transfers to osteolysis and implant wear, and from women's health and disparities issues to fracture repair and tissue engineering. A complete list of recent and upcoming research symposia is available on http://www.aaos.org/research/opportunities/symposia/.
If you are interested in submitting a proposal for a research symposium, contact Erin L. Ransford, AAOS manager of research advocacy, at email@example.com
Dr. Hernigou's coauthors of "Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study"are Charles Henri Flouzat Lachaniette; Jerome Delambre; Sebastien Zilber; Pascal Duffiet; Nathalie Chevallier; and Helen Rouard. The authors' disclosure information can be accessed at www.aaos.org/disclosure
Maureen Leahy is assistant managing editor of AAOS Now. She can be reached at firstname.lastname@example.org
About the AAOS/ORS Biologic Treatments for Orthopaedic Injuries Research Symposium
The AAOS/ORS Research Symposium, Biologic Treatments for Orthopaedic Injuries, was held Nov. 5–7, 2015, in Rosemont, Ill. Co-chaired by Robert LaPrade, MD, PhD; Constance Chu, MD; Jason Dragoo, MD; and Jason Koh, MD, the event reviewed and identified knowledge gaps in emerging biologic treatments for articular cartilage, muscle, tendon, and bone injuries.
The symposium's goals were to translate current bench research into accelerated and directly measurable improvements and patient-reported outcomes, to provide a forum for multidisciplinary discussion and collaboration, and to develop a consensus and identify ways to improve strategies for translational and clinical application of biologic treatments for musculoskeletal injuries.
Participants included more than 50 orthopaedic surgeons, young investigators, researchers, industry representatives, government representatives, and other medical specialists. During the 2-day program, the following topics were addressed:
- From Bench to the Bedside: Translating Basic Science into Clinical Care
- Therapeutic Platelet-Rich Plasma
- Minimally Manipulated Progenitor Cells
- Augmentation of Soft Tissue Repair
- Cell-Free and Cell-Based Scaffold Strategies for the Repair, Reconstruction and/or Regeneration of Tendon, Ligament, Muscle, and Articular Cartilage Tissues
The next symposium in the series is AAOS/ORS Tackling Joint Disease by Understanding Crosstalk between Cartilage and Bone Research Symposium, scheduled for April 28–30, 2016. For more information on these symposia, contact Erin L. Ransford, AAOS manager of research development, at email@example.com
- This study sought to determine whether the use of bone-marrow-derived MSCs during arthroscopic rotator cuff repair would improve tendon healing.
- The researchers compared outcomes of patients who had undergone arthroscopic rotator cuff repair with and without MSC augmentation.
- In both the short- and long-term, patients who received MSCs healed faster and had fewer retears than patients who did not receive MSCs.