A Double-Blind, Randomized, Placebo-Controlled Trial of Mesenchymal Stem Cells for the Treatment of Patients with Full-Thickness Rotator Cuff Tears

Jose Ramon Lamas¹, Pilar Tornero-Esteban², Carlos García Fernández³, Luis Rodriguez Rodriguez², Fernando Marco⁴ and Benjamín Fernández-Gutiérrez⁵, ¹Rheumatology Service, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain, ²Rheumatology, Rheumatology Service, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain, ³Ortopaedics Surgery and Traumatology Service, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain, ⁴Traumatology, Ortopaedics Surgery and Traumatology Service, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain, ⁵Department of Rheumatology, Hospital Clínico San Carlos, Madrid, Spain

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: mesenchymal stem cells and treatment, Shoulder Pain

Session Information

Date: Monday, November 9, 2015

Title: Orthopedics, Low Back Pain and Rehabilitation Poster

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:

Rotator cuff lesions cause shoulder pain and disability. The outcome after surgical repair of full-thickness rotator cuff tears has been controversial due to the high rate of re-rupture. New therapeutic alternatives are needed to overcome the limited tendon healing, including the use of growth factors, cytokines and/or tissue engineering approaches using mesenchymal stem cells (MSCs). The purpose of this study was to evaluate the safety and effectiveness of autologous MSCs implantation in patients with full-thickness rotator cuff tears.

Methods:

Thirteen patients were included in the study. They were double-blind randomized into two groups. Control group: (n=5) was treated with a collagen type I implant (OrthADAPT™). Treatment group: (n=8) was treated with type I collagen membrane combined with 20×10⁶autologous Bone Marrow-MSCs (BM-MSCs).

Bone marrow (BM) was aseptically drawn under local anesthesia from right posterior superior iliac spine and immediately anticoagulated by heparin. Collected bone marrow (50ml) was processed to isolate and to expand BM-MSCs in vitro. The day of surgery, 20×10⁶cells BM-MSCs were resuspended in 1ml of saline solution and seeded over the OrthADAPT™ for 10 minutes prior implantation into the patient.

Patients were evaluated preoperatively and at one year follow-up by: (1) tendon status by MRI (Magnetic Resonance Imaging), (2) functional recovery using the Constant Score (CS) and (3) pain score (10 cm visual analog score [VAS]). The primary endpoint of the study was to achieve a functional improvement of at least 20 points in the CS. Differences between groups were analyzed using the Mann-Whitney U test, values of p ≤ 0.05 were considered significants. The study was registered (Eudra-CT: 2007-007630-19) and was in accordance with ethical standards for research on human subjects.

Results:

Only the treatment group met the clinical functional improvement criteria, registering differences of 31 points in the CS one year post-intervention (p=0.0073). Additionally, comparable reductions in mean VAS, re-tear rate and repair integrity were found in both groups.

Constant’s Score	Control group (n=5)		Treatment group (n=8)
Constant’s Score	Preoperative	12 months	Preoperative	12 months
Contralateral Shoulder	81 [77.5−94.5]	84[75−91.5]	89 [79−91]	91 [87−96]
Injured shoulder	55 [42.5−58]	71 [49.75−78.5]	45.5 [35.25−51.75]	76.5 [62.25−85]a

Three patients enrolled in the treatment group (37.5%) and one in the control group (25%) developed postoperative complications. These 4 patients showed swelling and symptoms of recurrent tear including pain and reduced range of motion within 3 months post-operation. The 4 patients underwent surgery to remove the patch. Histological analysis revealed the existence of chronic synovitis with granulomatous tissue. Microbiological tests were negative in all cases. These complications were solved after additional surgery.

Conclusion:

These results provide preliminary satisfactory clinical outcomes related to the use of MSCs for the treatment of full thickness rotator cuff tears. Nevertheless, the occurrence of adverse events, likely related to patch instability indicated the need for further controlled studies.

Disclosure: J. R. Lamas, None; P. Tornero-Esteban, None; C. García Fernández, None; L. Rodriguez Rodriguez, None; F. Marco, None; B. Fernández-Gutiérrez, None.

To cite this abstract in AMA style:

Lamas JR, Tornero-Esteban P, García Fernández C, Rodriguez Rodriguez L, Marco F, Fernández-Gutiérrez B. A Double-Blind, Randomized, Placebo-Controlled Trial of Mesenchymal Stem Cells for the Treatment of Patients with Full-Thickness Rotator Cuff Tears [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/a-double-blind-randomized-placebo-controlled-trial-of-mesenchymal-stem-cells-for-the-treatment-of-patients-with-full-thickness-rotator-cuff-tears/. Accessed .

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-double-blind-randomized-placebo-controlled-trial-of-mesenchymal-stem-cells-for-the-treatment-of-patients-with-full-thickness-rotator-cuff-tears/