Zachary Grant

Introduction. Anterior Cruciate Ligament (ACL) tears have an incidence of between 36.9 and 60.9 per 100,000 persons/year, resulting in approximately 200,000 injuries annually.⁵ They most commonly occur in athletes involved in sports that require contact and/or sharp, sudden movements.² The current method of repair involves surgically removing the damaged ACL and replacing it with a graft, which is most typically a tendon from a different part of the knee or from a cadaver.³ This method is 75% to 90% effective, with approximately 10% to 15% of patients requiring a revision.⁵ While the reasons for failure range from poor tendon-bone union to total tendon detachment, it has led researchers to seek alternative treatments that will decrease this failure rate.⁵ One of the potential solutions to this dilemma involves using Bone Marrow-Derived Mesenchymal Stem Cells (BMSCs) at the tendon-bone interface. BMSCs have the ability to differentiate into osteoblasts, adipocytes and chondrocytes, can control inflammation via cytokine release, and can expand without loss of differentiated phenotype.⁴ Studies have shown that, when BMSCs are added to rabbit test subjects, the tendon-bone interface appears more natural and results in test subjects having greater load bearing weight and increased stiffness.^1,6 These findings suggest a potential future therapy to aid in ACL surgical repair. Methods. BMSCs require a constant supply of growth factors to be maximally utilized. To best meet this demand, two studies were conducted: one where researchers infected BMSCs with vectors containing bone morphogenic protein 2 (BMP-2) and/or basic fibroblast growth factor (bFGF), and another with only upregulated Transforming Growth Factor-b (TGF-b). The infected BMSCs were then placed at the surgical repair site in rabbit test subjects and the healing progression was assessed via histological examination, and by comparing the amount of healing at the surgical site, the maximum load bearing weight, and the stiffness of the tendon. Results. The rabbits that had BMSCs infected with BMP-2 and bFGF together, as well as those with upregulated TGF-b, showed a more natural-looking tendon-bone interface on histological examination, improved healing, higher load bearing weights, and increased stiffness, when compared the control groups. Conclusions. These results show the promising potential of using BMSCs as an additional aid to ACL post-surgical recovery. Additionally, this treatment could possibly reduce the failure rate of these repairs, which would lead to an improved quality of life for patients.

1. Chen B, Li B, Qi YJ, et al. Enhancement of tendon-to-bone healing after anterior cruciate ligament reconstruction using bone marrow-derived mesenchymal stem cells genetically modified with bFGF/BMP2. Scientific reports. 2016;6:25940.
2. Kiapour AM, Murray MM. Basic science of anterior cruciate ligament injury and repair. Bone Joint Res. 2014;3(2):20-31.
3. Mayo Clinic Staff. ACL Reconstruction: What You Can Expect. ACL Reconstruction: What You Can Expect. http://www.mayoclinic.org/tests-procedures/acl-reconstruction/details/what-you-can-expect/rec-20166743 Published January 12, 2017. Accessed March 21, 2017.
4. Saltzman BM, Kuhns BD, Weber AE, Yanke A, Nho SJ. Stem Cells in Orthopedics: A Comprehensive Guide for the General Orthopedist. American journal of orthopedics (Belle Mead, N.J.) 2016;45(5):280-326
5. Samitier G, Marcano AI, Alentorn-Geli E, Cugat R, Farmer KW, Moser MW. Failure of Anterior Cruciate Ligament Reconstruction. Archives of Bone and Joint Surgery. 2015;3(4):220-240.
6. Wang R, Xu B, Xu HG. Up-Regulation of TGF-beta Promotes Tendon-to-Bone Healing after Anterior Cruciate Ligament Reconstruction using Bone Marrow-Derived Mesenchymal Stem Cells through the TGF-beta/MAPK Signaling Pathway in a New Zealand White Rabbit Model. Cell Physiol Biochem. 2017;41(1):213-226.