BlueCross BlueShield of Tennessee Medical Policy Manual

Orthopedic Applications of Stem Cell Therapy


Mesenchymal stem cells (MSCs) have the capability to differentiate into a variety of tissue types, including various musculoskeletal tissues. MSCs are associated with the blood vessels within bone marrow, synovium, fat, and muscle, where they can be mobilized for endogenous repair as occurs with healing of bone fractures. Potential uses of MSCs for orthopedic applications include treatment of damaged bone, cartilage, ligaments, tendons and intervertebral discs. However, the ability to induce cell division and differentiation without adverse effects, such as the formation of neoplasms, remains a significant concern.

Bone marrow aspirate is considered the most accessible source and, thus, the most common place to isolate MSCs for treatment of musculoskeletal disease. However, harvesting MSCs from bone marrow requires a procedure that may result in donor-site morbidity. In addition, the number of MSCs in bone marrow is low, and the number and differentiation capacity of bone marrow‒derived MSCs decreases with age, limiting their efficiency when isolated from older individuals.

Tissues such as muscle, cartilage, tendon, ligaments, and vertebral discs show limited capacity for endogenous repair. Therefore, tissue engineering techniques are being developed to improve the efficiency of repair or regeneration of damaged musculoskeletal tissues. Tissue engineering focuses on the integration of biomaterials with MSCs and/or bioactive molecules such as growth factors. It is believed that the success of tissue engineering with MSCs will also require an appropriate 3-dimensional scaffold or matrix, such as demineralized bone matrix (e.g., Vitoss® Bioactive Foam Bone Graft Substitute, CopiOs® Bone Void Filler, DBX® Demineralized bone matrix putty), culture conditions for tissue-specific induction, and implantation techniques that provide appropriate biomechanical support and stimulation.




This technology continues in the early stages of development. Concentrated autologous MSCs do not require approval by FDA. No products using engineered or expanded MSCs have been approved by FDA for orthopedic applications. Overall, there is a lack of evidence that clinical outcomes are improved. The small randomized and nonrandomized comparative trials done to date provide insufficient evidence to evaluate the effect on health outcomes.


Akgun, I., Unlu, M., Erdal, O., Ogut, T., Erturk, M., Ovali, E., et al. (2015). Matrix-induced autologous mesenchymal stem cell implantation versus matrix-induced autologous chondrocyte implantation in the treatment of chondral defects of the knee: a 2-year randomized study. Archives of Orthopedic and Trauma Surgery, 135 (2), 251-263. Abstract retrieved January 18, 2017 from PubMed database.

BlueCross BlueShield Association. Medical Policy Reference Manual. (7:2017). Orthopedic applications of stem-cell therapy (including allografts and bone substitutes used with autologous bone marrow) (8.01.52). Retrieved November 20, 2017 from BlueWeb. (36 articles and/or guidelines reviewed)

ECRI Institute. Emerging Technology Evidence Report. (2013, June). Autologous mesenchymal stem cells for treating knee osteoarthritis. Retrieved January 2, 2015 from ECRI Institute. (88 articles and/or guidelines reviewed)

Filardo, G., Madry, H., Jelic, M., Roffi, A., Cucchiarini, M., & Kon, E. (2013). Mesenchymal stem cells for the treatment of cartilage lesions: from preclinical findings to clinical application in orthopaedics. Knee Surgery, Sports Traumatology, Arthroscopy, 21 (8), 1717-1729. Abstract retrieved January 18, 2017 from PubMed database.

Hernigou, P., Trousselier, M., Roubineau, F., Bouthors, C., Chevallier, N., Rouard, H., et al. (2016). Stem cell therapy for the treatment of hip osteonecrosis: a 30-year review of progress. Clinics in Orthopedic Surgery, 8 (1), 1-8. (Level 2 evidence)

Kim, Y.S., Park, E.H., Kim, Y.C., & Koh, Y.G. (2013). Clinical outcomes of mesenchymal stem cell injection with arthroscopic treatment in older patients with osteochondral lesions of the talus. The American Journal of Sports Medicine, 41 (5), 1090-1099. Abstract retrieved January 18, 2017 from PubMed database.

Pak, J., Lee, J., Park, K., Park, M., Lang, L., and Lee, S. (2017) Current use of autologous adipose tissue derived stromal vascular fraction cells for orthopedic applications. Journal of Biomedical Science, 24 (9),12 pages. (Level 2 evidence)

Vega, A., Martin-Ferrero, M., Del Canto, F., Alberca, M., Garcia, V., Munar, A., et al. (2015). Treatment of knee osteoarthritis with allogeneic bone marrow mesenchymal stem cells: a randomized controlled trial. Transplantation, 99 (8), 1681-1690. Abstract retrieved January 18, 2017 from PubMed database.

Winifred S. Hayes, Inc. Medical Technology Directory. (2015, December; last search update November 2016). Autologous stem cell therapy for treatment of avascular necrosis of the hip. Retrieved January 18, 2017 from (61 articles and/or guidelines reviewed)

Wong, K.L., Lee, K.B., Tai, B.C., Law, P., Lee, E.H., & Hui, J.H. (2013). Injectable cultured bone marrow-derived mesenchymal stem cells in varus knees with cartilage defects undergoing high tibial osteotomy: a prospective, randomized controlled clinical trial with 2 years’ follow-up. Arthroscopy, 29 (12), 2020-2028. Abstract retrieved January 18, 2017 from PubMed database.




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