Code Description CPT
20999 Unlisted procedure, musculoskeletal system, general
38206 Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; autologous
38241 Hematopoietic progenitor cell (HPC); autologous transplantation
Orthopedic Applications of Stem Cell Therapy (Including Allografts and Bone Substitutes Used with Autologous Bone Marrow)
Mesenchymal stem cells are adult stem cells which are usually found in the bone marrow. These stem cells can generate other types of cells that are part of the body’s musculoskeletal system, such as bone, cartilage, and muscle. Stem cells are being studied as a way to treat orthopedic problems like damaged bone, ligaments, tendons, and the discs between the bones of the spine. Using stem cells to treat orthopedic problems is unproven. Studies have not yet shown the best ways to gather and deliver these cells. Studies also have not yet shown that using stem cells for orthopedic conditions leads to better health results compared to usual treatments.
Note: The Introduction section is for your general knowledge and is not to be taken as policy coverage criteria. The rest of the policy uses specific words and concepts familiar to medical professionals. It is intended for providers. A provider can be a person, such as a doctor, nurse, psychologist, or dentist. A provider also can be a place where medical care is given, like a hospital, clinic, or lab. This policy informs them about when a service may be covered.
Policy Coverage Criteria
Note: This policy does not address unprocessed allograft bone. Service Investigational
Mesenchymal stem cell therapy
Allograft bone products containing viable stem cells
Allograft or synthetic bone graft substitutes
Coding
Mesenchymal stem cell therapy is considered investigational for all orthopedic applications, including use in repair or regeneration of musculoskeletal tissue.
Allograft bone products containing viable stem cells, including but not limited to demineralized bone matrix (DBM) with stem cells, are considered investigational for all orthopedic applications.
Allograft or synthetic bone graft substitutes that must be combined with autologous blood or bone marrow are considered investigational for all orthopedic applications.
Benefit Application
The Regenexx® procedure is currently performed at select centers in the United States. Therefore, requests for it may be made for an out-of-network facility.
Evidence Review
Description
Mesenchymal stem cells (MSCs) have the capability to differentiate into a variety of tissue types, including various musculoskeletal tissues. Potential uses of MSCs for orthopedic applications include treatment of damaged bone, cartilage, ligaments, tendons and intervertebral discs.
Background Mesenchymal Stem Cells
MSCs are multipotent cells (also called stromal multipotent cells) that can differentiate into various tissues including organs, trabecular bone, tendon, articular cartilage, ligaments, muscle, and fat. 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. Tissues such as muscle, cartilage, tendon, ligaments, and vertebral discs show limited capacity for endogenous repair because of the limited presence of the triad of tissue functional components: vasculature, nerves, and lymphatics. Orthobiologics is a term introduced to describe interventions using cells and biomaterials to support healing and repair. Cell therapy is the application of MSCs directly to a musculoskeletal site. Tissue engineering techniques use MSCs and/or bioactive molecules such as growth factors and scaffold combinations to improve the efficiency of repair or regeneration of damaged musculoskeletal tissues.
Bone-marrow aspirate is considered to be 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 an additional 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 patients.
In vivo, the fate of stem cells is regulated by signals in the local 3-dimensional microenvironment from the extracellular matrix and neighboring cells. It is believed that the success of tissue engineering with MSCs will also require an appropriate 3-dimensional scaffold or matrix, culture conditions for tissue-specific induction, and implantation techniques that provide appropriate biomechanical forces and mechanical stimulation. The ability to induce cell division and differentiation without adverse effects, such as the formation of neoplasms, remains a significant concern. Given that each tissue type requires different culture conditions, induction factors (signaling proteins, cytokines, growth factors), and implantation techniques, each preparation must be individually examined.
Summary of Evidence
For individuals who have cartilage defects, meniscal defects, joint fusion procedures, or osteonecrosis who receive stem cell therapy, the evidence includes small randomized controlled trials and nonrandomized comparative trials. Relevant outcomes are symptoms, morbid events, functional outcomes, quality of life, and treatment-related morbidity. Use of mesenchymal stem cells (MSCs) for orthopedic conditions is an active area of research. Despite continued research into the methods of harvesting and delivering treatment, there are uncertainties regarding the optimal source of cells and the delivery method. Studies have included MSCs from bone marrow, adipose tissue, peripheral blood, and synovial tissue. The largest body of evidence is on use of autologous MSCs, either concentrated or expanded in culture, for cartilage repair. This evidence includes small randomized and nonrandomized comparative trials with insufficient data to evaluate health outcomes. In addition, expanded MSCs for orthopedic applications are not U.S. Food and Drug Administration (FDA)*approved (concentrated autologous MSCs do not require FDA approval). Overall, there is a lack of evidence that clinical outcomes are improved. The evidence is insufficient to determine the effects of the technology on health outcomes.
Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this review are listed in Table 1. Many are observational studies with commercially available products (eg, Cartistem, AlloStem, Trinity Evolution, Osteocel Plus).
Practice Guidelines and Position Statements
American Association of Orthopaedic Surgeons
The 2013 and 2014 American Association of Orthopaedic Surgeons’ guidelines on treatment of glenohumeral joint osteoarthritis have indicated:
* Treatment using allograft, autograft, biologic, and interpositional grafts in patients with glenohumeral joint osteoarthritis is inconclusive
, and that
* Treatment using growth factor injections and/or platelet rich plasma for patients with symptomatic osteoarthritis of the knee is inconclusive.
