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This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

02-38240-02

Original Effective Date: 09/15/14

Reviewed: 10/31/17

Revised: 11/15/17

Subject: Orthopedic Applications of Stem-Cell Therapy

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Position Statement Billing/Coding Reimbursement Program Exceptions Definitions Related Guidelines
           
Other References Updates    
           

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.

MSCs are multipotent cells (also called stromal multipotent cells) that possess the ability to 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. 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 efficacy 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. 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.

Regulatory Status

Concentrated autologous MSCs do not require approval by FDA.

Demineralized bone matrix (DBM), which is processed allograft bone, is considered minimally processed tissue and does not require FDA approval. At least 4 commercially available DBM products are reported to contain viable stem cells:

Other products contain DBM and are designed to be mixed with bone marrow aspirate. Some of the products that are currently available are:

Other commercially available products are intended to be mixed with bone marrow aspirate and have received 510(k) clearance, such as:

Concentrated autologous MSCs do not require approval by FDA. No products using engineered or expanded MSCs have been approved by FDA for orthopedic applications.

POSITION STATEMENT:

Mesenchymal stem-cell therapy is considered experimental or 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, is considered experimental or investigational for all orthopedic applications.

Allograft or synthetic bone graft substitutes that must be combined with autologous blood or bone marrow are considered experimental or investigational for all orthopedic applications.

There is insufficient published clinical evidence to support the safety and effectiveness of these therapies for repair or regeneration of musculoskeletal tissue.

BILLING/CODING INFORMATION:

CPT Coding:

38206

Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; autologous

38230

Bone marrow harvesting for transplantation; allogeneic

38241

Hematopoietic progenitor cell (HPC); allogeneic transplantation per donor

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Advantage products: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline reviewed date.

DEFINITIONS:

No guideline specific definitions apply.

RELATED GUIDELINES:

02-38240-01, Allogeneic Bone Marrow and Stem Cell Transplantation
02-38241-01, Autologous Bone Marrow and Stem Cell Transplantation

OTHER:

None applicable.

REFERENCES:

  1. Agar G, Blumenstein S, Bar-Ziv Y, Kardosh R, Schrift-Tzadok M, Gal-Levy R, Fischler T, Goldschmid R, Yayon A. The Chondrogenic Potential of Mesenchymal Cells and Chondrocytes from Osteoarthritic Subjects: A Comparative Analysis. Cartilage. 2011 Jan;2(1):40-9.
  2. Blue Cross Blue Shield Association Medical Policy Reference Manual (MPRM). 8.01.52, Orthopedic Applications of Stem-Cell Therapy (Including Allografts and Bone Substitutes Used With Autologous Bone Marrow).(July 2017).
  3. American Academy of Orthopaedic Surgeons. Stem cells and orthopaedics. Your Orthopaedic Connection 2007. Accessed at http://orthoinfo.aaos.org on 07/25/14.
  4. American Academy of Orthopaedic Surgeons. Stem cell therapy in orthopaedics. AAOS Now (February 2012). Accessed at http://www.aaos.org/news/aaosnow on 07/25/14.
  5. Blashki D, Murphy MB, Ferrari M, Simmons PJ, Tasciotti E. Mesenchymal stem cells from cortical bone demonstrate increased clonal incidence, potency, and developmental capacity compared to their bone marrow-derived counterparts. J Tissue Eng. 2016 Aug 16;7:2041731416661196.
  6. Burke J, Hunter M, Kolhe R, Isales C, Hamrick M, Fulzele S. Therapeutic potential of mesenchymal stem cell based therapy for osteoarthritis. Clin Transl Med. 2016 Dec;5(1):27.
  7. ClinicalTrials.gov. NCT01041001, Study to Compare the Efficacy and Safety of Cartistem® and Microfracture in Patients With Knee Articular Cartilage Injury or Defect (last updated April 2012).
  8. ClinicalTrials.gov. NCT01626677, Follow-Up Study of CARTISTEM® Versus Microfracture for the Treatment of Knee Articular Cartilage Injury or Defect (last updated November 2013).
  9. ClinicalTrials.gov. NCT00885729, Mesenchymal Stem Cells in a Clinical Trial to Heal Articular Cartilage Defects (last updated October 2012).
  10. ClinicalTrials.gov. NCT01459640, Intra-Articular Autologous Bone Marrow Mesenchymal Stem Cells Transplantation to Treat Mild to Moderate Osteoarthritis (last updated October 2011).
  11. ClinicalTrials.gov. NCT01413061, Study of Subtalar Arthrodesis Using AlloStem® Versus Autologous Bone Graft (last updated October 2013).
  12. ClinicalTrials.gov. NCT01809769: Autologous Adipose Tissue Derived Mesenchymal Stem Cells Therapy for Patients With Knee Osteoarthritis. Cellular Biomedicine Group Ltd. April 1, 2016.
  13. Cooney DS, et al. Mesenchymal Stem Cells Enhance Nerve Regeneration in a Rat Sciatic Nerve Repair and Hindlimb Transplant Model. Sci Rep. 2016 Aug 11;6:31306.
  14. Cui B, Li E, Yang B, Wang B. Human umbilical cord blood-derived mesenchymal stem cell transplantation for the treatment of spinal cord injury. Exp Ther Med. 2014 May;7(5):1233-1236.
  15. Cui GH, Wang YY, Li CJ, Shi CH, Wang WS. Efficacy of mesenchymal stem cells in treating patients with osteoarthritis of the knee: A meta-analysis. Exp Ther Med. 2016 Nov;12(5):3390-3400.
  16. Dominici M, Le Blanc K, Mueller I et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8(4):315-7.
  17. ECRI Institute Health Technology Forecast: Autologous and Allogeneic Mesenchymal Stem Cell Therapy for Treating Osteoarthritis (11/02/12).
  18. Embree MC, Chen M, et al. Exploiting endogenous fibrocartilage stem cells to regenerate cartilage and repair joint injury. Nat Commun. 2016 Oct 10;7:13073.
  19. Kehoe O, Cartwright A, Askari A, El Haj AJ, Middleton J. Intra-articular injection of mesenchymal stem cells leads to reduced inflammation and cartilage damage in murine antigen-induced arthritis. J Transl Med. 2014 Jun 3;12:157.
  20. Koh YG, Choi YJ. Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis. Knee 2012; 19(6):902-7.
  21. Matsukura Y, Muneta T, Tsuji K, Koga H, Sekiya I. Mesenchymal stem cells in synovial fluid increase after meniscus injury. Clin Orthop Relat Res. 2014 May;472(5):1357-64.
  22. Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Exp Mol Med. 2013 Nov 15;45:e54. doi: 10.1038/emm.2013.94.
  23. Nejadnik H, Hui JH, Feng Choong EP et al. Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study. Am J Sports Med 2010; 38(6):1110-6.
  24. Pierannunzii L, Zagra L. Bone grafts, bone graft extenders, substitutes and enhancers for acetabular reconstruction in revision total hip arthroplasty. EFORT Open Rev. 2017 Mar 13;1(12):431-439.
  25. Pot MW, Gonzales VK, Buma P, IntHout J, van Kuppevelt TH, de Vries RB, Daamen WF. Improved cartilage regeneration by implantation of acellular biomaterials after bone marrow stimulation: a systematic review and meta-analysis of animal studies. PeerJ. 2016 Sep 8;4:e2243.
  26. Sato M, Uchida K, Nakajima H, Miyazaki T, Guerrero AR, Watanabe S, Roberts S, Baba H. Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis. Arthritis Res Ther. 2012 Feb 7;14(1):R31.
  27. Song F, Tang J, Geng R, Hu H, Zhu C, Cui W, Fan W. Comparison of the efficacy of bone marrow mononuclear cells and bone mesenchymal stem cells in the treatment of osteoarthritis in a sheep model. Int J Clin Exp Pathol. 2014 Mar 15;7(4):1415-26.
  28. U.S. Food and Drug Administration. Assuring safety and efficacy of stem-cell based products. Accessed at http://www.fda.gov on 07/25/14.
  29. Uth K, Trifonov D. Stem cell application for osteoarthritis in the knee joint: A minireview. World J Stem Cells. 2014 Nov 26;6(5):629-36.
  30. Vadalà G, Russo F, Ambrosio L, Loppini M, Denaro V. Stem cells sources for intervertebral disc regeneration. World J Stem Cells. 2016 May 26;8(5):185-201.
  31. Wang Y, Han ZB, Song YP, Han ZC. (2012). Safety of Mesenchymal Stem Cells for Clinical Application. Stem Cells International, 2012.
  32. Xu J, Wang B, Sun Y, Wu T, Liu Y, Zhang J, Lee WY, Pan X, Chai Y, Li G. Human fetal mesenchymal stem cell secretome enhances bone consolidation in distraction osteogenesis. Stem Cell Res Ther. 2016 Sep 10;7(1):134.
  33. Yagi H, Kitagawa Y. The role of mesenchymal stem cells in cancer development. Front Genet. 2013 Nov 27;4:261. doi: 10.3389/fgene.2013.00261.
  34. Zakaria Z, Seman CN, et al. Histological Evaluation of Hydroxyapatite Granules with and without Platelet-Rich Plasma versus an Autologous Bone Graft: Comparative study of biomaterials used for spinal fusion in a New Zealand white rabbit model. Sultan Qaboos Univ Med J. 2016 Nov;16(4):e422-e429.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Medical Policy & Coverage Committee on 10/31/17.

GUIDELINE UPDATE INFORMATION:

09/15/14

New Medical Coverage Guideline.

09/15/15

Scheduled review. Position statement maintained; updated description section, index terms and references.

11/15/16

Scheduled review. Position statement maintained. Updated references.

11/15/17

Scheduled review. Revised description section. Position statement maintained. Updated references.

Date Printed: December 18, 2017: 11:30 AM