BlueCross BlueShield of Tennessee Medical Policy Manual

Stem Cell Therapy for Peripheral Artery Disease


Peripheral arterial disease (PAD) refers to all noncoronary vascular diseases affecting the peripheral arteries and is typically applied to those individuals with lower extremity disease.  PAD is characterized by narrowing of the arterial vessels and eventual reduction in or occlusion of distal perfusion. The disease spectrum of PAD varies from asymptomatic to intermittent claudication and critical limb ischemia, which results in pain at rest, ulcerated skin lesions, and significant risk for risk of stroke, myocardial infarction, gangrene, and limb loss. Modification of risk factors with statins, converting enzyme inhibitors, insulin sensitizers, tobacco cessation, exercise, and diet reduces morbidity and mortality. However medical therapies are ineffective at increasing limb perfusion.

Therapeutic regrowth of collateral arterial vessels by the introduction of hematopoietic stem cell from red bone marrow (which is contained in most bones) is an experimental approach to restore perfusion. While there have been numerous small studies examining the safety and effectiveness of stem cell therapy for PAD the results have varied and definitive clinical trials are needed.


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Based on initial evidence from case series and small randomized trials, stem cells may hold promise as a treatment for critical limb ischemia due to peripheral arterial disease. Results from randomized controlled trials with a larger number of participants are needed to adequately evaluate the impact on net health outcomes. Further information on the safety and durability of the treatment is needed.


BlueCross BlueShield Association. Medical Policy Reference Manual. (1:2016). Stem-cell therapy for peripheral artery disease (8.01.55). Retrieved January 20, 2017 from BlueWeb. (20 articles and/or guidelines reviewed)

Botham, C., Bennett, W., and Cooke, J. (2013, October) Clinical trials of adult stem cell therapy for peripheral artery disease. Methodist Debakey Cardiovasc Journal. 2013 Oct-Dec; 9(4): 201–205. (Level 1 evidence)

European Society of Cardiology. (2011). ESC guidelines on the diagnosis and treatment of peripheral artery diseases. Retrieved February 26, 2016 from

Franz, R., Shah, K., Pin, R., Hankins, T., Hartman, J., & Wright, M. (2015). Autologous bone marrow mononuclear cell implantation therapy is an effective limb salvage strategy for patients with severe peripheral arterial disease. Journal of Vascular Surgery, 62 (3), 673-680. Abstract retrieved February 26, 2016 from PubMed database.

Liu, Y., Xu, Y., Fang, F., Zhang, J., Guo, L., and Weng, Z. (2015, April) Therapeutic efficacy of stem cell-based therapy in peripheral arterial disease: a meta-analysis. PLOS One. .0125032. (Level 1 evidence)

Palmetto Government Benefits Administrator (2017, January) Local Coverage Determination (LCD): Non-Covered Category III CPT Codes (L34555). Retrieved January 20, 2017 from:

Peeters Weem, S., Teraa, M., de Borst, G., Verhaar, M., & Moll, F. (2015). Bone marrow derived cell therapy in critical limb ischemia: a meta-analysis of randomized placebo controlled trials. European Journal of Vascular and Endovascular Surgery, 50 (6), 775-783. Abstract retrieved February 26, 2016 from PubMed database.

Ravel, Z. and Losordo, D. (2013, April) Cell therapy of peripheral arterial disease: from experimental findings to clinical trials. Circulatory Research. April 26; 112(9). (Level 1 evidence)

U. S. Food and Drug Administration. (2002, October). Center for Devices and Radiological Health. Pre-market approval decisions K071934 (MarrowStim™). Retrieved January 20, 2017 from

U. S. Food and Drug Administration. (2010, December). Center for Devices and Radiological Health. Pre-market approval decisions K10334 (SmartPRep®). Retrieved July 14, 2011 from




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