Medical policy: Stem Cell Therapy for Peripheral Arterial Disease

Policy number: MP 2.089

Effective date: 6/1/2026

Policy

Treatment of peripheral arterial disease, including critical limb ischemia, with injection or infusion of stem cells from concentrated bone marrow, expanded in vitro, stimulated from peripheral blood, or from an allogeneic source is considered investigational as there is insufficient evidence to support a general conclusion concerning the health outcomes or benefits associated with this procedure.

Cross-reference:

MP 2.033 Recombinant and Autologous Platelet Derived Growth Factors as Treatment of Wound Healing and Other Non-Orthopedic Conditions
MP 2.080 Orthopedic Applications of Stem Cell Therapy Including Allograft and Bone Substitute Products used with Autologous Bone Marrow

Product variations

This policy is only applicable to certain programs and products administered by Capital Blue Cross and subject to benefit variations. Please see additional information below.

FEP PPO - Refer to FEP Medical Policy Manual. The FEP Medical Policy Manual can be found at: FEP Medical Policy Manual.

Description/background

Peripheral Arterial Disease

Peripheral arterial disease (PAD) is a common atherosclerotic syndrome that is associated with significant morbidity and mortality. A less-common cause of PAD is Buerger disease (also called thromboangiitis obliterans), which is a nonatherosclerotic segmental inflammatory disease that occurs in younger patients and is associated with tobacco use. The development of PAD is characterized by narrowing and occlusion of arterial vessels and eventual reduction in distal perfusion. Critical limb ischemia is the end stage of lower extremity PAD in which severe obstruction of blood flow results in ischemic pain at rest, ulcers, and a significant risk for limb loss.

Physiology

Two endogenous compensating mechanisms may occur with occlusion of arterial vessels, capillary growth (angiogenesis), and development of collateral arterial vessels (arteriogenesis). Capillary growth is mediated by hypoxia-induced release of chemokines and cytokines such as vascular endothelial growth factor (VEGF) and occurs by sprouting of small endothelial tubes from pre-existing capillary beds. The resulting capillaries are small and cannot sufficiently compensate for a large, occluded artery. Arteriogenesis, with collateral vessel growth, is initiated by increasing shear forces against vessel walls when blood flow is redirected from the occluded transport artery to the small collateral branches, leading to an increase in the diameter of pre-existing collateral arterioles.

The mechanism underlying arteriogenesis includes the migration of bone marrow-derived monocytes to the perivascular space. The bone marrow-derived monocytes adhere to and invade the collateral vessel wall. It is not known if the expansion of the collateral arteriole is due to the incorporation of stem cells into the wall of the vessel or to cytokines released by monocyte bone marrow cells that induce the proliferation of resident endothelial cells. It has been proposed that bone marrow-derived monocytic cells may be the putative circulating endothelial progenitor cells. Notably, the same risk factors for advanced ischemia (diabetes, smoking, hyperlipidemia, and advanced age) are also risk factors for a lower number of circulating progenitor cells.

Treatment

Use of autologous stem cells freshly harvested and allogeneic stem cells are reported to have a role in the treatment of PAD. Stem cells can be administered in a variety of routes, derived from different progenitors, and be grouped with different co-factors, many of which are being studied in order to determine the best clinical option for patients. The primary outcome in stem cell therapy trials regulated by the U.S. Food and Drug Administration (FDA) is amputation-free survival, defined as time to major amputation and/or death from any cause. Other outcomes for critical limb ischemia include the Rutherford criteria for limb status, healing of ulcers, the Ankle-Brachial Index (ABI), transcutaneous oxygen pressure, and pain-free walking. The ABI measures arterial segmental pressures on the ankle and brachium and indexes ankle systolic pressure against brachial systolic pressure (normative range, 0.95 to 1.2 mm Hg).

Regulatory status

Several point-of-care concentrations of bone marrow aspirate have been cleared by the FDA through the 510(k) process and are summarized in Table 1.

Table 1. FDA Approved Point-of-Care Concentration of Bone Marrow Aspirate Devices

U.S. Food and Drug Administration product code: JQC.

Rationale

Summary of evidence

For individuals who have peripheral arterial disease (PAD) who receive stem cell therapy, the evidence includes small randomized trials and systematic reviews. Relevant outcomes are overall survival, symptoms, change in disease status, morbid events, functional outcomes, quality of life, and treatment-related morbidity. The current literature on stem cells as a treatment for CLI due to PAD consists primarily of phase 2 studies using various cell preparation methods and methods of administration. A meta-analysis of the trials with the lowest risk of bias has shown no significant benefit of stem cell therapy for overall survival, amputation-free survival, or amputation rates. Three randomized controlled trials (RCTs) have been published that used granulocyte colony-stimulating factor (GM-CSF)-mobilized peripheral blood mononuclear cells (PBMNC). The route of administration of cell therapy and the primary outcomes differed between studies. In the trial that added cell therapy to guideline-based care, there were no significant differences in progression-free survival and frequency of limb amputation at 1 year of follow-up. There was a substantial rate of subsequent surgical intervention in both arms. Well-designed RCTs with a larger number of subjects and low-risk of bias are needed to evaluate the health outcomes of these various procedures. Several are in progress, including multicenter randomized, double-blind, placebo-controlled trials. More data on the safety and durability of these treatments are also needed. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Definitions

N/A

Disclaimer

Capital Blue Cross’ medical policies are used to determine coverage for specific medical technologies, procedures, equipment, and services. These medical policies do not constitute medical advice and are subject to change as permitted by law or applicable clinical evidence from independent treatment guidelines. Treating providers are solely responsible for medical advice and treatment of members. These policies are not a guarantee of coverage or payment. Payment of claims is subject to a determination regarding the member’s benefit program and eligibility on the date of service, and a determination that the services are medically necessary and appropriate. Final processing of a claim is based upon the terms of contract that applies to the member’s benefit program, including benefit limitations and exclusions. If a provider or a member has a question concerning this medical policy, please contact Capital Blue Cross’ Provider Services or Member Services.

Coding information

Note: This list of codes may not be all-inclusive, and codes are subject to change at any time. The identification of a code in this section does not denote coverage as coverage is determined by the terms of member benefit information. In addition, not all covered services are eligible for separate reimbursement.

Investigational; therefore, not covered:

References

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