Stem Cell Therapy for Peripheral Arterial Disease

POLICY NUMBER

A.8.01.55

DESCRIPTION

Peripheral arterial disease is a common atherosclerotic syndrome associated with significant morbidity and mortality. Critical limb ischemia (CLI) 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. Use of autologous stem cells freshly harvested and allogeneic stem cells are reported to have a role in the treatment of PAD.

Peripheral Arterial Disease

Peripheral arterial disease (PAD) is a common atherosclerotic syndrome associated with significant morbidity and mortality. A less common cause of PAD is Buerger disease (also called thromboangitis 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 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. Arteriogeneis with collateral growth is, in contrast, 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 monocytic 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 peripheral arterial disease. 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, transcutaneous oxygen pressure, and pain-free walking. The Ankle-Brachial Index measures arterial segmental pressures on the ankle and brachium and indexes ankle systolic pressure against brachial systolic pressure (normal range 0.95 to 1.2 mm Hg).

Several point-of-care concentrations of bone marrow aspirate have been cleared by the Food and Drug Administration through the 510(k) process and summarized in the table below.

FDA Approved Point-of-Care Concentration of Bone Marrow Aspirate Devices

Related medical policies are as follows:

• Recombinant and Autologous Platelet-Derived Growth Factors for Wound Healing and Other Non-Orthopedic Conditions

• Progenitor Cell Therapy for the Treatment of Damaged Myocardium Due to Ischemia

• Orthopedic Applications of Stem Cell Therapy (Including Allografts and Bone Substitutes Used with Autologous Bone Marrow

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.

POLICY EXCEPTIONS

None 

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

POLICY HISTORY

07/21/2011: Approved by Medical Policy Advisory Committee.

07/17/2012: Policy reviewed; no changes.

08/14/2013: Policy reviewed; no changes.

06/16/2014: Policy reviewed; description updated regarding devices. Policy statement unchanged.

07/23/2015: Code Reference section updated for ICD-10.

10/16/2015: Policy reviewed; description updated. No change in policy statement. Updated investigative definition in the policy guidelines section.

03/16/2016: Policy description updated regarding devices. Policy statement unchanged.

05/26/2016: Policy number A.8.01.55 added.

08/16/2017: Policy description updated regarding devices. Investigational policy statement revised to include specific sources of stem cells: expanded in vitro, stimulated from peripheral blood, or from an allogeneic source.

03/12/2018: Policy reviewed; no changes.

03/18/2019: Policy description updated regarding treatment and devices. Policy statement unchanged.

02/26/2020: Policy description updated regarding treatment and devices. Policy statement unchanged.

03/30/2021: Policy description updated regarding devices. Policy statement unchanged.

02/21/2022: Policy reviewed; no changes.

03/13/2023: Policy description updated regarding devices. Policy statement unchanged.

02/28/2024: Policy description updated regarding devices. Policy statement unchanged.

04/09/2025: Policy reviewed; no changes.

SOURCE(S)

Blue Cross Blue Shield Association policy # 8.01.55 

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

Investigational Codes

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