Medical Policy


Subject: Stem Cell Therapy for Peripheral Vascular Disease
Document #: TRANS.00036 Publish Date:    10/17/2018
Status: Reviewed Last Review Date:    09/13/2018


This document addresses the use of autologous or allogeneic stem cell therapy for the treatment of peripheral vascular disease (PVD), which is also known as peripheral artery disease (PAD).  This document does not address umbilical cord, hematopoietic stem cell or other stem cell transplantation.

Position Statement

Investigational and Not Medically Necessary:

The use of stem cell therapy for the treatment of peripheral vascular disease (PVD) is considered investigational and not medically necessary.


The use of autologous or allogeneic stem cell therapy (SCT) as a treatment of PVD has been the subject of many peer-reviewed published articles.  Most of the available evidence is in the form of small case series studies with less than 30 subjects (Bartsch, 2006, 2007; Durdue, 2006; Huang, 2004; Kawamoto, 2007; Lara-Hernandez, 2010; Van Tongeren, 2008).  There are a few studies with greater than 100 participants, but as with the smaller studies, most use case series methodology (Horie, 2011; Matoba, 2008).  The studies themselves vary in follow-up duration, specific method of transplantation (i.e., intravenous [IV], intramuscular [IM], and intra-arterial [IA]), type of stem cells transplanted (peripheral bone marrow mononuclear cells [PBMNCs], bone marrow mononuclear cells [BMMNCs], or mesenchymal stem cells [MCSs]), and underlying etiology of the vascular disease (e.g., diabetes, thromboangitis obliterans [TAO], arteriosclerosis obliterans [ASO]).  Additionally, some studies are limited to the treatment of lower limb PVD, while others include subjects with upper limb PVD as well.  These case series tend to report positive impact of SCT with rare transplantation-related complications.  However, there are significant concerns about these case series which are prone to publication bias (only positive case series published) as well as the lack of prospective, randomized comparison groups.

Several nonrandomized trials have been reported for autologous stem cell treatments (Higashi, 2004; Katamata, 2007).  Ondara and colleagues (2011) reported a study that was a re-analysis of data previously published by Horie (2010) and Matoba (2008).  The authors reported that after adjustment for history of dialysis and Fontaine class, there were no significant differences between the treatment with BMMNC compared to PBMNC with respect to overall survival or amputation-free survival.  They also reported that the negative prognostic factors affecting overall survival or amputation-free survival were the number of CD34-positive cells collected, history of dialysis, Fontaine class, male sex, and older age.

A double-blind placebo-controlled randomized controlled trial (RCT) has been published on the use of allogeneic SCT to treat PVD (Gupta, 2015).  This small study involved 20 subjects with critical limb ischemia who were unable to undergo traditional revascularization procedures.  Data for 19 subjects were reported.  Experimental group subjects received IM injections of allogeneic BMMNC (200 million in 15 ml) while control subjects received placebo infusions.  All subjects were followed for at least 2 years, with blinding only up to the 6-month time point.  No procedural-related adverse events were reported.  Overall, 58 adverse events were reported, with 13 occurring in 6 experimental group subjects and 45 reported in 8 placebo group subjects.  Of these, 25 were related to abnormalities in laboratory values, but the investigators did not attribute any of them to the BMMNC treatment.  Another 14 events were related to complications of critical limb ischemia.  Significant increase in Ankle Brachial Pressure Index (ABPI) and ankle pressure were seen in the BMMNC group compared to the placebo group, with mean ABPI improvement of 0.214 and 0.004 respectively after 6 months (p=0.0018).  The authors noted that no significant differences were seen between groups with regard to serum cytokine levels and blood lymphocyte profile, indicating than no T-cell proliferative response was elicited.  The authors concluded that the use of allogeneic BMMNC is safe when injected via IM route at a dose of 2 million cells/kg body weight.  They also state that improved ABPI and ankle pressure showed positive trend, warranting further studies.

There are several RCTs available addressing the use of autologous stem cell therapy to treat PVD.  The first reported study included only 22 subjects with bilateral leg ischemia due to undisclosed etiology (Tateishi-Yuyama, 2002).  For each subject, one leg was randomly selected to receive IM transplantation with BMMNC, the other was treated with IM PBMNC.  At 24 weeks, legs injected with BMMNC were significantly improved compared to PBMNC with respect to ankle-brachial index (ABI) (p<0.0001), transcutaneous oxygen pressure (TcO2, p<0.0001), pain at rest (p=0.025), and pain-free walking (p=0.0001).  The next study included 28 subjects with critical limb ischemia (CLI) due to advanced Type 2 diabetes (Huang, 2005).  Study subjects were randomized to receive either stem cell therapy with PBMNCs administered via IM injection or IV prostaglandin therapy.  The authors reported that there was significant improvement (p=0.05) in the stem cell group compared to the control group in terms of lower limb pain, ulcer healing, lower limb perfusion, ankle brachial index, and angiographic scores.  The number of CLI-related amputations were also significantly better in the stem cell group (1 vs. 5, p=0.007).  However, the study was not blinded, there was no placebo or sham intervention arm, and the study sample was very small.  It is unclear whether the differences reported are attributable to the treatments given or other factors.  Huang and colleagues (Huang, 2007) published an additional study that involved 150 subjects with TAO randomized to receive stem cell therapy with either PBMNCs or with BMMNCs via IM injection.  Ankle-brachial index, skin temperature and pain at rest were all better in the PBMNC group.  These findings contradict those reported by Tateishi-Yuyama, as discussed above (2002).  An RCT conducted by Van Tongeren and others included 27 subjects with CLI of the legs due to undisclosed etiology (2008).  Subjects were randomly assigned to receive BMMNC via either IM or a combination of IM/IA injections.  At 12 months, 2 IM/IA group subjects had amputations vs. 7 in the IM only group.  In the remaining participants, regardless of group, treatment resulted in significant improvements in pain-free walking distance, overall pain, and ABI.  A single study investigated the use of bone marrow derived mesenchymal cells (MSCs) compared to standard care.  The transplant group had significant improvement in pain-free walking distance and reduction in ulcer size as compared to the control group.  This is also the only study to provide histological data, reporting that biopsy microsection of implanted tissues showed development of dermal cells (mainly fibroblasts), including mature and immature inflammatory cells.

Fadini and others published the results of a meta-analysis of previously published studies (2010).  This analysis looked at the results of autologous SCT for PVD with regard to the endpoints of change in ABI, TcO2, pain-free walking time, ulcer healing and amputations.  Significant improvements were reported for all the measures when all studies were analyzed.  When only controlled studies were considered, no significant differences were found for ABI and TcO2.   Outcomes were evaluated between subjects with ASO vs. TSO.  For subjects with TAO compared to those with ASO, significant benefits were noted for changes in ABI (p=0.021), TcO2 (p=0.03), pain scale (p=0.003), and pain-free walking distance (p=0.019).  When looking at the data comparing PBMNCs vs. BMMNCs, PBMNCs were significantly better at improving resting pain (p=0.006) and BMMNCs were better with regard to ulcer healing times (p=0.038).  No other significant differences were noted.  The route of administration was also evaluated, comparing IM vs. IM/IA.  The authors reported that ABI and TcO2 were significantly improved in subjects receiving IM but not IM/IA administration.  With the exception of ulcer healing time, all other measures demonstrated equal benefit between groups.  There was insufficient data to evaluate ulcer healing times.  The authors note that most studies evaluated were not properly designed to report on safety-related issues and systematic reporting of adverse events was rare.

In 2011, Powell reported the interim results of the RESTORE-CLI study, which was a randomized, double-blind, sham controlled trial.  The study compared treatment of CLI of the lower limbs with either autologous bone marrow aspirate vs. sham treatment.  The plan was to enroll 150 subjects randomized in a 2:1 fashion.  This interim report provided data on 33 subjects who completed the 12-month study period and another 13 subjects who had reached the 6 month follow-up visit (n=46 total, n=32 autologous group , n=14 controls).  The authors reported that there was no difference in adverse or serious adverse events between groups.  The statistical analysis revealed a significant increase in time to treatment failure (p=0.0053) and amputation-free survival in subjects receiving autologous treatment (p=0.038).  Major amputation occurred in 19% of autologous-treated subjects compared to 43% of controls (p=0.14).  There was evidence of improved wound healing in the autologous-treated subjects when compared with controls at 12 months.  Following this interim analysis, this study was halted due to a positive efficacy signal and the sponsor’s plan to develop a phase III program.

A small RCT was published by Szabo and colleagues in 2013.  The study involved 19 subjects with late-stage no-option PVD randomly assigned to undergo either standard of care or treatment with VesCell™ autologous stem cell therapy.  Follow-up assessments were conducted at 1 and 3 months, and at 2 years.  No adverse events were attributed to the treatment methods during the study.  However, 80% of the control subjects and 50% of the VesCell group subjects experienced adverse events.  At 3 months, the difference in limb loss between the two groups was statistically significant (p=0.01).  At 2 years, major amputation-free proportion was 70% in treated group and 40% in control group.  At 3 months, the average change in ABI was -0.01 in the control group, and +0.36 ± 0.11 (p=0.01).  At 2 years, the average change from baseline was 0.62 ± 0.07, (p=0.001).  Transcutaneous oxygen pressure (TcPO2) was significantly improved in the VesCell group only at the 3 month time point (6.06 ± 4.0 in the VesCell group vs. -3.5 ± 5.4 in the control group; p=0.03).  These results are interesting, but the small sample size limits the utility of these findings.

The results of another randomized, double-blind, placebo controlled trial involving 160 subjects with CLI receiving autologous BMMNCs (n=81) vs. sham treatment (n=79) was published in 2015 (The JUVENTAS Trial, Teraa, 2015).  In this study, all subjects completed the 6 month time point, and 79% (127/160) completed the planned 12 month study.  No differences were reported between groups with regard to the primary outcome, with amputation rates of 19% and 13% in the BMMNC group and control group, respectively (p=0.31).  Additionally, no significant differences were noted between groups with regard to the combined safety outcome (15% vs. 19%, relative risk [RR]=1.46), all-cause mortality (5% vs. 6%, RR=0.78), or combined risk for amputation or death (23% vs. 16%, RR=1.43).  The authors concluded, “Repetitive inter-arterial infusion of autologous BMMNCs into the common femoral artery did not reduce major amputation rates in subjects with severe, non-revascularizable limb ischemia compared to placebo.”

A prospective observational case series study of 40 subjects with either systemic sclerosis (n=11) or ASO (n=29) who underwent implantation with autologous bone marrow mononuclear cells was reported (Takagi, 2014).  The authors reported that there was a case of amputation in each group within 4 weeks after therapy.  At 3 months, TcPO2 significantly improved in subjects with systemic sclerosis (lcSSc, p<0.01) and those with ASO (p<0.05).  At the 2 year follow-up, the limb amputation rate was 9.1% in the lcSSc group and 20.7% in the ASO group (p=0.36), and the recurrence rate was 18.2% in the lcSSc group and 17.2% in the ASO group (p=0.95).  The authors concluded that “bone marrow mononuclear cell implantation is safe and effective for intractable digital ulcers in lcSSc and ASO and is a promising therapeutic option for peripheral digital ulcer patients.”  However, this conclusion is significantly weakened when considering the methodological weaknesses of this small, open-label, nonrandomized study.

The most recent recommendations from the American Heart Association and the American College of Cardiology on the management of patients with lower extremity peripheral artery disease do not have any reference to the use of SCT for PVD (Gerhard-Herman, 2017).

While the existing evidence to-date shows some potential benefit of autologous SCT for PVD, this evidence is from predominately small, uncontrolled, non-blind, nonrandomized studies.  Furthermore, the data from available RCTs is somewhat contradictory.  There are significant outstanding questions regarding optimal selection criteria for treatment candidate and cell type, method of administration, and whether or not similar benefits can be derived with the treatment of lower and upper extremities.  Further investigation in the form of well-done, large scale, randomized controlled trials is needed to answer these questions and provide guidance for the use of SCT for PVD in the clinical setting.


Several medical conditions, including diabetes, TAO (also known as Buerger’s disease) and ASO, are known to lead to damage to the arteries and other blood vessels leading to the extremities.  These conditions, collectively referred to as peripheral vascular disease (PVD) or peripheral artery disease (PAD), lead to impaired blood flow and oxygen delivery to the hands and feet, and eventually to tissue damage.  In most cases, this condition is treated with surgical revascularization.  However, in extreme cases surgery is not an option and a condition known as CLI develops.  This leads to severe tissue damage and the only treatment option left is limb amputation.

Autologous SCT has been proposed as a therapeutic option for a wide array of medical conditions from various types of cancer to Parkinson’s disease to heart disease.  SCT involves the harvesting of immature progenitor stem cells from somewhere in a person’s body, processing them in the lab to separate them from other cells and multiply the numbers, and then implanting them back into the person, either into the blood stream or at the specific site of concern.  This technique has been proposed based on the fact that some types of stem cells have been found to reproduce and differentiate into new mature cells at the site of implantation, replacing injured or otherwise diseased cells and restoring tissue and organ function.

SCT has been proposed as a treatment for PAD.  The theory is that implantation of stem cells from the bone marrow into the affected limbs could trigger the growth of new blood vessels, increasing blood flow to the extremities and treating complications that develop due to PAD.  At this time, two approaches for SCT treatment for PAD have been described in the medical literature.  The first involves the direct harvesting of bone marrow stem cells (either BMMNCs or MCSs) from the bone marrow.  The other method involves administering a hormone called Granulocyte-Colony Stimulating Factor (G-CSF) to the person to be treated.  This stimulates the bone marrow to produce mononuclear stem cells and release them into the blood stream.  These cells, now called peripheral PBMNCs, are then collected as part of a blood sample collected from a vein.  Regardless of the type of cells used, the collected stem cell samples are processed to isolate and multiply the cells, which are then transplanted back into the person being treated.  Several different transplantation methods have been described in the scientific literature, including injection into a vein, artery, or muscle of the affected limb.

At this time the use of SCT for PVD is in the preliminary stages of investigation.  There is much yet to be understood about this medical procedure before it should be widely used.

There are several products or services proposed for the processing of stem cells for PVD treatment, including the VesCell (TheraVitae, Bangkok , Thailand), the SmartPReP 2® Bone Marrow Aspirate Concentrate System (Harvest Technologies Corp., Plymouth, MA), and the MarrowStim P.A.D. kit™ (Biomet Biologics, Warsaw, Indiana).


Bone marrow mononuclear stem cells: A type of bone marrow-derived cell from which blood vessels are created and repaired.

Mesenchymal stem cells: A type of bone marrow-derived cell from which muscles are created.

Stem cells: A cell from which other types of cells develop. For example, blood cells develop from blood-forming stem cells.

Stem cell therapy: A medical treatment that involves the implantation of stem cells into the body with the goal of growing new or repairing damaged or defective tissues and organs.  This type of treatment has been proposed for a wide variety of conditions, including Parkinson’s disease, heart disease, and spinal cord injury.


The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Investigational and Not Medically Necessary:
When the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.




Intramuscular autologous bone marrow cell therapy, with preparation of harvested cells, multiple injections, one leg, including ultrasound guidance, if performed; complete procedure including unilateral or bilateral bone marrow harvest


Intramuscular autologous bone marrow cell therapy, with preparation of harvested cells, multiple injections, one leg, including ultrasound guidance, if performed; complete procedure excluding unilateral or bilateral bone marrow harvest


Intramuscular autologous bone marrow cell therapy, with preparation of harvested cells, multiple injections, one leg, including ultrasound guidance, if performed; unilateral or bilateral bone marrow harvest only for intramuscular autologous bone marrow cell therapy



ICD-10 Diagnosis



All diagnoses

When services are also Investigational and Not Medically Necessary:




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


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


Bone marrow harvesting for transplantation; allogeneic


Bone marrow harvesting for transplantation; autologous


Unlisted procedure, hemic or lymphatic system [when specified as bone marrow cell therapy or stem cell therapy IM, IV or IA for peripheral vascular disease]



ICD-10 Procedure



Pheresis of hematopoietic stem cells, single



ICD-10 Diagnosis



Diabetes mellitus due to underlying condition with circulatory complications


Drug or chemical induced diabetes mellitus with circulatory complications


Type 1 diabetes mellitus with circulatory complications


Type 2 diabetes mellitus with circulatory complications


Other specified diabetes mellitus with circulatory complications


Atherosclerosis of native arteries of the extremities


Atherosclerosis of autologous vein bypass graft(s) of the extremities


Other peripheral vascular disease


Peer Reviewed Publications:

  1. Amann B, Luedemann C, Ratei R, Schmidt-Lucke JA. Autologous bone marrow cell transplantation increases leg perfusion and reduces amputations in patients with advanced critical limb ischemia due to peripheral artery disease. Cell Transplant. 2009; 18(3):371-380.
  2. Bartsch T, Brehm M, Zeus T, et al. Transplantation of autologous mononuclear bone marrow stem cells in patients with peripheral arterial disease (the TAM-PAD study).  Clin Res Cardiol. 2007; 96(12):891-899.
  3. Bartsch T, Brehm M, Zeus T, Strauer BE. Autologous mononuclear stem cell transplantation in patients with peripheral occlusive arterial disease. J Cardiovasc Nurs. 2006c; 21(6):430-432.
  4. Carstens MH, Gómez A, Cortés R, et al. Non-reconstructable peripheral vascular disease of the lower extremity in ten patients treated with adipose-derived stromal vascular fraction cells. Stem Cell Res. 2017; 18:14-21.
  5. Dash NR, Dash SN, Routray P, et al. Targeting nonhealing ulcers of lower extremity in human through autologous bone marrow-derived mesenchymal stem cells. Rejuvenation Res. 2009; 12(5):359-366.
  6. De Vriese AS, Billiet J, Van Droogenbroeck J, et al. Autologous transplantation of bone marrow mononuclear cells for limb ischemia in a Caucasian population with atherosclerosis obliterans.  J Intern Med. 2008; 263(4):395-403.
  7. Durdu S, Akar AR, Arat M, et al. Autologous bone-marrow mononuclear cell implantation for patients with Rutherford grade II-III thromboangiitis obliterans. J Vasc Surg. 2006; 44(4):732-739.
  8. Esato K, Hamano K, Li TS, et al. Neovascularization induced by autologous bone marrow cell implantation in peripheral arterial disease. Cell Transplant. 2002; 11(8):747-752.
  9. Fadini GP, Agostini C, Avogaro A. Autologous stem cell therapy for peripheral arterial disease meta-analysis and systematic review of the literature. Atherosclerosis. 2010; 209(1):10-17.
  10. Franz RW, Parks A, Shah KJ, et al. Use of autologous bone marrow mononuclear cell implantation therapy as a limb salvage procedure in patients with severe peripheral arterial disease. J Vasc Surg. 2009; 50(6):1378-1390.
  11. Gupta PK, Chullikana A, Parakh R,et al. A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia. J Transl Med. 2013; 11:143.
  12. Higashi Y, Kimura M, Hara K, et al. Autologous bone-marrow mononuclear cell implantation improves endothelium-dependent vasodilation in patients with limb ischemia. Circulation. 2004; 109(10):1215-1218.
  13. Horie T, Onodera R, Akamastu M, et al. Long-term clinical outcomes for patients with lower limb ischemia implanted with G-CSF-mobilized autologous peripheral blood mononuclear cells. Atherosclerosis. 2010; 208(2):461-466.
  14. Hoshino J, Ubara Y, Hara S, et al. Quality of life improvement and long-term effects of peripheral blood mononuclear cell transplantation for severe arteriosclerosis obliterans in diabetic patients on dialysis. Circ J. 2007; 71(8):1193-1198.
  15. Huang P, Li S, Han M, et al. Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes. Diabetes Care. 2005; 28(9):2155-2160.
  16. Huang PP, Li SZ, Han MZ, et al. Autologous transplantation of peripheral blood stem cells as an effective therapeutic approach for severe arteriosclerosis obliterans of lower extremities. Thromb Haemost. 2004; 91(3):606-609.
  17. Huang PP, Yang XF, Li SZ, et al. Randomised comparison of G-CSF-mobilized peripheral blood mononuclear cells versus bone marrow-mononuclear cells for the treatment of patients with lower limb arteriosclerosis obliterans. Thromb Haemost. 2007; 98(6):1335-1342.
  18. Ishida A, Ohya Y, Sakuda H, et al. Autologous peripheral blood mononuclear cell implantation for patients with peripheral arterial disease improves limb ischemia. Circ J. 2005; 69(10):1260-1265.
  19. Kajiguchi M, Kondo T, Izawa H, et al. Safety and efficacy of autologous progenitor cell transplantation for therapeutic angiogenesis in patients with critical limb ischemia. Circ J. 2007; 71(2):196-201.
  20. Kamata Y, Takahashi Y, Iwamoto M, et al. Local implantation of autologous mononuclear cells from bone marrow and peripheral blood for treatment of ischaemic digits in patients with connective tissue diseases. Rheumatology (Oxford). 2007; 46(5):882-884.
  21. Kawamoto A, Katayama M, Handa N, et al. Intramuscular transplantation of G-CSF-mobilized CD34(+) cells in patients with critical limb ischemia: a phase I/IIa, multicenter, single-blinded, dose-escalation clinical trial. Stem Cells. 2009; 27(11):2857-2864.
  22. Kawamura A, Horie T, Tsuda I, et al. Clinical study of therapeutic angiogenesis by autologous peripheral blood stem cell (PBSC) transplantation in 92 patients with critically ischemic limbs. J Artif Organs. 2006; 9(4):226-233.
  23. Kawamura A, Horie T, Tsuda I, et al. Prevention of limb amputation in patients with limbs ulcers by autologous peripheral blood mononuclear cell implantation. Ther Apher Dial. 2005; 9(1):59-63.
  24. Koshikawa M, Shimodaira S, Yoshioka T, et al. Therapeutic angiogenesis by bone marrow implantation for critical hand ischemia in patients with peripheral arterial disease: a pilot study. Curr Med Res Opin. 2006; 22(4):793-798.
  25. Lara-Hernandez R, Lozano-Vilardell P, Blanes P, et al. Safety and efficacy of therapeutic angiogenesis as a novel treatment in patients with critical limb ischemia. Ann Vasc Surg. 2010; 24(2):287-294.
  26. Lenk K, Adams V, Lurz P, et al. Therapeutical potential of blood-derived progenitor cells in patients with peripheral arterial occlusive disease and critical limb ischaemia. Eur Heart J. 2005; 26(18):1903-1909.
  27. Matoba S, Tatsumi T, Murohara T, et al.; TACT Follow-up Study Investigators. Long-term clinical outcome after intramuscular implantation of bone marrow mononuclear cells (Therapeutic Angiogenesis by Cell Transplantation [TACT] trial) in patients with chronic limb ischemia. Am Heart J. 2008; 156(5):1010-1018.
  28. Miyamoto K, Nishigami K, Nagaya N, et al. Unblinded pilot study of autologous transplantation of bone marrow mononuclear cells in patients with thromboangiitis obliterans. Circulation. 2006; 114(24):2679-2684.
  29. Miyamoto M, Yasutake M, Takano H, et al. Therapeutic angiogenesis by autologous bone marrow cell implantation for refractory chronic peripheral arterial disease using assessment of neovascularization by 99mTc-tetrofosmin (TF) perfusion scintigraphy. Cell Transplant. 2004; 13(4):429-437.
  30. Napoli C, Farzati B, Sica V, et al. Beneficial effects of autologous bone marrow cell infusion and antioxidants/L-arginine in patients with chronic critical limb ischemia. Eur J Cardiovasc Prev Rehabil. 2008; 15(6):709-718.
  31. Onodera R, Teramukai S, Tanaka S, et al.; BMMNC Follow-Up Study Investigators; M-PBMNC Follow-Up Study Investigators. Bone marrow mononuclear cells versus G-CSF-mobilized peripheral blood mononuclear cells for treatment of lower limb ASO: pooled analysis for long-term prognosis. Bone Marrow Transplant. 2011; 46(2):278-284.
  32. Powell RJ, Comerota AJ, Berceli SA, et al. Interim analysis results from the RESTORE-CLI, a randomized, double-blind multicenter phase II trial comparing expanded autologous bone marrow-derived tissue repair cells and placebo in patients with critical limb ischemia. J Vasc Surg. 2011; 54(4):1032-1041.
  33. Saigawa T, Kato K, Ozawa T, et al. Clinical application of bone marrow implantation in patients with arteriosclerosis obliterans, and the association between efficacy and the number of implanted bone marrow cells. Circ J. 2004; 68(12):1189-1193.
  34. Saito Y, Sasaki K, Katsuda Y, et al. Effect of autologous bone-marrow cell transplantation on ischemic ulcer in patients with Buerger's disease. Circ J. 2007; 71(8):1187-1192.
  35. Szabó GV1, Kövesd Z, Cserepes J, et al. Peripheral blood-derived autologous stem cell therapy for the treatment of patients with late-stage peripheral artery disease-results of the short- and long-term follow-up. Cytotherapy. 2013; 15(10):1245-1252.
  36. Takagi G, Miyamoto M, Tara S, et al. Therapeutic vascular angiogenesis for intractable macroangiopathy-related digital ulcer in patients with systemic sclerosis: a pilot study. Rheumatology (Oxford). 2014; 53(5):854-859.
  37. Tateishi-Yuyama E, Matsubara H, Murohara T, et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet. 2002; 360(9331):427-435.
  38. Teraa M, Sprengers RW, Schutgens RE, et al. Effect of repetitive intra-arterial infusion of bone marrow mononuclear cells in patients with no-option limb ischemia: the randomized, double-blind, placebo-controlled Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-arterial Supplementation (JUVENTAS) trial. Circulation. 2015; 131(10):851-860.
  39. Van Tongeren RB, Hamming JF, Fibbe WE, et al. Intramuscular or combined intramuscular/intra-arterial administration of bone marrow mononuclear cells: a clinical trial in patients with advanced limb ischemia. J Cardiovasc Surg (Torino). 2008; 49(1):51-58.
  40. Wester T, Jørgensen JJ, Stranden E, et al. Treatment with autologous bone marrow mononuclear cells in patients with critical lower limb ischaemia. A pilot study. Scand J Surg. 2008; 97(1):56-62.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC Guideline on the management of patients with lower extremity peripheral artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017; 69(11):e71-e126.
Websites for Additional Information
  1. National Cancer Institute. Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation. Available at: Accessed on July 11, 2018. 

Bone Marrow
MarrowStim P.A.D. kit
SmartPReP2 Bone Marrow Aspirate Concentrate System
Stem Cell Transplantation

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. 

Document History






Medical Policy & Technology Assessment Committee (MPTAC) review. Updated References section.



MPTAC review. The document header wording updated from “Current Effective Date” to “Publish Date.” Updated Rationale and References sections.



MPTAC review. Updated Rationale and References sections.



MPTAC review. Updated Rationale, Background, Coding and Reference sections. Removed ICD-9 codes from Coding section.



MPTAC review. Updated Rationale, Background, and Reference sections.



MPTAC review.



MPTAC review. Updated Coding section with 01/01/2013 CPT descriptor changes.



MTAC review. Updated Coding section with 01/01/2012 CPT changes; removed 38230.



MTAC review. Initial document development