Skip to main content
Journal cover image

Autologous bone marrow mononuclear cell therapy is safe and promotes amputation-free survival in patients with critical limb ischemia.

Publication ,  Journal Article
Murphy, MP; Lawson, JH; Rapp, BM; Dalsing, MC; Klein, J; Wilson, MG; Hutchins, GD; March, KL
Published in: J Vasc Surg
June 2011

OBJECTIVE: The purpose of this Phase I open label nonrandomized trial was to assess the safety and efficacy of autologous bone marrow mononuclear cell (ABMNC) therapy in promoting amputation-free survival (AFS) in patients with critical limb ischemia (CLI). METHODS: Between September 2005 and March 2009, 29 patients (30 limbs), with a median age of 66 years (range, 23-84 years; 14 male, 15 female) with CLI were enrolled. Twenty-one limbs presented with rest pain (RP), six with RP and ulceration, and three with ulcer only. All patients were not candidates for surgical bypass due to absence of a patent artery below the knee and/or endovascular approaches to improving perfusion was not possible as determined by an independent vascular surgeon. Patients were treated with an average dose of 1.7 ± 0.7 × 10(9) ABMNC injected intramuscularly in the index limb distal to the anterior tibial tuberosity. The primary safety end point was accumulation of serious adverse events, and the primary efficacy end point was AFS at 1 year. Secondary end points at 12 weeks posttreatment were changes in first toe pressure (FTP), toe-brachial index (TBI), ankle-brachial index (ABI), and transcutaneous oxygen measurements (TcPO(2)). Perfusion of the index limb was measured with positron emission tomography-computed tomography (PET-CT) with intra-arterial infusion of H(2)O(15). RP, using a 10-cm visual analogue scale, quality of life using the VascuQuol questionnaire, and ulcer healing were assessed at each follow-up interval. Subpopulations of endothelial progenitor cells were quantified prior to ABMNC administration using immunocytochemistry and fluorescent-activated cell sorting. RESULTS: There were two serious adverse events; however, there were no procedure-related deaths. Amputation-free survival at 1 year was 86.3%. There was a significant increase in FTP (10.2 ± 6.2 mm Hg; P = .02) and TBI (0.10 ± 0.05;P = .02) and a trend in improvement in ABI (0.08 ± 0.04; P = .73). Perfusion index by PET-CT H(2)O(15) increased by 19.3 ± 3.1, and RP decreased significantly by 2.2 ± 0.6 cm (P = .02). The VascuQol questionnaire demonstrated significant improvement in quality of life, and three of nine ulcers (33%) healed completely. KDR(+) but not CD34(+) or CD133(+) subpopulations of ABMNC were associated with improvement in limb perfusion. CONCLUSION: This Phase I study has demonstrated safety, and the AFS rates suggest efficacy of ABMNC in promoting limb salvage in "no option" CLI. Based on these results, we plan to test the concept that ABMNCs improve AFS at 1 year in a Phase III randomized, double-blinded, multicenter trial.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Vasc Surg

DOI

EISSN

1097-6809

Publication Date

June 2011

Volume

53

Issue

6

Start / End Page

1565 / 74.e1

Location

United States

Related Subject Headings

  • Young Adult
  • Transplantation, Autologous
  • Prospective Studies
  • Middle Aged
  • Male
  • Leukocytes, Mononuclear
  • Ischemia
  • Humans
  • Female
  • Extremities
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Murphy, M. P., Lawson, J. H., Rapp, B. M., Dalsing, M. C., Klein, J., Wilson, M. G., … March, K. L. (2011). Autologous bone marrow mononuclear cell therapy is safe and promotes amputation-free survival in patients with critical limb ischemia. J Vasc Surg, 53(6), 1565-74.e1. https://doi.org/10.1016/j.jvs.2011.01.074
Murphy, Michael P., Jeffrey H. Lawson, Brian M. Rapp, Michael C. Dalsing, Janet Klein, Michael G. Wilson, Gary D. Hutchins, and Keith L. March. “Autologous bone marrow mononuclear cell therapy is safe and promotes amputation-free survival in patients with critical limb ischemia.J Vasc Surg 53, no. 6 (June 2011): 1565-74.e1. https://doi.org/10.1016/j.jvs.2011.01.074.
Murphy MP, Lawson JH, Rapp BM, Dalsing MC, Klein J, Wilson MG, et al. Autologous bone marrow mononuclear cell therapy is safe and promotes amputation-free survival in patients with critical limb ischemia. J Vasc Surg. 2011 Jun;53(6):1565-74.e1.
Murphy, Michael P., et al. “Autologous bone marrow mononuclear cell therapy is safe and promotes amputation-free survival in patients with critical limb ischemia.J Vasc Surg, vol. 53, no. 6, June 2011, pp. 1565-74.e1. Pubmed, doi:10.1016/j.jvs.2011.01.074.
Murphy MP, Lawson JH, Rapp BM, Dalsing MC, Klein J, Wilson MG, Hutchins GD, March KL. Autologous bone marrow mononuclear cell therapy is safe and promotes amputation-free survival in patients with critical limb ischemia. J Vasc Surg. 2011 Jun;53(6):1565–74.e1.
Journal cover image

Published In

J Vasc Surg

DOI

EISSN

1097-6809

Publication Date

June 2011

Volume

53

Issue

6

Start / End Page

1565 / 74.e1

Location

United States

Related Subject Headings

  • Young Adult
  • Transplantation, Autologous
  • Prospective Studies
  • Middle Aged
  • Male
  • Leukocytes, Mononuclear
  • Ischemia
  • Humans
  • Female
  • Extremities