Long-term effect of autologous progenitor cell therapy to induce neo angiogenesis in patients with critical limb ischemia transplantated via intramuscular vs combined intramuscular and distal retrograde intra venous
Luis Padilla1,2*, Juan Rodriguez-Trejo3, Ignacio Escotto3, Manuel López-Hernandez4, Mauricio González5, José De Diego6, Neftaly Rodrgiuez3, Jesús Tapia2, Takeshi Landero1, Carranza Pilar Hazel1, Olguin Juarez Horacio1, Mauricio Di Silvio1,7, Paul Mondragon-Teran8
1Department of Experimental Surgery, Microsurgery Unit, Centro Medico Nacional “20 de Noviembre” ISSSTE, Mexico City, Mexico.
2Surgery Department, Faculty of Medicine, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico.
3Angiology, Vascular and Endovascular Surgery Unit, Centro Medico Nacional “20 de Noviembre” ISSSTE, Mexico City, Mexico.
4Haematology Unit, Centro Medico Nacional “20 de Noviembre” ISSSTE, Mexico City, Mexico.
5Bank of Blood Unit, Centro Medico Nacional “20 de Noviembre” ISSSTE, Mexico City, Mexico.
6Pediatric Hematology Unit Centro Medico Nacional ‘20 de Noviembre’ ISSSTE, Mexico City, Mexico.
7Department of Research, Hospital General de México OD, Secretaria de Salud México, Mexico City, Mexico.
8Department of Biomedical Research, Centro Medico Nacional “20 de Noviembre” ISSSTE, Mexico City, Mexico.
DOI: 10.4236/scd.2012.24020   PDF    HTML     4,162 Downloads   7,190 Views   Citations

Abstract

Critical limb ischemia is a medical condition that decreases blood flow and limb oxygen supply; this disease in its late stages of progression leads to only two possible options: either surgical bypass revascularization or limb amputation. We investigated a novel method using autologous transplantation of progenitor cells derived from mobilized peripheral blood bone marrow mononuclear cells to evaluate its long-term effect as a cell therapy to induce neo-angiogenesis and restore blood flow in the affected ischemic limbs. A total of 20 ischemic limbs from critical limb ischemia diagnosed patients, non candidates to surgical revascularization were transplanted with autologous progenitor cells by either intramuscular combined with intravenous (group A) or intramuscular (group B) procedure. Patients were monitored during 31 months. Treatment efficacy was evaluated according to the following parameters: ankle brachial index which increased at a range of 0.29-1.0 in group A and 0.40-0.90 in group B; pain-free walking distance which increased at a range of 50-600 m in group A and 50-300 m in group B; and blood perfusion (measured by Laser Doppler) which increased at a range of 48-299 in group A and 135-225 in group B. We achieved 90% treated ischemic limbs free of amputation in both transplanted groups. Results here described provide a safe, efficient and minimally invasive therapy with progenitor cells to induce angiogenesis and preserve limbs from amputation in CLI diagnosed patients.

Share and Cite:

Padilla, L. , Rodriguez-Trejo, J. , Escotto, I. , López-Hernandez, M. , González, M. , De Diego, J. , Rodrgiuez, N. , Tapia, J. , Landero, T. , Pilar Hazel, C. , Juarez Horacio, O. , Di Silvio, M. and Mondragon-Teran, P. (2012) Long-term effect of autologous progenitor cell therapy to induce neo angiogenesis in patients with critical limb ischemia transplantated via intramuscular vs combined intramuscular and distal retrograde intra venous. Stem Cell Discovery, 2, 155-162. doi: 10.4236/scd.2012.24020.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Ouriel, K. (2001) Detection of peripheral arterial disease in primary care. The Journal of the American Medical Association, 286, 1380-1381. doi:10.1001/jama.286.11.1380
[2] Criqui, M.H., Langer, R.D., Fronek, A., Feigelson, H.S., Klauber, M.R., McCann, T.J. and Bronwer, D. (1992) Mortality over a period of 10 years in patients with peripheral arterial disease. The New England Journal of Medicine, 326, 381-386. doi:10.1056/NEJM199202063260605
[3] Aranguren, X.L., Verfaillie, C.M. and Luttun, A. (2009) Emerging hurdles in stem cell therapy for peripheral vascular disease. Journal of Molecular Medicine, 87, 3-16. doi:10.1007/s00109-008-0394-3
[4] Ouriel, K. (2001) Peripheral arterial disease. The Lancet, 358, 1257-1264. doi:10.1016/S0140-6736(01)06351-6
[5] Luther, M., Lepantalo, M., Alback, A. and Mazke, S. (1996) Amputation rates as a measure of vascular surgical results. British Journal of Surgery, 83, 241-244. doi:10.1002/bjs.1800830229
[6] Coffman, J. D. (1991) Intermittent claudication—Be conservative. The New England Journal of Medicine, 325, 577-578.
[7] Beker, G.J., Furguson, J.G., Bakal, C.W., McKinnison, M.G.K. et al. (1993) Angioplasty, bypass surgery and amputation for lower extremity peripheral arterial disase in Maryland: A closer look. Radiology, 186, 635-638.
[8] Rutherford, R.B., Flanigon, D.P., Gupta, S.L., Johnsin, K., et al. (1986) Suggested standards for reports dealing with lower extremity ischemia. Journal of Vascular Surgery, 4, 80-94.
[9] Deweese, J.A., Leather, R. and Porter, J. (1993) Practice guidelines: Lower extremity revascularization. Journal of Vascular Surgery, 18, 280-294. doi:10.1016/0741-5214(93)90609-P
[10] Norgen, L., Hiatt, W.R., Dormandy, J.A., et al. (2007) TASC II working group inter society consensus for the management of pheripheral artherial disease (TASC II). European Journal of Vascular and Endovascular Surgery, 33, 1-75.
[11] Di Stefano, R., Limbruno, U., Barone, D. and Balbarini, A. (2004) Therapeutic angiogenesis of critical lower limb ischemia review of the literature and prospects of research on stem cells. Italian Heart Journal, 5, 1-13.
[12] Boccalon, H., Lehert, P. and Mosnier, M. (2000) Assessment of the prevalence of atherosclerotic lower limb arteriopathy in France as a systolic index in a vascular risk population. Journal Des Maladies Vasculaires, 25, 38-46.
[13] The European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products. (2002) Notes for guidance on clinical investigation of medicinal products for the treatment of peripheral arterial occlusive disease. CPMP/EWP714/98.
[14] Marston, W.A., Davies, S.W., Armstrong, B., Farber, M.A., Mendes, R.C. and Fulton, J.J. (2006) Natural history of limbs with arterial insufficiency and chronic ulceration treated without revascularization. Journal of Vascular Surgery, 44, 108-114. doi:10.1016/j.jvs.2006.03.026
[15] Hilleman, D.E. (1998) Management of peripheral arterial. Disease. American Journal of Health Promotion, 55, 521-527.
[16] Dormady, J.A. and Rutherford, R.B. (2000) Management of peripheral arterial disease (PAD). TASC working group. Journal of Vascular Surgery, 31, S1-S278.
[17] Aronow, W.S. (2005) Management of peripheral arterial disease. Cardiology in Review, 13, 61-68. doi:10.1097/01.crd.0000126082.86717.12
[18] Franz, R., Parks, A., Shah, K.J., Hankins, T., Hartman, J.F. and Wright, M.L. (2009) Use of autologus bone marrow mononuclear cell implantation therapy as a limb salvage procedure in patients with severe peripheral arterial disease. Journal of Vascular Surgery, 50, 1378-1390. doi:10.1016/j.jvs.2009.07.113
[19] Huang, P.P., Yang, X.F., Li, S.Z., Wen, J.C., Zhang, Y. and Han, Z.C. (2007) 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. Thrombosis and Haemostasis, 98, 1335-1342.
[20] Amann, B., Luedeman, C., Ratei, R. and Schmidt-Lucke, A.J. (2009) Autologus bone marrow transplantation increases leg perfusion and reduces amputations in patients with advanced critical limb ischemia due to peripheral artery disease. Cell Transplantation, 18, 371-380. doi:10.3727/096368909788534942
[21] Bartsch, T., Brehm, M., Zeus, T., Kogler, G., Wernet, P. and Strauer, B.E. (2007) Transplantation of autologus mononuclear bone marrow stem cells in patients with periphera arterial disease (The TAM-PAD study). Clinical Research in Cardiology, 96, 891-899. doi:10.1007/s00392-007-0569-x
[22] Powell, R.J., Comerota, A.J., Berceli, S.A., Guzman, R., Henry, D.T., Tzeng, E., Velazquez, O., Marston, W.A., Bartel, R.L., Longcore, A., Stern, T. and Watling, S. (2011) Interim results from the RESTORE-CLI, a randomized, double-blidn multicenter phase II trial comparing expanded autologus bone marrow-derived tissue repair cells and placebo in patients with critical limb ischemia. Journal of Vascular Surgery, 54, 1032-1041. doi:10.1016/j.jvs.2011.04.006
[23] Cobellis, G., Silvestroni, A., Lillo, S., Sica, G., Botti, C., Maione, C., Schiavone, V., Rocco, S., Brando, G. and Sica, V. (2008) Long-term effects of repeated autologus transplantation of bone marrow cells in patients affected by peripheral arterial disease. Bone Marrow Transplantation, 42, 667-672. doi:10.1038/bmt.2008.228
[24] Padilla, L., De la Garza, A.S., Villegas, F., Esperante, S., Rojas, E., Miranda, A., Figueroa, S., Schalch, P., Krotzsch, E. and Di Silvio, M. (2003) Administration of bone marrow cells into surgically induced fibrocollagenous tunnels induces angiogenesis in ischemic rat hindlimb model. Microsurgery, 23, 568-574. doi:10.1002/micr.10208
[25] Padilla, L., Villegas, F., Glennie, G., Escotto, I., Schalch, P., Avila, G., Rodriguez-Trejo, J., Figueroa, S., De la Garza, A.S., Krotzsch, E. and Di Silvio, M. (2007) Bone marrow mononuclear cells stimulate angiogenesis when transplanted into surgically induced fibrocollagenous tunnels: Results from a canine ischemic hinlimb model. Microsurgery, 27, 91-97. doi:10.1002/micr.20289
[26] Yeh, Y. and Cummins, H. (1964) Localized fluid flows measurements with He-Ne laser spectrometer. Applied Physics Letters, 4, 176-178. doi:10.1063/1.1753925
[27] Kvernobo, K. and Slagsvold, C.E. (1998) Laser Doppler flowmetry in evaluation of lower limb resting skin circulation: A study in healthy controls and atherosclerotic patients. Scandinavian Journal of Clinical & Laboratory Investigation, 48, 621-626. doi:10.3109/00365518809085781
[28] Padilla, S.L., Rodriguez, T.J., Escotto, S.L., De Diego, F.J., Rodriguez, R.N., Kr?tzsch, E., Villegas, A., Landero, T., Carranza, H., Goldberg, J. and Di Silvio, M. (2009) Progenitor mononuclear cell transplantation derived from the bone marrow through distal retrogressive endovenous route in order to induce angiogenesis. Cirujano General, 31, 213-218.
[29] Tepper, O.M., Capla, J.M., Galiano, R.D. and Callaghan, M.J. (2009) Adult vasculogenesis occurs through in situ recruitment, proliferation and tubulization of circulating bone marrow derived cells. Blood, 105, 1068-1077. doi:10.1182/blood-2004-03-1051
[30] Lawall, H., Bramage, P. and Amann, B. (2010) Stem cell and progenitor cell therapy in peripheral arterial disease. Journal of Thrombosis and Haemostasis, 103, 696-709.
[31] Van Tongeren, R. and Hamming, J. (2008) Intramuscular or combined intramuscular/intra-arterial administration of bone marrow mononuclear cells; a clinical trial in patients with advanced limb ischemia. Journal of Cardiothoracic Surgery, 49, 51-58.

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.