Células madre pluripotenciales en el tratamiento de la isquemia de miembros inferiores. Primer caso en Paraguay y nuestra experiencia en el Hospital de Clínicas de la Universidad Nacional de Asunción

Jorge Flores; N Cazal; L Recalde; J Ferreira; R Corbeta

doi:10.18004/An.fcm/1816-8949.048.02.065-072

Authors

Jorge Flores Primera Cátedra y Servicio de Clínica Quirúrgica. Facultad de Ciencias Médicas, Universidad Nacional de Asunción
N Cazal Hemocentro del Hospital de Clínicas. Facultad de Ciencias Médicas, Universidad Nacional de Asunción
L Recalde Hemocentro del Hospital de Clínicas. Facultad de Ciencias Médicas, Universidad Nacional de Asunción
J Ferreira Departamento de Hematología. Facultad de Ciencias Médicas, Universidad Nacional de Asunción.
R Corbeta Primera Cátedra y Servicio de Clínica Quirúrgica. Facultad de Ciencias Médicas, Universidad Nacional de Asunción.

DOI:

https://doi.org/10.18004/An.fcm/1816-8949.048.02.065-072

Keywords:

Critical ischemia, arterial revascularization, stems cells, Paraguay

Abstract

There is a group of patients with critical limb ischemia, whom are not adequate for surgical or endovascular revascularization. They present a high risk of amputation. In last decades, it has been identified a group of bone marrow CD34+ stem cells, that proliferate in case of tissue ischemia, migrate through the circulation to the ischemic tissue and originate new vessels. This event is complicated in vivo by the occlusion of arteries of the affected region. In this paper, we present our experience in two patients, who underwent harvesting of their bone marrow tissue, which has been strained and then sowed in the ischemic lower limb to develop new blood vessels, thus improving blood flow to this area and wound healing, avoiding lower limb amputation.

References

1. Schiavetta A, Maione C, Botti C, Marino G, Lillo S, Garrone A, et al. A phase II trial of autologous transplantation of bone marrow stem cells for critical limb ischemia: Results of the Naples and Pietra Ligure Evaluation of stem cells study. Stem Cells Transl Med. 2012;1(7):572-578.

2. Zankhana R, Losordo DW. Cell therapy of peripheral arterial disease. Circ Res 2013; 112(9): 1288-1302.

3. Suzuki H, Iso Y. Clinical aplication of vascular regenerative therapy for peripheral artery disease. Biomed Res Int. 2013;2013:179730.

4. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, et al. Isolation of putative progenitor endotelial cells for angiogenesis. Science 1997; 275: 964 – 967.

5. Kerwin KB, Pearl GJ, Molina CD, Coker PJ, Pineiro LA, Urschel HC Jr, et al. Avoidance of lower-limb amputation by surgical implantation of autologous stem cells. Proc (Bayl Univ Med Cent) 2013;26(3):285-287.

6. Gupta PK, Chullikana A, Parakh R, Desai S, Das A, Gottipamula S, et al. A doublé lind 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.

7. Yoo SY, Kwon SM. Angiogenesis and its therapeutic opportunities. Mediators Inflamm 2013;2013:127170.

8. Altaner C, Altanerova V, Cihova M, Hunakova L, Kaiserova K, Klepanec A, et al. Characterization of mesenchymal stem cells of no-options patients with critical limb ischemia treated by autologous bone marrow mononuclear cells. PLoS One. 2013 Sep 12;8(9):e73722.

9. Wang ZX, Li D, Cao JX, Liu YS, Wang M, Zhang XY, et al. Efficacy of autologous bone marrow mononuclear cell therapy in patients with peripheral arterial disease. J Atheroscler Tromb 2014; 21: 1183 – 1196.

10. Karakoyun R, Koksoy C, Yilmaz T, Altun H, Banli O, Albayrak A, et al. The angiogenic effects of ischemic conditioning in experimental critical limb ischemia. Eu J Vasc Endovasc Sug 2014; 47: 172-179.

11. Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, et al. Therapeutic angiogenesis for patients with limb ischemia by aotologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet 2002; 360: 427- 435.

12. Fujita Y, Kinoshita M, Furukawa Y, Nagano T, Hashimoto H, Hirami Y, et al. Phase II clinical trial of CD 34+ cell therapy to explore enpoint selection and timing in patients with critical limb ischemia. Circ J 2014; 78: 490 – 501.

13. Shimmamura M, Nakagami H, Koriyama H, Morishita R. Gene therapy and cell-based therapies for therapeutic angiogenesis in peripheral artery disease. Biomed Res Int 2013; 2013:186215.

14. Higashi Y, Kimura M, Hara K, Noma K, Jitsuiki D, Nakagawa K, et al. Autologous bone-marrow mononuclear cell implantation improves endothelium-dependent vasodilatation in patients with limb ischemia. Circulation 2004; 109: 1215 – 1218.

15. Kudo F, Nishibe T, Nishibe M, Yasuda K. Autologous transplantation of peripheral blood endotelial progenitor cells (CD 34+) for therapeutic angiogenesis in patients with critical limb ischemia. Int Angiol 2003; 22: 344 – 348.