Jornal Vascular Brasileiro
https://jvascbras.org/article/doi/10.1590/S1677-54492005000400011
Jornal Vascular Brasileiro
Review Article

A terapia celular no tratamento da isquemia crítica dos membros inferiores

José Dalmo de Araújo; José Dalmo de Araújo Filho; Emerson Ciorlin; Milton Artur Ruiz; Lílian Piron Ruiz; Oswaldo Tadeu Greco; Mario Roberto Lago; Roberto Vito Ardito

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Resumo

Os autores fazem um histórico sobre as pesquisas com células-tronco embrionárias e do cordão umbilical, suas respectivas vantagens e desvantagens. Seguem com as discussões sobre células-tronco adultas, sua definição, histórico, fontes e participação nos processos de regeneração tecidual, particularmente no endotélio. Ressaltam a importância de fatores que mobilizam as células-tronco adultas a partir da medula óssea: citocinas, angiopoietinas e outros fatores de crescimento. As células-tronco adultas mobilizam-se sob a forma de células endoteliais progenitoras, que têm origem comum com as células endoteliais a partir dos hemangioblastos. Os fatores de mobilização manifestam-se em condições de hipoxia e fazem com que as células endoteliais progenitoras se localizem nos locais de isquemia para produzir a neovasculogênese, que se faz por três possíveis mecanismos: a angiogênese (formação de novos capilares a partir de brotos de capilares já existentes), a arteriogênese (relacionada à circulação colateral) e a vasculogênese (vasos realmente novos). Fazem, a seguir, uma análise da literatura relativa à experimentação animal e aos estudos clínicos. Concluem ressaltando que as células-tronco adultas, embora tenham um grande potencial de uso, ainda demandam muito estudo e pesquisa para se firmar como método terapêutico.

Palavras-chave

terapia celular, células tronco, isquemia crítica

References

Thomson JA, Kovitz-Eldor J, Shapiro SS. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282:114-17.

Thomas ED, Lochte Jr H, Cannon JH. Supralethal whole body irradiation and isologous marrow transplantation in man. J Clin Invest. 1959;38(10):1709-16.

Alison M, Sarraf C. Hepatic stem cells. J Hepatol. 1998;29:676-82.

Gage FH. Mammalian neural stem cells. Science. 2000;287:1433-8.

Planat-Benard V, Silvestre JS, Cousin B. Plasticity of human adipose Lineage Cells toward endothelial cells: Physiological and therapeutic perspectives. Circulation. 2004;109:656-63.

Pittenger MF, Mackay AM, Beck SC. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143-7.

Olic D, Kajstura J, Chimenti S. Bone marrow cells regenerate infracted myocardium. Nature. 2001;410:701-5.

Shi BQ, Raffi S, Wu MH. Evidence for circulating bone marrow-derived endothelial cells. Blood. 1998;92:362-7.

Reys M, Lund T, Lenvik T. Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood. 2001;98:2615-25.

Yoon YS, Wecker A, Heyd L. Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction. J Clin Invest. 2005;115:326-38.

Asahara T, Masuda H, Takahashi T. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res.. 1999;85:221-8.

Minamino T, Miyauchi H, Yoshida T. Endothelial cell senescence in human atherosclerosis role of telomere in endothelial dysfunction. Circulation. 2002;105:1541-4.

Rauscher FM, Goldschmidt-Clermont PJ, Davis BH. Aging progenitor cell exhaustion, and atherosclerosis. Circulation. 2003;108:457-63.

Shimada T, Takeshita Y, Murohara T. Angiogenesis and vasculogenesis are impaired in the precocious-aging klotho mouse. Circulation. 2004;110:1148-55.

Sata M. Circulating vascular progenitor cells contribute to vascular repair, remodeling, and lesion formation. Trends Cardiovasc Med. 2003;13:249-53.

Gulati R, Jevremovic D, Peterson TE. Autologous culture-modified mononuclear cells confer vascular protection after arterial injury. Circulation. 2003;108:1520-6.

Fujiyama S, Amano K, Uehira K. Bone marrow monocyte lineage cells adhere on injure endothelium in a monocyte chemoattractant protein-1-dependent manner and accelerate reendothelialization as endothelial progenitor cells. Cir Res. 2003;93:980-9.

Sata M, Saiura A, Kunisato A. Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis. Nat Med. 2002;8:403-9.

Boisvert WA, Spangenberg J, Curtiss LK. Treatment of severe hypercholesterolemia in apolipoprotein E-deficient mice by bone marrow transplantation. J Clin Invest. 1995;96:1118-24.

Rehman J, Li Jingling, Parvathaneni L. Exercise acutely increases circulating endothelial progenitor cells and monocyte/macrophage-derived angiogenic cells. J Am Coll Cardiol. 2004;43:2314-8.

Dimmeler S, Aicher A, Vasa M. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-Kinase/Akt pathway. J Clin Invest. 2001;108:391-7.

Vasa M, Fichtlscherer S, Adler K. Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation. 2001;103:2885-90.

Hill JM, Zalos G, Halcox JP. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003;348:593-600.

Waltenberger J, Lange J, Kranz A. Vascular endothelial growth factor-A-induced chemotaxis of monocytes is attenuated in patients with diabetes mellitus: A potential predictor for the individual capacity to develop collaterals. Circulation. 2000;102:185-90.

Yamamoto K, Kondo T, Suzuti S. Molecular evaluation of endothelial progenitor cells in patients with ischemic limbs. Arterioscler Thromb Vasc Biol. 2004;24:e192-6.

Mancuso P, Burlini A, Pruneri G. Resting and activated endothelial cells are increased in the peripheral blood of cancer patient. Blood. 2001;97:3658-61.

Davidoff AM, Ng CY, Brown P. Bone marrow-derived cells contribute to tumor neovasculature and, when modified to express an angiogenesis inhibitor, can restrict tumor growth in mice. Clin Cancer Res. 2001;7:2870-9.

Ribatti D, Vacca A, Roncali L. Hematopoiesis and angiogenesis: a link between two apparently independent processes. J Haemother Stem Cell Res. 2000;9:13-9.

Eichmann A, Corbel C, Nataf V. Ligand-dependent development of the endothelial and hemopoietic lineages from embryonic mesodermal cells expressing vascular endothelial growth factor receptor-2. Proc Natl.Acad Sci USA. 1997;94:5141-6.

Shalaby F, Rossant J, Yamaguchi TP. Failure of blood-island formation and vasculogenesis in FLK-1 deficient nice. Nature. 1995;376:62-6.

Shalaby F, Ho J, Stranford WL. A requirement for flk-1 in primitive and definitive hematopoiesis and vasculogenesis. Cell. 1990;89:981-90.

Nishikawa SI, Nishikawa S, Hirashima M. Progressive lineage analysis by cell sorting and culture identifies FLK+VE cadherin+cells at a diverging point of endothelial and hematopoietic lineages. Development. 1998;125:47-1757.

Ribatti D, Vacca A, Nico B. Cross-talk between hematopoiesis and angiogenesis signaling pathways. Curr Mol Med. 2002;2:537-47.

Asahara T, Murohara T, Sullivan A. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275:964-7.

Stump MM, Jordan GL Jr, DeBakey ME. Endothelium grown from circulating blood on isolated intravascular Dacron hub. Am J Pathol. 1993;43:361.

Frazier OH, Baldwin RT, Eskin SG. Immunochemical identification of human endothelial cells on the lining of a ventricular assist device. Texas Heart Inst J. 1993;2:78.

Carmeliet P. Mechanisms of angiogenesis and arteriogenesis. Nat Med. 2000;6:389-95.

Schaper W, Secholz D. Factors regulating arteriogenesis. Thromb Vasc Biol. 2003;23:1143-51.

Simons M. Angiogenesis: Where do we stand now?. Circulation. 2005;111:1556-66.

Wang JS, Shum Tim D, Galipeau J. Marrow stromal cells for cellular cardiomyoplasty feasibility and potential clinical advantages. J Thorac Cardiovasc Surg. 2000;120:999-1005.

Iba O, Matsubara H, Nozawa Y. Angiogenesis by implantation of peripheral blood mononuclear cells and platelets into ischemic limbs. Circulation. 2002;106:2019-25.

Rehman J, Li J, Orschell CM, March KL. Peripheral blood "endothelial progenitor cells" are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation. 2003;107:1164-9.

Higashi Y, Kimura M, Hara K. Autologous bone-marrow mononuclear cell implantation improves endothelium-dependent vasodilation in patients with limb ischemia. Circulation. 2004;109:1215-8.

Herttuala SY, Alitalo K. Gene transfer as a tool to induce therapeutic vascular growth. Nat Med. 2003;9:694-701.

Comerota AJ, Throm RC, Miller KA. Naked plasmid DNA encoding fibroblast growth factor type 1 for the treatment of end-stage unreconstructible lower extremity ischemia: preliminary results of a phase I trial. J Vasc Surg. 2002;35:930-6.

Raffi S, Heissig B, Hattori K. Efficient mobilization and recruitment of marrow-derived endothelial and hematopoietic stem cells by adenoviral vectors expressing angiogenic factors. Gene Ther. 2002;9:631-41.

Takahashi T, Kalka C, Masuda H. Ischemia and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med. 1999;5:434-8.

Asahara T, Bauters C, Zheng LP. Synergistic effect of vascular endothelial growth factor and basic fibroblast growth factor on angiogenesis in vivo. Circulation. 1995;92(9^sSuppl):II365-71.

Hattori K, Dias S, Heissig B. Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells. J Exp Med. 2001;193:1005-14.

Iwaguro H, Yamaguchi J, Kalka C. Endothelial progenitor cell vascular endothelial growth factor gene transfer for vascular regeneration. Circulation. 2002;105:732-8.

Gross P, Herbrig K. Role of endothelial progenitor cells in cardiovascular pathology. Annales Academiae Medicae Bialostocenis. 2004;49:174-7.

Rafii S. Circulating endothelial precursors: mystery, reality, and promise. J Clin Invest. 2000;105:17-19.

Peichev M, Naiyer AJ. Expression of VEGFR-2 and AC133 by circulating human CD 34 cells identifies a population of functional endothelial precursors. Blood. 2000;95:952-8.

Khaldi AA, Sabti H, Galipeau J. Therapeutic angiogenesis using autologous bone marrow stromal cells: improved blood flow in a chronic limb ischemia model. Ann Thorac Surg. 2003;75:204-9.

Li Sheng T, Hamano K, Suzuki K. Improved angiogenic potency by implantation of ex vivo hypoxia prestimulated bone marrow cells in rats. Am J Physiol Heart Circ Physiol. 2002;283:H468-73.

Shintani S, Murohara T, Ikeda H. Augmentation of postnatal neovascularization with autologous bone marrow transplantation. Circulation. 2001;103:897-903.

Silvestre JS, Mallat Z, Duriez M. Antiangiogenic effect of interleukin-10 in ischemia-induced angiogenesis in mice hindlimb. Cir Res. 2000;87:448-52.

Yuyama ET, Matsubara H, Murohara T. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomized controlled trial. Lancet. 2002;360:427-35.

Kawamura A, Horie T, Tsuda I. Prevention of limb amputation in patients with limbs ulcers by autologous peripheral blood mononuclear cell implantation. Ther Apher Dial. 2005;9:59-63.

Huang PP, Li SZ, Han MZ. Autologous transplantation of peripheral blood stem cells as an effective therapeutic approach for severe arteriosclerosis obliterans of lower extremities. Thromb Haesmost. 2004;91:606-9.

Yang XF, Wu YX, Wang HM. Autologous peripheral blood stem cells transplantation in treatment of 62 cases of lower extremity ischemic disorder. Zhonghnua Nei Ke Za Zhi. 2005;44:95-8.

Ramirez PM, Balea ED, Padron CH. Trasplante de células madre autólogas en el miembro inferior isquémico de un paciente con arteriosclerosis obliterante crítica. Rev Cubana Hematol. Inmunol Hemoter. 2005;21:33-8.

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