Mobilized bone marrow cells repair the infarcted heart, improving function and survival

Proceedings of the National Academy of Sciences of the United States of America - Tập 98 Số 18 - Trang 10344-10349 - 2001
Donald Orlic1, Jan Kajstura1, Stefano Chimenti1, Federica Limana1, Igor Jakoniuk1, Federico Quaini1, Bernardo Nadal‐Ginard1, Axel Visel1, Annarosa Leri1, Piero Anversa1
1Cardiovascular Research Institute, Department of Medicine, New York Medical College, Valhalla, NY 10595; and Hematopoiesis Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institute of Health, Bethesda, MD 20892

Tóm tắt

Attempts to repair myocardial infarcts by transplanting cardiomyocytes or skeletal myoblasts have failed to reconstitute healthy myocardium and coronary vessels integrated structurally and functionally with the remaining viable portion of the ventricular wall. The recently discovered growth and transdifferentiation potential of primitive bone marrow cells (BMC) prompted us, in an earlier study, to inject in the border zone of acute infarcts Lin − c- kit POS BMC from syngeneic animals. These BMC differentiated into myocytes and vascular structures, ameliorating the function of the infarcted heart. Two critical determinants seem to be required for the transdifferentiation of primitive BMC: tissue damage and a high level of pluripotent cells. On this basis, we hypothesized here that BMC, mobilized by stem cell factor and granulocyte-colony stimulating factor, would home to the infarcted region, replicate, differentiate, and ultimately promote myocardial repair. We report that, in the presence of an acute myocardial infarct, cytokine-mediated translocation of BMC resulted in a significant degree of tissue regeneration 27 days later. Cytokine-induced cardiac repair decreased mortality by 68%, infarct size by 40%, cavitary dilation by 26%, and diastolic stress by 70%. Ejection fraction progressively increased and hemodynamics significantly improved as a consequence of the formation of 15 × 10 6 new myocytes with arterioles and capillaries connected with the circulation of the unaffected ventricle. In conclusion, mobilization of primitive BMC by cytokines might offer a noninvasive therapeutic strategy for the regeneration of the myocardium lost as a result of ischemic heart disease and, perhaps, other forms of cardiac pathology.

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Tài liệu tham khảo

10.1056/NEJM200106073442303

10.1016/0002-9149(60)90084-9

J Leor, M Patterson, M J Quinones, L H Kedes, R A Kloner Circulation 94,Suppl., II331–II336 (1996).

10.1172/JCI119070

10.1038/nm0898-929

S Tomita, R-K Li, R D Weisel, D A G Mickle, E-J Kim, T Sakai, Z-Q Jia Circulation 100,Suppl., II247–II256 (1999).

10.1016/S0140-6736(00)03617-5

10.1038/81326

10.1126/science.290.5497.1775

10.1038/35070587

10.1126/science.283.5401.534

10.1126/science.290.5497.1779

10.1182/blood.V84.5.1482.1482

10.1182/blood.V91.9.3247

10.1172/JCI119730

10.1161/01.RES.84.9.1007

10.1016/S0894-7317(05)80373-6

10.1161/01.RES.68.3.856

10.1161/01.CIR.89.1.151

10.1161/01.CIR.92.8.2306

10.1073/pnas.93.16.8630

10.1126/science.276.5317.1404

10.1161/01.RES.82.9.936

10.1177/43.8.7542682

H Hermann, U Aebi Subcellular Biochemistry: Intermediate Filaments, eds H Herrmann, E Harris (Plenum, New York) 31, 319–362 (1998).

10.1242/dev.118.2.489

10.1182/blood.V87.2.630.bloodjournal872630

10.1161/01.RES.81.6.932

10.1016/S1054-8807(00)00055-7

10.1038/86498

10.1161/01.CIR.81.4.1161

10.1161/01.CIR.102.1.14

10.1038/43919

10.1161/01.CIR.98.7.687

10.1016/0022-510X(95)00255-Z

10.1159/000017979

10.1016/S0168-8278(99)80139-1

10.1101/gad.9.17.2105

10.1101/gad.855501

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Proceedings of the National Academy of Sciences of the United States of America

Tập 98 Số 18

10344-10349

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