Bone Marrow Origin of Endothelial Progenitor Cells Responsible for Postnatal Vasculogenesis in Physiological and Pathological Neovascularization

Circulation Research - Tập 85 Số 3 - Trang 221-228 - 1999
Takayuki Asahara1, Haruchika Masuda1, Tomono Takahashi1, Christoph Kalka1, Christopher J. Pastore1, Marcy Silver1, Marianne Kearne1, Meredith Magner1, Jeffrey M. Isner1
1From the Departments of Medicine (Cardiology) and Biomedical Research, St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass.

Tóm tắt

Abstract —Circulating endothelial progenitor cells (EPCs) have been isolated in peripheral blood of adult species. To determine the origin and role of EPCs contributing to postnatal vasculogenesis, transgenic mice constitutively expressing β-galactosidase under the transcriptional regulation of an endothelial cell–specific promoter (Flk-1/LZ or Tie-2/LZ) were used as transplant donors. Localization of EPCs, indicated by flk-1 or tie-2/lacZ fusion transcripts, were identified in corpus luteal and endometrial neovasculature after inductive ovulation. Mouse syngeneic colon cancer cells (MCA38) were implanted subcutaneously into Flk-1/LZ/BMT (bone marrow transplantation) and Tie-2/LZ/BMT mice; tumor samples harvested at 1 week disclosed abundant flk-1/lacZ and tie-2/lacZ fusion transcripts, and sections stained with X-gal demonstrated that the neovasculature of the developing tumor frequently comprised Flk-1– or Tie-2–expressing EPCs. Cutaneous wounds examined at 4 days and 7 days after skin removal by punch biopsy disclosed EPCs incorporated into foci of neovascularization at high frequency. One week after the onset of hindlimb ischemia, lacZ-positive EPCs were identified incorporated into capillaries among skeletal myocytes. After permanent ligation of the left anterior descending coronary artery, histological samples from sites of myocardial infarction demonstrated incorporation of EPCs into foci of neovascularization at the border of the infarct. These findings indicate that postnatal neovascularization does not rely exclusively on sprouting from preexisting blood vessels (angiogenesis); instead, EPCs circulate from bone marrow to incorporate into and thus contribute to postnatal physiological and pathological neovascularization, which is consistent with postnatal vasculogenesis.

Từ khóa


Tài liệu tham khảo

10.1146/annurev.cb.11.110195.000445

10.1242/dev.102.3.471

10.1242/dev.116.2.435

His W. Leoithoblast und angioblast der wirbelthiere. Abhandl K S Ges Wiss Math Phys. 1900;22:171–328.

10.1172/JCI118454

Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275:965–967.

10.1182/blood.V92.2.362

10.1242/dev.125.8.1457

10.1016/S1097-2765(00)80154-9

10.1242/dev.105.3.473

Couffinhal T, Silver M, Zheng LP, Kearney M, Witzenbichler B, Isner JM. A mouse model of angiogenesis. Am J Pathol. 1998;152:1667–1679.

Michael LH, Entman ML, Hartley CJ, Youker KA, Zhu J, Hall SR, Hawkins HK, Berens K, Ballantyne CM. Myocardial ischemia and reperfusion: a murine model. Am J Physiol. 1995;269:H2147–H2154.

10.1038/376062a0

10.1038/376070a0

10.1073/pnas.92.11.4857

10.1002/aja.1000730206

10.1038/nm0398-336

10.1038/376066a0

10.1172/JCI117018

10.1016/S0140-6736(96)03361-2

10.1161/circ.89.5.7514110

10.1038/nm1095-1085

Li J, Brown LF, Hibberd MG, Grossman JD, Morgan JP, Simons M. VEGF, flk-1, and flt-1 expression in a rat myocardial infarction model of angiogenesis. Am J Physiol. 1996;270:H1803–H1811.

10.1242/dev.119.3.957

10.1002/aja.1002030109

10.1101/gad.8.16.1897

10.1126/science.279.5356.1528

10.1073/pnas.75.2.847

10.1016/0006-291X(89)92678-8

10.1073/pnas.84.16.5773

10.1126/science.277.5322.55

10.1126/science.276.5309.71

10.1056/NEJM197111182852108

10.1016/S0092-8674(00)80108-7

10.1353/pbm.1985.0049

10.1056/NEJM198612253152606

10.1126/science.2432664

10.1016/S0021-9258(19)49853-0

10.1006/clin.1996.0097

10.1038/nm0297-158

Hatva E, Bohling T, Jaaskelainen J, Perssico MG, Haltia M, Alitalo K. Vascular growth factors and receptors in capillary hemangioblastomas and hemangiopericytomas. Am J Pathol. 1996;148:763–775.

Kalka C Masuda H Takahashi T Li T Asahara T. Administration of culture-expanded endothelial progenitor cells (EPC) augments therapeutic neovascularization. Circulation. 1998;97 (suppl I):I-455. Abstract.

10.1016/0006-291X(92)91880-Y

Solovey A, Lin Y, Brown P, Choong S, Wayner E, Hebbel RP. Circulating activated endothelial cells in sickle cell anemia. N Engl J Med. 1997;337:1582–1590.

Thông tin
Thông tin xuất bản

Circulation Research

Tập 85 Số 3

221-228

Thông tin tác giả