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Review
. 1999 May;103(9):1231-6.
doi: 10.1172/JCI6889.

Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization

J M Isner  1 , T Asahara
Affiliations
Review

Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization

J M Isner et al. J Clin Invest. 1999 May.
No abstract available

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Figures

Figure 1
Figure 1
BMT model employed to study contribution of postnatal vasculogenesis to neovascularization of ischemic tissues. Transgenic mouse constitutively expressing LacZ gene transcriptionally regulated by an EC-specific promoter, Flk-1 or Tie-2, is used as BM donor. BM is harvested and transplanted to mouse of same genetic background, in which BM has been sublethally irradiated. After a period of 4 weeks to allow for reconstitution of transplanted BM, recipient mouse undergoes one or more interventions, all of which are intended to serve as stimulus for neovascularization. At arbitrarily selected time points following these interventions, animals are sacrificed and the respective tissues stained with X-gal to histologically identify cells in which expression of β-galactosidase produces blue cells. Use of an EC-specific promoter permits identification of blue cells, which have incorporated into foci of neovascularization as endothelial lineage cells.
Figure 2
Figure 2
Neovascularization encompasses both angiogenesis and vasculogenesis. Angiogenesis represents the classic paradigm for new vessel growth, as mature, differentiated ECs break free from their basement membrane and migrate as well as proliferate to form sprouts from parental vessels. Vasculogenesis involves participation of BM-derived EPCs, which circulate to sites of neovascularization where they differentiate in situ into mature ECs. Growth factors, cytokines, or hormones released endogenously in response to tissue ischemia, or administered exogenously for therapeutic neovascularization, act to promote EPC proliferation, differentiation, and mobilization from BM (via the peripheral circulation) to neovascular foci.
Figure 3
Figure 3
Therapeutic vasculogenesis. (top) Circulating EPCs may be harvested in analogous fashion to methods currently established for harvesting HSCs for autologous marrow transplantation. EPCs, purified and expanded ex vivo, may then be readministered, with or without angiogenic growth factors, to optimize therapeutic neovascularization. (middle) Harvested EPCs may be transfected ex vivo with genes encoding for proangiogenic factors. When incorporated into nascent vasculature, administered EPCs express growth-promoting factors directly at the site of, and thereby potentially augment, neovascularization. (bottom) If EPCs are transduced ex vivo with transgene encoding antitumorigenic factors, administered EPCs home to vascular infrastructure of developing neoplasm where they act as a “Trojan Horse” to express antiangiogenic factors that sabotage tumor growth and metastasis.
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