Murine Bone Marrow Transplantation Models that Enable the Study of EPC Recruitment

Abstract

It has recently been established that postnatal neovascularization is not restricted to angiogenesis, but also includes vasculogenesis (Asahara et al. 1997, Shi et al. 1998, Isner and Ashara 1999, Gunsilius et al. 2000). During adult vasculogenesis, bone marrow (BM)-derived endothelial progenitor cells (EPCs) are mobilized to the systemic circulation in response to certain cytokines or pharmacologic agents, and are recruited to ischemic tissue where they differentiate in situ. As there is currently no marker that can distinguish between BM-derived (vasculogenesis) versus resident endothelial lineage cells (angiogenesis), murine BM transplantation (BMT) models offer a powerful technique for studying the process of postnatal vasculogenesis. BM transplantation (BMT) models that enable one to distinguish BM-derived EPCs are designed for donor cells from either (1) transgenic mice in which the expression of marker gene is driven by endothelial-specific promoter (Asahara et al. 1999a, b, Takahashi et al. 1999, Llevadot et al. 2001, Murayama et al. 2002, Zhang et al. 2002), or (2) transgenic mice with a ubiquitously expressed marker gene or retroviral-infected wild-type BM, followed by endothelial staining (Crosby et al. 2000, Jackson et al. 2001, Lyden 2001 et al., Edelberg 2002 et al., Grant 2002 et al., Hess et al. 2002, Sata et al. 2002, Werner et al. 2002). Such models allow for:

• a) Identification of BM-derived EPCs in situ

• b) Quantification of BM-derived EPCs contribution in postnatal neovascularization

• c) Assessment of recruitment of BM-derived EPCs in response to various stimuli