Role of Progenitor Cells in Cardiovascular Medicine

来自我们实验室和其他实验室的数据表明，来自预先存在的血管结构的内皮细胞(EC)可能不 构成新船编队的唯一参与者。这些研究表明，循环细胞来源于 骨髓和表现出与EC身份一致的某些特征，能够归巢到 在生理和病理情况下，新生血管的形成和促进新血管的形成。这些 细胞，称为内皮祖细胞(EPC)或循环内皮祖细胞(CEP)已被证明 在各种环境中参与新生血管的形成，包括缺血组织、肿瘤和视网膜。这种可能性 内皮祖细胞参与新生血管形成可以被调节为治疗益处，这一点最近得到了进一步的研究 循环内皮祖细胞移植治疗肢体缺血性疾病试点临床试验建议 心肌。然而，尽管有这些令人鼓舞的数据，关于骨骼的作用仍有很多未知之处。 骨髓来源的细胞在组织修复和维持中的作用。广泛的文献揭示了开发治疗的潜力 然而，据报道，骨髓来源的细胞参与了新生的骨髓瘤的发生。 据报道，在某些研究中，血管形成的范围高达30%或更多，在其他研究中，甚至接近于零。 因此，内皮祖细胞促进缺血组织恢复的机制仍未完全确定为 它们的治疗潜力。我们的初步数据显示，骨髓来源的祖细胞的调节是 与改善急性和慢性心肌缺血的生理结局有关。此外，这些数据还 提示骨髓动员可提高基因治疗介导的治疗性血管生成的效果 内皮祖细胞。最后，我们的初步发现提供了关于内皮祖细胞潜在机制的重要线索 通过揭示内皮祖细胞存在的情况，改善缺血心肌的解剖和生理结局 缺陷或有缺陷，并导致不良的心脏结局。因此，在这项建议中，我们将采用一系列的 体内和体外模型系统，以确定内皮祖细胞在心肌缺血恢复中的作用，目标是 开发利用这些细胞的未来治疗策略。

Data from our laboratory and others indicates that endothelial cells (EC) from pre-existing vascular structures might not constitute the sole participants in new vessel formation. These studies have revealed that circulating cells, derived from the bone marrow and exhibiting certain features consistent with EC identity, are capable of homing to sites of neovascularization and contributing to the formation of new vessels in physiologic and pathologic circumstances. These cells, referred to as endothelial progenitors (EPC) or circulating endothelial progenitors (CEP) have been shown to participate in neovascularization in a variety of settings includingischemic tissue tumors, and the retina. The possibility that the participation of EPCs in neovascularization could be modulated to therapeutic benefit has recently been further suggested in pilot clinical trials of circulating EPC transplantation for ischemic diseases of the lower extremity and myocardium. Despite these encouraging data, however, a great deal remains unknownregarding the role of bone marrow derived cells in tissue repair and maintenance. Extensive literature reveals therapeutic potential for exploiting bone marrow derived progenitors, however the reported extent of participation of bone marrow derived cells in neo- vessel formation has been reported to range as high as 30 or more percent in certain studies, to close to zero in others. The mechanisms by which EPCs contribute to recovery of ischemic tissue, therefore, remain incompletely defined as does their therapeutic potential.Our preliminary data reveal that modulation of bone marrow derived progenitors is associated with improved physiologic outcome in acute and chronic myocardial ischemia. Moreover, these data also reveal that the results of gene therapy mediated therapeutic angiogenesis can be enhanced by bone marrow mobilization of EPCs. Finally, our preliminary findings provide important clues regarding potential mechanisms by which EPCs improve anatomic and physiologic outcome in ischemic myocardium, by revealing situations in which EPCs are deficient or defective, and result in poor cardiac outcome. Accordingly, in this proposal we will employ a series of in vivo and in vitro model systems to define the role of EPCs in recovery from myocardial ischemia with a goal of developing future therapeutic strategies exploiting these cells.