Beaudry Paul, Hida Yasuhiro, Udagawa Taturo, Alwayn Ian P, Greene Arin K, Arsenault Danielle, Folkman Judah, Heymach John V, Ryeom Sandra, Puder Mark
Vascular Biology Program, Department of Surgery, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
J Pediatr Surg. 2007 Jul;42(7):1190-8. doi: 10.1016/j.jpedsurg.2007.02.034.
Two classes of circulating endothelial cells (CECs) have been identified and are distinguished by the expression of the stem cell markers CD117 or CD133 together with endothelial-specific antigens. Stem cell marker-positive CECs originate from bone marrow and have been designated as circulating endothelial progenitors (CEPs). We have demonstrated that exogenous vascular endothelial growth factor (VEGF) effectively mobilizes CEP cells. Furthermore, it has been demonstrated that VEGF regulates liver regeneration after partial hepatectomy. Although local endothelial cells can regulate tissue mass during liver regeneration, the contribution of CEPs to this process is unknown. We discovered loss of CD117 and CD133 from murine CEP cells and that both markers underestimated the number of bone marrow-derived CEP cells. We therefore used wild type and green fluorescent protein (GFP)-bone marrow transplanted into wild-type mice and performed 70% hepatectomies. Furthermore, we found that treatment with exogenous VEGF accelerated liver regeneration after 70% hepatectomy, whereas immunohistochemical analysis showed a 7-fold increase in the incorporation of CEP cells into liver vasculature. These results suggest that CEP cells play a role in regulating liver regeneration and that VEGF treatment can mobilize CEP cells to accelerate this process.
已识别出两类循环内皮细胞（CEC），它们通过干细胞标志物CD117或CD133与内皮特异性抗原的表达来区分。干细胞标志物阳性的CEC起源于骨髓，被指定为循环内皮祖细胞（CEP）。我们已经证明，外源性血管内皮生长因子（VEGF）能有效动员CEP细胞。此外，已经证明VEGF可调节部分肝切除术后的肝脏再生。虽然局部内皮细胞在肝脏再生过程中可调节组织质量，但CEP对这一过程的贡献尚不清楚。我们发现小鼠CEP细胞中CD117和CD133缺失，且这两种标志物均低估了骨髓来源的CEP细胞数量。因此，我们将野生型和绿色荧光蛋白（GFP）骨髓移植到野生型小鼠体内，并进行了70%肝切除术。此外，我们发现外源性VEGF治疗可加速70%肝切除术后的肝脏再生，而免疫组织化学分析显示CEP细胞整合到肝脏血管系统中的数量增加了7倍。这些结果表明，CEP细胞在调节肝脏再生中发挥作用，VEGF治疗可动员CEP细胞加速这一过程。
