Laboratorio di Biologia Vascolare e Medicina Rigenerativa, Centro Cardiologico Monzino, Istituto di Ricovero e Cura a Carattere Scientifico, Via Parea 4, 20138 Milan, Italy.
Arterioscler Thromb Vasc Biol. 2011 Jul;31(7):1589-97. doi: 10.1161/ATVBAHA.111.226969. Epub 2011 Apr 28.
The vascular competence of human-derived hematopoietic progenitors for postnatal vascularization is still poorly characterized. It is unclear whether, in the absence of ischemia, hematopoietic progenitors participate in neovascularization and whether they play a role in new blood vessel formation by incorporating into developing vessels or by a paracrine action.
In the present study, human cord blood-derived CD34(+) (hCD34(+)) cells were transplanted into pre- and postgastrulation zebrafish embryos and in an adult vascular regeneration model induced by caudal fin amputation. When injected before gastrulation, hCD34(+) cells cosegregated with the presumptive zebrafish hemangioblasts, characterized by Scl and Gata2 expression, in the anterior and posterior lateral mesoderm and were involved in early development of the embryonic vasculature. These morphogenetic events occurred without apparent lineage reprogramming, as shown by CD45 expression. When transplanted postgastrulation, hCD34(+) cells were recruited into developing vessels, where they exhibited a potent paracrine proangiogenic action. Finally, hCD34(+) cells rescued vascular defects induced by Vegf-c in vivo targeting and enhanced vascular repair in the zebrafish fin amputation model.
These results indicate an unexpected developmental ability of human-derived hematopoietic progenitors and support the hypothesis of an evolutionary conservation of molecular pathways involved in endothelial progenitor differentiation in vivo.
人类造血祖细胞在出生后血管生成中的血管生成能力仍未得到充分描述。目前尚不清楚在没有缺血的情况下，造血祖细胞是否参与新生血管形成，以及它们是否通过整合到发育中的血管或旁分泌作用来发挥作用。
在本研究中，将人脐带血来源的 CD34+（hCD34+）细胞移植到斑马鱼胚胎的原肠胚前期和后期，并在尾部鳍切除诱导的成年血管再生模型中进行移植。当在原肠胚前期注射时，hCD34+细胞与假定的斑马鱼造血母细胞共分离，造血母细胞的特征是表达 Scl 和 Gata2，位于前侧和后侧侧中胚层，并参与胚胎血管的早期发育。这些形态发生事件发生时没有明显的谱系重编程，如 CD45 表达所示。当在原肠胚后期移植时，hCD34+细胞被招募到发育中的血管中，在那里它们表现出强烈的旁分泌促血管生成作用。最后，hCD34+细胞挽救了体内靶向 Vegf-c 诱导的血管缺陷，并增强了斑马鱼鳍切除模型中的血管修复。
这些结果表明人类造血祖细胞具有出乎意料的发育能力，并支持了体内内皮祖细胞分化涉及的分子途径进化保守的假说。
