Montali Marina, Panvini Francesca M, Barachini Serena, Ronca Francesca, Carnicelli Vittoria, Mazzoni Stefano, Petrini Iacopo, Pacini Simone
Department of Clinical and Experimental Medicine, Hematology Division, University of Pisa, Via Roma 56, 56126, Pisa, Italy.
Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy.
Stem Cell Res Ther. 2017 May 2;8(1):106. doi: 10.1186/s13287-017-0562-x.
Mesangiogenic progenitor cells (MPCs) have shown the ability to differentiate in-vitro toward mesenchymal stromal cells (MSCs) as well as angiogenic potential. MPCs have so far been described in detail as progenitors of the mesodermal lineage and appear to be of great significance in tissue regeneration and in hemopoietic niche regulation. On the contrary, information regarding the MPC angiogenic process is still incomplete and requires further clarification. In particular, genuine MPC angiogenic potential should be confirmed in-vivo.
In the present article, markers and functions associated with angiogenic cells have been dissected. MPCs freshly isolated from human bone marrow have been induced to differentiate into exponentially growing MSCs (P2-MSCs). Cells have been characterized and angiogenesis-related gene expression was evaluated before and after mesengenic differentiation. Moreover, angiogenic potential has been tested by in-vitro and in-vivo functional assays.
MPCs showed a distinctive gene expression profile, acetylated-low density lipoprotein uptake, and transendothelial migration capacity. However, mature endothelial markers and functions of endothelial cells, including the ability to form new capillaries, were absent, thus suggesting MPCs to be very immature endothelial progenitors. MPCs showed marked 3D spheroid sprouting activating the related molecular machinery, a clear in-vitro indication of early angiogenesis. Indeed, MPCs applied to chicken chorioallantoic membrane induced and participated in neovessel formation. All of these features were lost in mesengenic terminally differentiated P2-MSCs, showing definite separation of the two differentiation lineages.
Our results confirm the bona-fide angiogenic potential of MPCs and suggest that the high variability reported for MSC cultures, responsible for the controversies regarding MSC angiogenic potential, could be correlated to variable percentages of co-isolated MPCs in the different culture conditions so far used.
促血管生成祖细胞（MPCs）已显示出在体外向间充质基质细胞（MSCs）分化的能力以及血管生成潜力。到目前为止，MPCs已被详细描述为中胚层谱系的祖细胞，并且在组织再生和造血微环境调节中似乎具有重要意义。相反，关于MPC血管生成过程的信息仍然不完整，需要进一步阐明。特别是，真正的MPC血管生成潜力应在体内得到证实。
在本文中，已剖析了与血管生成细胞相关的标志物和功能。从人骨髓中新鲜分离的MPCs已被诱导分化为指数生长的MSCs（P2-MSCs）。在间充质分化之前和之后对细胞进行了表征，并评估了与血管生成相关的基因表达。此外，通过体外和体内功能试验测试了血管生成潜力。
MPCs显示出独特的基因表达谱、乙酰化低密度脂蛋白摄取和跨内皮迁移能力。然而，缺乏成熟的内皮标志物和内皮细胞功能，包括形成新毛细血管的能力，因此表明MPCs是非常不成熟的内皮祖细胞。MPCs显示出明显的三维球体芽生，激活了相关的分子机制，这是早期血管生成的明确体外指标。事实上，应用于鸡胚绒毛尿囊膜的MPCs诱导并参与了新血管形成。所有这些特征在间充质终末分化的P2-MSCs中均消失，表明这两个分化谱系有明确的分离。
我们的结果证实了MPCs的真正血管生成潜力，并表明报道的MSC培养物的高变异性，这是关于MSC血管生成潜力争议的原因，可能与迄今为止在不同培养条件下共分离的MPCs的可变百分比相关。
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