Abstract
BackgroundMesangiogenic 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.MethodsIn 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.ResultsMPCs 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.ConclusionOur 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.
Highlights
Mesangiogenic progenitor cells (MPCs) have shown the ability to differentiate in-vitro toward mesenchymal stromal cells (MSCs) as well as angiogenic potential
MPC isolation, characterization, and mesengenic differentiation MPCs were consistently isolated from human bone marrow in selective culture conditions [5], with an average yield of 1.2 ± 0.7% (n = 12)
The consistent activation of FLT-4 (VEGFR3) gene expression in sprouted MPCs sustains the idea of the “early stage” because this receptor has been detected in the embryonic veins immediately after differentiation from the angioblast
Summary
Mesangiogenic progenitor cells (MPCs) have shown the ability to differentiate in-vitro toward mesenchymal stromal cells (MSCs) as well as angiogenic potential. In a research study aimed to isolate human bone marrowderived mesenchymal stromal cells (MSCs) for clinical applications we identified a novel cell population, isolated in pooled human AB serum (PhABS) supplemented medium. We named these cells mesodermal progenitor cells (MPCs) for their ability to retain mesengenic, angiogenic, and apparently cardiomyogenic potential after multiple steps of differentiation [1]. A revised nomenclature for these cells was proposed due to the lack of convincing data about genuine differentiation toward cardiomyocytes These cells were renamed mesangiogenic progenitor cells, maintaining the acronym MPCs [2]. They were characterized by their distinctive gene expression profile [3] and growing/adhesion properties [4]
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