Are MSCs angiogenic cells? New insights on human nestin-positive bone marrow-derived multipotent cells

Abstract

Recent investigations have made considerable progress in the understanding of tissue regeneration driven by mesenchymal stromal cells (MSCs). Data indicate the anatomical location of MSC as residing in the “perivascular” space of blood vessels dispersed across the whole body. This histological localization suggests that MSCs contribute to the formation of new blood vessels in vivo. Indeed, MSCs can release angiogenic factors and protease to facilitate blood vessel formation and in vitro are able to promote/support angiogenesis. However, the direct differentiation of MCSs into endothelial cells is still matter of debate. Most of the conflicting data might arise from the presence of multiple subtypes of cells with heterogeneous morpho functional features within the MSC cultures. According to this scenario, we hypothesize that the presence of the recently described Mesodermal Progenitor Cells (MPCs) within the MSCs cultures is responsible for their variable angiogenic potential. Indeed, MPCs are Nestin-positive CD31-positive cells exhibiting angiogenic potential that differentiate in MSC upon proper stimuli. The ISCT criteria do not account for the presence of MPC within MSC culture generating confusion in the interpretation of MSC angiogenic potential. In conclusion, the discovery of MPC gives new insight in defining MSC ancestors in human bone marrow, and indicates the tunica intima as a further, and previously overlooked, possible additional source of MSC.

Isolating Mesangiogenic Progenitor Cells (MPCs) from Human Bone Marrow

“…We also believe that most controversies about MSC angiogenic potential could be related to the heterogeneous composition of expanded cultures consisting of sub-populations of MPCs and MSCs in variable percentages 23 .…”

Study of the involvement of allogeneic MSCs in bone formation using the model of transgenic mice

“…48 But despite the great number of studies in vitro and in vivo, the angiogenic potential of MSCs remains controversial. 49 In this study we report preliminary results indicating a possibility of vessel formation from seeded MSCs, without requiring cell cultivation under controlled conditions. This result may be explained by the fact that the differentiation potential of MSCs is variable.…”

“…52 The morphology and differentiation potential of MSCs are dependent upon their source, the culture conditions (supplements, seeding density, number of passages, culture time) and the topographic localization within each colony. 49,53,54 The characteristics of the 3 D scaffolds, such as their chemical composition, topography, and roughness, have been also recognized as significant factors in affecting the cells' behavior. The heterogeneity and morpho-functional variability of MSCs and their microenvironment may explain some of the conflicting data in different research works.…”

“…51 It is possible to hypothesize that the angiogenic potential of MSCs is subjected to a similar variability that is influenced by the same factors. 49 In general, there are many parameters that can affect the functions and behavior of MSCs. Cultures of MSCs are very heterogeneous, even within the same colony.…”

“…This variability is observed between different donors and between different colonies obtained from the same subject. 49,50 Colonies from the same individual can be characterized as mono-, bi-or tripotent, based on their ability to differentiate into one, 2 or 3 types of tissue: osteogenic, chondrogenic and adipogenic lineages. Furthermore, repeated passages were found to reduce the multilineage differentiation ability.…”