Abstract
Mesenchymal stem/stromal cells (MSCs) and MSC-like multipotent stem/progenitor cells have been widely investigated for regenerative medicine and deemed promising in clinical applications. In order to further improve MSC-based stem cell therapeutics, it is important to understand the cellular kinetics and functional roles of MSCs in the dynamic regenerative processes. However, due to the heterogeneous nature of typical MSC cultures, their native identity and anatomical localization in the body have remained unclear, making it difficult to decipher the existence of distinct cell subsets within the MSC entity. Recent studies have shown that several blood-vessel-derived precursor cell populations, purified by flow cytometry from multiple human organs, give rise to bona fide MSCs, suggesting that the vasculature serves as a systemic reservoir of MSC-like stem/progenitor cells. Using individually purified MSC-like precursor cell subsets, we and other researchers have been able to investigate the differential phenotypes and regenerative capacities of these contributing cellular constituents in the MSC pool. In this review, we will discuss the identification and characterization of perivascular MSC precursors, including pericytes and adventitial cells, and focus on their cellular kinetics: cell adhesion, migration, engraftment, homing, and intercellular cross-talk during tissue repair and regeneration.
Highlights
The availability of mesenchymal stem/stromal cells (MSCs) and MSC-like multipotent stem/progenitor cells marked a major milestone in stem cell therapies [1, 2]
Following the hypothesis that blood vessels throughout the body serve as a systemic reservoir of multipotent stem/progenitor cells, we and other researchers have identified, purified, and characterized distinct populations of MSC-like multilineage precursors from the vasculature of multiple human organs [17, 22]
We have previously demonstrated that when placed onto extracellular matrix (ECM)-coated plates, dissected fetal placental villi release a population of vascular cells, which possess high migratory activity and robust capacity to regenerate skeletal muscle fibers in dystrophic mice [70]
Summary
The availability of mesenchymal stem/stromal cells (MSCs) and MSC-like multipotent stem/progenitor cells marked a major milestone in stem cell therapies [1, 2]. Following the hypothesis that blood vessels throughout the body serve as a systemic reservoir of multipotent stem/progenitor cells, we and other researchers have identified, purified, and characterized distinct populations of MSC-like multilineage precursors from the vasculature of multiple human organs [17, 22]. These human blood vesselderived precursor cell subsets, including pericytes (PCs) [23], adventitial cells (ACs) [24], and myogenic endothelial cells (MECs) [25], can be isolated via fluorescence-activated cell sorting (FACS) based on their unique expression of cell surface antigens. Similar to BM-MSCs, MSCs derived from Wharton’s jelly exhibit plastic adherence, mesenchymal multipotency, and expression of CD10, CD13, CD29, CD44, CD73, CD90, CD105, and HLA-class I but are negative for CD11b, CD14, CD19, CD31, CD34, CD45, CD56, CD79, and HLA class II [45,46,47]
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