Vascular engineering seeks to design and construct functional blood vessels comprising endothelial cells (ECs) and perivascular cells (PCs), with the ultimate goal of clinical translation. While EC behavior has been extensively investigated, PCs play an equally significant role in the development of novel regenerative strategies, providing functionality and stability to vessels. The two major classes of PCs are vascular smooth muscle cells (vSMCs) and pericytes; vSMCs can be further sub-classified as either contractile or synthetic. The inclusion of these cell types is crucial for successful regeneration of blood vessels. Furthermore, understanding distinctions between vSMCs and pericytes will enable improved therapeutics in a tissue-specific manner. Here we focus on the approaches and challenges facing the use of PCs in vascular regeneration, including their characteristics, stem cell sources, and interactions with ECs. Finally, we discuss biochemical and microRNA (miR) regulators of PC behavior and engineering approaches that mimic various cues affecting PC function.
"vSMCs surround larger vessels such as arteries and veins, whereas pericytes typically surround smaller microvessels and capillaries (Alberts et al., 2002). The disparate vessel locations for each perivascular cell type suggest that further differences exist that should be investigated and better understood in vitro in order to appropriately rebuild blood vessels for therapeutic applications (Dar and Itskovitz-Eldor, 2013; Wanjare et al., 2013b). As the vasculature's support system, perivascular cells are primarily responsible for imparting contractility and producing and depositing extracellular matrix (ECM) proteins. "
[Show abstract][Hide abstract] ABSTRACT: Distinguishing between perivascular cell types remains a hurdle in vascular biology due to overlapping marker expressions and similar functionalities. Clarifying and defining heterogeneities in vitro among perivascular cells could lead to improved cell-based tissue regeneration strategies and a better understanding of human developmental processes. We studied contractile vascular smooth muscle cells (vSMCs), synthetic vSMCs, and pericytes derived from a common human pluripotent stem cell source. Using in vitro cultures, we show unique cell morphology, subcellular organelle organization (namely endoplasmic reticulum, mitochondria, and stress fibers), and expression of smooth muscle myosin heavy chain and elastin for each cell type. While differences in extracellular matrix deposition and remodeling were less pronounced, the multipotency, in vivo, migratory, invasion, and contractile functionalities are distinctive for each cell type. Overall, we define a repertoire of functional phenotypes in vitro specific for each of the human perivascular cell types, enabling their study and use in basic and translational research.
"Since the blood flow within a vessel is directly proportional to its diameter (Poiseuille 1840), they represent an important cell population for tissue homeostasis in various organs (Am et al. 2013; Itoh and Suzuki 2012). Moreover, the control mechanisms behind this are not quite clear, since pericytes in vitro and in vivo show various morphological and molecular-biological phenotypes (Wanjare et al. 2013) and therefore possibly various functions. Unequivocally, to identify a certain cell population, various characteristics are used. "
[Show abstract][Hide abstract] ABSTRACT: Pericytes are contractile cells that surround blood vessels. When contracting, they change the diameter of the vessel and therefore influence blood flow homeostasis; however, mechanisms controlling pericyte action are less well understood. Since blood flow regulation per se is controlled by the autonomic nervous system, the latter might also be involved in pericyte action. Hence, rat choroidal pericytes were analyzed for such a connection by using appropriate markers. Rat choroidal wholemounts and sections were prepared for immunohistochemistry of the pericyte marker chondroitin-sulfate-proteoglycan (NG2) and the pan-neuronal marker PGP9.5 or of tyrosine hydroxylase (TH), vasoactive intestinal polypeptide (VIP) and choline acetyl transferase (ChAT). Additionally, PGP9.5 and TH were analyzed in the choroid of DCX-dsRed2 transgenic rats, displaying red-fluorescent perivascular cells and serving as a putative model for studying pericyte function in vivo. Confocal laser-scanning microscopy revealed NG2-immunoreactive cells and processes surrounding the blood vessels. These NG2-positive cells were not co-localized with PGP9.5 but received close appositions of PGP9.5-, TH-, VIP- and ChAT-immunoreactive boutons and fibers. In the DCX-dsRed2 transgenic rat, PGP9.5 and TH were also densely apposed on the dsRed-positive cells adjacent to blood vessels. These cells were likewise immunoreactive for NG2, suggesting their pericyte identity. In addition to the innervation of vascular smooth muscle cells, the close relationship of PGP9.5 and further sympathetic (TH) and parasympathetic (VIP, ChAT) nerve fibers on NG2-positive pericytes indicated an additional target of the autonomic nervous system for choroidal blood flow regulation. Similar findings in the DCX-dsRed transgenic rat indicate the potential use of this animal model for in vivo experiments revealing the role of pericytes in blood flow regulation.
Cell and Tissue Research 12/2013; 356(1). DOI:10.1007/s00441-013-1769-5 · 3.57 Impact Factor
"Wanjare et al.  review the role of perivascular cells in blood vessel regeneration . Inclusion of perivascular cells in engineered blood vessels and understanding perivascular interactions with endothelial cells will be crucial in vascularizing stem cellderived tissue constructs. "
[Show abstract][Hide abstract] ABSTRACT: Stem cell engineering - discovery, diagnostics and therapies: This Special Issue is edited by Brenda Ogle and Sean Palecek and is based on presentations from the Third International Conference on Stem Cell Engineering, co-sponsored by the Society of Biological Engineering and the International Society for Stem Cell Research, held in Seattle, WA from April 29-May 2, 2012.
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