Article

Perivascular cells in blood vessel regeneration.

Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences-Oncology Center and Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, MD, USA.
Biotechnology Journal (Impact Factor: 3.71). 04/2013; 8(4):434-47. DOI: 10.1002/biot.201200199
Source: PubMed

ABSTRACT 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.

0 Followers
 · 
87 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Tissue engineered constructs are rendered useless without a functional vasculature owing to a lack of nutrients and oxygen. Cell-based approaches to reconstruct blood vessels can yield structures that mimic native vasculature and aid transplantation. Vascular derivatives of human induced pluripotent stem cells (hiPSCs) offer opportunities to generate patient specific therapies and potentially provide unlimited amounts of vascular cells. To be used in engineered vascular constructs and confer therapeutic benefit, vascular derivatives must exhibit additional key properties including ECM production to confer structural integrity and growth factor production to facilitate integration. In this study, we examine the hypothesis that vascular cells derived from hiPSCs exhibit these critical properties to facilitate their use in engineered tissues. Human iPSCs were co-differentiated toward early vascular cells (EVCs), a bicellular population of endothelial cells (ECs) and pericytes under varying low oxygen differentiation conditions; subsequently ECs were isolated and passaged. We found that EVCs differentiated under low oxygen conditions produced copious amounts of collagen IV and fibronectin as well vascular endothelial growth factor and angiopoietin 2. EVCs differentiated under atmospheric conditions did not demonstrate such abundant ECM expression, but exhibited greater expression of angiopoietin 1. Isolated ECs could proliferate up to three passages while maintaining EC marker vascular endothelial cadherin. Isolated ECs demonstrated an increased propensity to produce ECM compared to their EVC correlates and took on an arterial-like fate. These findings illustrate that hiPSC vascular derivates hold great potential for therapeutic use and should continue to be a preferred cell source for vascular construction.
    Stem Cells and Development 09/2014; DOI:10.1089/scd.2014.0377 · 4.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Perivascular multipotent cells, pericytes, contribute to the generation and repair of various tissues in response to injury. They are heterogeneous in their morphology, distribution, origin and markers, and elucidating their molecular and cellular differences may inform novel treatments for disorders in which tissue regeneration is either impaired or excessive. Moreover, these discoveries offer novel cellular targets for therapeutic approaches to many diseases. This review discusses recent studies that support the concept that pericyte subtypes play a distinctive role in myogenesis, neurogenesis, adipogenesis, fibrogenesis and angiogenesis.
    Clinical Science 01/2015; 128(2):81-93. DOI:10.1042/CS20140278 · 5.63 Impact Factor
  • Source
    [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.
    05/2014; 2(5):561-75. DOI:10.1016/j.stemcr.2014.03.004