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Characterizing human pluripotent-stem-cell-derived vascular cells for tissue engineering applications.

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 extracellular matrix (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. hiPSCs were codifferentiated 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 as 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 the EC marker vascular endothelial cadherin. Isolated ECs demonstrated an increased propensity to produce ECM compared with 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.

SUBMITTER: Kusuma S

PROVIDER: S-EPMC4313392 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Characterizing human pluripotent-stem-cell-derived vascular cells for tissue engineering applications.

Kusuma Sravanti S Facklam Amanda A Gerecht Sharon S

Stem cells and development 20141027 4

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 the ...[more]

PMID: 25233291

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Project description:Diffusion is a limiting factor in regenerating large tissues (100-200 ?m) due to reduced nutrient supply and waste removal leading to low viability of the regenerating cells as neovascularization of the implant by the host is a slow process. Thus, generating prevascularized tissue engineered constructs, in which endothelial (ECs) and mural (MCs) cells, such as smooth muscle cells (SMCs), and pericytes (PCs), are preassembled into functional in vitro vessels capable of rapidly connecting to the host vasculature could overcome this obstacle. Toward this purpose, using feeder-free and low serum conditions, we developed a simple, efficient and rapid in vitro approach to induce the differentiation of human pluripotent stem cells-hPSCs (human embryonic stem cells and human induced pluripotent stem cells) to defined SMC populations (contractile and synthetic hPSC-SMCs) by extensively characterizing the cellular phenotype (expression of CD44, CD73, CD105, NG2, PDGFR?, and contractile proteins) and function of hPSC-SMCs. The latter were phenotypically and functionally stable for at least 8 passages, and could stabilize vessel formation and inhibit vessel network regression, when co-cultured with ECs in vitro. Subsequently, using a methylcellulose-based hydrogel system, we generated spheroids consisting of EC/hPSC-SMC (vascular organoids), which were extensively phenotypically characterized. Moreover, the vascular organoids served as focal starting points for the sprouting of capillary-like structures in vitro, whereas their delivery in vivo led to rapid generation of a complex functional vascular network. Finally, we investigated the vascularization potential of these vascular organoids, when embedded in hydrogels composed of defined extracellular components (collagen/fibrinogen/fibronectin) that can be used as scaffolds in tissue engineering applications. In summary, we developed a robust method for the generation of defined SMC phenotypes from hPSCs. Fabrication of vascularized tissue constructs using hPSC-SMC/EC vascular organoids embedded in chemically defined matrices is a significant step forward in tissue engineering and regenerative medicine.

Dataset Information

Characterizing human pluripotent-stem-cell-derived vascular cells for tissue engineering applications.

Publications

Characterizing human pluripotent-stem-cell-derived vascular cells for tissue engineering applications.

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