Tissue-Engineered Human Vascular Media Produced in Vitro by the Self-Assembly Approach Present Functional Properties Similar to Those of Their Native Blood Vessels

Abstract

We have developed a tissue-engineering approach for the production of a completely biological blood vessel from cultured human cells. In the present study, we took advantage of this tissue-engineering method to demonstrate that it can be used to reproduce the subtle differences in the expression of receptors present on the media of native human blood vessels. Indeed, a small percentage (3 of 18) of native human umbilical cord veins (HUCVs) responded to endothelin, the most powerful vasopressor agent known to date, via both endothelin A (ET(A)) and endothelin B (ET(B)) receptor activation. In contrast, most HUCVs tested responded to ET via ET(A) receptor activation only. Tissue-engineered vascular media (TEVM) were next reconstructed by using vascular smooth muscle cells (VSMCs) isolated and cultured from HUCVs expressing both ET(A) and ET(B) receptors to determine the functional integrity of our TEVM model. The reconstructed TEVM presents an endothelin response similar to that of respective HUCVs from which VSMCs were isolated. Reverse transcriptase polymerase chain reaction on TEVM reconstructed in vitro correlated these vasocontractile profiles by showing the presence of messenger RNA for both ET(A) and ET(B) receptors. Taken together with recently published results on TEVM expressing only ET(A) receptor, these results show that our reconstructed TEVM present a similar ET response profile as the blood vessel from which the VSMCs were isolated and cultured. These findings indicate that subtle differences, such as receptor expression, are preserved in the reconstructed tissue. Therefore, our TEVM offers a valuable human in vitro model with which to study the functionality of human blood vessels, such as their vasoactive response, or to perform pharmacologic studies.

Tissue engineering of a collagen-based vascular media

“…Cell sheet tissue-engineered vascular medias (TEVM) have been extensively tested through use of a comprehensive panel of agents, 6 as well as investigations of the endothelin system. 7 Despite issues with cell culture, vasoactivity has been seen in TEVM that used adult smooth muscle cells [8][9][10] as well as TEVM using umbilical cord derived, 6,7,11,12 bone marrow progenitor, 13 and neonatal cells. 14,15 One reason why few groups have demonstrated function is that obtaining the number of cells necessary to make a TEVM requires extensive passaging of cells.…”

Polyphenol-Stabilized Tubular Elastin Scaffolds for Tissue Engineered Vascular Grafts

“…12,13 Typical tissue engineering approaches employ scaffolds and cells brought together in such a way as to restore function and facilitate regeneration of the replaced tissue. Several methods have been reported, including a completely cellular approach, 14,15 use of decellularized tissues, [16][17][18] and combinations of cells with natural or synthetic scaffolds, 11,19 including promising biodegradable elastomeric polymers. 10,20,21 With few exceptions, tissue engineering approaches have relied on scaffolds to provide biological and mechanical support for cells.…”

Concise Review: Epidermal Grafting: The Case for Pluripotent Stem Cells

“…The possibility indeed emerges to start associating specifically chosen cell populations derived from pluripotent stem cell lines in organs, using combined material science and biotechnology. Such a combination has already proven instrumental in creating, for example, vascular elements out of plastic and cultured endothelial cells [37]. Skin substitutes grown out of pluripotent stem cells derivatives may also cover, in a first instance, cartilage-type prostheses for an ear or a nose.…”