A Cautionary Tale for Autologous Vascular Tissue Engineering: Impact of Human Demographics on the Ability of Adipose-Derived Mesenchymal Stem Cells to Recruit and Differentiate into Smooth Muscle Cells

KrawiecJeffrey, T; Weinbaum, Justin S.; M., St. CroixClaudette; PhillippiJulie, A; Watkins, Simon C.; Peter, RubinJ.; VorpDavid, A

doi:10.1089/ten.tea.2014.0208

Cited by 32 publications

(41 citation statements)

References 108 publications

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“…Additionally, patients who need small‐diameter TEBVs often have the disease like diabetes or atherosclerosis,39, 40 so we need further study the inflammatory condition and resolution ways of small‐diameter TEBVs in these disease state.…”

Section: Discussionmentioning

confidence: 99%

Netrin‐1 Promotes Inflammation Resolution to Achieve Endothelialization of Small‐Diameter Tissue Engineering Blood Vessels by Improving Endothelial Progenitor Cells Function In Situ

Wan

Liu

et al. 2017

Advanced Science

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The transplant of small‐diameter tissue engineering blood vessels (small‐diameter TEBVs) (<6 mm) in vascular replacement therapy often fails because of early onset thrombosis and long‐standing chronic inflammation. The specific inflammation state involved in small‐diameter TEBVs transplants remains unclear, and whether promoting inflammation resolution would be useful for small‐diameter TEBVs therapy need study. The neural protuberant orientation factor 1 (Netrin‐1) is found present in endothelial cells of natural blood vessels and has anti‐inflammatory effects. This work generates netrin‐1‐modified small‐diameter TEBVs by using layer‐by‐layer self‐assembly to resolve the inflammation. The results show that netrin‐1 reprograms macrophages (MΦ) to assume an anti‐inflammatory phenotype and promotes the infiltration and subsequent efflux of MΦ from inflamed sites over time, which improves the local microenvironment and the function of early homing endothelial progenitor cells (EPCs). Small‐diameter TEBVs modified by netrin‐1 achieve endothelialization after 30 d and retain patency at 14 months. These findings suggest that promoting the resolution of inflammation in time is necessary to induce endothelialization of small‐diameter TEBVs and prevent early thrombosis and problems associated with chronic inflammation. Furthermore, this work finds that the MΦ‐derived exosomes can target and regulate EPCs, which may serve as a useful treatment for other inflammatory diseases.

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Section: Discussionmentioning

confidence: 99%

Netrin‐1 Promotes Inflammation Resolution to Achieve Endothelialization of Small‐Diameter Tissue Engineering Blood Vessels by Improving Endothelial Progenitor Cells Function In Situ

Wan

Liu

et al. 2017

Advanced Science

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“…Adipose-derived cell fractions were isolated from non-diabetic human patients using previously described methods 12, 15 . Informed consent was not required due to the University of Pittsburgh IRB determination that the study involved solely deidentified waste from the liposuction procedure.…”

Section: Methodsmentioning

confidence: 99%

“…These cells will be referred to in this manuscript as SVF. For this study, a cultured AD-MSC control was established from each SVF donor by passage expanding a portion of the SVF four times 9, 15 . Using this procedure, SVF was available for graft fabrication within a matter of hours whereas AD-MSCs took upwards of 4 weeks.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of the stromal vascular fraction of adipose tissue as the basis for a stem cell-based tissue-engineered vascular graft

Krawiec

Liao

Kwan

et al. 2017

Journal of Vascular Surgery

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Objective One of the rate-limiting barriers within the field of vascular tissue engineering is the lengthy fabrication time associated with expanding appropriate cell types in culture. One particularly attractive cell type for this purpose is the adipose-derived mesenchymal stem cell (AD-MSC), which is abundant and easily harvested from liposuction procedures. However, even this cell type has its drawbacks including the required culture period for expansion which could pose risks of cellular transformation or contamination. Eliminating culture entirely would be ideal to avoid these concerns. In this study we utilized the raw population of cells obtained after digestion of human liposuction aspirates – known as the stromal vascular fraction (SVF) – as an abundant, culture-free cell source for tissue engineered vascular grafts (TEVG). Methods SVF cells and donor-paired cultured AD-MSCs were first assessed for their abilities to differentiate into vascular smooth muscle cells (SMCs) after angiotensin II stimulation and to secrete factors (e.g. conditioned media) that promote SMC migration. Next, both cell types were incorporated into TEVG scaffolds, implanted as an aortic graft in a Lewis rat model, and assessed for their patency and composition. Results In general, cells from human SVF were able to perform the same functions as AD-MSCs isolated from the same donor via culture expansion. Specifically, cells within the SVF performed two important functions, namely, they were able to differentiate into SMCs (SVF calponin expression: 16.4% ± 7.7 vs. AD-MSC: 19.9% ± 1.7) and could secrete pro-migratory factors (SVF migration rate relative to control: 3.1 ± 0.3 vs. AD-MSC: 2.5 ± 0.5). Additionally, SVF was also capable of being seeded within biodegradable, elastomeric, porous scaffolds that, when implanted in vivo for 8 weeks, generated patent TEVGs (SVF: 83% patency vs. AD-MSC: 100% patency) populated with primary vascular components (e.g. SMCs, endothelial cells, collagen, and elastin). Conclusion Human adipose tissue can be utilized as a culture-free cell source to create TEVGs, laying the groundwork for the rapid production of cell-seeded grafts.

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“…The quality of the ASC is related to the health condition of the donor. Cells from elderly and diabetic people have a reduced ability to promote SMC migration and differentiation potential toward SMCs [Krawiec et al, 2015]. A baculovirus-transduced VEGF-expressing ASC sheet for the treatment of myocardial infarction was proven to effectively prevent myocardial wall thinning, suppress myocardial fibrosis and enhance blood vessel formation in a rabbit myocardial infarction model [Yeh et al, 2014].…”

Section: Uc-mscs and Ascsmentioning

confidence: 99%

Scaffolds and Cell-Based Tissue Engineering for Blood Vessel Therapy

Hsia

Yao

Chen

et al. 2016

Cells Tissues Organs

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The increasing morbidity of cardiovascular diseases in modern society has made it crucial to develop a small-caliber blood vessel. In the absence of appropriate autologous vascular grafts, an alternative prosthesis must be constructed for cardiovascular disease patients. The aim of this article is to describe the advances in making cell-seeded cardiovascular prostheses. It also discusses the combinations of types of scaffolds and cells, especially autologous stem cells, which are suitable for application in tissue-engineered vessels with the favorable properties of mechanical strength, antithrombogenicity, biocompliance, anti-inflammation, fatigue resistance and long-term durability. This article highlights the advancements in cellular tissue-engineered vessels in recent years.

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A Cautionary Tale for Autologous Vascular Tissue Engineering: Impact of Human Demographics on the Ability of Adipose-Derived Mesenchymal Stem Cells to Recruit and Differentiate into Smooth Muscle Cells

Cited by 32 publications

References 108 publications

Netrin‐1 Promotes Inflammation Resolution to Achieve Endothelialization of Small‐Diameter Tissue Engineering Blood Vessels by Improving Endothelial Progenitor Cells Function In Situ

Netrin‐1 Promotes Inflammation Resolution to Achieve Endothelialization of Small‐Diameter Tissue Engineering Blood Vessels by Improving Endothelial Progenitor Cells Function In Situ

Evaluation of the stromal vascular fraction of adipose tissue as the basis for a stem cell-based tissue-engineered vascular graft

Scaffolds and Cell-Based Tissue Engineering for Blood Vessel Therapy

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