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

Abstract

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.

Future Perspectives on the Role of Stem Cells and Extracellular Vesicles in Vascular Tissue Regeneration

“…Bone marrow derived MSCs (BM-MSCs), purified from BM-MNCs, have demonstrated favorable preclinical findings in TEVGs ( 45 – 47 ). Similarly, adipose derived MSCs (ADMSCs) ( 48 , 55 ) and muscle derived MSCs ( 49 , 56 ) have been used in TEVG studies. Studies employing pericytes are also included in this review ( 50 ) as they have been shown to express MSC markers and display the capacity for tri-lineage differentiation [as reviewed in Crisan et al ( 57 )].…”

Mesenchymal stromal cells’ role in tumor microenvironment: involvement of signaling pathways

“…For instance, MSCs regulate chemotaxis, activation, function, and survival of neutrophils via an IL-6-STAT3-ERK1/2 signaling cascade in gastric cancer and related solid cancers 99,131 . These MSC-primed neutrophils promote the differentiation of normal MSCs into CAFs 131 .…”

Development of a Semi-Automated, Bulk Seeding Device for Large Animal Model Implantation of Tissue Engineered Vascular Grafts

“…The design of our novel bulk seeding device for large, "human-sized" scaffolds was first conceived during the doctoral dissertation work of Soletti (2008). It is based on our lab's previously published and validated custom rotational vacuum seeding device which has been used to produce TEVGs for small animal testing (Nieponice et al, 2010;Soletti et al, 2011;Krawiec et al, 2016Krawiec et al, , 2017Haskett et al, 2018). The common concept is to achieve bulk seeding of rotating, porous, tubular scaffolds via local luminal delivery of cells under applied vacuum.…”

“…The advancement of tissue engineered vascular grafts (TEVGs) in recent years, and their ability to form functional neo-vessels, presents as a promising clinical option for the treatment of vascular disease (Cunnane et al, 2018). TEVGs often incorporate cells into biodegradable scaffolds through various cell-seeding techniques (Villalona et al, 2010;Weinbaum et al, 2020), and the presence of cells has demonstrated improved TEVG patency rates through reduced thrombosis and stenosis (Nieponice et al, 2010;Soletti et al, 2011;Krawiec et al, 2016Krawiec et al, , 2017Haskett et al, 2018).…”