Small-diameter tissue engineered vascular grafts (TEVGs) that incorporate autologous cells may provide an immuno-compatible treatment solution for patients with cardiovascular disease. We and others have shown that mesenchymal stem cells can promote remodeling of a biodegradable scaffold into native-like tissue that includes important vascular matrix proteins, such as collagen and elastin, and cells which contribute to vascular homeostasis, such as vascular smooth muscle cells and endothelial cells. Most recently, we have created TEVGs in this manner using adipose-derived mesenchymal stem cells from human donors. This application will address three critical barriers to translation of our current TEVG technology to the clinic. First, in our current TEVG paradigm, adipose-derived stem cells (AD-MSCs) are culture-expanded before seeding into biodegradable scaffolds. This presents a concern for the cells transforming or becoming contaminated, and also could represent significant costs with respect to personnel and materials. In addition, the presence of animal-sourced culture media supplements is a regulatory hurdle for any biological technology. Second, while the dynamic culture of a seeded graft for 48 hours - also part of our current TEVG protocol - is rapid compared to alternate approaches, it carries the same costs and risks as stated above for cell culture. Finally, our current TEVG has been optimized as an aortic interposition graft in the rat. Creating human-sized TEVG constructs for clinical translation wil require scale-up of at least one important process: seeding of cells into the scaffold. To address these concerns and advance our TEVG technology closer toward clinical feasibility, we propose the following three Specific Aims: 1) Evaluate the potential of using cells directly harvested from the stromal vascular fraction (SVF) immediately following liposuction (i.e., without time in culture) for fabricating our TEVG; 2) Eliminate the need for in-vitro bioreactor culture of our seeded construct to yield a TEVG that is safely and rapidly fabricated and ready to implant; and 3) Develop a new bulk-seeding device with the ability to deliver cells at high efficiency into human-sized scaffolds. Upon completion of this study, we expect to have developed an innovative bedside TEVG fabrication strategy using an alternative human adipose-derived cell source and a novel bulk-seeding device for long tubular scaffolds, and requiring no in vitro culture period. This will provide the basis of a new, innovative paradigm in vascular tissue engineering by eliminating significant regulatory barriers to clinical translation.
We will evaluate cells obtained from the fat of human subjects as a component of a tissue engineered blood vessel. If this work is successful, it could lead to an effective new arterial bypass graft that could be fabricated from a patient's fat cells t the bedside, and potentially implanted during the same hospital stay.
| Haskett, Darren G; Saleh, Kamiel S; Lorentz, Katherine L et al. (2018) An exploratory study on the preparation and evaluation of a ""same-day"" adipose stem cell-based tissue-engineered vascular graft. J Thorac Cardiovasc Surg 156:1814-1822.e3 |
| Krawiec, Jeffrey T; Liao, Han-Tsung; Kwan, LaiYee Lily et al. (2017) Evaluation of the stromal vascular fraction of adipose tissue as the basis for a stem cell-based tissue-engineered vascular graft. J Vasc Surg 66:883-890.e1 |
