Novel Approaches for Enhancing Cell Survival and Function in Vivo

Authors

Ou Wang, University of Nebraska-LincolnFollow

First Advisor

Yuguo Lei

Second Advisor

William H. Velander

Date of this Version

Winter 12-3-2021

Citation

Wang, O. (2021). Novel Approaches For Enhancing Cell Survival And Function In Vivo [Doctoral dissertation, University of Nebraska-Lincoln].

Comments

A DISSERTATION Presented to the Faculty of The Graduate College at the University of Nebraska In Partial Fulfillment of Requirements For the degree of Doctor of Philosophy, Major: Engineering (Biomedical Engineering), Under the Supervision of Professors Yuguo Lei & William H. Velander. Lincoln, Nebraska: December 2021

Copyright © 2021 Ou Wang

Abstract

FDA has approved several cell-based therapeutics and hundreds of cell therapy clinical trials are ongoing. Cells will be a significant type of medicine after small molecule and protein drugs. However, several obstacles need to be addressed to achieve the widespread use of cellular therapeutics. The first challenge is the low efficacy of cell transplantation due to low retention, survival, integration, and function of cells in vivo. The second challenge is producing a massive number of cells for clinical treatment with cost-effectively and reproducibly technologies.

In this thesis, we proposed and investigated two approaches to address these challenges. To begin with, we engineered two novel biomaterials to deliver cells to enhance their in vivo retention and function. The first biomaterial is a recombinant fibrin matrix which significantly improved cell delivery efficiency and safety. The second biomaterial is a novel γγ’F1:pFN complex fibrin matrix, which enhanced cell culture and improved wound healing. In the second approach, we engineered injectable, microscale, 3D tissues to address the challenges. Brown adipose microtissues were prepared and injected to alleviate obesity and associated type 2 diabetes mellitus(T2DM). In addition, we showed a novel, scalable and cell-friendly cell culture technology (AlgTubes) for scalable microtissue manufacturing. Animal cells were used for preliminary study and can be used for food science to produce cultured meat. This technology has the potential to produce any cell therapy-related cell types in the future. Finally, we also systematically proposed engineering a physiologically relevant microenvironment for large-scale therapeutic cell and microtissue production.

Advisors: Yuguo Lei &William H. Velander