47. HUMANIZED MOUSE MODEL FOR THE STUDY OF THE HUMAN IMMUNE RESPONSE TO XENOGENEIC AND ALLOGENEIC BIOMATERIAL THERAPIES

Department: Bioengineering
Faculty Advisor(s): Karen L. Christman

Primary Student
Name: Raymond M Wang
Email: rmw010@ucsd.edu
Phone: 617-538-6971
Grad Year: 2019

Abstract
Advancements in tissue engineering have developed novel therapies with promising preclinical results for treating chronic tissue injuries and diseases. However, preclinical studies often utilize standard and/or immune deficient animal models despite numerous unique characteristics of human immune cells that have lead to harmful results in clinical trials. To study the complex cellular interactions that contribute to the human immune response, humanized mice have been developed from NOD/SCID/γnull immunodeficient mice surgically implanted with human liver and thymus, and injected with CD34+ human fetal liver cells. These mice generate the multi-lineages of human immune cells and have demonstrated similar human immune rejection of incompatible embryonic stem cell allografts. Utilizing injectable extracellular matrix hydrogels derived from decellularized porcine and human myocardium, we used this model to study the human immune response to xenogeneic and allogeneic decellularized biomaterials. For general evaluation, material was subcutaneously injected into the dorsal region of mice, and isolated at early and mid time points to determine short-term immune cell dynamics. Analysis by immunostaining and qRT-PCR of macrophages and T-cells polarization markers, and immune cytokines demonstrated that fully decellularized materials elicit a pro-remodeling response while a strong negative response is observed when cellular debris is still present. Cellular infiltration into the xenogeneic porcine myocardial matrix was also greater suggesting a tissue source specific response. However, the response was not more inflammatory compared to allogeneic material likely due to removal of xenogeneic epitopes known to elicit strong negative immune responses and/or rejection. Based on comparisons with other standard mouse models, humanized mice were able to respond differentially to xenogeneic and allogeneic biomaterials, and therefore could be a useful model to study how human immune cells react to biomaterial therapies.

Industry Application Area(s)
Life Sciences/Medical Devices & Instruments | Materials

Related Links:

  1. http://christman.eng.ucsd.edu/home

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