59. humanized mouse model for assessing the human immune response to xenogeneic and allogeneic decellularized biomaterials

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
Introduction: Biomaterial effectiveness and safety depends on the human immune response, yet standard animal models provide limited representation of this response. We studied the use of a humanized mouse model, which generates multi-lineages of human immune cells, for evaluating the human immune response to xenogeneic and allogeneic extracellular matrix (ECM) based biomaterials. Methods: Humanized mice were generated by implanting human liver, thymus and CD34+ fetal liver cells into NOD/SCID/&#947; immunodeficient mice. Humanized and Balb/c mice were subcutaneously injected with myocardial ECM hydrogels derived from decellularized porcine and human tissue, and a nondecellularized control. Injections isolated at 7 days were assessed for pro-remodeling versus pro-inflammatory T-helper cell (Th2/Th1) and macrophage (M2/M1) response by cell infiltration with immunohistochemistry and polarization with PCR (n=8-12). Results are reported as mean±SEM with p<0.05 considered significant. Results: Significantly greater Th-cell infiltration into porcine versus human hydrogels (53.6±9.9 versus 14.3±6.9 cells/mm2) was observed in humanized mice with no significant difference between these materials in Balb/c mice. M2 trends were determined for decellularized versus nondecellularized materials. Gene expression ratio for polarization demonstrated significant Th2 and trending M2 profiles for porcine (2.95±0.15, 1.6±0.4) versus nondecellularized (1.0±0.2, 1.0±0.2) with trends for human hydrogels (1.36±0.2, 0.84±0.2). Conclusions: Humanized mice uniquely responded to porcine myocardial ECM hydrogels with greater Th-cell infiltration, and a stronger Th2 and M2 profile compared to human and nondecellularized, suggesting a greater pro-remodeling response to the xenogeneic biomaterial. These results demonstrate this model?s usefulness for assessing the degree and polarization of the human immune response to biomaterial therapies.

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

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