Decellularization of Bovine Pericardium Reduces the Human Xenoreactive Immune Response

Student Researcher:
Jimmy Kang

Supervisor / Principle Investigator:
Jeevan Nagendran

Additional Authors:
Dr. Sabin Bozso
Dr. Darren Freed
Dr. Jayan Nagendran

MD Class of 2021

ABSTRACT

Background: Emerging evidence suggests bovine bioprosthetic valves used in cardiac surgery provoke a xenoreactive immune response that results in its deterioration. We aim to characterize the human immune response to decellularized bovine pericardium (BP) to determine its suitability as a xenograft scaffold for future tissue engineered heart valves.

Methods: We decellularized commercially available BP used in constructing bioprosthetic valves with 1% SDS and 1% Triton X-100 washes. Native BP was used as positive controls, and human pericardium and no tissue group exposure group were used as negative controls. We exposed the groups with 5ml of heparinized human blood mixed with 5ml of PBS in 15ml tubes and placed them inside of a 37C incubator. To quantify the immune response, we collected and analyzed blood and tissue samples of both groups after 3 days and 5 days of incubation.

Results: We show that decellularized BP elicited a decreased immune response resulting in a significant reduction of TNF-a and IFN-y production compared to native BP control. Furthermore, immunohistochemical stained sections of BP showed reduction in cellular infiltrates (CD3, CD68, plasma cells, neutrophils) in the decellularized group. Transmission and scanning electron microscopy also revealed intact extracellular matrix with no cell structures on the decellularized BP sections. The efficacy of decellularization was confirmed with DAPI-nuclei staining that showed a complete absence of nuclei on the decellularized BP compared to abundant cellularity of the control BP.

Conclusions: Taken together, our data suggest decellularization of xenograft tissue such as bovine pericardium can result in a significantly less pro-inflammatory cytokine production and a blunted human xenoreactive immune response with an intact extracellular matrix. As such, decellularized BP may be an effective xenograft scaffold for future tissue engineered heart valves utilizing autologous cells.

 
 

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