Quantifying the Immune Response to a Tissue-Engineered Porcine Extracellular Matrix

Abstract

Aim: Structural valvular deterioration of xenogenic heart valve replacements is thought to be due to a chronic immune response. We sought to engineer porcine extracellular matrix that elicits minimal inflammatory immune response. Materials & methods: Whole blood, bone marrow and pericardium were collected from patients undergoing elective cardiac surgery. Porcine extracellular matrix was decellularized, reseeded with homologous mesenchymal stem cells and exposed to whole blood. Results: DAPI stain confirmed the absence of cells after decellularization, and presence of mesenchymal stem cells after recellularization. There was a significant reduction in IL-1β and TNF-α production in the recellularized matrix. Conclusion: Recellularization of porcine matrix is successful at attenuating the xenogenic immune response and may provide a suitable scaffold to address the current limitations of prosthetic heart valve replacements.

Graphical abstract

Plain language summary

Deterioration of tissue heart valve replacements is thought to be due to a chronic immune response. We sought to remove cells from a pig derived tissue and replace those cells with human stem cells to create a scaffold that results in a reduced immune response. Whole blood, bone marrow and pericardium were collected from patients undergoing elective cardiac surgery. The pig derived tissue had the cells removed, were replaced with human stem cells and exposed to whole blood. Tissue stain confirmed the absence of cells after removal, and presence of stem cells after replacement of cells. There was a significant reduction in markers of immune response in the recellularized tissue. Removal of cells from pig derived tissue and replacement with human stem cells is successful at reducing the immune response to animal tissue and may provide a suitable scaffold to address the current limitations of heart valve replacement options.

Tweetable abstract

Recellularization of an acellular porcine matrix is successful at reducing the xenogenic immune response and may provide a suitable scaffold to address the current limitations of heart valve replacements.

Keywords::

• heart valve replacements
• stem cells
• tissue engineered heart valves
• tissue engineering
• valvular heart disease

Author contributions

R EL-Andari: conceptualization, methodology, formal analysis, investigation, resources, data curation, writing, funding acquisition. SJ Bozso, JJH Kang, NM Fialka: conceptualization, methodology, investigation and writing. D Al-Adra, SR Meyer, MC Moon, DH Freed, J Nagendran, Jeevan Nagendran: conceptualization, methodology, validation, review and editing, project administration.

Financial & competing interests disclosure

This work was funded by the Department of Surgery Summer Studentship, University Hospital Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from each patient before collection of tissue samples.

Additional information

Funding

This work was funded by the Department of Surgery Summer Studentship, University Hospital Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.