Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: Immune rejection of transplanted stem/progenitor cells is a major stumbling block in designing effective therapy for myocardial infarction (MI). Human neonatal cardiac progenitor cells (nCPCs) showed superior cardiac functional recovery compared to adult CPCs in immune competent rat MI model. However, molecular mechanisms underlying immune evasion by transplanted nCPCs in the infarcted myocardium was unexplored. Here, we demonstrate for the first-time the expression and function of CD47 in human nCPCs and its novel mechanism of immune evasion increases its regenerative potential in rat MI model.
*Methods: Cardiac functional outcome following nCPCs/aCPCs in rat MI model was measured by echocardiography. Transplanted cell retention, in vivo phagocytosis and CD68+ cells was assessed by immunohistochemistry. In vitro phagocytosis analysis for aCPCs/nCPCs were performed with THP-1 derived macrophages. THP-1 differentiated macrophages were validated for the expression of CD68 and absence of CD31. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for proteomic analysis of nCPCs and aCPCs. CD47 expression in nCPCs was blocked by anti-CD47/ siRNA transections/lenti-virus expressing CD47 shRNAs approaches. CD47 knock down efficiency by siRNA and lenti-virus were validated by immunoblot. Isotype antibody, scrambled siRNA and lentivirus expressing empty vector served as control.
*Results: Transplanted nCPCs showed significant increased cell retention, reduced phagocytosis and CD68+ cells compared to aCPCs in vivo rat MI model. Comparative proteomic analysis between nCPCs and aCPCs showed that CD47, a transmembrane protein highly up-regulated in nCPCs. Increased CD47 expression in nCPCs inhibited phagocytosis compared to aCPCs in vitro and in vivo (p<0.05). Further, CD47 blockade in nCPCs using anti-CD47, siRNA and shRNA lentiviral based approaches increased in vitro, in vivo phagocytosis, CD68+ cells and reduced cell retention and MI recovery in vivo.
*Conclusions: In conclusion, increased CD47 expression in nCPCs evade phagocytosis by CD47/SIRPα immune regulatory axis to demonstrates its immune evasion potential and its therapeutic applications in regenerative medicine.
To cite this abstract in AMA style:Gunasekaran M, Mishra R, Sharma S, Saha P, Wang L, Arfat MYasir, Davidson L, Fu X, Shah A, Abdullah M, Li D, Kaushal S. Novel Mechanism of Immune Evasion by Human Neonatal Cardiac Progenitor Cells Recovers Ailing Myocardium in Rat Myocardial Infarct Model [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/novel-mechanism-of-immune-evasion-by-human-neonatal-cardiac-progenitor-cells-recovers-ailing-myocardium-in-rat-myocardial-infarct-model/. Accessed April 18, 2021.
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