Early Stem Cell Engraftment Predicts Late Cardiac Functional Recovery

Author:

Liu Junwei1,Narsinh Kazim H.1,Lan Feng1,Wang Li1,Nguyen Patricia K.1,Hu Shijun1,Lee Andrew1,Han Leng1,Gong Yongquan1,Huang Mei1,Nag Divya1,Rosenberg Jarrett1,Chouldechova Alexandra1,Robbins Robert C.1,Wu Joseph C.1

Affiliation:

1. From the Department of Cardiothoracic Surgery (Y.G., R.C.R.), Department of Medicine, Division of Cardiology (J.L., K.H.N., F.L., L.W., P.K.N., S.H., A.L., L.H., M.H., J.C.W.), the Department of Radiology (J.L., K.H.N., F.L., L.W., P.K.N., S.H., A.L., L.H., M.H., D.N., J.R., J.C.W.), the Stanford Cardiovascular Institute (R.C.R., J.C.W.), and the Institute for Stem Cell Biology and Regenerative Medicine (R.C.R., J.C.W.), Stanford University School of Medicine, Stanford, CA; the Department of...

Abstract

Background— Human cardiac progenitor cells have demonstrated great potential for myocardial repair in small and large animals, but robust methods for longitudinal assessment of their engraftment in humans is not yet readily available. In this study, we sought to optimize and evaluate the use of positron emission tomography (PET) reporter gene imaging for monitoring human cardiac progenitor cell (hCPC) transplantation in a mouse model of myocardial infarction. Methods and Results— hCPCs were isolated and expanded from human myocardial samples and stably transduced with herpes simplex virus thymidine kinase (TK) PET reporter gene. Thymidine kinase-expressing hCPCs were characterized in vitro and transplanted into murine myocardial infarction models (n=57). Cardiac echocardiographic, magnetic resonance imaging and pressure-volume loop analyses revealed improvement in left ventricular contractile function 2 weeks after transplant (hCPC versus phosphate-buffered saline, P <0.03). Noninvasive PET imaging was used to track hCPC fate over a 4-week time period, demonstrating a substantial decline in surviving cells. Importantly, early cell engraftment as assessed by PET was found to predict subsequent functional improvement, implying a “dose–effect” relationship. We isolated the transplanted cells from recipient myocardium by laser capture microdissection for in vivo transcriptome analysis. Our results provide direct evidence that hCPCs augment cardiac function after their transplantation into ischemic myocardium through paracrine secretion of growth factors. Conclusions— PET reporter gene imaging can provide important diagnostic and prognostic information regarding the ultimate success of hCPC treatment for myocardial infarction.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine,Radiology Nuclear Medicine and imaging

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