Monitoring of cell therapy and assessment of cardiac function using magnetic resonance imaging in a mouse model of myocardial infarction.
We have developed a mouse severe combined immunodeficient (SCID) model of myocardial infarction based on permanent coronary artery occlusion that allows long-term functional analysis of engrafted human embryonic stem cell-derived cardiomyocytes, genetically marked with green fluorescent protein (GFP), in the mouse heart. We describe methods for delivery of dissociated cardiomyocytes to the left ventricle that minimize scar formation and visualization and validation of the identity of the engrafted cells using the GFP emission spectrum, and histological techniques compatible with GFP epifluorescence, for monitoring phenotypic changes in the grafts in vivo. In addition, we describe how magnetic resonance imaging can be adapted for use in mice to monitor cardiac function non-invasively and repeatedly. The model can be adapted to include multiple control or other cell populations. The procedure for a cohort of six mice can be completed in a maximum of 13 weeks, depending on follow-up, with 30 h of hands-on time.
van Laake
Linda W
LW
Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
Passier
Robert
R
Monshouwer-Kloots
Jantine
J
Nederhoff
Marcel G
MG
Ward-van Oostwaard
Dorien
D
Field
Loren J
LJ
van Echteld
Cees J
CJ
Doevendans
Pieter A
PA
Mummery
Christine L
CL
D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D017690:Cell Transplantation / Q000295:instrumentation / Q000379:methods; D002921:Cicatrix; D054059:Coronary Occlusion / Q000276:immunology / Q000628:therapy; D016616:Cryoultramicrotomy; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000166:cytology / Q000637:transplantation*; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins / Q000032:analysis; D006801:Humans; D016867:Immunocompromised Host; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D009203:Myocardial Infarction / Q000276:immunology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000637:transplantation
D049452:Green Fluorescent Proteins