Comparison of transplantation of adipose tissue- and bone marrow-derived mesenchymal stem cells in the infarcted heart

TY - JOUR

T1 - Comparison of transplantation of adipose tissue- and bone marrow-derived mesenchymal stem cells in the infarcted heart

AU - van der Bogt, Koen E A

AU - Schrepfer, Sonja

AU - Yu, Jin

AU - Sheikh, Ahmad Y

AU - Hoyt, Grant

AU - Govaert, Johannes A

AU - Velotta, Jeffrey B

AU - Contag, Christopher H

AU - Robbins, Robert C

AU - Wu, Joseph C

PY - 2009/3/15

Y1 - 2009/3/15

N2 - BACKGROUND: Mesenchymal stem cells hold promise for cardiovascular regenerative therapy. Derivation of these cells from the adipose tissue might be easier compared with bone marrow. However, the in vivo fate and function of adipose stromal cells (ASC) in the infarcted heart has never been compared directly to bone marrow-derived mesenchymal cells (MSC).METHODS: ASC and MSC were isolated from transgenic FVB mice with a beta-actin promoter driving firefly luciferase and green fluorescent protein double fusion reporter gene, and they were characterized using flow cytometry, microscopy, bioluminescence imaging and luminometry. FVB mice (n=8 per group) underwent myocardial infarction followed by intramyocardial injection of 5x10(5) ASC, MSC, fibroblasts (Fibro, positive control), or saline (negative control). Cell survival was measured using bioluminescence imaging for 6 weeks and cardiac function was monitored by echocardiography and pressure-volume analysis. Ventricular morphology was assessed using histology.RESULTS: ASC and MSC were CD34(-), CD45(-), c-Kit(-), CD90(+), Sca-1(+), shared similar morphology and had a population doubling time of approximately 2 days. Cells expressed Fluc reporter genes in a number-dependent fashion as confirmed by luminometry. After cardiac transplantation, both cell types showed drastic donor cell death within 4 to 5 weeks. Furthermore, transplantation of either cell type was not capable of preserving ventricular function and dimensions, as confirmed by pressure-volume-loops and histology.CONCLUSION: This is the first study comparing the in vivo behavior of both cell types in the infarcted heart. ASC and MSC do not tolerate well in the cardiac environment, resulting in acute donor cell death and a subsequent loss of cardiac function similar to control groups.

AB - BACKGROUND: Mesenchymal stem cells hold promise for cardiovascular regenerative therapy. Derivation of these cells from the adipose tissue might be easier compared with bone marrow. However, the in vivo fate and function of adipose stromal cells (ASC) in the infarcted heart has never been compared directly to bone marrow-derived mesenchymal cells (MSC).METHODS: ASC and MSC were isolated from transgenic FVB mice with a beta-actin promoter driving firefly luciferase and green fluorescent protein double fusion reporter gene, and they were characterized using flow cytometry, microscopy, bioluminescence imaging and luminometry. FVB mice (n=8 per group) underwent myocardial infarction followed by intramyocardial injection of 5x10(5) ASC, MSC, fibroblasts (Fibro, positive control), or saline (negative control). Cell survival was measured using bioluminescence imaging for 6 weeks and cardiac function was monitored by echocardiography and pressure-volume analysis. Ventricular morphology was assessed using histology.RESULTS: ASC and MSC were CD34(-), CD45(-), c-Kit(-), CD90(+), Sca-1(+), shared similar morphology and had a population doubling time of approximately 2 days. Cells expressed Fluc reporter genes in a number-dependent fashion as confirmed by luminometry. After cardiac transplantation, both cell types showed drastic donor cell death within 4 to 5 weeks. Furthermore, transplantation of either cell type was not capable of preserving ventricular function and dimensions, as confirmed by pressure-volume-loops and histology.CONCLUSION: This is the first study comparing the in vivo behavior of both cell types in the infarcted heart. ASC and MSC do not tolerate well in the cardiac environment, resulting in acute donor cell death and a subsequent loss of cardiac function similar to control groups.

KW - Actins/genetics

KW - Adipose Tissue/cytology

KW - Animals

KW - Bone Marrow Transplantation/methods

KW - Cell Death

KW - Cell Division

KW - Disease Models, Animal

KW - Echocardiography

KW - Female

KW - Flow Cytometry

KW - Genes, Reporter

KW - Mesenchymal Stem Cell Transplantation/methods

KW - Mesenchymal Stem Cells/cytology

KW - Mice

KW - Mice, Inbred Strains

KW - Mice, Transgenic

KW - Myocardial Infarction/diagnostic imaging

KW - Promoter Regions, Genetic

KW - Regeneration

U2 - 10.1097/TP.0b013e31819609d9

DO - 10.1097/TP.0b013e31819609d9

M3 - SCORING: Journal article

C2 - 19295307

VL - 87

SP - 642

EP - 652

JO - TRANSPLANTATION

JF - TRANSPLANTATION

SN - 0041-1337

IS - 5

ER -