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


CONCLUSIONS
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.
van der Bogt
Koen E A
KE
Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA 94305-5324, USA.
Schrepfer
Sonja
S
Yu
Jin
J
Sheikh
Ahmad Y
AY
Hoyt
Grant
G
Govaert
Johannes A
JA
Velotta
Jeffrey B
JB
Contag
Christopher H
CH
Robbins
Robert C
RC
Wu
Joseph C
JC
D000199:Actins / Q000235:genetics; D000273:Adipose Tissue / Q000166:cytology / Q000473:pathology / Q000637:transplantation*; D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods; D016923:Cell Death; D002455:Cell Division; D004195:Disease Models, Animal; D004452:Echocardiography; D005260:Female; D005434:Flow Cytometry; D017930:Genes, Reporter; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000601:surgery*; D011401:Promoter Regions, Genetic; D012038:Regeneration
D000199:Actins