Multipotent human stromal cells improve cardiac function after myocardial infarction in mice without long-term engraftment.
The aim of this study was to determine whether intravenously administered multipotent stromal cells from human bone marrow (hMSCs) can improve cardiac function after myocardial infarction (MI) without long-term engraftment and therefore whether transitory paracrine effects or secreted factors are responsible for the benefit conferred. hMSCs were injected systemically into immunodeficient mice with acute MI. Cardiac function and fibrosis after MI in the hMSC-treated group were significantly improved compared with controls. However, despite the cardiac improvement, there was no evident hMSC engraftment in the heart 3 weeks after MI. Microarray assays and ELISAs demonstrated that multiple protective factors were expressed and secreted from the hMSCs in culture. Factors secreted by hMSCs prevented cell death of cultured cardiomyocytes and endothelial cells under conditions that mimicked tissue ischemia. The favorable effects of hMSCs appear to reflect the impact of secreted factors rather than engraftment, differentiation, or cell fusion.
Iso
Yoshitaka
Y
Center for Gene Therapy, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
Spees
Jeffrey L
JL
Serrano
Claudia
C
Bakondi
Benjamin
B
Pochampally
Radhika
R
Song
Yao-Hua
YH
Sobel
Burton E
BE
Delafontaine
Patrick
P
Prockop
Darwin J
DJ
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005355:Fibrosis / Q000473:pathology / Q000628:therapy; D006801:Humans; D051379:Mice; D039902:Multipotent Stem Cells / Q000637:transplantation*; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D020411:Oligonucleotide Array Sequence Analysis; D017154:Stromal Cells / Q000637:transplantation*; D013997:Time Factors