Injection of bone marrow mesenchymal stem cells in the borderline
area of infarcted myocardium: Heart status and cell distribution
Hao Zhang, MD, PhDa,*, Peng Song, MDa,*, Yue Tang, MD, PhDb, Xiao-
ling Zhang, BSa, Shi-hua Zhao, MDc, Ying-jie Wei, PhDa, Sheng-shou
Hu, MDa,*
a Research Center for Cardiac Regenerative Medicine, the Ministry of
Health and Department of Surgery, Fu Wai Hospital, Beijing, China
b Animal Research Center, Fu Wai Hospital, Beijing, China
c Unit of Magnetic Resonance Imaging, Fu Wai Hospital, Beijing,
China.
Received for publication April 19, 2007; revisions received June 25,
2007; accepted for publication July 19, 2007.
* Address for reprints: Sheng-Shou Hu, MD, Chief, Department of
Surgery, Director, Research Center for Cardiac Regenerative Medicine,
President, Cardiovascular Institute & Fu Wai Hospital, Professor,
Chinese Academy of Medical Sciences, 167A Beilishilu, Beijing 100037,
Peoples Republic of China. (Email: shengshouhu@
Objective: This study aimed to test the distribution of
intramyocardially injected cells in variations in heart status in a
porcine model of myocardial infarction.
Methods: Bone marrow–derived mesenchymal stem cells were obtained
from male swine and labeled with iron oxide during culture. One week
after creation of a myocardial infarction in female swine, the
survivors were randomly divided into 4 groups. Cardiopulmonary bypass
was set up to arrest the heart, and then labeled cells (1 x 108) were
intramyocardially injected into the border zone of the infarcted zone
in group 1 (n = 6). The same volume of cells was grafted into the
beating heart in group 2 (n = 6). In groups 3 and 4, saline was
injected in either the arresting or beating heart. Three days later,
cell distribution was assessed by T2* change with magnetic resonance
imaging and sex-determining region on Y-chromosome (SRY) with
quantitative polymerase chain reaction.
Results: The cells were identified in the heart, spleen, lung, and
liver. Most injected cells were localized in the myocardium in groups
1 and 2; however, the amount of cells was much higher in group 1 (T2*
change: 22.3 ± 2.2 vs 17 ± 0.84; SRY gene: 0.15 ± 0.062 vs 0.072 ±
0.003).
Conclusions: Even after intramyocardial injection, many cells
migrated to extracardiac organs, especially to the spleen. Our
results indicated that injection in the arresting heart could favor
retaining more cells in the myocardium. Thus, it was an optimal
approach to deliver mesenchymal stem cells during open chest surgery.
Abbreviations and Acronyms BM = bone marrow; IMI = intramyocardial
injection; MI = myocardial infarction; MRI = magnetic resonance
imaging; MSCs = mesenchymal stem cells; qRT-PCR = quantitative real-
time polymerase chain reaction; SRY = Y-chromosome gene
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