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Dose‐response relationship of human CD34+ cells in an athymic rat model of myocardial infarction
Author(s) -
Brooks Ben,
McKee Jeff,
Rice Deborah,
Baumgartner Bernhard,
Motlagh Delara,
Amrani David
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.824.8
Subject(s) - ligation , medicine , myocardial infarction , cd34 , saline , cardiology , transplantation , infarction , doxorubicin , stem cell , chemotherapy , biology , genetics
The athymic rat model of myocardial infarction is routinely used to evaluate the efficacy of cell‐based, proangiogenic therapeutics. Most studies employ a range of cells (10 4 to 2X10 6 per rat) with little to no justification as to why a particular dose was used and whether the dose is clinically relevant based on allometric scaling. Adding to the uncertainty of dose is which route of administration will yield the greatest therapeutic benefit. It's been shown that the intravenous administration of 10 4 , 10 6 or 2X10 6 human CD34+ cells has positive, dose‐dependent effects on histopathological and functional endpoints in an athymic rat model of myocardial infarction (Schuster et al 2004). The purpose of this work was to evaluate if a similar dose‐response could be demonstrated with human CD34+ cells transplanted by direct intramyocardial injection. Athymic (HSD:RH‐FOXN1RNU) rats underwent left anterior descending artery ligation followed by direct intramyocardial injection of saline, 10 5 , or 10 6 human CD34+ cells. Echocardiography was performed before ligation and at 4 and 32 days post‐ligation. The intramyocardial transplantation of human CD34+ cells improved cardiac performance as demonstrated by improvements in left ventricular fractional shortening and left anterior wall motion as compared with saline‐treated animals but no dose‐response was observed. In conclusion, these data suggest that the dose‐response relationship of human CD34+ cells may be shifted to the left when transplanted into the athymic rat by direct intramyocardial injection as compared to the intravenous route. Baxter Healthcare Corporation provided all research support.