Effect of human stem cells labeled with ferumoxides-poly-L-lysine on hematologic and biochemical measurements in rats.
OBJECTIVE
To determine whether ferumoxides-poly-l-lysine (PLL) complex-labeled mesenchymal stem cells (MSCs) or ferumoxides-PLL complex alone alters hematologic, blood chemistry, renal function, and/or liver function measurements after being intravenously infused into rats.


METHODS
Twenty-five rats (group 1) received intravenous injections of labeled MSCs, and 25 additional rats (group 2) received intravenous injections of ferumoxides-PLL complex only. Complete blood counts, liver and renal function test results, and serum electrolyte and iron concentrations were measured for 42 days after the injections and compared with those measured in five control rats (group 3). To determine the duration of labeled MSCs in the circulation, venous blood was serially drawn from five additional rats (group 4) that were injected with labeled MSCs. Analyses of variance (ANOVA) followed by Fisher protected least significant difference post hoc tests were used to statistically analyze results. P < .05 was considered to indicate significance in all analyses.


RESULTS
Administration of neither labeled MSCs nor ferumoxides-PLL complex had a significant effect on hematologic or blood chemistry indicators of organ function. Of the parameters measured, only hemoglobin concentration and mean corpuscular volume (MCV) in the rats injected with labeled MSCs, as well as MCV and hemoglobin, alkaline phosphatase, aspartate aminotransferase, and direct bilirubin concentrations in the rats injected with ferumoxides-PLL complex, varied significantly during the 42-day postinjection period (P < .05, ANOVA). No other measurements, including serum electrolyte and iron concentrations, changed significantly during the test period (P > .05). Furthermore, injected labeled MSCs had cleared from the peripheral circulation by 15 minutes after injection.


CONCLUSIONS
Results indicate that infusing cells that are magnetically labeled with ferumoxides-PLL complex into rats does not alter biochemical or hematologic measures of organ function in a clinically relevant or preclusive manner.
Yocum
Gene T
GT
Experimental Neuroimaging Section, Laboratory of Diagnostic Radiology Research, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
Wilson
Lindsey B
LB
Ashari
Parwana
P
Jordan
E Kay
EK
Frank
Joseph A
JA
Arbab
Ali S
AS
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001774:Blood Chemical Analysis; D003287:Contrast Media / Q000493:pharmacokinetics / Q000494:pharmacology*; D003911:Dextrans; D004338:Drug Combinations; D004573:Electrolytes / Q000097:blood; D004909:Erythrocyte Indices; D005260:Female; D052203:Ferrosoferric Oxide; D006452:Hemoglobinometry; D006801:Humans; D007275:Injections, Intravenous; D007501:Iron / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D007677:Kidney Function Tests; D008111:Liver Function Tests; D058185:Magnetite Nanoparticles; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D008657:Metabolic Clearance Rate / Q000502:physiology; D010087:Oxides / Q000493:pharmacokinetics / Q000494:pharmacology*; D011107:Polylysine / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011923:Rats, Nude
D003287:Contrast Media; D003911:Dextrans; D004338:Drug Combinations; D004573:Electrolytes; D058185:Magnetite Nanoparticles; D010087:Oxides; D011107:Polylysine; D007501:Iron; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase; C065507:ferumoxides; D001663:Bilirubin; D052203:Ferrosoferric Oxide