Potential role of tracing stem cell transplantation and effects on the immune cell function of ferumoxytol combining with heparin and protamine in vivo/in vitro.
Cell labeling and tracing have played an increasingly important role in the field of stem cell transplantation. Nanocomplexes combining three Food and Drug Administration (FDA)-approved drugs: heparin (H), protamine (P), and ferumoxytol (F) (HPF nanocomplexes) display high labeling efficiency in human adipose tissue-derived stem cells (hADSCs), but their biological safety has not been determined. In this study, we tested the labeling efficiency of HPF in hADSCs through in vitro cytotoxicity studies and in vivo murine preclinical studies using HPF-labeled hADSCs. The labeling process did not cause cell apoptosis and had little effect on cell proliferation. In vivo magnetic resonance imaging (MRI) showed that the HPF-labeled cells produced a hypointense signal that did not affect liver and kidney functions. However, after injection of HPF-labeled cells into mice, lymphocyte transformation testing showed that T and B lymphocyte proliferation was significantly increased. These findings suggest that extensive safety testing of HPF nanocomplexes is necessary; the process to evaluate HPF as an investigative new drug application could therefore be postponed.
Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian, 116011, China.
Jingyuan
J
Zhao
Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian, 116011, China.
Xin
X
Guan
Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian, 116011, China.
Yang
Y
Liu
College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
Hua
H
Piao
Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian, 116011, China.
Rutao
R
Liu
Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian, 116011, China.
Xiang
X
Zhou
Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
Bo
B
Sun
College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
Yue
Y
Du
Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian, 116011, China.
Jing
J
Liu
D000273:Adipose Tissue / Q000166:cytology; D000328:Adult; D017209:Apoptosis; D002454:Cell Differentiation; D049109:Cell Proliferation; D048430:Cell Shape; D002470:Cell Survival; D058948:Cell Tracking; D002478:Cells, Cultured; D005260:Female; D052203:Ferrosoferric Oxide / Q000737:chemistry* / Q000633:toxicity; D006493:Heparin / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity; D011479:Protamines / Q000737:chemistry* / Q000633:toxicity; D013194:Staining and Labeling; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology
D011479:Protamines; D006493:Heparin; D052203:Ferrosoferric Oxide
MRI; cell labeling; ferumoxytol; lymphocyte proliferation; stem cells