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KMID : 1011820200610010088
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Investigative and Clinical Urology
2020 Volume.61 No. 1 p.88 ~ p.98
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Establishment of NOAEL for intracavernous injections of human bone marrow-derived mesenchymal stem cells in rats
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Kim Jong-Keun
Jang Myoung-Jin
Kim Bo-Hyun
Choi Ki-Ryung
Song Gee-Hyun
Shin Ha-Chul
Suh Na-Young
Kim Yong-Man
You Dal-San
Ahn Tai-Young
Kim Choung-Soo
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Abstract
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Purpose: To assess the possible negative health effects of human bone marrow-derived mesenchymal stem cells (hBMSCs) on fertility and early embryonic development following intracavernous injections in rats.
Materials and Methods: A total of 88 Crl:CD(SD) male and female rats were equally divided into 4 groups in a random manner: control group (normal saline), low-dose group (2×105 hBMSCs), moderate-dose group (1×106 hBMSCs), and high-dose group (2×106 hBMSCs). hBMSCs or normal saline was injected into the penis of the rats 3 times at 2-week-intervals prior to mating. We compared each group with respect to parameters of reproduction and histopathology.
Results: For male rats, various degrees of flushing and swelling were observed at the penile injection site in all the groups, although the severity increased in a dose-dependent manner in the hBMSC injection groups. There were no statistically significant differences in mean body weights and food consumption among all the groups of both sexes. There were no statistically significant differences in reproductive parameters among all the groups of both sexes. The absolute and relative organ weights did not significantly differ among the groups. At the time of necropsy, no remarkable findings were observed in gross examinations in all groups. On histopathological analysis, minimal mononuclear cell infiltration was observed in the right epididymis of each rat in the moderate- and high-dose groups.
Conclusions: The non-toxic amount of hBMSCs for male fertility and early embryogenesis in rats under the test conditions was determined to be 2×106 cells/head.
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KEYWORD
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Embryonic development, Fertility, Rats, Stem cell transplantation, Toxic actions
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