Investig Clin Urol.  2020 Jan;61(1):88-98. 10.4111/icu.2020.61.1.88.

Establishment of NOAEL for intracavernous injections of human bone marrow-derived mesenchymal stem cells in rats

Affiliations
  • 1Department of Urology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea.
  • 2Asan Institute for Life Science, Asan Medical Center, Seoul, Korea.
  • 3Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. cskim@amc.seoul.kr
  • 4NKMAX Co., Ltd., Seongnam, Korea.
  • 5Department of Urology, Kangwon National University School of Medicine, Chuncheon, Korea.
  • 6Pharmicell Co., Ltd., Seongnam, Korea.
  • 7Department of Pharmaceutical Engineering, College of Medical Sciences, Soon Chun Hyang University, Asan, Korea.

Abstract

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.

Keyword

Embryonic development; Fertility; Rats; Stem cell transplantation; Toxic actions

MeSH Terms

Animals
Body Weight
Embryonic Development
Epididymis
Female
Fertility
Flushing
Humans*
Male
Mesenchymal Stromal Cells*
No-Observed-Adverse-Effect Level*
Organ Size
Penis
Pregnancy
Rats*
Reproduction
Stem Cell Transplantation
Toxic Actions
Toxic Actions
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