# Reproductive and Developmental Toxicity of Human Umbilical Cord Blood Mononuclear Cells

## TL;DR

This study shows that human umbilical cord blood mononuclear cells do not harm fertility or fetal development in rats, even at high doses.

## Contribution

The study provides new evidence on the safety of hUCB-MNCs in reproductive and developmental contexts.

## Key findings

- Administration of hUCB-MNCs at high doses did not affect fertility rates or pregnancy outcomes in rats.
- Fetal development showed no anomalies or adverse effects in experimental groups.
- The placental barrier and low immunogenicity of hUCB-MNCs likely contribute to their safety profile.

## Abstract

Background/Objectives: The attention of world science has been focused on human umbilical cord blood cell (hUCB) products for the treatment of various human diseases. The prospects for using hUCB stem from the availability of the material, non-invasive collection procedure, low immunogenicity, multipotency and non-tumorigenicity. But information about the acute toxicity, reproductive and developmental toxicity of hUCB mononuclear cells (MNCs) remains insufficient. Thus, the aim of this study is to assess the reproductive and developmental toxicity of human umbilical cord blood mononuclear cells on Wistar rats. Methods: In the fertility and early embryonic development study, human umbilical cord blood mononuclear cells (hUCB-MNCs) were administered at dose levels of 4.28 × 108 cells/kg and 8.57 × 108 cells/kg to male and female rats during the pre-mating, mating and gestation period. In the embryo–fetal development study, the pregnant female rats also received hUC-MNCs at doses of 4.28 × 108 cells/kg and 8.57 × 108 cells/kg. Results: In gestational data, including fertility rate, pregnancy rate, corpora lutea and implantation sites counts, dead and absorption fetuses’ number, body weight and craniocaudal size of fetuses, anomalies in fetal development showed no statistically significant changes in 4.28 × 108 cells/kg (low dose) and 8.57 × 108 cells/kg (high dose) dose groups of hUCB-MNCs to negative control group. External, visceral and skeletal examination of the fetuses in all experimental groups also showed no changes. Embryo–fetal development study in low and high groups of hUCB-MNCs application also showed no changes in the negative control group. Conclusions: This reproductive and developmental toxicity study demonstrates that hUCB-MNCs administered intravenously at doses up to 8.57 × 108 cells/kg do not cause adverse effects on fertility, embryo–fetal development, or postnatal offspring viability in Wistar rats. The absence of reproductive toxicity is mechanistically attributable to three intrinsic properties of hUCB-MNCs: their low immunogenicity, which prevents maternal immune activation; the protective function of the intact placental barrier; and their transient, paracrine-dominant mode of action, which limits exposure duration.