Effect of Human Peripheral Blood Mononuclear Cells on Mouse Endometrial Cell Proliferation: A Potential Therapeutics for Endometrial Regeneration

Gynecol Obstet Invest. 2022;87(2):105-115. doi: 10.1159/000524232. Epub 2022 Mar 29.

Abstract

Objectives: The persistently thin endometrium is a major cause of repeated implantation failure; however, there is no definite treatment for it yet. This study aimed to confirm the potential of human peripheral blood mononuclear cells (hPBMCs) as a therapeutic agent for endometrial regeneration.

Design: An experimental study was carried out.

Participants/materials, setting, methods: To assess the in vitro effect of hPBMC, the human primary endometrial epithelial cell lines SNU-685 and SNU-1077 were co-cultured with or without 1 × 105 hPBMCs for 24 h. To evaluate the in vivo effect, either 1 × 105 hPBMCs in PBS or PBS alone were injected into the left uterine horn of nonobese diabetic-severe combined immune-deficient mice, and the right untreated uterine horn was used as control.

Results: Co-culture with hPBMCs stimulated significant proliferation in both SNU-685 and SNU-1077 cell lines (p = 0.002 and 0.044, respectively). Moreover, treatment with hPBMCs significantly increased the thickness in all parts of the endometrium compared with that in the untreated control uterine horn (proximal: 1.69 ± 0.19 vs. 1.00 ± 0.10, p = 0.009; middle: 1.51 ± 0.14 vs. 1.00 ± 0.12, p = 0.010; distal: 1.72 ± 0.22 vs. 1.00 ± 0.12, p = 0.003, respectively). Compared with the PBS injection group, the hPBMC injection group had significantly thickened endometrium in the middle (p = 0.036) and distal segments (p = 0.002) of the uterine horn. Immunohistochemical analysis revealed the presence of exogenously injected hPBMCs in the uterus of recipient mice. hPBMC-recipient mice had cyclic uterus with normal histology in the endometrium.

Limitations: hPBMCs were not applied directly to a mouse model with thin endometrium, so further study is needed.

Conclusion: The beneficial effect of hPBMCs on endometrium may suggest their clinical feasibility for the safe treatment of infertile patients with persistently thin endometrium.

Keywords: Endometrial epithelial cells; Endometrial regeneration; Endometrial thickness; Human peripheral blood mononuclear cells; Thin endometrium.

MeSH terms

  • Animals
  • Cell Proliferation
  • Endometrium* / pathology
  • Female
  • Humans
  • Leukocytes, Mononuclear*
  • Mice
  • Regeneration
  • Uterus