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

Abstract

<b><i>Objectives:</i></b> 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. <b><i>Design:</i></b> An experimental study was carried out. <b><i>Participants/Materials, Setting, Methods:</i></b> 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. <b><i>Results:</i></b> Co-culture with hPBMCs stimulated significant proliferation in both SNU-685 and SNU-1077 cell lines (<i>p</i> = 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, <i>p</i> = 0.009; middle: 1.51 ± 0.14 vs. 1.00 ± 0.12, <i>p</i> = 0.010; distal: 1.72 ± 0.22 vs. 1.00 ± 0.12, <i>p</i> = 0.003, respectively). Compared with the PBS injection group, the hPBMC injection group had significantly thickened endometrium in the middle (<i>p</i> = 0.036) and distal segments (<i>p</i> = 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. <b><i>Limitations:</i></b> hPBMCs were not applied directly to a mouse model with thin endometrium, so further study is needed. <b><i>Conclusion:</i></b> The beneficial effect of hPBMCs on endometrium may suggest their clinical feasibility for the safe treatment of infertile patients with persistently thin endometrium.