Reconstruction of endometrial histoarchitecture and receptivity genes in Asherman’s syndrome patients using a 3D acellular amnion bilayer scaffold seeded with endometrial cells
Budi Wiweko A B C * , Normalina Sandora
C * , Muharam Raden B C , Achmad Kemal Harzif A B C , Tyas Rahmah Kusuma C , Nur Amalina Fitria C , Benati Karimah C , Mila Maidarti A B C , Kanadi Sumapraja A B C , Gita Pratama A B C , Muhammad Dwi Priangga A C , Natasha Karlina Law D and Andon Hestiantoro A B C
A
B
C
D
Handling Editor: Ellen Menkhorst
Abstract
Thin endometrium with Asherman’s syndrome is a challenge in in vitro fertilisation, as patients cannot conceive even if the embryo is well.
This study aimed to regenerate thin endometria unresponsive to treatments, using autologous endometrial cells and acellular amnion bilayer as a womb patch.
This preliminary quasi-experimental study investigated thin endometria before and after intervention with an amnion bilayer (AB) and AB with self-endometrial cells (AB + Cells). Patients were IVF candidates with oligomenorrhea, endometrial thickness (EMT) < 7 mm, unresponsive towards hormonal treatment, and three courses of platelet-rich plasma applications. Intervention responses were indicated by (i) EMT measurement, (ii) endometrial cell epitopes, (iii) histoarchitecture and immunohistochemistry, and (iv) relative expression of the endometrial receptivity genes.
Average EMT increased significantly from 5.03 ± 0.95 mm to 6.75 ± 1.39 mm after AB, and further to 7.33 ± 1.92 mm after AB + Cells. Cell density was significantly higher after AB + Cells. The histoarchitecture after AB + Cells developed into a complex tubular system, and E-cadherin and oestrogen receptor alpha (ER-α) was detected. Homeobox A10 (HOXA10) expression increased significantly, up to 4.5-fold after AB + Cells treatment compared with before treatment (P = 0.01), while leukaemia inhibitory factor (LIF) and osteopontin (SPP1) levels also increased, but not significantly. Significant changes in gene expression and cell populations were observed, with improvements in receptivity genes.
Patients with thin endometria showed improvement in EMT, histoarchitecture, and receptivity genes after AB and AB + Cells intervention.
The study demonstrates the potential of using a 3D amnion bilayer scaffold with endometrial cells to improve endometrial regeneration.
Keywords: 3-D scaffold, amnion bilayer, Asherman’s syndrome, endometrial cell therapy, endometrial receptivity, histoarchitecture, thin endometrium, tissue engineering.
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