Targeted uterine artery infusion of bone marrow-derived mesenchymal stem cells for severe intrauterine adhesions: a randomized controlled trial with exploratory translational analyses
- 1The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655 China
- 2GuangDong Engineering Technology Research Center of Fertility Preservation, Guangzhou, 510655 China
- 3Guangzhou (Huangpu) Zhongliu Biomedical Innovation Center, Guangzhou, China
Abstract
Background: Severe intrauterine adhesions (IUA) represent a profound failure of endometrial regeneration, characterized by excessive fibrosis and vascular insufficiency. Mesenchymal stem cell-based therapies show regenerative potential, but clinical evidence is inconsistent, and optimal delivery routes and localized microvascular mechanisms of action in human endometrium remain unclear.
Methods: This prospective, randomized controlled trial was conducted from July 2020 to December 2024. A total of 60 women with severe intrauterine adhesions (IUA) were randomly assigned (1:1) to receive targeted uterine artery infusion of bone marrow-derived MSCs (BMSCs) plus hormone replacement therapy (HRT), or HRT alone. The primary outcome was endometrial thickness, with secondary outcomes including clinical pregnancy rate, miscarriage rate, and live birth rate. Histological, transcriptomic, and in vitro functional assays were performed as exploratory analyses to characterize treatment-associated tissue and vascular remodeling.
Results: Compared with the control group, the BMSC group showed a greater increase in endometrial thickness (0.79 ± 0.66 mm vs. 0.20 ± 0.44 mm, P < 0.001). In the exploratory per- protocol analysis among participants who underwent embryo transfer, the BMSC group showed a higher clinical pregnancy rate than the control group (50.0% vs. 23.3%, P = 0.038), while the live birth rate was numerically higher but not statistically significant (34.6% vs. 16.7%, P = 0.122). No serious treatment-related adverse events were observed. Exploratory histological and transcriptomic analyses indicated that BMSC treatment was associated with increased microvascular density and the upregulation of angiogenic pathways (e.g., NOTCH/VEGF). In vitro assays showed increased pericyte migration and pericyte-endothelial association under BMSC-associated conditions.
Conclusions: Targeted uterine artery infusion of allogeneic BMSCs was feasible and was associated with improved endometrial thickness in women with severe IUA. Secondary reproductive outcomes and exploratory mechanistic analyses suggested potential clinical and microvascular benefits, but these findings require confirmation in larger multicenter trials powered for live birth and long-term safety.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13287-026-05216-w.
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BibTeX
@article{chang2026targeted,
title = {{Targeted uterine artery infusion of bone marrow-derived mesenchymal stem cells for severe intrauterine adhesions: a randomized controlled trial with exploratory translational analyses}},
author = {Yajie Chang and Qi Guo and Zhi Zeng and Ping Yuan and Dandan Wang and Dao Peng and Haiyang Lai and Weixi Chen and Zhi Wang and Cizhao Huang and Bo Zhang and Xiaoyan Liang},
journal = {Stem Cell Research \& Therapy},
year = {2026},
month = aug,
doi = {10.1186/s13287-026-05216-w},
url = {https://doi.org/10.1186/s13287-026-05216-w},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Targeted uterine artery infusion of bone marrow-derived mesenchymal stem cells for severe intrauterine adhesions: a randomized controlled trial with exploratory translational analyses
AU - Yajie Chang
AU - Qi Guo
AU - Zhi Zeng
AU - Ping Yuan
AU - Dandan Wang
AU - Dao Peng
AU - Haiyang Lai
AU - Weixi Chen
AU - Zhi Wang
AU - Cizhao Huang
AU - Bo Zhang
AU - Xiaoyan Liang
PY - 2026
DA - 2026/08/07
JO - Stem Cell Research & Therapy
DO - 10.1186/s13287-026-05216-w
UR - https://doi.org/10.1186/s13287-026-05216-w
AB - Background: Severe intrauterine adhesions (IUA) represent a profound failure of endometrial regeneration, characterized by excessive fibrosis and vascular insufficiency. Mesenchymal stem cell-based therapies show regenerative potential, but clinical evidence is inconsistent, and optimal delivery routes and localized microvascular mechanisms of action in human endometrium remain unclear. Methods: This prospective, randomized controlled trial was conducted from July 2020 to December 2024. A total of 60 women with severe intrauterine adhesions (IUA) were randomly assigned (1:1) to receive targeted uterine artery infusion of bone marrow-derived MSCs (BMSCs) plus hormone replacement therapy (HRT), or HRT alone. The primary outcome was endometrial thickness, with secondary outcomes including clinical pregnancy rate, miscarriage rate, and live birth rate. Histological, transcriptomic, and in vitro functional assays were performed as exploratory analyses to characterize treatment-associated tissue and vascular remodeling. Results: Compared with the control group, the BMSC group showed a greater increase in endometrial thickness (0.79 ± 0.66 mm vs. 0.20 ± 0.44 mm, P < 0.001). In the exploratory per- protocol analysis among participants who underwent embryo transfer, the BMSC group showed a higher clinical pregnancy rate than the control group (50.0% vs. 23.3%, P = 0.038), while the live birth rate was numerically higher but not statistically significant (34.6% vs. 16.7%, P = 0.122). No serious treatment-related adverse events were observed. Exploratory histological and transcriptomic analyses indicated that BMSC treatment was associated with increased microvascular density and the upregulation of angiogenic pathways (e.g., NOTCH/VEGF). In vitro assays showed increased pericyte migration and pericyte-endothelial association under BMSC-associated conditions. Conclusions: Targeted uterine artery infusion of allogeneic BMSCs was feasible and was associated with improved endometrial thickness in women with severe IUA. Secondary reproductive outcomes and exploratory mechanistic analyses suggested potential clinical and microvascular benefits, but these findings require confirmation in larger multicenter trials powered for live birth and long-term safety. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13287-026-05216-w.
SN - 1757-6512
ER -