Incorporation of Decidual Stromal Cells Derived Exosomes in Sodium Alginate Hydrogel as an Innovative Therapeutic Strategy for Advancing Endometrial Regeneration and Reinstating Fertility

Author:

Liang Yuxiang12ORCID,Shuai Qizhi1,Zhang Xiao1,Jin Shanshan1,Guo Yuqian1,Yu Zhaowei1,Xu Xinrui1,Ao Ruifang1,Peng Zhiwei1,Lv Huimin13,He Sheng4,Wang Chunfang2,Song Guohua2,Liu Zhizhen1,Zhao Hong1,Feng Qilong1,Du Ruochen2,Zheng Bin5,Chen Zhaoyang2,Xie Jun1

Affiliation:

1. Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University), Ministry of Education Shanxi Key Laboratory of Birth Defect and Cell Regeneration Taiyuan Shanxi 030001 China

2. Shanxi Key Laboratory of Human Disease and Animal Models Experimental Animal Center of Shanxi Medical University Taiyuan Shanxi 030001 China

3. Department of Obstetrics and Gynecology, Third Hospital of Shanxi Medical University (Shanxi Bethune Hospital) Shanxi Academy of Medical Sciences Taiyuan 030032 China

4. Department of Radiology The First Hospital of Shanxi Medical University Taiyuan Shanxi 030001 China

5. School of Pharmacy Shanxi Medical University Taiyuan Shanxi 030001 China

Abstract

AbstractIntrauterine adhesion (IUA) stands as a prevalent medical condition characterized by endometrial fibrosis and scar tissue formation within the uterine cavity, resulting in infertility and, in severe cases, recurrent miscarriages. Cell therapy, especially with stem cells, offers an alternative to surgery, but concerns about uncontrolled differentiation and tumorigenicity limit its use. Exosomes, more stable and immunogenicity‐reduced than parent cells, have emerged as a promising avenue for IUA treatment. In this study, a novel approach has been proposed wherein exosomes originating from decidual stromal cells (DSCs) are encapsulated within sodium alginate hydrogel (SAH) scaffolds to repair endometrial damage and restore fertility in a mouse IUA model. Current results demonstrate that in situ injection of DSC‐derived exosomes (DSC‐exos)/SAH into the uterine cavity has the capability to induce uterine angiogenesis, initiate mesenchymal‐to‐epithelial transformation (MET), facilitate collagen fiber remodeling and dissolution, promote endometrial regeneration, enhance endometrial receptivity, and contribute to the recovery of fertility. RNA sequencing and advanced bioinformatics analysis reveal miRNA enrichment in exosomes, potentially supporting endometrial repair. This finding elucidates how DSC‐exos/SAH mechanistically fosters collagen ablation, endometrium regeneration, and fertility recovery, holding the potential to introduce a novel IUA treatment and offering invaluable insights into the realm of regenerative medicine.

Funder

National Natural Science Foundation of China

Publisher

Wiley

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