In situ delivery of apoptotic bodies derived from mesenchymal stem cells via a hyaluronic acid hydrogel: A therapy for intrauterine adhesions

Stem cell-based and stem cell-derived exosome-based therapies have shown promising potential for endometrial regeneration and the clinical treatment of intrauterine adhesions (IUAs). Evidence shows that apoptosis occurs in a majority of grafted stem cells, and apoptotic bodies (ABs) play a critical...

Full description

Bibliographic Details
Main Authors: Liaobing Xin, Cheng Wei, Xiaomei Tong, Yangyang Dai, Dong Huang, Jianmin Chen, Lie Ma, Songying Zhang
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2022-06-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X21004898
_version_ 1797205443801513984
author Liaobing Xin
Cheng Wei
Xiaomei Tong
Yangyang Dai
Dong Huang
Jianmin Chen
Lie Ma
Songying Zhang
author_facet Liaobing Xin
Cheng Wei
Xiaomei Tong
Yangyang Dai
Dong Huang
Jianmin Chen
Lie Ma
Songying Zhang
author_sort Liaobing Xin
collection DOAJ
description Stem cell-based and stem cell-derived exosome-based therapies have shown promising potential for endometrial regeneration and the clinical treatment of intrauterine adhesions (IUAs). Evidence shows that apoptosis occurs in a majority of grafted stem cells, and apoptotic bodies (ABs) play a critical role in compensatory tissue regeneration. However, the therapeutic potential of AB-based therapy and its mechanism have not been explored in detail. Here, a cell-free therapeutic strategy was developed by incorporating mesenchymal stem cell-derived ABs into a hyaluronic acid (HA) hydrogel to achieve endometrial regeneration and fertility restoration. Specifically, we found that the ABs could induce macrophage immunomodulation, cell proliferation, and angiogenesis in vitro. The HA hydrogel promoted the retention of ABs and facilitated their continuous release. In a murine model of acute endometrial damage and a rat model of IUAs, in situ injection of the AB-laden HA hydrogel could efficiently reduce fibrosis and promote endometrial regeneration, resulting in the fertility restoration. Consequently, ABs show good potential as therapeutic vesicles, and the AB-laden HA hydrogel appears to be a clinically feasible and cell-free alternative for endometrial regeneration and IUA treatment.
first_indexed 2024-04-24T08:51:13Z
format Article
id doaj.art-9f1afd207bbb4abe985b50ef1f462f28
institution Directory Open Access Journal
issn 2452-199X
language English
last_indexed 2024-04-24T08:51:13Z
publishDate 2022-06-01
publisher KeAi Communications Co., Ltd.
record_format Article
series Bioactive Materials
spelling doaj.art-9f1afd207bbb4abe985b50ef1f462f282024-04-16T12:01:24ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2022-06-0112107119In situ delivery of apoptotic bodies derived from mesenchymal stem cells via a hyaluronic acid hydrogel: A therapy for intrauterine adhesionsLiaobing Xin0Cheng Wei1Xiaomei Tong2Yangyang Dai3Dong Huang4Jianmin Chen5Lie Ma6Songying Zhang7Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province. No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, ChinaAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province. No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, ChinaAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province. No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, ChinaAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China; MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province. No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, ChinaAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province. No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, ChinaAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province. No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, ChinaMOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province. No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China; Corresponding author. MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province. No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China; Corresponding author. Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University; Hangzhou, 310016, China.Stem cell-based and stem cell-derived exosome-based therapies have shown promising potential for endometrial regeneration and the clinical treatment of intrauterine adhesions (IUAs). Evidence shows that apoptosis occurs in a majority of grafted stem cells, and apoptotic bodies (ABs) play a critical role in compensatory tissue regeneration. However, the therapeutic potential of AB-based therapy and its mechanism have not been explored in detail. Here, a cell-free therapeutic strategy was developed by incorporating mesenchymal stem cell-derived ABs into a hyaluronic acid (HA) hydrogel to achieve endometrial regeneration and fertility restoration. Specifically, we found that the ABs could induce macrophage immunomodulation, cell proliferation, and angiogenesis in vitro. The HA hydrogel promoted the retention of ABs and facilitated their continuous release. In a murine model of acute endometrial damage and a rat model of IUAs, in situ injection of the AB-laden HA hydrogel could efficiently reduce fibrosis and promote endometrial regeneration, resulting in the fertility restoration. Consequently, ABs show good potential as therapeutic vesicles, and the AB-laden HA hydrogel appears to be a clinically feasible and cell-free alternative for endometrial regeneration and IUA treatment.http://www.sciencedirect.com/science/article/pii/S2452199X21004898Apoptotic bodiesMesenchymal stem cellsEndometrial regenerationIntrauterine adhesionsTissue engineering
spellingShingle Liaobing Xin
Cheng Wei
Xiaomei Tong
Yangyang Dai
Dong Huang
Jianmin Chen
Lie Ma
Songying Zhang
In situ delivery of apoptotic bodies derived from mesenchymal stem cells via a hyaluronic acid hydrogel: A therapy for intrauterine adhesions
Bioactive Materials
Apoptotic bodies
Mesenchymal stem cells
Endometrial regeneration
Intrauterine adhesions
Tissue engineering
title In situ delivery of apoptotic bodies derived from mesenchymal stem cells via a hyaluronic acid hydrogel: A therapy for intrauterine adhesions
title_full In situ delivery of apoptotic bodies derived from mesenchymal stem cells via a hyaluronic acid hydrogel: A therapy for intrauterine adhesions
title_fullStr In situ delivery of apoptotic bodies derived from mesenchymal stem cells via a hyaluronic acid hydrogel: A therapy for intrauterine adhesions
title_full_unstemmed In situ delivery of apoptotic bodies derived from mesenchymal stem cells via a hyaluronic acid hydrogel: A therapy for intrauterine adhesions
title_short In situ delivery of apoptotic bodies derived from mesenchymal stem cells via a hyaluronic acid hydrogel: A therapy for intrauterine adhesions
title_sort in situ delivery of apoptotic bodies derived from mesenchymal stem cells via a hyaluronic acid hydrogel a therapy for intrauterine adhesions
topic Apoptotic bodies
Mesenchymal stem cells
Endometrial regeneration
Intrauterine adhesions
Tissue engineering
url http://www.sciencedirect.com/science/article/pii/S2452199X21004898
work_keys_str_mv AT liaobingxin insitudeliveryofapoptoticbodiesderivedfrommesenchymalstemcellsviaahyaluronicacidhydrogelatherapyforintrauterineadhesions
AT chengwei insitudeliveryofapoptoticbodiesderivedfrommesenchymalstemcellsviaahyaluronicacidhydrogelatherapyforintrauterineadhesions
AT xiaomeitong insitudeliveryofapoptoticbodiesderivedfrommesenchymalstemcellsviaahyaluronicacidhydrogelatherapyforintrauterineadhesions
AT yangyangdai insitudeliveryofapoptoticbodiesderivedfrommesenchymalstemcellsviaahyaluronicacidhydrogelatherapyforintrauterineadhesions
AT donghuang insitudeliveryofapoptoticbodiesderivedfrommesenchymalstemcellsviaahyaluronicacidhydrogelatherapyforintrauterineadhesions
AT jianminchen insitudeliveryofapoptoticbodiesderivedfrommesenchymalstemcellsviaahyaluronicacidhydrogelatherapyforintrauterineadhesions
AT liema insitudeliveryofapoptoticbodiesderivedfrommesenchymalstemcellsviaahyaluronicacidhydrogelatherapyforintrauterineadhesions
AT songyingzhang insitudeliveryofapoptoticbodiesderivedfrommesenchymalstemcellsviaahyaluronicacidhydrogelatherapyforintrauterineadhesions