Research progress of stem cell therapy for endometrial injury

doi:10.1016/j.mtbio.2022.100389

Review

. 2022 Aug 8:16:100389.

doi: 10.1016/j.mtbio.2022.100389. eCollection 2022 Dec.

Research progress of stem cell therapy for endometrial injury

Juan Cen^{1

2}, Yichen Zhang², Yindu Bai², Shenqian Ma^{1

3}, Chuan Zhang⁴, Lin Jin^{1

5}, Shaofeng Duan², Yanan Du³, Yuqi Guo^{1

6}

Affiliations

¹ Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China.
² Key Laboratory of Natural Medicine and Immune Engineering, School of Pharmacy, Henan University, Kaifeng, 475001, China.
³ Department of Biomedical Engineering, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, 100084, China.
⁴ School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Shanghai Jiao Tong University, Shanghai, 200240, China.
⁵ International Joint Research Laboratory for Biomedical Nanomaterials of Henan, Zhoukou Normal University, Zhoukou, 466001, China.
⁶ Engineering Research Center for Gynecological Oncology Nanomedicine of Henan Province, Zhengzhou, 450003, China.

PMID: 36033375
PMCID: PMC9403503
DOI: 10.1016/j.mtbio.2022.100389

Review

Research progress of stem cell therapy for endometrial injury

Juan Cen et al. Mater Today Bio. 2022.

. 2022 Aug 8:16:100389.

doi: 10.1016/j.mtbio.2022.100389. eCollection 2022 Dec.

Authors

Juan Cen^{1

2}, Yichen Zhang², Yindu Bai², Shenqian Ma^{1

3}, Chuan Zhang⁴, Lin Jin^{1

5}, Shaofeng Duan², Yanan Du³, Yuqi Guo^{1

6}

Affiliations

¹ Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China.
² Key Laboratory of Natural Medicine and Immune Engineering, School of Pharmacy, Henan University, Kaifeng, 475001, China.
³ Department of Biomedical Engineering, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, 100084, China.
⁴ School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Shanghai Jiao Tong University, Shanghai, 200240, China.
⁵ International Joint Research Laboratory for Biomedical Nanomaterials of Henan, Zhoukou Normal University, Zhoukou, 466001, China.
⁶ Engineering Research Center for Gynecological Oncology Nanomedicine of Henan Province, Zhengzhou, 450003, China.

PMID: 36033375
PMCID: PMC9403503
DOI: 10.1016/j.mtbio.2022.100389

Abstract

Endometrial damage is an important factor leading to infertility and traditional conventional treatments have limited efficacy. As an emerging technology in recent years, stem cell therapy has provided new hope for the treatment of this disease. By comparing the advantages of stem cells from different sources, it is believed that menstrual blood endometrial stem cells have a good application prospect as a new source of stem cells. However, the clinical utility of stem cells is still limited by issues such as colonization rates, long-term efficacy, tumor formation, and storage and transportation. This paper summarizes the mechanism by which stem cells repair endometrial damage and clarifies the material basis of their effects from four aspects: replacement of damaged sites, paracrine effects, interaction with growth factors, and other new _targets. According to the pathological characteristics and treatment requirements of intrauterine adhesion (IUA), the research work to solve the above problems from the aspects of functional bioscaffold preparation and multi-functional platform construction is also summarized. From the perspective of scaffold materials and component functions, this review will provide a reference for comprehensively optimizing the clinical application of stem cells.

Keywords: Endometrial injury; Hydrogel; IUA; Scaffold material; Stem cell therapy.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

**Fig. 1**
Mechanisms of endometrial injury and main treatment strategies.

**Fig. 2**
Human derived stem cells. Stem cells which have been reported to treat endometrial injury were labeled with blue color. Neural stem cells (NSCs); Bone marrow derived mesenchymal stem cells (BMSCs); Adipose-derived stem cells (ADSCs); skeletal Muscle mesenchymal stem cells (MDSCs); Gingival mesenchymal stem cells (GMSCs); Tonsil mesenchymal stem cells (TMSCs); Synovium-derived mesenchymal stem cells (SMSCs); human Umbilical cord blood mesenchymal stem cells (UCB- MSCs); Endometrial mesenchymal stem cells (EnSCs); Menstrual blood derived mesenchymal stem cells (MenSCs); human Placental mesenchymal stem cells (P-MSCs); Umbilical cord mesenchymal stem cells (UC-MSCs); embryonic stem cells (ESCs); Amniotic fluid mesenchymal stem cells (AF-MSCs); human amniotic mesenchymal stromal cells (AMSCs).

**Fig. 3**
Mechanism of stem cells to repair endometrial damage.

**Fig. 4**
Major scaffold systems for IUA treatment in stem cell therapy. A: Polymer-based hydrogel, polymer could be Pluronic F-127, AP, HP, PLGA, PGS, PEG, GelMA or ColMA. Polymer-based hydrogels can encapsulate multiple components like stem cells, drug molecules, growth factor, etc [18,19,[114], [115], [116], [117], [118], [119], [120], [121]]. B: Polymer-based hydrogel, polymer could be ABA-type triblock copolymers (A Block: DEAEMA-co-MEO2MA-co-OEGMA, B Block: PEG [119]); LCST, low critical solution temperature. C: Polysaccharide-based hydrogels, e.g. Fibrin/HA-Stem Cells [124]; D: Protein-based hydrogels, e.g. 3D-printed gelatin/alginate hydrogel [136]; E: Protein-based hydrogel, e.g. Collagen hydrogel [134]; F: Cellular component materials: e.g. ECM scaffold [148]; G: Other materials, e.g. single walled carbon nanotubes (SWCNTs) [149].

**Fig. 5**
Common multifunctional short peptides and their positive effects on stem cell transplantation.

See this image and copyright information in PMC

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References

1. Deans R., Abbott J. Review of intrauterine adhesions. J. Minim. Invasive Gynecol. 2010;17:555–569. doi: 10.1016/j.jmig.2010.04.016. - DOI - PubMed
1. Xu L., Ding L., Wang L., Cao Y., Zhu H., Lu J., Li X.a., Song T., Hu Y., Dai J. Umbilical cord-derived mesenchymal stem cells on scaffolds facilitate collagen degradation via upregulation of MMP-9 in rat uterine scars. Stem Cell Res. Ther. 2017;8:84. doi: 10.1186/s13287-017-0535-0. - DOI - PMC - PubMed
1. Orçan S., Seven A., Isık H., Timur H., Caydere M., Ustün H., Batıoglu S. Resveratrol inhibits postoperative adhesion formation in a rat uterine horn adhesion model. Hum. Fertil. 2012;15:217–220. doi: 10.3109/14647273.2012.717337. - DOI - PubMed
1. Miwa I., Tamura H., Takasaki A., Yamagata Y., Shimamura K., Sugino N. Pathophysiologic features of "thin" endometrium. Fertil. Steril. 2009;91:998–1004. doi: 10.1016/j.fertnstert.2008.01.029. - DOI - PubMed
1. Takasaki A., Tamura H., Miwa I., Taketani T., Shimamura K., Sugino N. Endometrial growth and uterine blood flow: a pilot study for improving endometrial thickness in the patients with a thin endometrium. Fertil. Steril. 2010;93:1851–1858. doi: 10.1016/j.fertnstert.2008.12.062. - DOI - PubMed

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[1] Deans R., Abbott J. Review of intrauterine adhesions. J. Minim. Invasive Gynecol. 2010;17:555–569. doi: 10.1016/j.jmig.2010.04.016. - DOI - PubMed

[2] Deans R., Abbott J. Review of intrauterine adhesions. J. Minim. Invasive Gynecol. 2010;17:555–569. doi: 10.1016/j.jmig.2010.04.016. - DOI - PubMed

[3] Xu L., Ding L., Wang L., Cao Y., Zhu H., Lu J., Li X.a., Song T., Hu Y., Dai J. Umbilical cord-derived mesenchymal stem cells on scaffolds facilitate collagen degradation via upregulation of MMP-9 in rat uterine scars. Stem Cell Res. Ther. 2017;8:84. doi: 10.1186/s13287-017-0535-0. - DOI - PMC - PubMed

[4] Xu L., Ding L., Wang L., Cao Y., Zhu H., Lu J., Li X.a., Song T., Hu Y., Dai J. Umbilical cord-derived mesenchymal stem cells on scaffolds facilitate collagen degradation via upregulation of MMP-9 in rat uterine scars. Stem Cell Res. Ther. 2017;8:84. doi: 10.1186/s13287-017-0535-0. - DOI - PMC - PubMed

[5] Orçan S., Seven A., Isık H., Timur H., Caydere M., Ustün H., Batıoglu S. Resveratrol inhibits postoperative adhesion formation in a rat uterine horn adhesion model. Hum. Fertil. 2012;15:217–220. doi: 10.3109/14647273.2012.717337. - DOI - PubMed

[6] Orçan S., Seven A., Isık H., Timur H., Caydere M., Ustün H., Batıoglu S. Resveratrol inhibits postoperative adhesion formation in a rat uterine horn adhesion model. Hum. Fertil. 2012;15:217–220. doi: 10.3109/14647273.2012.717337. - DOI - PubMed

[7] Miwa I., Tamura H., Takasaki A., Yamagata Y., Shimamura K., Sugino N. Pathophysiologic features of "thin" endometrium. Fertil. Steril. 2009;91:998–1004. doi: 10.1016/j.fertnstert.2008.01.029. - DOI - PubMed

[8] Miwa I., Tamura H., Takasaki A., Yamagata Y., Shimamura K., Sugino N. Pathophysiologic features of "thin" endometrium. Fertil. Steril. 2009;91:998–1004. doi: 10.1016/j.fertnstert.2008.01.029. - DOI - PubMed

[9] Takasaki A., Tamura H., Miwa I., Taketani T., Shimamura K., Sugino N. Endometrial growth and uterine blood flow: a pilot study for improving endometrial thickness in the patients with a thin endometrium. Fertil. Steril. 2010;93:1851–1858. doi: 10.1016/j.fertnstert.2008.12.062. - DOI - PubMed

[10] Takasaki A., Tamura H., Miwa I., Taketani T., Shimamura K., Sugino N. Endometrial growth and uterine blood flow: a pilot study for improving endometrial thickness in the patients with a thin endometrium. Fertil. Steril. 2010;93:1851–1858. doi: 10.1016/j.fertnstert.2008.12.062. - DOI - PubMed

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Research progress of stem cell therapy for endometrial injury

Affiliations

Research progress of stem cell therapy for endometrial injury

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Conflict of interest statement

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