Mesenchymal stem cell therapy ameliorates metabolic dysfunction and restores fertility in a PCOS mouse model through interleukin-10
BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in reproductive-age women. Excessive inflammation and elevated androgen production from ovarian theca cells are key features of PCOS. Human bone marrow mesenchymal stem cells (BM-hMSC) and their secreted factors (secretome) exhibit robust anti-inflammatory capabilities in various biological systems. We evaluated the therapeutic efficacy of BM-hMSC and its secretome in both in vitro and in vivo PCOS models.
METHODS: For in vitro experiment, we treated conditioned media from BM-hMSC to androgen-producing H293R cells and analyzed androgen-producing gene expression. For in vivo experiment, BM-hMSC were implanted into letrozole (LTZ)-induced PCOS mouse model. BM-hMSC effect in androgen-producing cells or PCOS model mice was assessed by monitoring cell proliferation (immunohistochemistry), steroidogenic gene expression (quantitative real-time polymerase chain reaction [qRT-PCR] and Western blot, animal tissue assay (H&E staining), and fertility by pup delivery.
RESULTS: BM-hMSC significantly downregulate steroidogenic gene expression, curb inflammation, and restore fertility in treated PCOS animals. The anti-inflammatory cytokine interleukin-10 (IL-10) played a key role in mediating the effects of BM-hMSC in our PCOS models. We demonstrated that BM-hMSC treatment was improved in metabolic and reproductive markers in our PCOS model and able to restore fertility.
CONCLUSION: Our study demonstrates for the first time the efficacy of intra-ovarian injection of BM-hMSC or its secretome to treat PCOS-related phenotypes, including both metabolic and reproductive dysfunction. This approach may represent a novel therapeutic option for women with PCOS. Our results suggest that BM-hMSC can reverse PCOS-induced inflammation through IL-10 secretion. BM-hMSC might be a novel and robust therapeutic approach for PCOS treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Stem cell research & therapy - 12(2021), 1 vom: 07. Juli, Seite 388 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chugh, Rishi Man [VerfasserIn] |
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| Links: |
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| Themen: |
130068-27-8 |
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| Anmerkungen: |
Date Completed 12.07.2021 Date Revised 12.07.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1186/s13287-021-02472-w |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM327797460 |
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| 100 | 1 | |a Chugh, Rishi Man |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Mesenchymal stem cell therapy ameliorates metabolic dysfunction and restores fertility in a PCOS mouse model through interleukin-10 |
| 264 | 1 | |c 2021 | |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in reproductive-age women. Excessive inflammation and elevated androgen production from ovarian theca cells are key features of PCOS. Human bone marrow mesenchymal stem cells (BM-hMSC) and their secreted factors (secretome) exhibit robust anti-inflammatory capabilities in various biological systems. We evaluated the therapeutic efficacy of BM-hMSC and its secretome in both in vitro and in vivo PCOS models | ||
| 520 | |a METHODS: For in vitro experiment, we treated conditioned media from BM-hMSC to androgen-producing H293R cells and analyzed androgen-producing gene expression. For in vivo experiment, BM-hMSC were implanted into letrozole (LTZ)-induced PCOS mouse model. BM-hMSC effect in androgen-producing cells or PCOS model mice was assessed by monitoring cell proliferation (immunohistochemistry), steroidogenic gene expression (quantitative real-time polymerase chain reaction [qRT-PCR] and Western blot, animal tissue assay (H&E staining), and fertility by pup delivery | ||
| 520 | |a RESULTS: BM-hMSC significantly downregulate steroidogenic gene expression, curb inflammation, and restore fertility in treated PCOS animals. The anti-inflammatory cytokine interleukin-10 (IL-10) played a key role in mediating the effects of BM-hMSC in our PCOS models. We demonstrated that BM-hMSC treatment was improved in metabolic and reproductive markers in our PCOS model and able to restore fertility | ||
| 520 | |a CONCLUSION: Our study demonstrates for the first time the efficacy of intra-ovarian injection of BM-hMSC or its secretome to treat PCOS-related phenotypes, including both metabolic and reproductive dysfunction. This approach may represent a novel therapeutic option for women with PCOS. Our results suggest that BM-hMSC can reverse PCOS-induced inflammation through IL-10 secretion. BM-hMSC might be a novel and robust therapeutic approach for PCOS treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Cell transplantation | |
| 650 | 4 | |a Cytokines | |
| 650 | 4 | |a Interleukin | |
| 650 | 4 | |a Mesenchymal stem cells (MSCs) | |
| 650 | 7 | |a Interleukin-10 |2 NLM | |
| 650 | 7 | |a 130068-27-8 |2 NLM | |
| 700 | 1 | |a Park, Hang-Soo |e verfasserin |4 aut | |
| 700 | 1 | |a El Andaloussi, Abdeljabar |e verfasserin |4 aut | |
| 700 | 1 | |a Elsharoud, Amro |e verfasserin |4 aut | |
| 700 | 1 | |a Esfandyari, Sahar |e verfasserin |4 aut | |
| 700 | 1 | |a Ulin, Mara |e verfasserin |4 aut | |
| 700 | 1 | |a Bakir, Lale |e verfasserin |4 aut | |
| 700 | 1 | |a Aboalsoud, Alshimaa |e verfasserin |4 aut | |
| 700 | 1 | |a Ali, Mohamed |e verfasserin |4 aut | |
| 700 | 1 | |a Ashour, Dalia |e verfasserin |4 aut | |
| 700 | 1 | |a Igboeli, Prosper |e verfasserin |4 aut | |
| 700 | 1 | |a Ismail, Nahed |e verfasserin |4 aut | |
| 700 | 1 | |a McAllister, Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Al-Hendy, Ayman |e verfasserin |4 aut | |
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