Academic Journal
Important role of the SDF-1/CXCR4 axis in the homing of systemically transplanted human amnion-derived mesenchymal stem cells (hAD-MSCs) to ovaries in rats with chemotherapy-induced premature ovarian insufficiency (POI)
| Title: | Important role of the SDF-1/CXCR4 axis in the homing of systemically transplanted human amnion-derived mesenchymal stem cells (hAD-MSCs) to ovaries in rats with chemotherapy-induced premature ovarian insufficiency (POI) |
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| Authors: | Li Ling, Jiying Hou, Dandan Liu, Dongyuan Tang, Yanqin Zhang, Qianru Zeng, Heng Pan, Ling Fan |
| Source: | Stem Cell Research & Therapy, Vol 13, Iss 1, Pp 1-19 (2022) |
| Publisher Information: | BMC, 2022. |
| Publication Year: | 2022 |
| Collection: | LCC:Medicine (General) LCC:Biochemistry |
| Subject Terms: | Premature ovarian insufficiency (POI), Human amnion-derived mesenchymal stem cells (hAD-MSCs), Transplantation, Stem cell homing, Stromal cell-derived factor-1 (SDF-1), CXC chemokine receptor 4 (CXCR4), Medicine (General), R5-920, Biochemistry, QD415-436 |
| More Details: | Abstract Background Chemotherapy can induce premature ovarian insufficiency (POI). POI causes multiple sequelae and is currently incurable. As shown in our previous studies, systemically transplanted human amnion-derived mesenchymal stem cells (hAD-MSCs) home to ovaries with chemotherapy-induced POI and subsequently reduce ovarian injury and improve ovarian function in rats with POI. However, the cellular mechanisms that direct the migration and homing of hAD-MSCs to ovaries with chemotherapy-induced POI are incompletely understood. This study investigated the role of the SDF-1/CXCR4 axis in the migration and homing of systemically transplanted hAD-MSCs to ovaries with chemotherapy-induced POI and its relevant downstream signalling pathways. Methods CXCR4 expression in hAD-MSCs was assessed using Western blotting and immunofluorescence staining. hAD-MSC migration was tested using Transwell migration assays. SDF-1 levels were detected using ELISA. Seventy-two female SD rats were randomly divided into the control, POI, hAD-MSCs and hAD-MSCs + AMD3100 groups. Cyclophosphamide was used to establish rat POI models. For inhibitor treatment, hAD-MSCs were pretreated with AMD3100 before transplantation. PKH26-labeled hAD-MSCs were injected into the tail vein of POI rats 24 h after chemotherapy. After hAD-MSC transplantation, the homing of hAD-MSCs to ovaries and ovarian function and pathological changes were examined. We further investigated the molecular mechanisms by detecting the PI3K/Akt and ERK1/2 signalling pathways. Results hAD-MSCs expressed CXCR4. SDF-1 induced hAD-MSC migration in vitro. SDF-1 levels in ovaries and serum were significantly increased in rats with chemotherapy-induced POI, and ovaries with POI induced the homing of hAD-MSCs expressing CXCR4. Blocking the SDF-1/CXCR4 axis with AMD3100 significantly reduced the number of hAD-MSCs homing to ovaries with POI and further reduced their efficacy in POI treatment. The binding of SDF-1 to CXCR4 activated the PI3K/Akt signalling pathway, and LY294002 significantly inhibited hAD-MSC migration induced by SDF-1 in vitro. Moreover, inhibition of the PI3K/Akt signalling pathway significantly reduced the number of systemically transplanted hAD-MSCs homing to chemotherapy-induced ovaries in rats with POI. Conclusions SDF-1/CXCR4 axis partially mediates the migration and homing of systemically transplanted hAD-MSCs to the ovaries of rats with chemotherapy-induced POI, and the PI3K/Akt signalling pathway might be involved in the migration and homing of hAD-MSCs mediated by the SDF-1/CXCR4 axis. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1757-6512 |
| Relation: | https://doaj.org/toc/1757-6512 |
| DOI: | 10.1186/s13287-022-02759-6 |
| Access URL: | https://doaj.org/article/4fb655dd535d47efb87b08e9b8574904 |
| Accession Number: | edsdoj.4fb655dd535d47efb87b08e9b8574904 |
| Database: | Directory of Open Access Journals |
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| ISSN: | 17576512 |
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| DOI: | 10.1186/s13287-022-02759-6 |
| Published in: | Stem Cell Research & Therapy |
| Language: | English |