Role of immediate early genes in the development of salivary gland organoids in polyisocyanopeptide hydrogels
Human salivary gland organoids have opened tremendous possibilities for regenerative medicine in patients undergoing radiotherapy for the treatment of head and neck cancer. However, their clinical translation is greatly limited by the current use of Matrigel for organoid derivation and expansion. He...
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| Format: | Article |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1100541/full |
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| author | Paulien Schaafsma Paulien Schaafsma Laura Kracht Mirjam Baanstra Mirjam Baanstra Anne L. Jellema-de Bruin Anne L. Jellema-de Bruin Robert P. Coppes Robert P. Coppes |
| author_facet | Paulien Schaafsma Paulien Schaafsma Laura Kracht Mirjam Baanstra Mirjam Baanstra Anne L. Jellema-de Bruin Anne L. Jellema-de Bruin Robert P. Coppes Robert P. Coppes |
| author_sort | Paulien Schaafsma |
| collection | DOAJ |
| description | Human salivary gland organoids have opened tremendous possibilities for regenerative medicine in patients undergoing radiotherapy for the treatment of head and neck cancer. However, their clinical translation is greatly limited by the current use of Matrigel for organoid derivation and expansion. Here, we envisage that the use of a fully, synthetic hydrogel based on the oligo (-ethylene glycol) functionalized polymer polyisocyanopeptides (PICs) can provide an environment suitable for the generation and expansion of salivary gland organoids (SGOs) after optimization of PIC polymer properties. We demonstrate that PIC hydrogels decorated with the cell-binding peptide RGD allow SGO formation from salivary gland (SG)-derived stem cells. This self-renewal potential is preserved for only 4 passages. It was found that SGOs differentiated prematurely in PIC hydrogels affecting their self-renewal capacity. Similarly, SGOs show decreased expression of immediate early genes (IEGs) after culture in PIC hydrogels. Activation of multiple signalling pathways involved in IEG expression by β-adrenergic agonist isoproterenol, led to increased stem cell self-renewal capacity as measured by organoid forming efficiency (OFE). These results indicate that PIC hydrogels are promising 3D matrices for SGOs, with the option to be used clinically, after further optimization of the hydrogel and culture conditions. |
| first_indexed | 2024-04-10T18:14:14Z |
| format | Article |
| id | doaj.art-f06ee0e4ca614e75bd338cd73c2e1139 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-10T18:14:14Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-f06ee0e4ca614e75bd338cd73c2e11392023-02-02T10:02:30ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-02-011010.3389/fmolb.2023.11005411100541Role of immediate early genes in the development of salivary gland organoids in polyisocyanopeptide hydrogelsPaulien Schaafsma0Paulien Schaafsma1Laura Kracht2Mirjam Baanstra3Mirjam Baanstra4Anne L. Jellema-de Bruin5Anne L. Jellema-de Bruin6Robert P. Coppes7Robert P. Coppes8Department of Biomedical Sciences of Cells and Systems, Section Molecular Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Biomedical Sciences of Cells and Systems, Section Molecular Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Biomedical Sciences of Cells and Systems, Section Molecular Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Biomedical Sciences of Cells and Systems, Section Molecular Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Biomedical Sciences of Cells and Systems, Section Molecular Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsHuman salivary gland organoids have opened tremendous possibilities for regenerative medicine in patients undergoing radiotherapy for the treatment of head and neck cancer. However, their clinical translation is greatly limited by the current use of Matrigel for organoid derivation and expansion. Here, we envisage that the use of a fully, synthetic hydrogel based on the oligo (-ethylene glycol) functionalized polymer polyisocyanopeptides (PICs) can provide an environment suitable for the generation and expansion of salivary gland organoids (SGOs) after optimization of PIC polymer properties. We demonstrate that PIC hydrogels decorated with the cell-binding peptide RGD allow SGO formation from salivary gland (SG)-derived stem cells. This self-renewal potential is preserved for only 4 passages. It was found that SGOs differentiated prematurely in PIC hydrogels affecting their self-renewal capacity. Similarly, SGOs show decreased expression of immediate early genes (IEGs) after culture in PIC hydrogels. Activation of multiple signalling pathways involved in IEG expression by β-adrenergic agonist isoproterenol, led to increased stem cell self-renewal capacity as measured by organoid forming efficiency (OFE). These results indicate that PIC hydrogels are promising 3D matrices for SGOs, with the option to be used clinically, after further optimization of the hydrogel and culture conditions.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1100541/fullxerostomiasalivary gland stem cellsmatrigelself-renewalpremature differentiationPIC hydrogels |
| spellingShingle | Paulien Schaafsma Paulien Schaafsma Laura Kracht Mirjam Baanstra Mirjam Baanstra Anne L. Jellema-de Bruin Anne L. Jellema-de Bruin Robert P. Coppes Robert P. Coppes Role of immediate early genes in the development of salivary gland organoids in polyisocyanopeptide hydrogels Frontiers in Molecular Biosciences xerostomia salivary gland stem cells matrigel self-renewal premature differentiation PIC hydrogels |
| title | Role of immediate early genes in the development of salivary gland organoids in polyisocyanopeptide hydrogels |
| title_full | Role of immediate early genes in the development of salivary gland organoids in polyisocyanopeptide hydrogels |
| title_fullStr | Role of immediate early genes in the development of salivary gland organoids in polyisocyanopeptide hydrogels |
| title_full_unstemmed | Role of immediate early genes in the development of salivary gland organoids in polyisocyanopeptide hydrogels |
| title_short | Role of immediate early genes in the development of salivary gland organoids in polyisocyanopeptide hydrogels |
| title_sort | role of immediate early genes in the development of salivary gland organoids in polyisocyanopeptide hydrogels |
| topic | xerostomia salivary gland stem cells matrigel self-renewal premature differentiation PIC hydrogels |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1100541/full |
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