Human iPSC-derived chondrocytes mimic juvenile chondrocyte function for the dual advantage of increased proliferation and resistance to IL-1β
Abstract Background Induced pluripotent stem cells (iPSC) provide an unlimited patient-specific cell source for regenerative medicine. Adult cells have had limited success in cartilage repair, but juvenile chondrocytes (from donors younger than 13 years of age) have been identified to generate super...
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| Format: | Article |
| Language: | English |
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BMC
2017-11-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-017-0696-x |
| _version_ | 1811301836474286080 |
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| author | Jieun Lee Piera Smeriglio Constance R. Chu Nidhi Bhutani |
| author_facet | Jieun Lee Piera Smeriglio Constance R. Chu Nidhi Bhutani |
| author_sort | Jieun Lee |
| collection | DOAJ |
| description | Abstract Background Induced pluripotent stem cells (iPSC) provide an unlimited patient-specific cell source for regenerative medicine. Adult cells have had limited success in cartilage repair, but juvenile chondrocytes (from donors younger than 13 years of age) have been identified to generate superior cartilage. With this perspective, the aim of these studies was to compare the human iPSC-derived chondrocytes (hiChondrocytes) to adult and juvenile chondrocytes and identify common molecular factors that govern their function. Methods Phenotypic and functional characteristics of hiChondrocytes were compared to juvenile and adult chondrocytes. Analyses of global gene expression profiling, independent gene expression, and loss-of-function studies were utilized to test molecular factors having a regulatory effect on hiChondrocytes and juvenile chondrocyte function. Results Here, we report that the iPSC-derived chondrocytes mimic juvenile chondrocytes in faster cell proliferation and resistance to IL-1β compared to adult chondrocytes. Whole genome transcriptome analyses revealed unique ECM factors and immune response pathways to be enriched in both juvenile and iPSC-derived chondrocytes as compared to adult chondrocytes. Loss-of-function studies demonstrated that CD24, a cell surface receptor enriched in both juvenile chondrocytes and hiChondrocytes, is a regulatory factor in both faster proliferation and resistance to proinflammatory cues in these chondrocyte populations. Conclusions Our studies identify that hiChondrocytes mimic juvenile chondrocytes for the dual advantage of faster proliferation and a reduced response to the inflammatory cytokine IL-1β. While developmental immaturity of iPSC-derived cells can be a challenge for tissues like muscle and brain, our studies demonstrate that it is advantageous for a tissue like cartilage that has limited regenerative ability in adulthood. |
| first_indexed | 2024-04-13T07:17:16Z |
| format | Article |
| id | doaj.art-d57b433f82f446d2b972dcb9390a02cb |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-13T07:17:16Z |
| publishDate | 2017-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-d57b433f82f446d2b972dcb9390a02cb2022-12-22T02:56:43ZengBMCStem Cell Research & Therapy1757-65122017-11-018111110.1186/s13287-017-0696-xHuman iPSC-derived chondrocytes mimic juvenile chondrocyte function for the dual advantage of increased proliferation and resistance to IL-1βJieun Lee0Piera Smeriglio1Constance R. Chu2Nidhi Bhutani3Department of Orthopaedic Surgery, Stanford University School of MedicineDepartment of Orthopaedic Surgery, Stanford University School of MedicineDepartment of Orthopaedic Surgery, Stanford University School of MedicineDepartment of Orthopaedic Surgery, Stanford University School of MedicineAbstract Background Induced pluripotent stem cells (iPSC) provide an unlimited patient-specific cell source for regenerative medicine. Adult cells have had limited success in cartilage repair, but juvenile chondrocytes (from donors younger than 13 years of age) have been identified to generate superior cartilage. With this perspective, the aim of these studies was to compare the human iPSC-derived chondrocytes (hiChondrocytes) to adult and juvenile chondrocytes and identify common molecular factors that govern their function. Methods Phenotypic and functional characteristics of hiChondrocytes were compared to juvenile and adult chondrocytes. Analyses of global gene expression profiling, independent gene expression, and loss-of-function studies were utilized to test molecular factors having a regulatory effect on hiChondrocytes and juvenile chondrocyte function. Results Here, we report that the iPSC-derived chondrocytes mimic juvenile chondrocytes in faster cell proliferation and resistance to IL-1β compared to adult chondrocytes. Whole genome transcriptome analyses revealed unique ECM factors and immune response pathways to be enriched in both juvenile and iPSC-derived chondrocytes as compared to adult chondrocytes. Loss-of-function studies demonstrated that CD24, a cell surface receptor enriched in both juvenile chondrocytes and hiChondrocytes, is a regulatory factor in both faster proliferation and resistance to proinflammatory cues in these chondrocyte populations. Conclusions Our studies identify that hiChondrocytes mimic juvenile chondrocytes for the dual advantage of faster proliferation and a reduced response to the inflammatory cytokine IL-1β. While developmental immaturity of iPSC-derived cells can be a challenge for tissues like muscle and brain, our studies demonstrate that it is advantageous for a tissue like cartilage that has limited regenerative ability in adulthood.http://link.springer.com/article/10.1186/s13287-017-0696-xHuman iPSC-derived chondrocytesCartilageInflammationJuvenile chondrocytesCD24 |
| spellingShingle | Jieun Lee Piera Smeriglio Constance R. Chu Nidhi Bhutani Human iPSC-derived chondrocytes mimic juvenile chondrocyte function for the dual advantage of increased proliferation and resistance to IL-1β Stem Cell Research & Therapy Human iPSC-derived chondrocytes Cartilage Inflammation Juvenile chondrocytes CD24 |
| title | Human iPSC-derived chondrocytes mimic juvenile chondrocyte function for the dual advantage of increased proliferation and resistance to IL-1β |
| title_full | Human iPSC-derived chondrocytes mimic juvenile chondrocyte function for the dual advantage of increased proliferation and resistance to IL-1β |
| title_fullStr | Human iPSC-derived chondrocytes mimic juvenile chondrocyte function for the dual advantage of increased proliferation and resistance to IL-1β |
| title_full_unstemmed | Human iPSC-derived chondrocytes mimic juvenile chondrocyte function for the dual advantage of increased proliferation and resistance to IL-1β |
| title_short | Human iPSC-derived chondrocytes mimic juvenile chondrocyte function for the dual advantage of increased proliferation and resistance to IL-1β |
| title_sort | human ipsc derived chondrocytes mimic juvenile chondrocyte function for the dual advantage of increased proliferation and resistance to il 1β |
| topic | Human iPSC-derived chondrocytes Cartilage Inflammation Juvenile chondrocytes CD24 |
| url | http://link.springer.com/article/10.1186/s13287-017-0696-x |
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