CDKN2B upregulation prevents teratoma formation in multipotent fibromodulin-reprogrammed cells
| Autor: | Christos S Haveles, Zane Mills, Chia Soo, Eric Chen, Jong Kil Kim, Pu Yang, Xiaoxiao Pang, Kang Ting, Grace X. Chang, Chenshuang Li, Wenlu Jiang, Emily A. Berthiaume, Pin Ha, Xinli Zhang, Zhong Zheng |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Biology Regenerative medicine Cell Line 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Humans Induced pluripotent stem cell FREP Cyclin-Dependent Kinase Inhibitor p15 Regeneration (biology) Multipotent Stem Cells Teratoma General Medicine Cellular Reprogramming Cell biology Up-Regulation Gene Expression Regulation Neoplastic 030104 developmental biology 030220 oncology & carcinogenesis Stem cell Reprogramming Fibromodulin Adult stem cell Research Article |
| Zdroj: | The Journal of clinical investigation. 129(8) |
| ISSN: | 1558-8238 |
| Popis: | Tumorigenicity is a well-documented risk to overcome for pluripotent or multipotent cell applications in regenerative medicine. To address the emerging demand for safe cell sources in tissue regeneration, we established a novel, protein-based reprogramming method that does not require genome integration or oncogene activation to yield multipotent fibromodulin (FMOD)-reprogrammed (FReP) cells from dermal fibroblasts. When compared with induced pluripotent stem cells (iPSCs), FReP cells exhibited a superior capability for bone and skeletal muscle regeneration with markedly less tumorigenic risk. Moreover, we showed that the decreased tumorigenicity of FReP cells was directly related to an upregulation of cyclin-dependent kinase inhibitor 2B (CDKN2B) expression during the FMOD reprogramming process. Indeed, sustained suppression of CDKN2B resulted in tumorigenic, pluripotent FReP cells that formed teratomas in vivo that were indistinguishable from iPSC-derived teratomas. These results highlight the pivotal role of CDKN2B in cell fate determination and tumorigenic regulation and reveal an alternative pluripotent/multipotent cell reprogramming strategy that solely uses FMOD protein. |
| Databáze: | OpenAIRE |
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