Academic Journal
Large-scale engineering of hiPSC-derived nephron sheets and cryopreservation of their progenitors
| العنوان: | Large-scale engineering of hiPSC-derived nephron sheets and cryopreservation of their progenitors |
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| المؤلفون: | Wiersma, L.E., Avramut, M.C., Lievers, E., Rabelink, T.J., Berg, C.W. van den |
| المصدر: | Stem Cell Research and Therapy |
| سنة النشر: | 2022 |
| المجموعة: | Leiden Repository (Leiden University) |
| مصطلحات موضوعية: | Induced pluripotent stem cells, Kidney organoids, Kidney transplantation, Scale-up, Engineering, Cryopreservation, Regenerative medicine |
| الوصف: | Background: The generation of human induced pluripotent stem cells (hiPSCs) has opened a world of opportunities for stem cell-based therapies in regenerative medicine. Currently, several human kidney organoid protocols are available that generate organoids containing kidney structures. However, these kidney organoids are relatively small ranging up to 0.13 cm(2) and therefore contain a small number of nephrons compared to an adult kidney, thus defying the exploration of future use for therapy. Method: We have developed a scalable, easily accessible, and reproducible protocol to increase the size of the organoid up to a nephron sheet of 2.5 cm(2) up to a maximum of 12.6 cm(2) containing a magnitude of nephrons. Results: Confocal microscopy showed that the subunits of the nephrons remain evenly distributed throughout the entire sheet and that these tissue sheets can attain similar to 30,000-40,000 glomerular structures. Upon transplantation in immunodeficient mice, such nephron sheets became vascularized and matured. They also show reuptake of injected low-molecular mass dextran molecules in the tubular structures, indicative of glomerular filtration. Furthermore, we developed a protocol for the cryopreservation of intermediate mesoderm cells during the differentiation and demonstrate that these cells can be successfully thawed and recovered to create such tissue sheets. Conclusion: The scalability of the procedures, and the ability to cryopreserve the cells during differentiation are important steps forward in the translation of these differentiation protocols to future clinical applications such as transplantable auxiliary kidney tissue. ; Nephrology |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | lumc-id: 177463126; https://hdl.handle.net/1887/3564820 |
| DOI: | 10.1186/s13287-022-02881-5 |
| الاتاحة: | https://hdl.handle.net/1887/3564820 https://doi.org/10.1186/s13287-022-02881-5 |
| رقم الانضمام: | edsbas.B7355F17 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s13287-022-02881-5 |
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