Novel techniques for engineering neural tissue using human induced pluripotent stem cells

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dc.contributor.authorDe la Vega Reyes, Laura
dc.contributor.supervisorWillerth, Stephanie
dc.date.accessioned2019-12-24T19:01:53Z
dc.date.copyright2019en_US
dc.date.issued2019-12-24
dc.degree.departmentDepartment of Mechanical Engineering
dc.degree.levelDoctor of Philosophy Ph.D.en_US
dc.description.abstractTissue engineering (TE) uses a combination of biomaterial scaffolds, cells, and drug delivery systems (DDS) to create tissues that resemble the human physiology. Such engineered tissues could be used to treat, repair, replace, and augment damaged tissues or organs, for disease modeling, and drug screening purposes. This work describes the development and use of novel strategies for engineering neural tissue using a combination of drug delivery systems (DDS), human induced pluripotent stem cells (hiPSCs), and bioprinting technologies for the generation of a drug screening tool to be used in the process of drug discovery and development. The DDS consisted of purmorphamine (puro) loaded microspheres that were fabricated using an oil-in-water single emulsion with 84% encapsulation efficiency and showed the slow release of puro for up to 46 days in vitro. Puro and retinoic acid (RA)-loaded microspheres were combined with hiPSCs-derived neural aggregates (NAs) that differentiated into neural tissues expressing βT-III and showed increased neural extension. hiPCS-derived neural progenitor cells (NPCs) were bioprinted on a layer-by-layer using a fibrin based-bioink and extrusion based- bioprinting. The bioprinted structures showed >81% cellular viability after 7 days of culture in vitro and the expression of the mature motor neuron (MN) markers HB9 and CHAT. Lastly, hiPCS-derived NPCs were bioprinted in combination with puro and RA-loaded microspheres and cultured for 45 days in vitro. The microspheres slowly released the drug and after 30 and 45 days the tissues contained mature neurons, astrocytes and oligodendrocytes expressing CHAT, GFAP, and O4, respectively. Changes in membrane potential indicated tissue responsiveness to different types of treatments such as acetylcholine and gamma-aminobutyric acid (GABA). In the future the bioprinted tissues could contain localized regions of varied drug releasing microspheres using a concentration gradient to promote differentiation into specific cell types in order to create more complex tissues. Moreover, these tissues will benefit from the presence of a neurovascular unit (NVU). Upon validation, the engineered tissues could be used as preclinical tools to test potential drugs and be used for personalized medicine by using patient specific hiPSCs.en_US
dc.description.embargo2020-11-19
dc.description.scholarlevelGraduateen_US
dc.identifier.bibliographicCitationDe la Vega L, Karmirian K, Willerth SM. Engineering Neural Tissue from Human Pluripotent Stem Cells Using Novel Small Molecule Releasing Microspheres. Advanced Biosystems. 2018;0(0):1800133. De la Vega L, Rosas Gomez D, Abelseth E, Abelseth L, Alisson da Silva V, Willerth SM. 3D bioprinting human induced pluripotent stem cell-derived neural tissues using a novel Lab-on-a-Printer technology. Applied Science 2018 In press.en_US
dc.identifier.bibliographicCitationDe la Vega L, Karmirian K, Willerth SM. Engineering Neural Tissue from Human Pluripotent Stem Cells Using Novel Small Molecule Releasing Microspheres. Advanced Biosystems. 2018;0(0):1800133.en_US
dc.identifier.bibliographicCitationDe la Vega L, Rosas Gomez D, Abelseth E, Abelseth L, Alisson da Silva V, Willerth SM. 3D bioprinting human induced pluripotent stem cell-derived neural tissues using a novel Lab-on-a-Printer technology. Applied Science 2018 In press.en_US
dc.identifier.urihttp://hdl.handle.net/1828/11427
dc.languageEnglisheng
dc.language.isoenen_US
dc.rightsAvailable to the World Wide Weben_US
dc.subjectStem Cellsen_US
dc.subjectBiomedical Engineeringen_US
dc.subjectBiomaterialsen_US
dc.subjectTissue Engineeringen_US
dc.subjectNeural tissueen_US
dc.subjectRegenerative medicineen_US
dc.subjectBioinken_US
dc.subjectDrug delivery systemen_US
dc.subjectmicrosphereen_US
dc.subjectRetinoic Aciden_US
dc.subjectPurmorphamineen_US
dc.subjectSpinal corden_US
dc.subjectPluripotent Stem Cellsen_US
dc.subjectFibrinen_US
dc.subject3D bioprintingen_US
dc.titleNovel techniques for engineering neural tissue using human induced pluripotent stem cellsen_US
dc.typeThesisen_US

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