Cover Page
The handle http://hdl.handle.net/1887/80758 holds various files of this Leiden University
dissertation.
Author: Halaidych, O.V.
Title: Towards functional analysis of cerebrovascular cell types derived from human
induced pluripotent stem cells
Stellingen behorend bij het proefschrift getiteld:
Towards Functional Analysis of Cerebrovascular Cell Types
Derived from Human Induced Pluripotent Stem Cells
Oleh Halaidych
1. “Blood vessels in the brain are organized with surprising precision, support-ing the major brain circuits tasked with sensation, memory, and motion. Proper structural and functional brain connectivity, synaptic activity, and information processing all require precise regulation of cerebral blood flow (CBF), oxygen delivery, and energy metabolite supply.” Z. Zhao, A.R. Nelson, C. Betsholtz, B.V. Zlokovic, Establishment and Dysfunction of the Blood-Brain Barrier, Cell. 163 (2015) pp. 1064–1078.
2. “There is a growing list of CNS pathologies involving an element of BBB dys-function, including multiple sclerosis, hypoxia and ischemia, edema, Parkinson’s disease and Alzheimer’s disease, epilepsy, tumors, glaucoma, and lysosomal storage diseases.” N.J. Abbott, A.A.K. Patabendige, D.E.M. Dolman, S.R. Yusof, D.J. Begley, Structure and function of the blood-brain barrier., Neurobiology of Disease, 37 (2010), pp 13–25.
3. “The emergence of reprogramming as an approach to derive human induced pluripotent stem cells (hiPSCs) from patients and healthy individuals combined with efficient gene modification has led to unprecedented opportunities over the last several years to model human diseases.” R. Passier, V. Orlova, C. Mummery, Complex Tissue and Disease Modeling using hiPSCs. Cell Stem Cell. 18 (2016), pp 309–321.
4. “Issues that still need to be addressed include the lack of mature phenotypes in both hESC and hiPSC derivatives, the extent of improvement over animal mod-els for drug discovery, and the degree of complexity that can be recapitulated with in vitro stem cell models.” R. Passier, V. Orlova, C. Mummery, Complex Tissue and Disease Modeling using hiPSCs. Cell Stem Cell. 18 (2016), pp 309–321.
6. “The relatively new and rapidly growing field of “Organ-on-chip” technology brings a new class of in vitro models that combine heterotypic cellular cultures and micro-engineered devices, or “microfluidic chips”, to model processes of tissue- and organ-level physiology. This thesis.
7. “The availability of automated functional assays as well as robust quantitative methods would benefit accurate characterization of Ca2+ signaling and
contrac-tion in heterogeneous perivascular cell types and facilitate screening of potential pharmaceutical treatments for associated vascular diseases.” This thesis. 8. “Overall, the field of modeling processes of human physiology in vitro has
never been as exciting as nowadays and it provides stimulating challenges for curious minds.” This thesis.
9. “Product of optimism and knowledge is a constant.” Lev Landau (1908-1968). A solution to an easy problem brings expected results. On the other hand, when there is no or very little hope for success, cracking a hard puzzle is rewarding. 10. “The first principle is that you must not fool yourself and you are the easiest
