Induced Microglia Differentiation from Pluripotent Stem Cells
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Solution Overview
Problem
There is a deficiency in acquiring human microglia cells to investigate their roles in CNS development and neurological disorders, as studying these cells is challenging due to their rarity and difficulty in obtaining them from human fetal or adult CNS tissue.
Innovation Solution
A method is developed to produce human microglial-like cells (iMGLs) from pluripotent stem cells (PSCs) by differentiating them into induced hematopoietic progenitor cells (iHPCs) and then into iMGLs using specific differentiation media, which resemble fetal and adult microglia in terms of gene expression and function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If microglia cells are obtained from human fetal or adult CNS tissue, then the cells are authentic primary microglia, but the acquisition is difficult and the cells are rare
Solution Approach 1:
The patent creates in vitro differentiated microglia-like cells (iMGLs) from human pluripotent stem cells as a copy or model of primary microglia. These iMGLs replicate the key functional and molecular characteristics of authentic microglia, including expression of microglial markers (P2RY12, TMEM119, CX3CR1), cytokine secretion profiles, and phagocytic activity, providing a renewable alternative that is easier to obtain while maintaining reliability for research purposes
2Reliability
If microglia cells are obtained from human fetal or adult CNS tissue, then the cells are primary microglia, but the quantity obtained is limited
Solution Approach 1:
The patent uses human pluripotent stem cells (hPSCs), which can be expanded and maintained in culture indefinitely, as a preliminary source that can generate large quantities of microglia-like cells on demand. This preliminary action of establishing a renewable hPSC bank allows researchers to produce unlimited quantities of iMGLs for various experiments without being constrained by the limited availability of primary microglia from human tissue
Data Source
AI summary
Disclosed herein are various embodiments relating to methods of producing iMGLs, for example, from pluripotent stem cells (PSCs), methods of using iMGLs, and compositions of iMGLs. Also disclosed herein are methods to study various neurological disorders, such as for studying Alzheimer's disease. In addition, disclosed herein are methods of investigating genotypic and phenotypic effects of microglia cells in various physiological and pathological environments in the CNS and brain.