Implications and limitations of cellular reprogramming for psychiatric drug development
Brian T D Tobe1, Michael G Brandel, Jeffrey S Nye
11] Program in Stem Cell and Regenerative Biology, Sanford-Burnham Medical Research Institute, Burnham Institute for Medical Research, La Jolla, CA, USA [2] Department of Psychiatry, Veterans Administration Medical Center, La Jolla, CA, USA.
Experimental & Molecular Medicine
|November 16, 2013
Summary
Human-induced pluripotent stem cells (hiPSCs) offer new ways to model psychiatric diseases in the lab. Challenges remain in cell derivation, differentiation, and identifying disease-specific phenotypes for drug discovery.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Psychiatric Genetics
Background:
- Human-induced pluripotent stem cells (hiPSCs) derived from patient somatic cells enable in vitro modeling of neural physiology in psychiatric disorders.
- Current technological hurdles impede the widespread application of hiPSCs for psychiatric disease research.
Purpose of the Study:
- To outline the challenges and potential of using hiPSCs for modeling psychiatric diseases.
- To highlight the need for well-characterized patient cohorts and efficient differentiation protocols.
- To discuss the implications of reprogramming artifacts and drug effects on hiPSC-based research.
Main Methods:
- Review of current methodologies in hiPSC derivation and characterization for psychiatric research.
- Analysis of challenges in generating disease-relevant cell types and identifying cellular phenotypes.
- Discussion of strategies for converting cellular phenotypes into screening assays for drug discovery.
Main Results:
- Initial studies are beginning to identify cellular phenotypes relevant to psychiatric conditions.
- Coordination of patient material with comprehensive clinical, genetic, and neuroimaging data is underway.
- Psychiatric drugs have been observed to affect reprogramming efficiency in vitro, indicating potential complexities.
Conclusions:
- Despite significant challenges, hiPSC technology holds promise for advancing the translational pipeline in psychiatric therapeutics.
- Addressing issues in cell sourcing, standardization, and phenotype identification is crucial for successful implementation.
- Further research is needed to understand the impact of reprogramming and drug interactions on hiPSC models.
Related Concept Videos
01:29Somatic to iPS Cell Reprogramming
2.1K
Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
2.1K
01:06Induced Pluripotent Stem Cells
4.8K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
4.8K
01:21EPS and iPS Cells in Disease Research
3.2K
Embryonic and induced pluripotent stem cells are excellent models for disease research because of their ability to self-renew and differentiate into most cell types. Somatic cells from a patient are isolated and reprogrammed into induced pluripotent stem cells or iPSCs. These iPSCs are later differentiated into the desired cell type, which mirrors the diseased cell of the patient. In this way, disease models have been created for investigating diseases such as Down syndrome, type I diabetes,...
3.2K
01:24Methods of Nuclear Reprogramming
1.4K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
1.4K
01:22iPS Cell Differentiation
2.2K
The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
2.2K