Related Experiment Video
Updated: Oct 1, 2025
Author Spotlight: Advancing Understanding Through Technological Innovations in Psychoneuroimmunology
Published on: May 31, 2024
Patient-Derived In Vitro Models of Microglial Function and Synaptic Engulfment in Schizophrenia
Steven D Sheridan1, Joy E Horng1, Roy H Perlis1
1Center for Genomic Medicine and Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
Abstract:
Multiple lines of evidence implicate dysregulated microglia-mediated synaptic pruning in the pathophysiology of schizophrenia. In vitro human cellular studies represent a promising means of pursuing this hypothesis, complementing efforts with animal models and postmortem human data while addressing their limitations. The challenges in culturing homogeneous populations of cells derived from postmortem or surgical biopsy brain material from patients, and their limited availability, has led to a focus on differentiation of induced pluripotent stem cells. These methods too have limitations, in that they disrupt the epigenome and can demonstrate line-to-line variability due in part to extended time in culture, partial reprogramming, and/or residual epigenetic memory from the cell source, yielding large technical artifacts. Yet another strategy uses direct transdifferentiation of peripheral mononuclear blood cells, or umbilical cord blood cells, to microglia-like cells. Any of these approaches can be paired with patient-derived synaptosomes from differentiated neurons as a simpler alternative to co-culture. Patient-derived microglia models may facilitate identification of novel modulators of synaptic pruning and identification of biomarkers that may allow more targeted early interventions.
Insights
Schizophrenia research explores microglia
Area of Science:
- Neuroscience
- Cell Biology
- Psychiatry
Background:
- Schizophrenia pathophysiology is linked to abnormal microglia-mediated synaptic pruning.
- In vitro human cellular studies offer a valuable approach to investigate this link.
- Limitations exist in current cell culture methods, including patient-derived cells and induced pluripotent stem cells.
Purpose of the Study:
- To explore the potential of patient-derived microglia models for schizophrenia research.
- To identify novel modulators of synaptic pruning and potential biomarkers for early intervention.
Main Methods:
- Utilizing induced pluripotent stem cells for microglia differentiation.
- Employing direct transdifferentiation of peripheral blood cells to create microglia-like cells.
- Pairing these cellular models with patient-derived synaptosomes for functional studies.
Main Results:
- Acknowledges technical artifacts and variability in current stem cell differentiation methods.
- Highlights the potential of transdifferentiation and synaptosome co-culture approaches.
- Suggests patient-derived microglia models can overcome limitations of existing methods.
Conclusions:
- Patient-derived microglia models hold promise for advancing schizophrenia research.
- These models can facilitate the discovery of therapeutic targets and biomarkers.
- Improved cellular models are crucial for understanding microglia's role in schizophrenia.
More Related Videos
11:19Human Microglia-like Cells: Differentiation from Induced Pluripotent Stem Cells and In Vitro Live-cell Phagocytosis Assay using Human Synaptosomes
Published on: August 18, 2022
07:45An In Vitro Model for the Study of Cellular Pathophysiology in Globoid Cell Leukodystrophy
Published on: October 21, 2014