Human forebrain endothelial cell therapy for psychiatric disorders
Debkanya Datta1,2,3, Sivan Subburaju1,2,3, Sarah Kaye1,3
1Angiogenesis and Brain Development Laboratory, Huntington Medical Research Institutes (HMRI), 686 S Fair Oaks Avenue, Pasadena, CA, 91105, USA.
Molecular Psychiatry
|July 15, 2020
Summary
Transplanting human stem cell-derived interneurons is a promising therapy for neuropsychiatric disorders. Co-transplanting these with human periventricular endothelial cells significantly speeds up migration and improves treatment outcomes.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Cellular Biology
Background:
- Reductions in GABAergic interneurons are linked to severe neuropsychiatric disorders.
- Current stem cell therapies for these disorders face challenges due to slow neuron migration.
- Periventricular endothelial cells guide interneuron migration and possess relevant signaling pathways.
Purpose of the Study:
- To investigate the therapeutic potential of co-transplanting human interneurons with human periventricular endothelial cells.
- To determine if this strategy accelerates interneuron migration and improves treatment efficacy in a preclinical model.
Main Methods:
- Generated and characterized human periventricular endothelial cells from human pluripotent stem cells.
- Co-cultured human interneurons with these endothelial cells in vitro.
- Performed xenograft studies in mice, comparing neuron-only transplants with co-transplants.
- Assessed interneuron migration, distribution, and behavioral outcomes in a preclinical psychiatric disorder model.
Main Results:
- Co-culture significantly accelerated human interneuron migration in vitro.
- In vivo, co-transplantation led to faster migration and wider distribution of grafted interneurons compared to neuron-only grafts.
- The co-transplantation strategy rescued abnormal behavioral symptoms within one month in a preclinical model.
Conclusions:
- Co-transplantation of human interneurons with human periventricular endothelial cells enhances migration and therapeutic efficacy.
- This strategy offers a promising approach for cell-based therapies in neuropsychiatric disorders.
- Angiogenesis-mediated strategies hold potential for advancing psychiatric disorder treatments.
