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Cerebral Organoids Repair Ischemic Stroke Brain Injury
- Source :
- Translational Stroke Research
- Publication Year :
- 2019
- Publisher :
- Springer US, 2019.
-
Abstract
- Stroke is the second leading cause of death and main cause of disability worldwide, but with few effective therapies. Although stem cell-based therapy has been proposed as an exciting regenerative medicine strategy for brain injury, there are limitations. The developed cerebral organoids (COs) represent a promising transplantation source for stroke that remains to be answered. Here, we transplanted COs at 55 days and explored the feasibility in the rat middle cerebral artery occlusion (MCAO) model of stroke. COs transplantation at 6 h or even 24 h after MCAO significantly reduces brain infarct volume and improves neurological motor function. Transplanted COs show the potential of multilineage differentiation to mimic in vivo cortical development, support motor cortex region-specific reconstruction, form neurotransmitter-related neurons, and achieve synaptic connection with host brain via in situ differentiation and cell replacement in stroke. Cells from transplanted COs show extensive migration into different brain regions along corpus callosum. The mechanisms underlying COs transplantation therapy are also associated with enhanced neurogenesis, synaptic reconstruction, axonal regeneration and angiogenesis, and decreased neural apoptosis with more survival neurons after stroke. Moreover, COs transplantation promotes predominantly exogenous neurogenesis in the transplantation periphery of ipsilateral cortex and predominantly endogenous neurogenesis in the hippocampus and subventricular zone. Together, we demonstrate the efficacy and underlying mechanisms of COs transplantation in stroke. This preliminary but promising study provides first-hand preclinical evidence for COs transplantation as a potential and effective intervention for stroke treatment. Electronic supplementary material The online version of this article (10.1007/s12975-019-00773-0) contains supplementary material, which is available to authorized users.
- Subjects :
- Male
medicine.medical_specialty
Neurology
Neurogenesis
Subventricular zone
Hippocampus
Corpus callosum
Brain Ischemia
Rats, Sprague-Dawley
medicine
Animals
Humans
Cerebral organoids
Stroke
Cells, Cultured
Ischemic Stroke
Transplantation
business.industry
General Neuroscience
Functional recovery
Cell Differentiation
Recovery of Function
medicine.disease
Organoids
Brain damage repair
medicine.anatomical_structure
Brain Injuries
Original Article
Neurology (clinical)
Stem cell
Cardiology and Cardiovascular Medicine
business
Neuroscience
Stem Cell Transplantation
Subjects
Details
- Language :
- English
- ISSN :
- 1868601X and 18684483
- Volume :
- 11
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Translational Stroke Research
- Accession number :
- edsair.doi.dedup.....8ea4e47713bcd4743f540006a25d479d