Cerebral organoids transplantation improves neurological motor function in rat brain injury.

Abstract

BACKGROUND AND PURPOSE:

Cerebral organoids (COs) have been used for studying brain development, neural disorders, and species-specific drug pharmacology and toxicology, but the potential of COs transplantation therapy for brain injury remains to be answered.

METHODS:

With preparation of traumatic brain injury (TBI) model of motor dysfunction, COs at 55 and 85 days (55 and 85 d-CO) were transplanted into damaged motor cortex separately to identify better transplantation donor for brain injury. Further, the feasibility, effectiveness, and underlying mechanism of COs transplantation therapy for brain injury were explored.

RESULTS:

55 d-CO was demonstrated as better transplantation donor than 85 d-CO, evidenced by more neurogenesis and higher cell survival rate without aggravating apoptosis and inflammation after transplantation into damaged motor cortex. Cells from transplanted COs had the potential of multilinage differentiation to mimic in-vivo brain cortical development, support region-specific reconstruction of damaged motor cortex, form neurotransmitter-related neurons, and migrate into different brain regions along corpus callosum. Moreover, COs transplantation upregulated hippocampal neural connection proteins and neurotrophic factors. Notably, COs transplantation improved neurological motor function and reduced brain damage.

CONCLUSIONS:

This study revealed 55 d-CO as better transplantation donor and demonstrated the feasibility and efficacy of COs transplantation in TBI, hoping to provide first-hand preclinical evidence of COs transplantation for brain injury.

• Authors: Zhi Wang, Shu-Na Wang, Tian-Ying Xu, Chen Hong, Ming-He Cheng, Peng-Xi Zhu, Jian-Sheng Lin, Ding-Feng Su, Chao-Yu Miao
• Journal: CNS neuroscience & therapeutics (CNS Neurosci Ther) Vol. 26 Issue 7 Pg. 682-697 (07 2020) ISSN: 1755-5949 [Electronic] England
• PMID: 32087606 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

Topics

• Animals
• Brain Injuries (physiopathology, therapy)
• Brain Tissue Transplantation (methods)
• Cell Movement (physiology)
• Cells, Cultured
• Embryonic Stem Cells (physiology, transplantation)
• Humans
• Male
• Motor Skills (physiology)
• Motor Skills Disorders (physiopathology, therapy)
• Neurogenesis (physiology)
• Organoids (physiology, transplantation)
• Rats
• Rats, Sprague-Dawley