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Updated: Jun 10, 2026
Transplantation of Human Induced Pluripotent Stem Cell-Derived Microglia in Immunocompetent Mice Brain via Non-Invasive Transnasal Route
Published on: May 31, 2022
Human microglia transplanted in rat focal ischemia brain induce neuroprotection and behavioral improvement
Dashdemberel Narantuya1, Atsushi Nagai, Abdullah Md Sheikh
1Department of Neurology, Shimane University School of Medicine, Izumo, Japan.
Background And Purpose:
Microglia are resident immunocompetent and phagocytic cells of central nervous system (CNS), which produce various cytokines and growth factors in response to injury and thereby regulate disease pathology. The purpose of this study is to investigate the effects of microglial transplantation on focal cerebral ischemia model in rat.
Methods:
Transient middle cerebral artery occlusion (MCAO) in rats was induced by the intraluminal filament technique. HMO6 cells, human microglial cell line, were transplanted intravenously at 48 hours after MCAO. Functional tests were performed and the infarct volume was measured at 7 and 14 days after MCAO. Migration and cell survival of transplanted microglial cells and host glial reaction in the brain were studied by immunohistochemistry. Gene expression of neurotrophic factors, cytokines and chemokines in transplanted cells and host rat glial cells was determined by laser capture microdissection (LCM) and quantitative real time-PCR.
Results:
HMO6 human microglial cells transplantation group demonstrated significant functional recovery compared with control group. At 7 and 14 days after MCAO, infarct volume was significantly reduced in the HMO group. In the HMO6 group, number of apoptotic cells was time-dependently reduced in the infarct core and penumbra. In addition, number of host rat microglia/macrophages and reactive astrocytes was significantly decreased at 7 and 14 days after MCAO in the penumbra. Gene expression of various neurotrophic factors (GDNF, BDNF, VEGF and BMP7) and anti-inflammatory cytokines (IL4 and IL5) was up-regulated in transplanted HMO6 cells of brain tissue compared with those in culture. The expression of GDNF and VEGF in astrocytes in penumbra was significantly up-regulated in the HMO6 group.
Conclusions:
Our results indicate that transplantation of HMO6 human microglial cells reduces ischemic deficits and apoptotic events in stroke animals. The results were mediated by modulation of gliosis and neuroinflammation, and neuroprotection provided by neurotrophic factors of endogenous and transplanted cells-origin.
Insights
Transplanting human microglial cells (HMO6) improved functional recovery and reduced brain damage in a rat stroke model. This cell therapy modulated neuroinflammation and gliosis, offering neuroprotection via growth factors.
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Microglia are key immune cells in the central nervous system (CNS), producing cytokines and growth factors that influence disease pathology.
- Microglial dysfunction is implicated in various neurological disorders, including stroke.
Purpose of the Study:
- To investigate the therapeutic potential of transplanting human microglial cells (HMO6) in a rat model of focal cerebral ischemia.
- To evaluate the impact of microglial transplantation on functional recovery, infarct volume, and cellular/molecular changes post-stroke.
Main Methods:
- Focal cerebral ischemia was induced in rats using transient middle cerebral artery occlusion (MCAO).
- HMO6 human microglial cells were intravenously transplanted 48 hours post-MCAO.
- Functional recovery, infarct volume, cell survival, glial reaction, and gene expression of neurotrophic factors and cytokines were assessed.
Main Results:
- Microglial transplantation significantly improved functional recovery and reduced infarct volume at 7 and 14 days post-MCAO.
- Transplanted cells reduced apoptosis and modulated host glial responses (microglia/macrophages, astrocytes) in the ischemic penumbra.
- Upregulation of neurotrophic factors (GDNF, BDNF, VEGF, BMP7) and anti-inflammatory cytokines (IL4, IL5) was observed in transplanted cells and host astrocytes.
Conclusions:
- Transplantation of HMO6 human microglial cells offers a promising therapeutic strategy for stroke, reducing ischemic deficits and apoptosis.
- The neuroprotective effects are attributed to the modulation of neuroinflammation and gliosis, alongside the release of neurotrophic factors from both transplanted and endogenous cells.
