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Updated: Dec 7, 2025
Purification of Prominin-1+ Stem Cells from Postnatal Mouse Cerebellum
Published on: April 12, 2020
Systemic multipotent adult progenitor cells protect the cerebellum after asphyxia in fetal sheep
Ruth Gussenhoven1,2, Daan R M G Ophelders1,3, Jeroen Dudink4
1Department of Pediatrics, Maastricht University Medical Centre, Maastricht, The Netherlands.
Insights
Multipotent adult progenitor cells (MAPCs) protected the preterm cerebellum from hypoxic-ischemic encephalopathy (HIE) injury. Diffusion tensor imaging confirmed microstructural improvements, supporting MAPC therapy for HIE treatment.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Neonatalogy
Background:
- Cerebellar involvement in hypoxic-ischemic encephalopathy (HIE) is increasingly recognized.
- Preterm infant HIE often involves cerebellar structural damage.
- Multipotent adult progenitor cells (MAPCs) show neuroprotective potential.
Purpose of the Study:
- To evaluate the neuroprotective effects of intravenous MAPC administration in the preterm ovine cerebellum following global hypoxia-ischemia (HI).
- To assess the efficacy of MAPC therapy in preventing structural and microstructural damage in the preterm cerebellum.
Main Methods:
- Preterm ovine fetuses underwent transient global HI via umbilical cord occlusion.
- Intravenous MAPC doses were administered post-reperfusion.
- Histopathological analysis and diffusion tensor imaging (DTI) were used to assess cerebellar injury and MAPC treatment effects.
Main Results:
- Global HI induced significant cortical injury, impaired Purkinje cell development, and disrupted white matter organization in the cerebellum.
- MAPC treatment markedly prevented cortical injury and attenuated white matter damage.
- DTI successfully detected HI-induced injury and demonstrated MAPC-mediated neuroprotection.
Conclusions:
- Early systemic MAPC therapy offers significant neuroprotection to the preterm cerebellum following global HI in a large animal model.
- DTI is a valuable tool for detecting cerebellar injury and evaluating cell-based therapies in HIE.
- These findings support MAPC therapy as a potential treatment for HIE, particularly cerebellar involvement.
Abstract:
Involvement of the cerebellum in the pathophysiology of hypoxic-ischemic encephalopathy (HIE) in preterm infants is increasingly recognized. We aimed to assess the neuroprotective potential of intravenously administered multipotent adult progenitor cells (MAPCs) in the preterm cerebellum. Instrumented preterm ovine fetuses were subjected to transient global hypoxia-ischemia (HI) by 25 minutes of umbilical cord occlusion at 0.7 of gestation. After reperfusion, two doses of MAPCs were administered intravenously. MAPCs are a plastic adherent bone-marrow-derived population of adult progenitor cells with neuroprotective potency in experimental and clinical studies. Global HI caused marked cortical injury in the cerebellum, histologically indicated by disruption of cortical strata, impeded Purkinje cell development, and decreased dendritic arborization. Furthermore, global HI induced histopathological microgliosis, hypomyelination, and disruption of white matter organization. MAPC treatment significantly prevented cortical injury and region-specifically attenuated white matter injury in the cerebellum following global HI. Diffusion tensor imaging (DTI) detected HI-induced injury and MAPC neuroprotection in the preterm cerebellum. This study has demonstrated in a preclinical large animal model that early systemic MAPC therapy improved structural injury of the preterm cerebellum following global HI. Microstructural improvement was detectable with DTI. These findings support the potential of MAPC therapy for the treatment of HIE and the added clinical value of DTI for the detection of cerebellar injury and the evaluation of cell-based therapy.
