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Published on: December 20, 2012
Multipotent adult progenitor cells for hypoxic-ischemic injury in the preterm brain
Reint K Jellema1,2,3, Daan R M G Ophelders4,5, Alex Zwanenburg6,7
1School of Mental Health and Neuroscience (MHENS), Maastricht University, Universiteitssingel 40, Maastricht, 6229, ER, The Netherlands. reint.jellema@maastrichtuniversity.nl.
Insights
Multipotent adult progenitor cells (MAPC) therapy shows promise for treating preterm infants suffering from hypoxic-ischemic encephalopathy. MAPC cells reduced seizures and inflammation, improving brain outcomes in a preclinical model.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Neonatal Research
Background:
- Preterm infants face risks of hypoxic-ischemic encephalopathy (HIE), a condition with no current treatment.
- Mesenchymal stem cells show potential for treating HIE brain injury.
- Multipotent adult progenitor cells (MAPC) possess enhanced anti-inflammatory and regenerative properties compared to mesenchymal stem cells.
Purpose of the Study:
- To investigate the neuroprotective effects of MAPC cell therapy in a preterm animal model of global hypoxia-ischemia (HI).
- To evaluate the impact of MAPC therapy on brain function, inflammation, and structural integrity following HI.
- To explore the potential of MAPC cells as a therapeutic strategy for HIE in preterm infants.
Main Methods:
- Preterm sheep fetuses underwent induced global hypoxia-ischemia (HI).
- MAPC cells were administered systemically during a 7-day reperfusion period.
- Vital parameters, electroencephalogram (EEG), and histological analyses of the brain were conducted.
Main Results:
- MAPC therapy reduced seizure activity and maintained baroreflex sensitivity post-HI.
- MAPC cells prevented microglial proliferation and hypomyelination in the preterm brain.
- MAPC therapy modulated both cerebral and peripheral splenic inflammatory responses.
Conclusions:
- MAPC cell therapy demonstrated functional and structural neuroprotection in a preclinical model of preterm HI.
- Further research is needed to elucidate the mechanisms and long-term effects of MAPC neuroprotection.
- This study provides a foundation for clinical trials evaluating MAPC therapy for HIE in preterm infants.
Background:
Preterm infants are at risk for hypoxic-ischemic encephalopathy. No therapy exists to treat this brain injury and subsequent long-term sequelae. We have previously shown in a well-established pre-clinical model of global hypoxia-ischemia (HI) that mesenchymal stem cells are a promising candidate for the treatment of hypoxic-ischemic brain injury. In the current study, we investigated the neuroprotective capacity of multipotent adult progenitor cells (MAPC®), which are adherent bone marrow-derived cells of an earlier developmental stage than mesenchymal stem cells and exhibiting more potent anti-inflammatory and regenerative properties.
Methods:
Instrumented preterm sheep fetuses were subjected to global hypoxia-ischemia by 25 min of umbilical cord occlusion at a gestational age of 106 (term ~147) days. During a 7-day reperfusion period, vital parameters (e.g., blood pressure and heart rate; baroreceptor reflex) and (amplitude-integrated) electroencephalogram were recorded. At the end of the experiment, the preterm brain was studied by histology.
Results:
Systemic administration of MAPC therapy reduced the number and duration of seizures and prevented decrease in baroreflex sensitivity after global HI. In addition, MAPC cells prevented HI-induced microglial proliferation in the preterm brain. These anti-inflammatory effects were associated with MAPC-induced prevention of hypomyelination after global HI. Besides attenuation of the cerebral inflammatory response, our findings showed that MAPC cells modulated the peripheral splenic inflammatory response, which has been implicated in the etiology of hypoxic-ischemic injury in the preterm brain.
Conclusions:
In a pre-clinical animal model MAPC cell therapy improved the functional and structural outcome of the preterm brain after global HI. Future studies should establish the mechanism and long-term therapeutic effects of neuroprotection established by MAPC cells in the developing preterm brain exposed to HI. Our study may form the basis for future clinical trials, which will evaluate whether MAPC therapy is capable of reducing neurological sequelae in preterm infants with hypoxic-ischemic encephalopathy.
