Cytotherapy. 2025 Oct 29:101998. doi: 10.1016/j.jcyt.2025.10.008. Online ahead of print.
ABSTRACT
BACKGROUND AIMS: Neonatal hypoxic-ischemic encephalopathy (HIE) remains a leading cause of infant mortality and long-term neurologic disability. Although therapeutic hypothermia (TH) is the current standard treatment, its effectiveness is limited, with many infants either ineligible or showing incomplete recovery. As a result, alternative therapies, such as mesenchymal stem cells (MSCs) derived from induced pluripotent stem cells (iMSCs), are being explored. iMSCs have shown considerable promise in preclinical studies because of their consistent properties, which help overcome some of the challenges associated with traditional MSCs. This study evaluated the efficacy of iMSCs and their secretome in promoting recovery after neonatal hypoxic-ischemic (HI) brain injury in a well-established rodent model.
METHODS: The Rice-Vannucci model was used to induce HI brain injury to the developing brain on postnatal day 10 (P10) Wistar Han rat pups. Two days post-injury, 50 000 iMSCs or their secretome were administered intranasally. Over the next 30 days, motor and cognitive functions were assessed through a series of behavioral tests. In addition, brain lesion size, neurogenesis and glial reactivity were examined by immunohistochemistry to evaluate the extent of neurorepair and inflammation.
RESULTS: HI-lesioned animals treated with intranasal iMSCs or their secretome demonstrated improved motor capabilities and enhanced recognition memory compared with untreated lesioned animals. Both iMSCs and their secretome administration led to a reduction in brain lesion size and increased neurogenesis in the hippocampus. Moreover, glial reactivity, including astrocyte and microglia activation, was significantly reduced 30 days after injury, suggesting a more favorable neuroinflammatory environment in treated groups.
CONCLUSIONS: These findings highlight the potential of iMSCs and their secretome to enhance functional recovery and reduce brain damage after neonatal HI. The similar therapeutic outcomes achieved with the iMSC secretome suggest that the secreted factors play a central role in driving neurorepair. More studies are still necessary to gain a better understanding of the mechanisms underlying iMSCs’ neuroprotective and neuroreparative effects.
PMID:41258855 | DOI:10.1016/j.jcyt.2025.10.008
