Microglia transcriptome systematic scoring to evaluate the efficacy of human cord derived mesenchymal stem cells treatment protocols in a rat model of inflammation associated preterm infant brain injury.
In this study, we undertook comprehensive dose, timing, and route of administration testing integrating multimodal data from preclinical models of brain injury common in preterm-born infants to validate the most effective therapeutic option for cord-derived mesenchymal stem cell product (HuMSC). We developed a scoring protocol based on microglia transcriptome analyses and myelin protein expression to evaluate the efficacy of the HuMSC product in a rat model of inflammation-associated preterm infant brain injury. We identified the superiority of treatment delivered in the tertiary phase of injury over treatments in the acute or subacute stages and the superiority of intranasal over intravenous HuMSC delivery. Overall design: We define the control (Ctrl) uninjured group as the PBS-treated (sham treatment) animals not subjected to injury, the injured group as IL-1ß-exposed that did not receive human umbilical cord-derived mesenchymal stromal cells (HuMSCs) injection but received PBS (sham treatment), and the treated group as IL-1ß-exposed which received a HuMSCs treatment (diluted in PBS). Eighteen treatment protocols were tested: three different doses (dose1: 20 M cells/kg, dose2: 50 M cells/kg, and dose3: 125 M cells/kg); three different time points (acute phase at P5, the subacute phase at P10 and the tertiary phase at P20); and two routes of administration (intranasal versus intravenous) and results were compared to injured and sham-treated.