Umbilical Cord Blood Mononuclear Cell Treatment for Neonatal Rats With Hypoxic Ischemia

Abstract

BackgroundHypoxic-ischemic encephalopathy (HIE) occurs when an infant’s brain has not received adequate oxygen and blood supply, resulting in ischemic and hypoxic damage. Currently, supportive care and hypothermia therapy have been the standard treatment for HIE. However, there are still over 20% of treated infants died and 19–30% survived with significant disability. HIE animal model was first established by Rice et al., involving the ligation of one common carotid artery followed by hypoxia. In this study, we investigated human umbilical cord blood (HUCB) and its two components mononuclear cell (MNC) and red cell fraction (RCF) in both short and long term study using a modified HIE rat model.MethodsIn this modified HIE model, both common carotid arteries were occluded, breathing 8% oxygen in a hypoxic chamber for 60-min, followed by the release of the common carotid arteries ligature, mimicking reperfusion injury. For cell therapeutic study, cells were intravenously injected to HIE rat pups, and both behavioral and histological changes were assessed at selected time points.ResultStatistically significant behavioral improvements were demonstrated on Day 7 and 1 month between saline treated HIE rats and UCB/MNC treated rats. However, at 3 months, the therapeutic improvements were only showed between saline treated HIE animals and MNC treated HIE rats. For histological analysis 1 month after cell injection, the number of functional neurons were statistically increased between saline treated HIE and UCB/MNC/RCF treated HIE rats. At 3 months, the significant increase in functional neurons was only present in MNC treated HIE rats.ConclusionWe have used a bilateral temporary occlusion of 60 min, a moderately brain damaged model, for cell therapeutic studies. HUCB mononuclear cell (MNC) therapy showed benefits in neonatal HIE rats in both short and long term behavioral and histological assessments.

Mononuclear cell therapy of neonatal hypoxic‐ischemic encephalopathy in preclinical versus clinical studies: A systematic analysis of therapeutic efficacy and study design

“…Although some studies reported extreme effect sizes, a leave-one-outanalyses did not indicate that the overall clear efficacy of MNC treatments in HIE animal models may be caused by single studies reporting particularly good therapeutic outcomes. Thus, there is no strong Pimentel-Coelho et al 29 de Paula et al 30 Rosenkranz et al 19 Wasielewski et al 31 Rosenkranz et al 32 Wang et al 26 Greggio et al 33 Wang et al 34 Hattori et al 35 Grandvuillemin et al 18 Nakanishi et al 36 Sato et al 37 Penny et al 38 Cho et al 39 Penny et al 40 Lyu et al 41 Note: Analysis was conducted in a total of five risks of bias domains, including selection bias (D1), performance bias (D2), detection bias (D3), reporting bias (D4), attrition bias (D5), and overall bias. Low (green circles), some (yellow circles), and high (red circles) concerns for bias, as well as no information (blue circles) are indicated.…”