Abstract
Increasing evidence has suggested that human umbilical cord blood cells (hUCBC) have a favorable effect on hypoxic–ischemic (HI) brain injury. However, the efficacy of using hUCBCs to treat this injury has been variable and the underlying mechanism remains elusive. Here, we investigated its effectiveness using stereological analysis in an allogeneic system to examine whether intraperitoneal injection of cells derived from UCBCs of green fluorescent protein (GFP)-transgenic rats could ameliorate brain injury in neonatal rats. Three weeks after the HI event, the estimated residual brain volume was larger and motor function improved more in the cell-injected rats than in the control (PBS-treated) rats. The GFP-positive cells were hardly detectable in the brain (0.0057% of injected cells) 9 days after injection. Although 60% of GFP-positive cells in the brain were Iba1-positive, none of these were positive for NeuroD or DCX. While the number of proliferating cells increased in the hippocampus, that of activated microglia/macrophages decreased and a proportion of M2 microglia/macrophages increased in the ipsilateral hemisphere of cell-injected rats. These results suggest that intraperitoneal injection of cells derived from UCBCs could ameliorate HI injury, possibly through an endogenous response and not by supplying differentiated neurons derived from the injected stem cells.
Highlights
Increasing evidence has suggested that human umbilical cord blood cells have a favorable effect on hypoxic–ischemic (HI) brain injury
We propose that administered umbilical cord blood cells (UCBCs) attenuate brain injury possibly through an unidentified endogenous response and not by supplying the brain with neurons that had differentiated from the injected stem cells
The total number of mononuclear cells (MNCs) obtained was much smaller than the amount needed for the intraperitoneal injection (0.72 ± 0.18 × cells per litter, Table 1) compared to the number of human UCBCs used for rat HI injury models[13,14,22]
Summary
Increasing evidence has suggested that human umbilical cord blood cells (hUCBC) have a favorable effect on hypoxic–ischemic (HI) brain injury. We investigated its effectiveness using stereological analysis in an allogeneic system to examine whether intraperitoneal injection of cells derived from UCBCs of green fluorescent protein (GFP)-transgenic rats could ameliorate brain injury in neonatal rats. While the number of proliferating cells increased in the hippocampus, that of activated microglia/macrophages decreased and a proportion of M2 microglia/macrophages increased in the ipsilateral hemisphere of cell-injected rats These results suggest that intraperitoneal injection of cells derived from UCBCs could ameliorate HI injury, possibly through an endogenous response and not by supplying differentiated neurons derived from the injected stem cells. There are several advantages to using UCBCs as a stem cell source in neonates They are readily available at birth and can be used for autologous transplantation. Many animal studies showed that UCBCs had a favorable effect in treating HI-induced damage, their outcomes appeared variable, www.nature.com/scientificreports/
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