†These authors contributed equally.
Background: Hypoxic-ischaemic encephalopathy (HIE) is a major cause of
neonatal disability and mortality. Although hypothermia therapy offers some
neuroprotection, the recovery of neurological function is limited. Therefore, new
synergistic therapies are necessary to improve the prognosis. Mesenchymal stem
cell-based therapy is emerging as a promising treatment option for HIE. In this
study, we studied the therapeutic efficacy of human placenta-derived mesenchymal
stem cells (PD-MSCs) in the HIE rat model and analyzed the underlying therapeutic
mechanisms. Methods: Rats were divided into 6 groups (n = 9 for each) as
follows: control, HIE model, HIE + normal saline, and HIE + PD-MSC
transplantation at days 7, 14 and 28 postpartum. Following PD-MSC
transplantation, neurological behavior was evaluated using rotarod tests,
traction tests, and the Morris water maze test. The degree of brain tissue damage
was assessed by histological examination and Nissl staining. Expression levels of
apoptosis-related proteins and inflammatory factors were quantified by Western
blotting and enzyme-linked immunosorbent assays. Immunofluorescence was used to
investigate the ability of PD-MSCs to repair the morphology and function of
hippocampal neurons with hypoxic-ischaemic (HI) injury. Results: PD-MSC
transplantation enhanced motor coordination and muscle strength in HIE rats. This
treatment also improved spatial memory ability by repairing pathological damage
and preventing the loss of neurons in the cerebral cortex. The most effective
treatment was observed in the HIE + PD-MSC transplantation at day 7 group.
Expression levels of microtubule-associated protein-2 (MAP-2), B-cell lymphoma-2
(BCL-2), interleukin (IL)-10, and transforming growth factor (TGF -