Improvement of human umbilical cord mesenchymal stem cell transplantation on glial cell and behavioral function in a neonatal model of periventricular white matter damage

Abstract

Periventricular white matter damage (PWMD) also termed periventricular leucomalacia in the preterm infant is of particular importance because no targeted therapy is presently available. Human umbilical cord mesenchymal stem cells (hUC-MSCs) have been studied in a variety of adult brain injury-related neurological disorders. Our aim was to determine whether hUC-MSC transplantation improves glial cell function in cerebral white matter and long-term behavioral function in a PWMD rat model. Rats on postnatal day (P) 3 underwent a permanent ligation of the left common carotid artery followed by 6% O2 for 4h. Immediately after the hypoxic–ischemic (HI), rats received a single intraperitoneal injection of hUC-MSCs, which were co-cultured with 5-bromodeoxyuridine (BrdU). BrdU+ cells in the brain were tested 24h after transplantation. Second, rats received hUC-MSC treatment once a day for 3 consecutive days. Glial cells (oligodendrocytes, astrocytes and microglia) were examined on 7 and 18 days post-HI, and behavioral outcomes were tested 27 days post-HI. Significantly, hUC-MSCs migrated mainly into the injured hemisphere. In addition, hUC-MSC treatment improved the long-term functional outcomes of rats, increased mature oligodendrocyte counts, and decreased the number of reactive astrocytes and activated microglia quantities after HI-induced damage in the premature brain. These results suggest that hUC-MSCs can pass through the blood–brain barrier and migrate towards the lesion site to improve brain damage. Therefore, hUC-MSCs have the potential to be utilized as a novel therapeutic strategy for PWMD.