ABSTRACT
<p><b>OBJECTIVE</b>To study the brain protection and the possible mechanism of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in neonatal rat model of hypoxic-ischemic brain damage (HIBD).</p><p><b>METHODS</b>Successfully establishing a neonatal rat model of HIBD, hUC-MSCs labeled with BrdU were transplanted into the lateral ventricle 24 hours after HIBD. The number of apoptotic cells and the expression of Caspase-3 were detected by TUNEL and Western blot respectively at 24 and 48 hours after transplantation. The neurological functions of HIBD rats were evaluated by Longa score, and the survival, differentiation and pro-differentiation effects of hUC-MSCs were identified by immunofluorescence at 1 to 3 weeks after transplantation.</p><p><b>RESULTS</b>At 24 and 48 hours after transplantation, apoptotic cells and Caspase-3 expression in the MSCs group were less than in the HIBD group (P<0.05). At 2 and 3 weeks after transplantation, the Longa score in the MSCs group was lower than in the HIBD group (P<0.05). After transplantation, positive cells labeled with BrdU were seen in the brain tissue. The expression levels of glial fibrillary acidic protein (GFAP) and neuron specific esterase (NSE) in the MSCs group were higher than in the HIBD and sham-operated control groups (P<0.05), and increased gradually with the transplantation time (P<0.05).</p><p><b>CONCLUSIONS</b>hUC-MSCs transplantation in HIBD rats can inhibit Caspase-3 expression and reduce apoptotic cells in the early stage, and in the later period, the survival hUC-MSCs can differentiate into neural-like cells and promote the differentiation of endogenous neural-like cells, providing protective effects to brain.</p>
Subject(s)
Animals , Female , Male , Rats , Animals, Newborn , Apoptosis , Caspase 3 , Metabolism , Cell Differentiation , Cord Blood Stem Cell Transplantation , Disease Models, Animal , Hypoxia-Ischemia, Brain , Pathology , Therapeutics , Mesenchymal Stem Cell Transplantation , Phosphopyruvate Hydratase , Rats, Sprague-DawleyABSTRACT
Severe neonatal hypoxic-ischemic encephalopathy (HIE)can result in serious outcomes including death during the newborn period and permanent neuropsychological handicaps in the form of cerebral palsy,learning disability,epilepsy and so on.So far,there have been no effective treatments in clinical practice.Stem cell transplantation therapy brings new hope for HIE treatment.Among them,umbilical cord-derived mesenchymal stem cells have many advantages such as rich source,easy collection,shorter doubling time,lower immunogenicity and long-term survi-val after transplantation,it will have a broad application prospects as a cell source for the treatment of neonatal HIE.