Transamniotic mesenchymal stem cell therapy for neural tube defects preserves neural function through lesion-specific engraftment and regeneration
JournalCell Death and Disease
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AbstractNeural tube defects (NTDs) lead to prenatal mortality and lifelong morbidity. Currently, surgical closure of NTD lesions results in limited functional recovery. We previously suggested that nerve regeneration was critical for NTD therapy. Here, we report that transamniotic bone marrow-derived mesenchymal stem cell (BMSC) therapy for NTDs during early development may achieve beneficial functional recovery. In our ex vivo rat embryonic NTD model, BMSCs injected into the amniotic cavity spontaneously migrated into the defective neural tissue. Hepatocyte growth factor and its receptor c-MET were found to play critical roles in this NTD lesion-specific migration. Using the in vivo rat fetal NTD model, we further discovered that the engrafted BMSCs specifically differentiated into the cell types of the defective tissue, including skin and different types of neurons in situ. BMSC treatment triggered skin repair in fetuses, leading to a 29.9 ± 5.6% reduction in the skin lesion area. The electrophysiological functional recovery assay revealed a decreased latency and increased motor-evoked potential amplitude in the BMSC-treated fetuses. Based on these positive outcomes, ease of operation, and reduced trauma to the mother and fetus, we propose that transamniotic BMSC administration could be a new effective therapy for NTDs. Copyright 2020, The Author(s).
SponsorsThis work was supported by the National Key Research and Development Program (2016YFC1000505), the National Natural Science Foundation of China (Grant numbers: 81871219, 81671469, 81901565, 81771595), the Specialized Research Fund for the Doctoral Program of Liaoning Province (201601136), and the Scientific Research Fund of Liaoning Provincial Education Department (LQNK201710). National Natural Science Foundation of China, NSFC: 81871219, 81901565, 81671469, 81771595
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85087792138&doi=10.1038%2fs41419-020-2734-3&partnerID=40&md5=e6a47805db282bfe9fd554ac6103d118; http://hdl.handle.net/10713/13371