Qingsong Ye1,2, Yanqing Wu3, Jiamin Wu1, Shuang Zou1, Ali Ahmed Al-Zaazaai1, Hongyu Zhang1, Hongxue Shi1, Ling Xie1, Yanlong Liu1, Ke Xu3, Huacheng He3, Fabiao Zhang4, Yiming Ji4, Yan He2, Jian Xiao1,2,3. 1. Institute of Stem Cells and Tissue Engineering, School of pharmaceutical Science and School of Stomatology, Wenzhou Medical University, Wenzhou, China. 2. UQ-WZMU Joint Group of Regenerative Medicine, School of Dentistry, The University of Queensland, Brisbane, Queensland, Australia. 3. The Institute of Life Sciences, Wenzhou University, Wenzhou, China. 4. Department of general surgery, Taizhou Hospital, Wenzhou Medical University, Taizhou, China.
Abstract
BACKGROUND/AIMS: Neonatal hypoxia-ischemia (HI) causes severe brain damage and significantly increases neonatal morbidity and mortality. Increasing evidences have verified that stem cell-based therapy has the potential to rescue the ischemic tissue and restore function via secreting growth factors after HI. Here, we had investigated whether intranasal neural stem cells (NSCs) treatment improves the recovery of neonatal HI, and NSCs overexpressing basic fibroblast growth factor (bFGF) has a better therapeutic effect for recovery than NSCs treatment only. METHODS: We performed permanent occlusion of the right common carotid artery in 9-day old ICR mice as animal model of neonatal hypoxia-ischemia. At 3 days post-HI, NSC, NSC-GFP, NSC-bFGF and vehicle were delivered intranasally. To determine the effect of intranasal NSC, NSC-GFP and NSC-bFGF treatment on recovery after HI, we analyzed brain damage, sensor-motor function and cell differentiation. RESULTS: It was observed that intranasal NSC, NSC-GFP and NSC-bFGF treatment decreased gray and white matter loss area in comparison with vehicle-treated mouse. NSC, NSC-GFP and NSC-bFGF treatment also significantly improved sensor motor function in cylinder rearing test and adhesive removal test, however, NSC-bFGF-treatment was more effective than NSC-treatment in the improvement of somatosensory function. Furthermore, compared with NSC and NSC-GFP, NSC-bFGF treatment group appeared to differentiate into more neurons. CONCLUSION: Taken together, intranasal administration of NSCs is a promising therapy for treatment of neonatal HI, but NSCs overexpressing bFGF promotes the survival and differentiation of NSCs, and consequently achieves a better therapeutic effect in improving recovery after neonatal HI.
BACKGROUND/AIMS: Neonatal hypoxia-ischemia (HI) causes severe brain damage and significantly increases neonatal morbidity and mortality. Increasing evidences have verified that stem cell-based therapy has the potential to rescue the ischemic tissue and restore function via secreting growth factors after HI. Here, we had investigated whether intranasal neural stem cells (NSCs) treatment improves the recovery of neonatal HI, and NSCs overexpressing basic fibroblast growth factor (bFGF) has a better therapeutic effect for recovery than NSCs treatment only. METHODS: We performed permanent occlusion of the right common carotid artery in 9-day old ICR mice as animal model of neonatal hypoxia-ischemia. At 3 days post-HI, NSC, NSC-GFP, NSC-bFGF and vehicle were delivered intranasally. To determine the effect of intranasal NSC, NSC-GFP and NSC-bFGF treatment on recovery after HI, we analyzed brain damage, sensor-motor function and cell differentiation. RESULTS: It was observed that intranasal NSC, NSC-GFP and NSC-bFGF treatment decreased gray and white matter loss area in comparison with vehicle-treated mouse. NSC, NSC-GFP and NSC-bFGF treatment also significantly improved sensor motor function in cylinder rearing test and adhesive removal test, however, NSC-bFGF-treatment was more effective than NSC-treatment in the improvement of somatosensory function. Furthermore, compared with NSC and NSC-GFP, NSC-bFGF treatment group appeared to differentiate into more neurons. CONCLUSION: Taken together, intranasal administration of NSCs is a promising therapy for treatment of neonatal HI, but NSCs overexpressing bFGF promotes the survival and differentiation of NSCs, and consequently achieves a better therapeutic effect in improving recovery after neonatal HI.
Authors: Madeleine J Smith; Madison Claire Badawy Paton; Michael C Fahey; Graham Jenkin; Suzanne L Miller; Megan Finch-Edmondson; Courtney A McDonald Journal: Stem Cells Transl Med Date: 2021-09-20 Impact factor: 6.940
Authors: Lusine Danielyan; Matthias Schwab; Georg Siegel; Bianca Brawek; Olga Garaschuk; Nithi Asavapanumas; Marine Buadze; Ali Lourhmati; Hans-Peter Wendel; Meltem Avci-Adali; Marcel A Krueger; Carsten Calaminus; Ulrike Naumann; Stefan Winter; Elke Schaeffeler; Annett Spogis; Sandra Beer-Hammer; Jonas J Neher; Gabriele Spohn; Anja Kretschmer; Eva-Maria Krämer-Albers; Kerstin Barth; Hong Jun Lee; Seung U Kim; William H Frey; Claus D Claussen; Dirk M Hermann; Thorsten R Doeppner; Erhard Seifried; Christoph H Gleiter; Hinnak Northoff; Richard Schäfer Journal: EBioMedicine Date: 2020-09-10 Impact factor: 8.143