{"title":"口服骨髓间充质干细胞可减轻坏死性小肠结肠炎的肠道损伤。","authors":"Yeong Seok Lee, Yong Hoon Jun, Juyoung Lee","doi":"10.3345/cep.2023.01151","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Necrotizing enterocolitis (NEC) is a major cause of morbidity in premature infants. However, effective treatment options for NEC are currently lacking.</p><p><strong>Purpose: </strong>This study aimed to determine the optimal dose of intraperitoneally administered bone marrow-derived mesenchymal stem cells (BM-MSCs) and investigate the therapeutic potential of orally administered BM-MSCs in NEC.</p><p><strong>Methods: </strong>Neonatal mice were fed maternal breast milk for the first 2 days of life. On day 3, the neonatal mice were randomly divided into control, negative control, and BM-MSC-treated groups. Lipopolysaccharide (LPS) was administered for 3 days, and cold stress (4°C, 10 minutes) was applied 3 times a day to induce NEC. High-dose (1×106 cells) or low-dose (1×105 cells) BM-MSCs were administered intraperitoneally 1 or 3 times between days 6 and 8 to treat the NEC. The orally administered group received a low dose of BM-MSCs on day 6. Furthermore, except for the control group, intraepithelial cells (IECs) of the small intestine of neonatal mice were treated with LPS and exposed to 5% O2/95% N2 hypoxic stress for 2 hours. Thereafter, each was treated with BM-MSCs.</p><p><strong>Results: </strong>Tissue injury, apoptosis, and inflammatory marker levels were significantly reduced after BM-MSC administration. Oral administration was as effective as intraperitoneal administration, even at a low dose (1×105 cells) of BM-MSCs. The efficacy of high (1×106 cells) or multiple divided doses of BM-MSCs did not differ from that of low-dose treatment. Significantly improved wound healing was observed after BM-MSC administration to injured IECs.</p><p><strong>Conclusion: </strong>The oral administration of BM-MSCs is a promising treatment option for NEC in infants. Further human studies of BM-MSCs are necessary to determine the optimal dose required to achieve safe and effective outcomes.</p>","PeriodicalId":36018,"journal":{"name":"Clinical and Experimental Pediatrics","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10915455/pdf/","citationCount":"0","resultStr":"{\"title\":\"Oral administration of bone marrow-derived mesenchymal stem cells attenuates intestinal injury in necrotizing enterocolitis.\",\"authors\":\"Yeong Seok Lee, Yong Hoon Jun, Juyoung Lee\",\"doi\":\"10.3345/cep.2023.01151\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Necrotizing enterocolitis (NEC) is a major cause of morbidity in premature infants. However, effective treatment options for NEC are currently lacking.</p><p><strong>Purpose: </strong>This study aimed to determine the optimal dose of intraperitoneally administered bone marrow-derived mesenchymal stem cells (BM-MSCs) and investigate the therapeutic potential of orally administered BM-MSCs in NEC.</p><p><strong>Methods: </strong>Neonatal mice were fed maternal breast milk for the first 2 days of life. On day 3, the neonatal mice were randomly divided into control, negative control, and BM-MSC-treated groups. Lipopolysaccharide (LPS) was administered for 3 days, and cold stress (4°C, 10 minutes) was applied 3 times a day to induce NEC. High-dose (1×106 cells) or low-dose (1×105 cells) BM-MSCs were administered intraperitoneally 1 or 3 times between days 6 and 8 to treat the NEC. The orally administered group received a low dose of BM-MSCs on day 6. Furthermore, except for the control group, intraepithelial cells (IECs) of the small intestine of neonatal mice were treated with LPS and exposed to 5% O2/95% N2 hypoxic stress for 2 hours. Thereafter, each was treated with BM-MSCs.</p><p><strong>Results: </strong>Tissue injury, apoptosis, and inflammatory marker levels were significantly reduced after BM-MSC administration. Oral administration was as effective as intraperitoneal administration, even at a low dose (1×105 cells) of BM-MSCs. The efficacy of high (1×106 cells) or multiple divided doses of BM-MSCs did not differ from that of low-dose treatment. Significantly improved wound healing was observed after BM-MSC administration to injured IECs.</p><p><strong>Conclusion: </strong>The oral administration of BM-MSCs is a promising treatment option for NEC in infants. Further human studies of BM-MSCs are necessary to determine the optimal dose required to achieve safe and effective outcomes.</p>\",\"PeriodicalId\":36018,\"journal\":{\"name\":\"Clinical and Experimental Pediatrics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10915455/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and Experimental Pediatrics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3345/cep.2023.01151\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"PEDIATRICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Experimental Pediatrics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3345/cep.2023.01151","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/19 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PEDIATRICS","Score":null,"Total":0}
Oral administration of bone marrow-derived mesenchymal stem cells attenuates intestinal injury in necrotizing enterocolitis.
Background: Necrotizing enterocolitis (NEC) is a major cause of morbidity in premature infants. However, effective treatment options for NEC are currently lacking.
Purpose: This study aimed to determine the optimal dose of intraperitoneally administered bone marrow-derived mesenchymal stem cells (BM-MSCs) and investigate the therapeutic potential of orally administered BM-MSCs in NEC.
Methods: Neonatal mice were fed maternal breast milk for the first 2 days of life. On day 3, the neonatal mice were randomly divided into control, negative control, and BM-MSC-treated groups. Lipopolysaccharide (LPS) was administered for 3 days, and cold stress (4°C, 10 minutes) was applied 3 times a day to induce NEC. High-dose (1×106 cells) or low-dose (1×105 cells) BM-MSCs were administered intraperitoneally 1 or 3 times between days 6 and 8 to treat the NEC. The orally administered group received a low dose of BM-MSCs on day 6. Furthermore, except for the control group, intraepithelial cells (IECs) of the small intestine of neonatal mice were treated with LPS and exposed to 5% O2/95% N2 hypoxic stress for 2 hours. Thereafter, each was treated with BM-MSCs.
Results: Tissue injury, apoptosis, and inflammatory marker levels were significantly reduced after BM-MSC administration. Oral administration was as effective as intraperitoneal administration, even at a low dose (1×105 cells) of BM-MSCs. The efficacy of high (1×106 cells) or multiple divided doses of BM-MSCs did not differ from that of low-dose treatment. Significantly improved wound healing was observed after BM-MSC administration to injured IECs.
Conclusion: The oral administration of BM-MSCs is a promising treatment option for NEC in infants. Further human studies of BM-MSCs are necessary to determine the optimal dose required to achieve safe and effective outcomes.