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-M...
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| Format: | Article |
| Language: | English |
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The Korean Pediatric Society
2024-03-01
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| Series: | Clinical and Experimental Pediatrics |
| Subjects: | |
| Online Access: | http://www.e-cep.org/upload/pdf/cep-2023-01151.pdf |
| _version_ | 1827325518987395072 |
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| author | Yeong Seok Lee Yong Hoon Jun Juyoung Lee |
| author_facet | Yeong Seok Lee Yong Hoon Jun Juyoung Lee |
| author_sort | Yeong Seok Lee |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T14:29:25Z |
| format | Article |
| id | doaj.art-c3aa004c57ae4d349e2c74fc17d05e5d |
| institution | Directory Open Access Journal |
| issn | 2713-4148 |
| language | English |
| last_indexed | 2024-03-07T14:29:25Z |
| publishDate | 2024-03-01 |
| publisher | The Korean Pediatric Society |
| record_format | Article |
| series | Clinical and Experimental Pediatrics |
| spelling | doaj.art-c3aa004c57ae4d349e2c74fc17d05e5d2024-03-06T05:28:02ZengThe Korean Pediatric SocietyClinical and Experimental Pediatrics2713-41482024-03-0167315216010.3345/cep.2023.0115120125555681Oral administration of bone marrow-derived mesenchymal stem cells attenuates intestinal injury in necrotizing enterocolitisYeong Seok Lee0Yong Hoon Jun1Juyoung Lee2 Department of Pediatrics, School of Medicine, Inha University, Incheon, Korea Department of Pediatrics, School of Medicine, Inha University, Incheon, Korea Department of Pediatrics, School of Medicine, Inha University, Incheon, KoreaBackground 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.http://www.e-cep.org/upload/pdf/cep-2023-01151.pdfnecrotizing enterocolitisneonatemesenchymal stem cells |
| spellingShingle | Yeong Seok Lee Yong Hoon Jun Juyoung Lee Oral administration of bone marrow-derived mesenchymal stem cells attenuates intestinal injury in necrotizing enterocolitis Clinical and Experimental Pediatrics necrotizing enterocolitis neonate mesenchymal stem cells |
| title | Oral administration of bone marrow-derived mesenchymal stem cells attenuates intestinal injury in necrotizing enterocolitis |
| title_full | Oral administration of bone marrow-derived mesenchymal stem cells attenuates intestinal injury in necrotizing enterocolitis |
| title_fullStr | Oral administration of bone marrow-derived mesenchymal stem cells attenuates intestinal injury in necrotizing enterocolitis |
| title_full_unstemmed | Oral administration of bone marrow-derived mesenchymal stem cells attenuates intestinal injury in necrotizing enterocolitis |
| title_short | Oral administration of bone marrow-derived mesenchymal stem cells attenuates intestinal injury in necrotizing enterocolitis |
| title_sort | oral administration of bone marrow derived mesenchymal stem cells attenuates intestinal injury in necrotizing enterocolitis |
| topic | necrotizing enterocolitis neonate mesenchymal stem cells |
| url | http://www.e-cep.org/upload/pdf/cep-2023-01151.pdf |
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