Dedifferentiated human umbilical cord mesenchymal stem cell reprogramming of endogenous hSDF-1α expression participates in neural restoration in hypoxic-ischemic brain damage rats
The transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) can promote hypoxic-ischemic brain damage (HIBD) nerve repair, but finding suitable seed cells to optimize transplantation and improve treatment efficiency is an urgent problem to be solved. In this study, we induced hUC-M...
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KeAi Communications Co., Ltd.
2021-05-01
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304220300209 |
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author | Zhou Xiaoqin Liu Jia Dai Mengjie Gu Jialu Bi Yang Wang Yuting Hu Huajian Liu Bo Zhang Xiaojun Li Zhongyue Chen Jie Li Tingyu Zhan Xue |
author_facet | Zhou Xiaoqin Liu Jia Dai Mengjie Gu Jialu Bi Yang Wang Yuting Hu Huajian Liu Bo Zhang Xiaojun Li Zhongyue Chen Jie Li Tingyu Zhan Xue |
author_sort | Zhou Xiaoqin |
collection | DOAJ |
description | The transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) can promote hypoxic-ischemic brain damage (HIBD) nerve repair, but finding suitable seed cells to optimize transplantation and improve treatment efficiency is an urgent problem to be solved. In this study, we induced hUC-MSCs into dedifferentiated hUC-MSCs (De-hUC-MSCs), and the morphology, stem cell surface markers, proliferation and tri-directional differentiation ability of the De-hUC-MSCs and hUC-MSCs were detected. A whole-gene chip was utilized for genome cluster, gene ontology and KEGG pathway analyses of differentially expressed genes. De-hUC-MSCs were transplanted into HIBD rats, and behavioral experiments and immunofluorescence assays were used to assess the therapeutic effect. A lentivirus vector for human stromal cell-derived factor-1 (hSDF-1α) was constructed, and the role of hSDF-1α in the neuroprotective effect and mechanism of De-hUC-MSCs was verified. De-hUC-MSCs displayed similar cell morphology, stem cell surface marker expression, cell proliferation and even three-dimensional differentiation ability as hUC-MSCs but exhibited greater treatment potential in vivo. The reprogramming mechanism of hSDF-1α participated in the dedifferentiation process. By successfully constructing a stable hSDF-1α cell line, we found that De-hUC-MSCs might participate in nerve repair through the hSDF-1α/CXCR4/PI3K/Akt pathway. De-hUC-MSCs reprogramming of endogenous hSDF-1α expression may mediate the hSDF-1α/CXCR4/PI3K/Akt pathway involved in nerve repair in HIBD rats. |
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spelling | doaj.art-e4b90938af0b44f087c04fdd7a005aea2023-09-02T19:35:15ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422021-05-0183331343Dedifferentiated human umbilical cord mesenchymal stem cell reprogramming of endogenous hSDF-1α expression participates in neural restoration in hypoxic-ischemic brain damage ratsZhou Xiaoqin0Liu Jia1Dai Mengjie2Gu Jialu3Bi Yang4Wang Yuting5Hu Huajian6Liu Bo7Zhang Xiaojun8Li Zhongyue9Chen Jie10Li Tingyu11Zhan Xue12Department of Gastroenterology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), 401122, PR China; International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 401122, PR ChinaDepartment of Gastroenterology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), 401122, PR China; International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 401122, PR ChinaDepartment of Neonatology, Chongqing Health Center for Women and Children, 400021, PR ChinaChild Health Centre of Northwest Women and Children's Hospital, USADepartment of Pediatric Research Institute, Chongqing Key Laboratory of Child Health and Nutrition, Children's Hospital of Chongqing Medical University, Chongqing, 401122, PR ChinaDepartment of Gastroenterology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), 401122, PR China; International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 401122, PR ChinaDepartment of Gastroenterology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), 401122, PR China; International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 401122, PR ChinaDepartment of Gastroenterology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), 401122, PR China; International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 401122, PR ChinaDepartment of Gastroenterology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), 401122, PR China; International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 401122, PR ChinaDepartment of Gastroenterology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), 401122, PR China; International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 401122, PR ChinaDepartment of Pediatric Research Institute, Chongqing Key Laboratory of Child Health and Nutrition, Children's Hospital of Chongqing Medical University, Chongqing, 401122, PR ChinaDepartment of Pediatric Research Institute, Chongqing Key Laboratory of Child Health and Nutrition, Children's Hospital of Chongqing Medical University, Chongqing, 401122, PR China; Corresponding author.Department of Gastroenterology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), 401122, PR China; International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 401122, PR China; Corresponding author.The transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) can promote hypoxic-ischemic brain damage (HIBD) nerve repair, but finding suitable seed cells to optimize transplantation and improve treatment efficiency is an urgent problem to be solved. In this study, we induced hUC-MSCs into dedifferentiated hUC-MSCs (De-hUC-MSCs), and the morphology, stem cell surface markers, proliferation and tri-directional differentiation ability of the De-hUC-MSCs and hUC-MSCs were detected. A whole-gene chip was utilized for genome cluster, gene ontology and KEGG pathway analyses of differentially expressed genes. De-hUC-MSCs were transplanted into HIBD rats, and behavioral experiments and immunofluorescence assays were used to assess the therapeutic effect. A lentivirus vector for human stromal cell-derived factor-1 (hSDF-1α) was constructed, and the role of hSDF-1α in the neuroprotective effect and mechanism of De-hUC-MSCs was verified. De-hUC-MSCs displayed similar cell morphology, stem cell surface marker expression, cell proliferation and even three-dimensional differentiation ability as hUC-MSCs but exhibited greater treatment potential in vivo. The reprogramming mechanism of hSDF-1α participated in the dedifferentiation process. By successfully constructing a stable hSDF-1α cell line, we found that De-hUC-MSCs might participate in nerve repair through the hSDF-1α/CXCR4/PI3K/Akt pathway. De-hUC-MSCs reprogramming of endogenous hSDF-1α expression may mediate the hSDF-1α/CXCR4/PI3K/Akt pathway involved in nerve repair in HIBD rats.http://www.sciencedirect.com/science/article/pii/S2352304220300209DedifferentiationHuman umbilical cord mesenchymal stem cellsHypoxic-ischemic brain damageNeurorestorationReprogrammingStromal cell-derived factor-1 |
spellingShingle | Zhou Xiaoqin Liu Jia Dai Mengjie Gu Jialu Bi Yang Wang Yuting Hu Huajian Liu Bo Zhang Xiaojun Li Zhongyue Chen Jie Li Tingyu Zhan Xue Dedifferentiated human umbilical cord mesenchymal stem cell reprogramming of endogenous hSDF-1α expression participates in neural restoration in hypoxic-ischemic brain damage rats Genes and Diseases Dedifferentiation Human umbilical cord mesenchymal stem cells Hypoxic-ischemic brain damage Neurorestoration Reprogramming Stromal cell-derived factor-1 |
title | Dedifferentiated human umbilical cord mesenchymal stem cell reprogramming of endogenous hSDF-1α expression participates in neural restoration in hypoxic-ischemic brain damage rats |
title_full | Dedifferentiated human umbilical cord mesenchymal stem cell reprogramming of endogenous hSDF-1α expression participates in neural restoration in hypoxic-ischemic brain damage rats |
title_fullStr | Dedifferentiated human umbilical cord mesenchymal stem cell reprogramming of endogenous hSDF-1α expression participates in neural restoration in hypoxic-ischemic brain damage rats |
title_full_unstemmed | Dedifferentiated human umbilical cord mesenchymal stem cell reprogramming of endogenous hSDF-1α expression participates in neural restoration in hypoxic-ischemic brain damage rats |
title_short | Dedifferentiated human umbilical cord mesenchymal stem cell reprogramming of endogenous hSDF-1α expression participates in neural restoration in hypoxic-ischemic brain damage rats |
title_sort | dedifferentiated human umbilical cord mesenchymal stem cell reprogramming of endogenous hsdf 1α expression participates in neural restoration in hypoxic ischemic brain damage rats |
topic | Dedifferentiation Human umbilical cord mesenchymal stem cells Hypoxic-ischemic brain damage Neurorestoration Reprogramming Stromal cell-derived factor-1 |
url | http://www.sciencedirect.com/science/article/pii/S2352304220300209 |
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