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...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2021-05-01
Series:Genes and Diseases
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2352304220300209
_version_ 1797715334050873344
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.
first_indexed 2024-03-12T08:05:22Z
format Article
id doaj.art-e4b90938af0b44f087c04fdd7a005aea
institution Directory Open Access Journal
issn 2352-3042
language English
last_indexed 2024-03-12T08:05:22Z
publishDate 2021-05-01
publisher KeAi Communications Co., Ltd.
record_format Article
series Genes and Diseases
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
work_keys_str_mv AT zhouxiaoqin dedifferentiatedhumanumbilicalcordmesenchymalstemcellreprogrammingofendogenoushsdf1aexpressionparticipatesinneuralrestorationinhypoxicischemicbraindamagerats
AT liujia dedifferentiatedhumanumbilicalcordmesenchymalstemcellreprogrammingofendogenoushsdf1aexpressionparticipatesinneuralrestorationinhypoxicischemicbraindamagerats
AT daimengjie dedifferentiatedhumanumbilicalcordmesenchymalstemcellreprogrammingofendogenoushsdf1aexpressionparticipatesinneuralrestorationinhypoxicischemicbraindamagerats
AT gujialu dedifferentiatedhumanumbilicalcordmesenchymalstemcellreprogrammingofendogenoushsdf1aexpressionparticipatesinneuralrestorationinhypoxicischemicbraindamagerats
AT biyang dedifferentiatedhumanumbilicalcordmesenchymalstemcellreprogrammingofendogenoushsdf1aexpressionparticipatesinneuralrestorationinhypoxicischemicbraindamagerats
AT wangyuting dedifferentiatedhumanumbilicalcordmesenchymalstemcellreprogrammingofendogenoushsdf1aexpressionparticipatesinneuralrestorationinhypoxicischemicbraindamagerats
AT huhuajian dedifferentiatedhumanumbilicalcordmesenchymalstemcellreprogrammingofendogenoushsdf1aexpressionparticipatesinneuralrestorationinhypoxicischemicbraindamagerats
AT liubo dedifferentiatedhumanumbilicalcordmesenchymalstemcellreprogrammingofendogenoushsdf1aexpressionparticipatesinneuralrestorationinhypoxicischemicbraindamagerats
AT zhangxiaojun dedifferentiatedhumanumbilicalcordmesenchymalstemcellreprogrammingofendogenoushsdf1aexpressionparticipatesinneuralrestorationinhypoxicischemicbraindamagerats
AT lizhongyue dedifferentiatedhumanumbilicalcordmesenchymalstemcellreprogrammingofendogenoushsdf1aexpressionparticipatesinneuralrestorationinhypoxicischemicbraindamagerats
AT chenjie dedifferentiatedhumanumbilicalcordmesenchymalstemcellreprogrammingofendogenoushsdf1aexpressionparticipatesinneuralrestorationinhypoxicischemicbraindamagerats
AT litingyu dedifferentiatedhumanumbilicalcordmesenchymalstemcellreprogrammingofendogenoushsdf1aexpressionparticipatesinneuralrestorationinhypoxicischemicbraindamagerats
AT zhanxue dedifferentiatedhumanumbilicalcordmesenchymalstemcellreprogrammingofendogenoushsdf1aexpressionparticipatesinneuralrestorationinhypoxicischemicbraindamagerats