Human Placenta-Derived Mesenchymal Stem Cells Ameliorate Diabetic Neuropathy via Wnt Signaling Pathway

Objectives. To investigate the effect of placenta-derived mesenchymal stem cells (PMSCs) on diabetic peripheral neuropathy and explore the role of Wnt signaling pathway. Method. Twenty-seven male db/db mice were randomly categorized into the control group, PMSC group, and PMSC treatment with Wnt inh...

Full description

Saved in:
Bibliographic Details
Main Authors: Songsong Pan, Sushant S. Hada, Yang Liu, Chao Hu, Mengdie Zhou, Shaoqiu Zheng, Minjie Xu, Changsheng Shi, Shiwu Yin, Xiaoyun Xie
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2022/6897056
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832561643538612224
author Songsong Pan
Sushant S. Hada
Yang Liu
Chao Hu
Mengdie Zhou
Shaoqiu Zheng
Minjie Xu
Changsheng Shi
Shiwu Yin
Xiaoyun Xie
author_facet Songsong Pan
Sushant S. Hada
Yang Liu
Chao Hu
Mengdie Zhou
Shaoqiu Zheng
Minjie Xu
Changsheng Shi
Shiwu Yin
Xiaoyun Xie
author_sort Songsong Pan
collection DOAJ
description Objectives. To investigate the effect of placenta-derived mesenchymal stem cells (PMSCs) on diabetic peripheral neuropathy and explore the role of Wnt signaling pathway. Method. Twenty-seven male db/db mice were randomly categorized into the control group, PMSC group, and PMSC treatment with Wnt inhibitor treatment group. Intervention was initiated in week 22. Thermal stimulation response was determined with a plantar analgesia tester. The mice were sacrificed on 7, 14, and 28 days. The morphology of sciatic nerves was observed by electron microscopy, and the expression of protein gene product (PGP) 9.5, S100β, and Ku80 was detected by immunofluorescence. Bax, β-catenin, and dishevelled1 (DVL1) were detected by western blot. Results. Thermal stimulation response was improved in the PMSC group on 14 and 28 days. Compared with the control group, PGP9.5 was increased in the PMSC group, accompanied by a significant increase in the expression of S100β. On the contrary, LGK974 inhibited the effect of PMSCs on thermal stimulation response and the expression of PGP9.5 and S100β. Both PGP9.5 and S100β were correlated with Ku80 in fluorescence colocalization. The myelin sheath of sciatic nerves in the PMSC group was uniform and dense compared with that in the control group. The effects of PMSCs promoting myelin repair were significantly inhibited in the PMSC+LGK974 group. Bax in the PMSC group expressed less than the control group. In contrast, the expressions of β-catenin and DVL1 were higher compared with that in the control group on the 14th and 28th days. The expression of DVL1 and β-catenin was lower in the PMSC+LGK974 group than in the PMSC group. Conclusions. PMSCs improved the symptoms of diabetic peripheral neuropathy, along with the improvement of nerve myelin lesions, promotion of nerve regeneration, and activation of Schwann cells, which might be related to the regulation of Wnt signaling pathway and inhibition of apoptosis.
format Article
id doaj-art-71703919f8a24984836eb736772afc96
institution Kabale University
issn 1687-9678
language English
publishDate 2022-01-01
publisher Wiley
record_format Article
series Stem Cells International
spelling doaj-art-71703919f8a24984836eb736772afc962025-02-03T01:24:35ZengWileyStem Cells International1687-96782022-01-01202210.1155/2022/6897056Human Placenta-Derived Mesenchymal Stem Cells Ameliorate Diabetic Neuropathy via Wnt Signaling PathwaySongsong Pan0Sushant S. Hada1Yang Liu2Chao Hu3Mengdie Zhou4Shaoqiu Zheng5Minjie Xu6Changsheng Shi7Shiwu Yin8Xiaoyun Xie9Department of Interventional and Vascular SurgeryDepartment of Interventional and Vascular SurgeryDivision of GeriatricsDepartment of Interventional and Vascular SurgeryDepartment of Interventional and Vascular SurgeryDepartment of Interventional and Vascular SurgeryDepartment of Interventional and Vascular SurgeryDepartment of Interventional TherapyDepartment of Interventional & Vascular SurgeryDepartment of Interventional and Vascular SurgeryObjectives. To investigate the effect of placenta-derived mesenchymal stem cells (PMSCs) on diabetic peripheral neuropathy and explore the role of Wnt signaling pathway. Method. Twenty-seven male db/db mice were randomly categorized into the control group, PMSC group, and PMSC treatment with Wnt inhibitor treatment group. Intervention was initiated in week 22. Thermal stimulation response was determined with a plantar analgesia tester. The mice were sacrificed on 7, 14, and 28 days. The morphology of sciatic nerves was observed by electron microscopy, and the expression of protein gene product (PGP) 9.5, S100β, and Ku80 was detected by immunofluorescence. Bax, β-catenin, and dishevelled1 (DVL1) were detected by western blot. Results. Thermal stimulation response was improved in the PMSC group on 14 and 28 days. Compared with the control group, PGP9.5 was increased in the PMSC group, accompanied by a significant increase in the expression of S100β. On the contrary, LGK974 inhibited the effect of PMSCs on thermal stimulation response and the expression of PGP9.5 and S100β. Both PGP9.5 and S100β were correlated with Ku80 in fluorescence colocalization. The myelin sheath of sciatic nerves in the PMSC group was uniform and dense compared with that in the control group. The effects of PMSCs promoting myelin repair were significantly inhibited in the PMSC+LGK974 group. Bax in the PMSC group expressed less than the control group. In contrast, the expressions of β-catenin and DVL1 were higher compared with that in the control group on the 14th and 28th days. The expression of DVL1 and β-catenin was lower in the PMSC+LGK974 group than in the PMSC group. Conclusions. PMSCs improved the symptoms of diabetic peripheral neuropathy, along with the improvement of nerve myelin lesions, promotion of nerve regeneration, and activation of Schwann cells, which might be related to the regulation of Wnt signaling pathway and inhibition of apoptosis.http://dx.doi.org/10.1155/2022/6897056
spellingShingle Songsong Pan
Sushant S. Hada
Yang Liu
Chao Hu
Mengdie Zhou
Shaoqiu Zheng
Minjie Xu
Changsheng Shi
Shiwu Yin
Xiaoyun Xie
Human Placenta-Derived Mesenchymal Stem Cells Ameliorate Diabetic Neuropathy via Wnt Signaling Pathway
Stem Cells International
title Human Placenta-Derived Mesenchymal Stem Cells Ameliorate Diabetic Neuropathy via Wnt Signaling Pathway
title_full Human Placenta-Derived Mesenchymal Stem Cells Ameliorate Diabetic Neuropathy via Wnt Signaling Pathway
title_fullStr Human Placenta-Derived Mesenchymal Stem Cells Ameliorate Diabetic Neuropathy via Wnt Signaling Pathway
title_full_unstemmed Human Placenta-Derived Mesenchymal Stem Cells Ameliorate Diabetic Neuropathy via Wnt Signaling Pathway
title_short Human Placenta-Derived Mesenchymal Stem Cells Ameliorate Diabetic Neuropathy via Wnt Signaling Pathway
title_sort human placenta derived mesenchymal stem cells ameliorate diabetic neuropathy via wnt signaling pathway
url http://dx.doi.org/10.1155/2022/6897056
work_keys_str_mv AT songsongpan humanplacentaderivedmesenchymalstemcellsamelioratediabeticneuropathyviawntsignalingpathway
AT sushantshada humanplacentaderivedmesenchymalstemcellsamelioratediabeticneuropathyviawntsignalingpathway
AT yangliu humanplacentaderivedmesenchymalstemcellsamelioratediabeticneuropathyviawntsignalingpathway
AT chaohu humanplacentaderivedmesenchymalstemcellsamelioratediabeticneuropathyviawntsignalingpathway
AT mengdiezhou humanplacentaderivedmesenchymalstemcellsamelioratediabeticneuropathyviawntsignalingpathway
AT shaoqiuzheng humanplacentaderivedmesenchymalstemcellsamelioratediabeticneuropathyviawntsignalingpathway
AT minjiexu humanplacentaderivedmesenchymalstemcellsamelioratediabeticneuropathyviawntsignalingpathway
AT changshengshi humanplacentaderivedmesenchymalstemcellsamelioratediabeticneuropathyviawntsignalingpathway
AT shiwuyin humanplacentaderivedmesenchymalstemcellsamelioratediabeticneuropathyviawntsignalingpathway
AT xiaoyunxie humanplacentaderivedmesenchymalstemcellsamelioratediabeticneuropathyviawntsignalingpathway