Cargando…

IGF-1C domain-modified hydrogel enhances therapeutic potential of mesenchymal stem cells for hindlimb ischemia

BACKGROUND: Poor cell engraftment and survival after transplantation limited the application of stem cell therapy. Synthetic biomaterials could provide an artificial microenvironment for stem cells, thereby improve cell survival and enhance the therapeutic efficiency of stem cells. METHODS: We synth...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhao, Nianhuan, Yue, Zhiwei, Cui, Jian, Yao, Yong, Song, Xianghe, Cui, Bangping, Qi, Xin, Han, Zhibo, Han, Zhong-Chao, Guo, Zhikun, He, Zuo-Xiang, Li, Zongjin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489284/
https://www.ncbi.nlm.nih.gov/pubmed/31036073
http://dx.doi.org/10.1186/s13287-019-1230-0
_version_ 1783414792762949632
author Zhao, Nianhuan
Yue, Zhiwei
Cui, Jian
Yao, Yong
Song, Xianghe
Cui, Bangping
Qi, Xin
Han, Zhibo
Han, Zhong-Chao
Guo, Zhikun
He, Zuo-Xiang
Li, Zongjin
author_facet Zhao, Nianhuan
Yue, Zhiwei
Cui, Jian
Yao, Yong
Song, Xianghe
Cui, Bangping
Qi, Xin
Han, Zhibo
Han, Zhong-Chao
Guo, Zhikun
He, Zuo-Xiang
Li, Zongjin
author_sort Zhao, Nianhuan
collection PubMed
description BACKGROUND: Poor cell engraftment and survival after transplantation limited the application of stem cell therapy. Synthetic biomaterials could provide an artificial microenvironment for stem cells, thereby improve cell survival and enhance the therapeutic efficiency of stem cells. METHODS: We synthesized a hydrogel by conjugating C domain peptide of insulin-like growth factor-1 (IGF-1C) onto chitosan (CS-IGF-1C hydrogel). Human placenta-derived mesenchymal stem cells (hP-MSCs), which constitutively express a red fluorescent protein (RFP) and renilla luciferase (Rluc), were co-transplanted with CS-IGF-1C hydrogel into a murine hindlimb ischemia model. Transgenic mice expressing firefly luciferase (Fluc) under the promoter of vascular endothelial growth factor receptor 2 (VEGFR2-Luc) were used. Dual bioluminescence imaging (BLI) was applied for tracking the survival of hP-MSCs by Rluc imaging and the VEGFR2 signal pathway activation by Fluc imaging. To investigate the therapeutic mechanism of CS-IGF-1C hydrogel, angiographic, real-time PCR, and histological analysis were carried out. RESULTS: CS-IGF-1C hydrogel could improve hP-MSCs survival as well as promote angiogenesis as confirmed by dual BLI. These results were consistent with accelerated skeletal muscle structural and functional recovery. Histology analysis confirmed that CS-IGF-1C hydrogel robustly prevented fibrosis as shown by reduced collagen deposition, along with increased angiogenesis. In addition, the protective effects of CS-IGF-1C hydrogel, such as inhibiting H(2)O(2)-induced apoptosis and reducing inflammatory responses, were proved by in vitro experiments. CONCLUSIONS: Taken together, IGF-1Cs provides a conducive niche for hP-MSCs to exert pro-mitogenic, anti-apoptotic, and pro-angiogenic effects, as well as to inhibit fibrosis. Thus, the incorporation of functional peptide into bioscaffolds represents a safe and feasible approach to augment the therapeutic efficacy of stem cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-019-1230-0) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-6489284
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-64892842019-06-05 IGF-1C domain-modified hydrogel enhances therapeutic potential of mesenchymal stem cells for hindlimb ischemia Zhao, Nianhuan Yue, Zhiwei Cui, Jian Yao, Yong Song, Xianghe Cui, Bangping Qi, Xin Han, Zhibo Han, Zhong-Chao Guo, Zhikun He, Zuo-Xiang Li, Zongjin Stem Cell Res Ther Research BACKGROUND: Poor cell engraftment and survival after transplantation limited the application of stem cell therapy. Synthetic biomaterials could provide an artificial microenvironment for stem cells, thereby improve cell survival and enhance the therapeutic efficiency of stem cells. METHODS: We synthesized a hydrogel by conjugating C domain peptide of insulin-like growth factor-1 (IGF-1C) onto chitosan (CS-IGF-1C hydrogel). Human placenta-derived mesenchymal stem cells (hP-MSCs), which constitutively express a red fluorescent protein (RFP) and renilla luciferase (Rluc), were co-transplanted with CS-IGF-1C hydrogel into a murine hindlimb ischemia model. Transgenic mice expressing firefly luciferase (Fluc) under the promoter of vascular endothelial growth factor receptor 2 (VEGFR2-Luc) were used. Dual bioluminescence imaging (BLI) was applied for tracking the survival of hP-MSCs by Rluc imaging and the VEGFR2 signal pathway activation by Fluc imaging. To investigate the therapeutic mechanism of CS-IGF-1C hydrogel, angiographic, real-time PCR, and histological analysis were carried out. RESULTS: CS-IGF-1C hydrogel could improve hP-MSCs survival as well as promote angiogenesis as confirmed by dual BLI. These results were consistent with accelerated skeletal muscle structural and functional recovery. Histology analysis confirmed that CS-IGF-1C hydrogel robustly prevented fibrosis as shown by reduced collagen deposition, along with increased angiogenesis. In addition, the protective effects of CS-IGF-1C hydrogel, such as inhibiting H(2)O(2)-induced apoptosis and reducing inflammatory responses, were proved by in vitro experiments. CONCLUSIONS: Taken together, IGF-1Cs provides a conducive niche for hP-MSCs to exert pro-mitogenic, anti-apoptotic, and pro-angiogenic effects, as well as to inhibit fibrosis. Thus, the incorporation of functional peptide into bioscaffolds represents a safe and feasible approach to augment the therapeutic efficacy of stem cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-019-1230-0) contains supplementary material, which is available to authorized users. BioMed Central 2019-04-29 /pmc/articles/PMC6489284/ /pubmed/31036073 http://dx.doi.org/10.1186/s13287-019-1230-0 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Zhao, Nianhuan
Yue, Zhiwei
Cui, Jian
Yao, Yong
Song, Xianghe
Cui, Bangping
Qi, Xin
Han, Zhibo
Han, Zhong-Chao
Guo, Zhikun
He, Zuo-Xiang
Li, Zongjin
IGF-1C domain-modified hydrogel enhances therapeutic potential of mesenchymal stem cells for hindlimb ischemia
title IGF-1C domain-modified hydrogel enhances therapeutic potential of mesenchymal stem cells for hindlimb ischemia
title_full IGF-1C domain-modified hydrogel enhances therapeutic potential of mesenchymal stem cells for hindlimb ischemia
title_fullStr IGF-1C domain-modified hydrogel enhances therapeutic potential of mesenchymal stem cells for hindlimb ischemia
title_full_unstemmed IGF-1C domain-modified hydrogel enhances therapeutic potential of mesenchymal stem cells for hindlimb ischemia
title_short IGF-1C domain-modified hydrogel enhances therapeutic potential of mesenchymal stem cells for hindlimb ischemia
title_sort igf-1c domain-modified hydrogel enhances therapeutic potential of mesenchymal stem cells for hindlimb ischemia
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489284/
https://www.ncbi.nlm.nih.gov/pubmed/31036073
http://dx.doi.org/10.1186/s13287-019-1230-0
work_keys_str_mv AT zhaonianhuan igf1cdomainmodifiedhydrogelenhancestherapeuticpotentialofmesenchymalstemcellsforhindlimbischemia
AT yuezhiwei igf1cdomainmodifiedhydrogelenhancestherapeuticpotentialofmesenchymalstemcellsforhindlimbischemia
AT cuijian igf1cdomainmodifiedhydrogelenhancestherapeuticpotentialofmesenchymalstemcellsforhindlimbischemia
AT yaoyong igf1cdomainmodifiedhydrogelenhancestherapeuticpotentialofmesenchymalstemcellsforhindlimbischemia
AT songxianghe igf1cdomainmodifiedhydrogelenhancestherapeuticpotentialofmesenchymalstemcellsforhindlimbischemia
AT cuibangping igf1cdomainmodifiedhydrogelenhancestherapeuticpotentialofmesenchymalstemcellsforhindlimbischemia
AT qixin igf1cdomainmodifiedhydrogelenhancestherapeuticpotentialofmesenchymalstemcellsforhindlimbischemia
AT hanzhibo igf1cdomainmodifiedhydrogelenhancestherapeuticpotentialofmesenchymalstemcellsforhindlimbischemia
AT hanzhongchao igf1cdomainmodifiedhydrogelenhancestherapeuticpotentialofmesenchymalstemcellsforhindlimbischemia
AT guozhikun igf1cdomainmodifiedhydrogelenhancestherapeuticpotentialofmesenchymalstemcellsforhindlimbischemia
AT hezuoxiang igf1cdomainmodifiedhydrogelenhancestherapeuticpotentialofmesenchymalstemcellsforhindlimbischemia
AT lizongjin igf1cdomainmodifiedhydrogelenhancestherapeuticpotentialofmesenchymalstemcellsforhindlimbischemia