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Integrin receptor-binding nanofibrous peptide hydrogel for combined mesenchymal stem cell therapy and nitric oxide delivery in renal ischemia/reperfusion injury

BACKGROUND: Mesenchymal-based therapy has been utilized as a practical approach in the treatment of renal ischemia/reperfusion (I/R) injury. However, low cell retention and survival in the ischemic site have remained challenging issues. To bridge this gap, the integrin receptor-binding RGD peptide-f...

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Autores principales: Najafi, Haniyeh, Abolmaali, Samira Sadat, Heidari, Reza, Valizadeh, Hadi, Tamaddon, Ali Mohammad, Azarpira, Negar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327234/
https://www.ncbi.nlm.nih.gov/pubmed/35883125
http://dx.doi.org/10.1186/s13287-022-03045-1
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author Najafi, Haniyeh
Abolmaali, Samira Sadat
Heidari, Reza
Valizadeh, Hadi
Tamaddon, Ali Mohammad
Azarpira, Negar
author_facet Najafi, Haniyeh
Abolmaali, Samira Sadat
Heidari, Reza
Valizadeh, Hadi
Tamaddon, Ali Mohammad
Azarpira, Negar
author_sort Najafi, Haniyeh
collection PubMed
description BACKGROUND: Mesenchymal-based therapy has been utilized as a practical approach in the treatment of renal ischemia/reperfusion (I/R) injury. However, low cell retention and survival in the ischemic site have remained challenging issues. To bridge this gap, the integrin receptor-binding RGD peptide-functionalized, s-nitroso-n-acetyl penicillamine (SNAP)-loaded hydrogel was used to transplant Wharton's jelly-mesenchymal stem cells (WJ-MSCs). METHODS: Apart from physicochemical and rheological characterizations that confirmed entangled interlocking β-sheets with nanofibrous morphology, real-time RT-PCR, ROS production, serum biomarker concentrations, and histopathological alterations were explored in a mouse model to assess the therapeutic efficacy of formulations in the treatment of renal I/R injury. RESULTS: The RGD-functionalized Fmoc-diphenylalanine (Fmoc-FF + Fmoc-RGD) hydrogel supported the spread and proliferation of WJ-MSCs in vivo. Notably, intralesional injection of nitric oxide donor combined with the embedded WJ-MSCs caused superior recovery of renal I/R injury compared to free WJ-MSCs alone in terms of histopathological scores and renal function indices. Compared to the I/R control group, oxidative stress and inducible nitric oxide synthase (iNOS) expression biomarkers showed a significant decline, whereas endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) expression exhibited a significant increment, indicating regeneration of the injured endothelial tissue. CONCLUSION: The findings confirmed that the hydrogels containing WJ-MSCs and nitric oxide donors can promote the regeneration of renal I/R injuries by increasing angiogenic factors and cell engraftment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-022-03045-1.
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spelling pubmed-93272342022-07-28 Integrin receptor-binding nanofibrous peptide hydrogel for combined mesenchymal stem cell therapy and nitric oxide delivery in renal ischemia/reperfusion injury Najafi, Haniyeh Abolmaali, Samira Sadat Heidari, Reza Valizadeh, Hadi Tamaddon, Ali Mohammad Azarpira, Negar Stem Cell Res Ther Research BACKGROUND: Mesenchymal-based therapy has been utilized as a practical approach in the treatment of renal ischemia/reperfusion (I/R) injury. However, low cell retention and survival in the ischemic site have remained challenging issues. To bridge this gap, the integrin receptor-binding RGD peptide-functionalized, s-nitroso-n-acetyl penicillamine (SNAP)-loaded hydrogel was used to transplant Wharton's jelly-mesenchymal stem cells (WJ-MSCs). METHODS: Apart from physicochemical and rheological characterizations that confirmed entangled interlocking β-sheets with nanofibrous morphology, real-time RT-PCR, ROS production, serum biomarker concentrations, and histopathological alterations were explored in a mouse model to assess the therapeutic efficacy of formulations in the treatment of renal I/R injury. RESULTS: The RGD-functionalized Fmoc-diphenylalanine (Fmoc-FF + Fmoc-RGD) hydrogel supported the spread and proliferation of WJ-MSCs in vivo. Notably, intralesional injection of nitric oxide donor combined with the embedded WJ-MSCs caused superior recovery of renal I/R injury compared to free WJ-MSCs alone in terms of histopathological scores and renal function indices. Compared to the I/R control group, oxidative stress and inducible nitric oxide synthase (iNOS) expression biomarkers showed a significant decline, whereas endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) expression exhibited a significant increment, indicating regeneration of the injured endothelial tissue. CONCLUSION: The findings confirmed that the hydrogels containing WJ-MSCs and nitric oxide donors can promote the regeneration of renal I/R injuries by increasing angiogenic factors and cell engraftment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-022-03045-1. BioMed Central 2022-07-26 /pmc/articles/PMC9327234/ /pubmed/35883125 http://dx.doi.org/10.1186/s13287-022-03045-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Najafi, Haniyeh
Abolmaali, Samira Sadat
Heidari, Reza
Valizadeh, Hadi
Tamaddon, Ali Mohammad
Azarpira, Negar
Integrin receptor-binding nanofibrous peptide hydrogel for combined mesenchymal stem cell therapy and nitric oxide delivery in renal ischemia/reperfusion injury
title Integrin receptor-binding nanofibrous peptide hydrogel for combined mesenchymal stem cell therapy and nitric oxide delivery in renal ischemia/reperfusion injury
title_full Integrin receptor-binding nanofibrous peptide hydrogel for combined mesenchymal stem cell therapy and nitric oxide delivery in renal ischemia/reperfusion injury
title_fullStr Integrin receptor-binding nanofibrous peptide hydrogel for combined mesenchymal stem cell therapy and nitric oxide delivery in renal ischemia/reperfusion injury
title_full_unstemmed Integrin receptor-binding nanofibrous peptide hydrogel for combined mesenchymal stem cell therapy and nitric oxide delivery in renal ischemia/reperfusion injury
title_short Integrin receptor-binding nanofibrous peptide hydrogel for combined mesenchymal stem cell therapy and nitric oxide delivery in renal ischemia/reperfusion injury
title_sort integrin receptor-binding nanofibrous peptide hydrogel for combined mesenchymal stem cell therapy and nitric oxide delivery in renal ischemia/reperfusion injury
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327234/
https://www.ncbi.nlm.nih.gov/pubmed/35883125
http://dx.doi.org/10.1186/s13287-022-03045-1
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