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


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Article Info

DATE

2022-07-26

AUTHORS

Haniyeh Najafi, Samira Sadat Abolmaali, Reza Heidari, Hadi Valizadeh, Ali Mohammad Tamaddon, Negar Azarpira

ABSTRACT

BackgroundMesenchymal-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). MethodsApart 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.ResultsThe 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.ConclusionThe 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. More... »

PAGES

344

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    http://scigraph.springernature.com/pub.10.1186/s13287-022-03045-1

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    35 schema:description BackgroundMesenchymal-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). MethodsApart 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.ResultsThe 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.ConclusionThe 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.
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    41 schema:keywords ConclusionThe findings
    42 Function Index
    43 R control group
    44 R injury
    45 RGD
    46 ROS production
    47 RT-PCR
    48 S-nitroso-N-acetyl penicillamine
    49 Wharton’s Jelly Mesenchymal Stem Cells
    50 alterations
    51 angiogenic factors
    52 approach
    53 biomarker concentrations
    54 biomarkers
    55 cell engraftment
    56 cell retention
    57 cell therapy
    58 cells
    59 challenging issue
    60 characterization
    61 concentration
    62 control group
    63 decline
    64 delivery
    65 donors
    66 efficacy
    67 endothelial nitric oxide synthase
    68 endothelial tissue
    69 engraftment
    70 expression
    71 expression biomarkers
    72 factor expression
    73 factors
    74 findings
    75 formulation
    76 gap
    77 group
    78 growth factor expression
    79 histopathological alterations
    80 histopathological scores
    81 hydrogels
    82 increment
    83 index
    84 injection
    85 injury
    86 intralesional injection
    87 ischemia/reperfusion injury
    88 ischemic sites
    89 issues
    90 low cell retention
    91 mesenchymal stem cell therapy
    92 methodsApart
    93 model
    94 morphology
    95 mouse model
    96 nanofibrous morphology
    97 nitric oxide delivery
    98 nitric oxide donor
    99 nitric oxide synthase
    100 oxidative stress
    101 oxide donor
    102 oxide synthase
    103 penicillamine
    104 peptides
    105 practical approach
    106 production
    107 proliferation
    108 real-time RT-PCR
    109 recovery
    110 regeneration
    111 renal function indices
    112 renal ischemia/reperfusion injury
    113 reperfusion injury
    114 retention
    115 rheological characterization
    116 scores
    117 serum biomarker concentrations
    118 significant decline
    119 significant increment
    120 sites
    121 spread
    122 stem cell therapy
    123 stem cells
    124 stress
    125 superior recovery
    126 survival
    127 synthase
    128 terms
    129 therapeutic efficacy
    130 therapy
    131 tissue
    132 treatment
    133 vascular endothelial growth factor (VEGF) expression
    134 vivo
    135 β-sheet
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