Umbilical Cord Mesenchymal Stromal Cells for Steroid-Refractory Acute Graft-versus-Host Disease

Donadel, Camila Dermínio; Pires, Bruno G; André, Nathália Cristine; Costa, Thalita Cristina Mello; Orellana, Maristela Delgado; Caruso, Sâmia Rigotto; Seber, Adriana; Ginani, Valeria Cortez; Gomes, Alessandra Araújo; Novis, Yana; Barros, George Maurício Navarro; Vilella, Neysimélia Costa; Martinho, Gláucia Helena; Vieira, Ana Cristina; Kondo, Andrea Tiemi; Hamerschlak, Nelson; Filho, Jayr Schmidt; Xavier, Erick Menezes; Fernandes, Juliana Folloni; Rocha, Vanderson; Covas, Dimas Tadeu; Calado, Rodrigo T.; Guerino-Cunha, Renato Luiz; Santis, Gil Cunha De

doi:10.3390/ph16040512

Cited by 5 publications

(3 citation statements)

References 46 publications

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“…Non-invasive access, higher proliferative capacity, lower immunogenicity, and the absence of ethical issues make them an ideal source for stem cell transplantation therapy [ 1 , 2 ]. Many preclinical studies and clinical trials have been carried out with good success in HucMSCs for the treatment of a wide range of pediatric diseases [ 3 , 4 ]. Interestingly, one study showed that MSCs were more effective in pediatric patients than in adult patients [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Study of the effect of keap1 on oxidative stress in human umbilical cord mesenchymal stem cells

Deng,

Chen,

Liu

et al. 2024

Mol Biol Rep

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Background HucMSCs had shown promising efficacy in treating childhood diseases, but oxidative stress induced by the poor microenvironment at the site of damage resulted in low cell survival after transplantation, thus preventing the cells from maximizing therapeutic efficacy. Therefore, this study aimed to investigate the role and mechanism of keap1 in oxidative stress injury of human umbilical cord mesenchymal stem cells (hucMSCs), and to provide theoretical support for improving the efficacy of stem cell therapy. Methods The hucMSCs were treated with hypoxic low-sugar-free serum (GSDH) to mimic the damaged site microenvironment after implantation. Adenoviral overexpression of keap1 gene of hucMSCs was performed in vitro, and cell proliferation ability was detected by CCK8 assay, crystal violet staining assay, and cell cycle assay. Cellular redox level was assessed by Amplex Red, MDA, and GSH/GSSG kit. Mitochondrial morphology was evaluated by mitotracker Red staining. ATP production was estimated by ATP detection kit. The mRNA and protein expression levels were tested by western blotting and RT-qPCR. Results GSDH treatment substantially upregulated keap1 expression. Subsequently, we found that overexpression of keap1 notably inhibited cell proliferation and caused cells to stagnate in G1 phase. At the same time, overexpression of keap1 induced the production of large amounts of H2O2 and the accumulation of MDA, but suppressed the GSH/GSSG ratio and the expression of antioxidant proteins NQO1 and SOD1, which caused oxidative stress damage. Overexpression of keap1 induced cells to produce a large number of dysfunctional mitochondria resulting in reduced ATP production. Moreover, Overexpression of keap1 significantly decreased the IKKβ protein level, while upregulating IkB mRNA levels and downregulating P50 mRNA levels. Conclusions Overexpression of keap1 may induce oxidative stress injury in hucMSCs by down-regulating IKKβ expression and inhibiting NF-κB pathway activation. This implies the importance of keap1 in hucMSCs and it may be a potential gene for genetic modification of hucMSCs.

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Section: Introductionmentioning

confidence: 99%

Study of the effect of keap1 on oxidative stress in human umbilical cord mesenchymal stem cells

Deng,

Chen,

Liu

et al. 2024

Mol Biol Rep

View full text Add to dashboard Cite

show abstract

“…Non-invasive access, higher proliferative capacity, lower immunogenicity, and the absence of ethical issues make them an ideal source for stem cell transplantation therapy 1,2 . Many preclinical studies and clinical trials have been carried out with good success in HucMSCs for the treatment of a wide range of pediatric diseases 3,4 . Interestingly, one study showed that MSCs were more effective in pediatric patients than in adult patients 5 .…”

Section: Introductionmentioning

confidence: 99%

Study of the effect of keap1 on oxidative stress in human umbilical cord mesenchymal stem cells

Deng,

Chen,

Liu

et al. 2023

Preprint

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Background: HucMSCs had shown promising efficacy in treating childhood diseases, but oxidative stress induced by the poor microenvironment at the site of damage resulted in low cell survival after transplantation, thus preventing the cells from maximizing therapeutic efficacy. Therefore, this study aimed to investigate the role and mechanism of keap1 in oxidative stress injury of human umbilical cord mesenchymal stem cells (hucMSCs), and to provide theoretical support for improving the efficacy of stem cell therapy. Methods: The hucMSCs were treated with hypoxic low-sugar-free serum (GSDH) to mimic the damaged site microenvironment after implantation. Adenoviral overexpression of keap1 gene of hucMSCs was performed in vitro, and cell proliferation ability was detected by CCK8 assay, crystal violet staining assay, and cell cycle assay; cellular redox level was assessed by Amplex Red, MDA, and GSH/GSSG kit; mitochondrial morphology was evaluated by mitotracker Red staining; ATP production was estimated by ATP detection kit; and the mRNA expression level of related proteins and related genes was tested by western blotting and RT-qPCR. Results: GSDH treatment substantially upregulated keap1 mRNA levels and protein levels. Subsequently, we found that overexpression of keap1 notably inhibited cell proliferation and caused cells to stagnate in G1 phase. At the same time, overexpression of keap1 induced the production of large amounts of H2O2 and the accumulation of MDA, but suppressed the GSH/GSSG ratio and the expression of antioxidant proteins NQO1 and SOD1, which caused oxidative stress damage. Overexpression of keap1 induced cells to produce a large number of dysfunctional mitochondria resulting in reduced ATP production. Moreover, Overexpression of keap1 significantly decreased the IKKβ protein level，while upregulating IkB mRNA levels and downregulating P50 mRNA levels. Conclusions: Overexpression of keap1 may induce oxidative stress injury in hucMSCs by down-regulating IKKβ expression and inhibiting NF-κB pathway activation. This implies the importance of keap1 in hucMSCs and it may be a potential gene for genetic modification of hucMSCs.

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“…Bone marrow transplant units are now rapidly expanding into the cellular therapy arena as car-T, NK cells, adoptive anti-virus specific T cells, and mesenchymal cells for GVHD are increasingly being used ( 30 – 32 ).…”

mentioning

confidence: 99%

Editorial: 50 years of BMT: risk stratification, donor matching and stem cell collection for transplantation

Hamerschlak,

Gómez-Almaguer,

McLornan

2023

Front. Oncol.

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Umbilical Cord Mesenchymal Stromal Cells for Steroid-Refractory Acute Graft-versus-Host Disease

Cited by 5 publications

References 46 publications

Study of the effect of keap1 on oxidative stress in human umbilical cord mesenchymal stem cells

Study of the effect of keap1 on oxidative stress in human umbilical cord mesenchymal stem cells

Study of the effect of keap1 on oxidative stress in human umbilical cord mesenchymal stem cells

Editorial: 50 years of BMT: risk stratification, donor matching and stem cell collection for transplantation

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