Hydrogen sulfide enhances the effectiveness of mesenchymal stem cell therapy in rats with heart failure: In vitro preconditioning versus in vivo co-delivery

Abdelmonem, Maha; Shahin, Nancy N.; Rashed, Laila A.; Amin, Hebat Allah; Shamaa, Ashraf A.; Shaheen, Amira

doi:10.1016/j.biopha.2019.01.045

Cited by 16 publications

(17 citation statements)

References 50 publications

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“…Both directly and indirectly-through the H 2 S-cysteineglutathione connection (see The H 2 S-cysteine-glutathione connection section)-H 2 S regulates the homeostasis of the cellular immune system (169,175). In addition, H 2 S is also able to improve progenitor-cell proliferation, viability, and therapeutic potential (1,56,97,156,283). Compositions of matter intended for the specific dietary management of a disease or condition, and orally or enterally administered under the supervision of a physician are eligible in several industrialized countries-including Japan-to receive marketing authorization as medical foods (United States), dietary foods for special medical purposes (European Union), foods for special dietary use (Canada), or foods for special medical purpose (China, Australia).…”

Section: H 2 S-poor Diseases and Other H 2 S-treatable Pathologiesmentioning

confidence: 99%

SG1002 and Catenated Divalent Organic Sulfur Compounds as Promising Hydrogen Sulfide Prodrugs

Gojon¹,

Morales²

2020

Antioxidants & Redox Signaling

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Significance: Sulfur has a critical role in protein structure/function and redox status/signaling in all living organisms. Although hydrogen sulfide (H 2 S) and sulfane sulfur (SS) are now recognized as central players in physiology and pathophysiology, the full scope and depth of sulfur metabolome's impact on human health and healthy longevity has been vastly underestimated and is only starting to be grasped. Since many pathological conditions have been related to abnormally low levels of H 2 S/SS in blood and/or tissues, and are amenable to treatment by H 2 S supplementation, development of safe and efficacious H 2 S donors deserves to be undertaken with a sense of urgency; these prodrugs also hold the promise of becoming widely used for disease prevention and as antiaging agents. Recent Advances: Supramolecular tuning of the properties of well-known molecules comprising chains of sulfur atoms (diallyl trisulfide [DATS], S 8) was shown to lead to improved donors such as DATS-loaded polymeric nanoparticles and SG1002. Encouraging results in animal models have been obtained with SG1002 in heart failure, atherosclerosis, ischemic damage, and Duchenne muscular dystrophy; with TC-2153 in Alzheimer's disease, schizophrenia, age-related memory decline, fragile X syndrome, and cocaine addiction; and with DATS in brain, colon, gastric, and breast cancer. Critical Issues: Mode-of-action studies on allyl polysulfides, benzyl polysulfides, ajoene, and 12 ringsubstituted organic disulfides and thiosulfonates led several groups of researchers to conclude that the anticancer effect of these compounds is not mediated by H 2 S and is only modulated by reactive oxygen species, and that their central model of action is selective protein S-thiolation. Future Directions: SG1002 is likely to emerge as the H 2 S donor of choice for acquiring knowledge on this gasotransmitter's effects in animal models, on account of its unique ability to efficiently generate H 2 S without byproducts and in a slow and sustained mode that is dose independent and enzyme independent. Efficient tuning of H 2 S donation characteristics of DATS, dibenzyl trisulfide, and other hydrophobic H 2 S prodrugs for both oral and parenteral administration will be achieved not only by conventional structural modification of a lead molecule but also through the new ''supramolecular tuning'' paradigm. Antioxid. Redox Signal. 33, 1010-1045.

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Section: H 2 S-poor Diseases and Other H 2 S-treatable Pathologiesmentioning

confidence: 99%

SG1002 and Catenated Divalent Organic Sulfur Compounds as Promising Hydrogen Sulfide Prodrugs

Gojon¹,

Morales²

2020

Antioxidants & Redox Signaling

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“…The group of Liang et al loaded a partially oxidized alginate (ALG-CHO) with the H 2 S donor 2-aminopyridine-5-thiocarboxamide and tetraaniline (a conductive oligomer), and adipose-derived stem cells (ADSCs) [116]. The hydrogel, which mimics the slow and continuous release of endogenous H 2 S, increased the ejection fraction value and reduced the infarction size in rats with myocardial infarction, thus evidencing that H 2 S released retained the H 2 S-dependent protective role on myocardial infarction and heart failure previously described [115] and offering a promising therapeutic strategy for treating infarction.…”

Section: H2s-releasing Scaffolds For Regenerative Medicinementioning

confidence: 86%

“…The group of Mauretti et al developed a photopolymerizable PEG-fibrinogen hydrogel incorporating albumin microbubbles functionalized with thiosulfate cyanide sulfurtransferase, one of the enzymes able to catalyze the H 2 S-production [114]. H 2 S produced by the scaffold increased cardiac progenitor cell proliferation, thus retaining the feature previously described by others [115]. The group of Liang et al loaded a partially oxidized alginate (ALG-CHO) with the H 2 S donor 2-aminopyridine-5-thiocarboxamide and tetraaniline (a conductive oligomer), and adipose-derived stem cells (ADSCs) [116].…”

Section: H2s-releasing Scaffolds For Regenerative Medicinementioning

confidence: 98%

Hydrogen Sulfide in Bone Tissue Regeneration and Repair: State of the Art and New Perspectives

Gambari

Grigolo

Grassi

2019

IJMS

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The importance of hydrogen sulfide (H2S) in the regulation of multiple physiological functions has been clearly recognized in the over 20 years since it was first identified as a novel gasotransmitter. In bone tissue H2S exerts a cytoprotective effect and promotes bone formation. Just recently, the scientific community has begun to appreciate its role as a therapeutic agent in bone pathologies. Pharmacological administration of H2S achieved encouraging results in preclinical studies in the treatment of systemic bone diseases, such as osteoporosis; however, a local delivery of H2S at sites of bone damage may provide additional opportunities of treatment. Here, we highlight how H2S stimulates multiple signaling pathways involved in various stages of the processes of bone repair. Moreover, we discuss how material science and chemistry have recently developed biomaterials and H2S-donors with improved features, laying the ground for the development of H2S-releasing devices for bone regenerative medicine. This review is intended to give a state-of-the-art description of the pro-regenerative properties of H2S, with a focus on bone tissue, and to discuss the potential of H2S-releasing scaffolds as a support for bone repair.

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“…Morin et al demonstrated that MEF2 and GATA4 physically interact in vivo and in vitro and that MEF2 regulates gene expression through protein-protein interaction with GATA4 [42]. Abdelmonem and colleagues demonstrated that augmented MEF2 and GATA4 expression after preconditioning reveals the ability of NaHS to enhance the differentiation of MSCs into cardiomyocytes, which is a critical step in the treatment of HF [38]. GATA4 administration reduces postinfarct ventricular brosis and improves ventricular function in a rat coronary ligation model.…”

Section: Discussionmentioning

confidence: 99%

Effect of RGOs on the Efficacy of Nkx2.5 Transfected Bone Marrow Mesenchymal Stem Cells Transplantation in Treatment Heart Failure in Rats

Wang¹,

Deng²,

Zhang³

et al. 2020

Preprint

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Background: Heart failure (HF) is one of the major serious diseases to do harm to human health. Drugs, interventional treatment and heart transplantation are currently the main methods to treat HF. However, they fail to improve the patient's condition. Mesenchymal stem cells (MSCs) can regenerate functional cardiomyocytes and are promising to become a new therapeutic measure to treat heart failure. We assumed that Rehmannia glutinosa oligosaccharide (RGOs) has the synergistic effect with Nkx2.5 transfected MSCs (Nkx2.5) transplantation in treatment heart failure. Methods: MSCs and Nkx2.5 were preconditioned by RGOs. The apoptosis rate was detected by flow cytometry and the expressions of cardiac specific genes were analyzed with quantitative real-time PCR and Western blot in vitro. Heart failure models were duplicated by injecting doxorubicin (total dose of 15mg/kg) intraperitoneally in male SD rats. When the models were prepared, rats were randomly divided into 6 groups: Control (CON), HF, MSCs, Nkx2.5, RGOs and RGOs combined with Nkx2.5 (RGOs+Nkx2.5) group. Echocardiography was used to detect cardiac function in rats. HE staining was used to observe the pathological changes of myocardium, and Masson staining was used to calculate the collagen volume fraction to detect the degree of myocardial fibrosis. The total mRNA was extracted to detect the following genes including cTnI, CX43, TGF-β1, Collagen I, MEF2 and GATA4 by Q-PCR. Protein of myocardial tissue was extracted to detect the expression of cTnI, CX43, MEF2 and GATA4, by western blot. Results: RGOs could not enhance cardiac specific gene expressions including CK, α-MHC, however it improved the survival of Nkx2.5 induced by H2O2 in vitro. In rat heart failure models, RGOs alone improved the heart pumping function and decreased collagen volume fraction (CVF), TGF-β1 and collagen I expression, and increased MEF2 and GATA4 mRNA expression. Moreover, RGOs cooperated with Nkx2.5 in improving left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV). Furthermore, RGOs and Nkx2.5 combination also increased CX43 expression, whereas decreased CVF and collagen I expression. Conclusion: RGOs has the synergistic effect with Nkx2.5 gene transfected MSCs transplantation in treatment with heart failure through decreasing myocardial fibrosis, inhibiting ventricular remodeling, and increasing the expressions of GATA4, MEF2.

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Hydrogen sulfide enhances the effectiveness of mesenchymal stem cell therapy in rats with heart failure: In vitro preconditioning versus in vivo co-delivery

Cited by 16 publications

References 50 publications

SG1002 and Catenated Divalent Organic Sulfur Compounds as Promising Hydrogen Sulfide Prodrugs

SG1002 and Catenated Divalent Organic Sulfur Compounds as Promising Hydrogen Sulfide Prodrugs

Hydrogen Sulfide in Bone Tissue Regeneration and Repair: State of the Art and New Perspectives

Effect of RGOs on the Efficacy of Nkx2.5 Transfected Bone Marrow Mesenchymal Stem Cells Transplantation in Treatment Heart Failure in Rats

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Hydrogen sulfide enhances the effectiveness of mesenchymal stem cell therapy in rats with heart failure: In vitro preconditioning versus in vivo co-delivery

Cited by 16 publications

References 50 publications

SG1002 and Catenated Divalent Organic Sulfur Compounds as Promising Hydrogen Sulfide Prodrugs

SG1002 and Catenated Divalent Organic Sulfur Compounds as Promising Hydrogen Sulfide Prodrugs

Hydrogen Sulfide in Bone Tissue Regeneration and Repair: State of the Art and New Perspectives

Effect of RGOs&nbsp;on the Efficacy of Nkx2.5 Transfected Bone Marrow Mesenchymal Stem Cells Transplantation in Treatment Heart Failure in Rats

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Effect of RGOs on the Efficacy of Nkx2.5 Transfected Bone Marrow Mesenchymal Stem Cells Transplantation in Treatment Heart Failure in Rats