Potential therapeutic effects of endothelial cells trans-differentiated from Wharton’s Jelly-derived mesenchymal stem cells on altered vascular functions in aged diabetic rat model

Motawea, Shaimaa M.; Noreldin, Rasha I.; Naguib, Yahya M.

doi:10.21203/rs.2.23838/v1

Cited by 5 publications

(7 citation statements)

References 34 publications

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“…During the aging process, tissues release cytokines such as IL-1β, IL-6, and TNF-α, proteins such CRP, and proinflammatory transcription factors such as the nuclear factor kappa B (NFκB). The circulating inflammatory mediators have been implicated in the pathogenesis and progression of tissue alteration and failure in the elderly [24]. Pro-inflammatory cytokines might induce the formation of reactive oxygen species (ROS) which could trigger an inflammatory response through the activation of transcription factor NFκB [44].…”

Section: Discussionmentioning

confidence: 99%

“…The administration of resveratrol significantly restored the redox balance. Age-dependent oxidative stress occurs when the production of ROS exceeds the antioxidant defence capacity [24]. ROS promotes lipid peroxidation, oxidation of proteins and nucleic acids, and structural alteration of the membranes resulting in cellular damage [47].…”

Section: Discussionmentioning

confidence: 99%

“…To evaluate the effects of aging and or resveratrol treatment on the studied groups, we examined the mRNA expression levels of forkhead box protein O1 (FoxO1), sirtuin 1 (SIRT1), receptor activator of nuclear factorkappa B ligand (RANKL), and osteoprotegerin (OPG) regulatory genes via real time quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay as described previously [22][23][24][25]. Total RNA was extracted following grounding frozen femur bone specimens using TRI reagent (Sigma-Aldrich, UK).…”

Section: Analysis Of Gene Expression Quantitative Rt-pcr (Qrt-pcr)mentioning

confidence: 99%

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Activation of FoxO1/SIRT1/RANKL/OPG pathway may underlie the therapeutic effects of resveratrol on aging-dependent male osteoporosis

Ameen

Yassien

Naguib

2020

BMC Musculoskelet Disord

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Background: Age-dependent male osteoporosis remains a poorly studied medical problem despite its significance. It is estimated that at least 1 of 5 men will suffer from osteoporotic consequences. Given that multiple mechanisms are involved in the process of senescence, much attention has been given to compounds with polymodal actions. To challenge such a health problem, we tested here the therapeutic potential of resveratrol in male osteoporosis. We also studied the possible molecular mechanisms that may underlie resveratrol effects. Methods: Thirty male Wistar albino rats were used in the present study. Rats were divided (10/group) into: control (3-4 months old weighing 150-200 g receiving vehicle), aged (18-20 months old, weighing 350-400 g and receiving vehicle), and resveratrol treated aged (18-20 months old, weighing 350-400 g and receiving resveratrol 20 mg/kg/day for 6 weeks) groups. Assessment of serum calcium, phosphate, bone specific alkaline phosphatase, inflammatory cytokines, oxidative stress markers, and rat femur gene expression of FoxO1, SIRT1, RANKL and OPG proteins was carried out. Histopathological assessment of different levels of rat femur was also performed. Results: Age-dependent osteoporosis resulted in significant increase in serum levels of phosphate, bone specific alkaline phosphatase, hsCRP, IL-1β, IL-6, TNF-α, MDA, NO, and RANKL gene expression. However, there was significant decrease in serum level of GSH, and gene expression of FoxO1, SIRT1 and OPG. Osteoporotic changes were seen in femur epiphysis, metaphysis and diaphysis. Resveratrol restored significantly age-dependent osteoporotic changes. Conclusion: We concluded that resveratrol can play an important role in the prevention of male osteoporosis. Resveratrol can counter the molecular changes in male osteoporosis via anti-inflammatory, anti-oxidant and gene modifying effects.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Analysis Of Gene Expression Quantitative Rt-pcr (Qrt-pcr)mentioning

confidence: 99%

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Activation of FoxO1/SIRT1/RANKL/OPG pathway may underlie the therapeutic effects of resveratrol on aging-dependent male osteoporosis

Ameen

Yassien

Naguib

2020

BMC Musculoskelet Disord

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“…The trans-differentiated ECs (tdECs) were injected by the tail vein 6 weeks after diabetes verification. The tdECs derived from hW-MSCs could counter the dysfunction of endothelium, inflammation and oxygen-induced stress [87].…”

Section: Other Mesenchymal Stem Cellsmentioning

confidence: 99%

Human stem cells – sources, sourcing and in vitro methods

Szubarga

Kamińska

Kotlarz

et al. 2021

Medical Journal of Cell Biology

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Stem cells are an important subject of research, and are increasingly used in the treatment of various diseases. Due to the development of advanced in vitro techniques, they have become an integral part of modern medicine. The sources of human stem cells are primarily bone marrow and adipose tissue, although non – embryonic stem cells are also scattered throughout the body. Notably, recent research has focused on stem cells found in the oral cavity, both in the dental pulp and oral mucosa. Furthermore, isolation of stem cells from umbilical cord blood is also becoming increasingly popular, while wharton’s jelly and amniotic fluid also seem to be an interesting source of stem cells. The safety and efficacy of stem cells use can be established by animal studies, which are a key element of preclinical research. Mouse, rat and pig models allow for testing of stem cell therapies. Recent studies primarily use mesenchymal stem cells such as mouse – adipose derived mesenchymal stem cells and mouse and rat hematopoietic stem cells. Great hope for future therapies is the use of bioengineering to program cells into induced stem cells, which have the biggest ability for differentiation and transdifferentiation, which carries no risk of teratogenesis. Stem cells are used in many areas of medicine, especially in regenerative medicine, with a growing interest in orthopedics and in the treatment of heart failure. Mesenchymal stem cells are the most used stem cell type, which despite their limited ability to differentiate, give great therapeutic results, mainly due to their immunomodulating effect. Recent studies have even shown that the use of mesenchymal stem cells may be useful in the treatment of COVID-19. Moreover, Research on the use of mesenchymal stem cells in the treatment of Crohn’s disease, acute-graft-versus-host disease and type I diabetes are also promising. The aim of the current review is to present and systematize current knowledge about stem cells, their use and related in vitro research. Running title: Research and use of human stem cells

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“…RT-PCR assays were performed in duplicate for all target and housekeeping genes using Applied Biosystems 7500 FAST 96-well PCR machine (USA). To evaluate the effects of GSH on CFX-induced AKI, the mRNA expression levels of glutathione peroxidise (GPx), glutathione reductase (GSR) and cytochrome P450-family 4-subfamily F1 (CYP4F1) genes were evaluated by RT-PCR assay as described previously [20][21][22]. Brie y, total RNA was extracted following homogenizing frozen or fresh kidney specimens using TRI reagent (Sigma-Aldrich, UK).…”

Section: Quantitative Rt-pcr (Qrt-pcr)mentioning

confidence: 99%

Reno-protective effect of exogenous glutathione on experimentally-induced acute kidney injury in male rats.

Naguib¹,

Elgizawy²

2020

Preprint

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Background: Acute kidney injury (AKI) or Acute renal failure (ARF) refers to the sudden damage or failure of the kidney within few hours or days and resulting in acute deterioration of the renal functions. If not properly treated, AKI may lead to chronic renal failure and possibly renal transplantation. The aim of the present study was to evaluate the role of exogenous glutathione (GSH) on ciprofloxacin (GFX)-induced AKI. We also studied the effect of glutathione administration on some genes of interest.Methods: Forty male Wistar albino rats were equally divided into 4 groups. The control group received intra-peritoneal injection of distilled water for 15 consequent days. The GSH treated group received concomitant intra-peritoneal injection of distilled water and glutathione (200 mg/kg/day) for 15 consequent days. The CFX treated group received concomitant intra-peritoneal injection of distilled water and ciprofloxacin (800 mg/kg/day) for 15 consequent days. The CFX+GSH treated group received concomitant intra-peritoneal injection of CFX and CSH for 15 consequent days. Serum levels of creatinine, urea, cystatin C and GGT were measured. Renal CYP4F1, GPx, GSR gene expression was evaluated.Results: Exogenous GSH had no significant effect on the kidney functions or the studied genes when compared to the control group. Treatment with CFX resulted in significant increase (P<0.05) in creatinine, urea, cystatin C and GGT serum levels when compared to the control group. CFX treatment also significantly (P<0.05) down-regulated renal GPx, GSR mRNA levels, while it up-regulated renal CYP4F1, when compared to the corresponding values in the control rats. Serum levels of urea, creatinine and cystatin C were significantly lower (P<0.05) in CFX+GSH group when compared to the CFX treated rats. There was significant up-regulation (P<0.05) of the renal, GPx, GSR and down-regulation of CYP4F1 mRNA levels in the CFX+GSH group when compared to the corresponding values in the CFX treated group.Conclusion: Our results suggest a potential prophylactic and possibly therapeutic roles of exogenous GSH administration in the treatment of drug-induced AKI. We also demonstrated that the underlying mechanism could be explained, at least in part, by the antioxidant and gene modifying properties of GSH.

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Potential therapeutic effects of endothelial cells trans-differentiated from Wharton’s Jelly-derived mesenchymal stem cells on altered vascular functions in aged diabetic rat model

Cited by 5 publications

References 34 publications

Activation of FoxO1/SIRT1/RANKL/OPG pathway may underlie the therapeutic effects of resveratrol on aging-dependent male osteoporosis

Activation of FoxO1/SIRT1/RANKL/OPG pathway may underlie the therapeutic effects of resveratrol on aging-dependent male osteoporosis

Human stem cells – sources, sourcing and in vitro methods

Reno-protective effect of exogenous glutathione on experimentally-induced acute kidney injury in male rats.

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