Secretome released from hydrogel-embedded adipose mesenchymal stem cells protects against the Parkinson’s disease related toxin 6-hydroxydopamine

Chierchia, Armando; Chirico, Nino; Boeri, Lucia; Raimondi, Ilaria; Riva, Giovanni; Raimondi, Manuela Teresa; Tunesi, Marta; Giordano, Carmen; Forloni, Gianluigi

doi:10.1016/j.ejpb.2017.09.014

Cited by 54 publications

(40 citation statements)

References 31 publications

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“…The reintroduction of SIRT3 into AFSCs reversed cellular viability under high glucose stress. Similarly, careful studies from several researchers have confirmed that SIRT3 activation preserves the mononuclear cells mobility [55], protects adipose mesenchymal stem cells against oxidative stress [56], reduces human mesenchymal stem cells senescence by maintaining mitochondrial ROS homeostasis [57], inhibits neural stem cells death [58], promotes bone marrow cell-mediated angiogenesis in post-myocardial infarction [59]. These evidences demonstrate that SIRT3 is the potential target for enhancing stem cell viability and function.…”

Section: Discussionmentioning

confidence: 99%

SIRT3 Facilitates Amniotic Fluid Stem Cells to Repair Diabetic Nephropathy Through Protecting Mitochondrial Homeostasis by Modulation of Mitophagy

Feng

Dai

et al. 2018

Cell Physiol Biochem

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Background/Aims: Amniotic fluid stem cells (AFSCs) transplantation is a promising therapeutic strategy for diabetic nephropathy. Sirtuin3 (SIRT3) is a novel mitochondrial protective factor. In the present study, we aimed to investigate whether SIRT3 protects against hyperglycemia-induced AFSCs damage and enhances the therapeutic efficiency of AFSCs in diabetic nephropathy. Methods: To establish the diabetic nephropathy model, db/ db mice were used. AFSCs were obtained and transplanted into the kidney tissue of db/ db mice. Gain-of-function assay with SIRT3 overexpression was performed in AFSCs via adenoviral transfections (Ad/SIRT3). Cellular viability and apoptosis were measured via MTT, TUNEL assay and western blotting. Mitochondrial function was assessed via JC1 staining, mPTP opening assay, mitochondrial respiratory function analysis, and immunofluorescence analysis of cyt-c. Mitophagy was assessed via western blotting and immunofluorescence analysis. Renal histopathology and morphometric analysis were conducted via H&E, Masson and PASM staining. Kidney function was detected via ELISA assay, western blotting and qPCR. Results: SIRT3 was downregulated in AFSCs under high glucose stimulation, where its expression was positively correlated with AFSCs survival and proliferation. Regaining SIRT3 activated mitophagy protecting AFSCs against high glucose-induced apoptosis via preserving mitochondrial function. Transplanting SIRT3-overexpressing AFSCs in db/db mice improved the abnormalities in glucose metabolic parameters, including the levels of glucose, insulin, C-peptide, HbA1c and inflammatory markers. In addition, the engraftment of SIRT3-modified AFSCs also reversed renal function, decreased renal hypertrophy, and ameliorated renal histological changes in db/db mice. Functional studies confirmed that SIRT3-modified AFSCs promoted glomerulus survival and reduced renal fibrosis. Conclusion: Collectively, our results demonstrate that AFSCs may be a promising therapeutic treatment for ameliorating diabetes and the development of diabetic nephropathy and that the overexpression of SIRT3 in AFSCs may further increase the efficiency of stem cell-based therapy.

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Section: Discussionmentioning

confidence: 99%

SIRT3 Facilitates Amniotic Fluid Stem Cells to Repair Diabetic Nephropathy Through Protecting Mitochondrial Homeostasis by Modulation of Mitophagy

Feng

Dai

et al. 2018

Cell Physiol Biochem

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“…Neuroblastoma SH-SY5Y cells were pretreated with the conditioned medium extracted from rat adipose tissue-derived MSCs (AT-MSCs) to check MSCs conditioned media's effect on pro-oxidizing agents. Neuroblastoma cells cocultured with conditioned media showed more decreased mortality and ROS generation when treated with H2O2 or 6-OHDA (6-hydroxydopamine), a dopaminergic selective toxin; than Neuroblastoma cells not preconditioned with conditioned media (166). MSCs conditioned medium is a good therapeutic candidate as neural stem cells, pretreated with conditioned medium (CM-NSCs) showed increased survival and enhanced migratory activity; but NSCs alone lacked these extra characteristics (167).…”

Section: Parkinson's Diseasementioning

confidence: 99%

Manipulated Mesenchymal Stem Cells Applications in Neurodegenerative Diseases

Sadatpoor

Salehi

Rahban

et al. 2020

IJSC

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Mesenchymal stem cells (MSCs) are multipotent stem cells that have multilinear differentiation and self-renewal abilities. These cells are immune-privileged as they express no or low level of class-II major histocompatibility complex (MHC-II) and other costimulatory molecules. Having neuroprotective and regenerative properties, MSCs can be used to ameliorate several intractable neurodegenerative disorders by affecting both innate and adaptive immune systems. Several manipulations like pretreating MSCs with different conditions or agents, and using molecules derived from MSCs or genetically manipulating them, are the common and practical ways that can be used to strengthen MSCs survival and potency. Improved MSCs can have significantly enhanced impacts on diseases compared to MSCs not manipulated. In this review, we describe some of the most important manipulations that have been exerted on MSCs to improve their therapeutic functions and their applications in ameliorating three prevalent neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and Huntington's disease.

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“…The incorporation of growth factors, such as brain-derived growth factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4/5), growth/differentiation factor 5 (GDF5) and GDNF, has been investigated for their potential to improve dopaminergic cell transplantation strategies (Clayton & Sullivan, 2007;Feng et al, 1999;Hyman et al, 1994;Jaumotte & Zigmond, 2014;Lin, Doherty, Lile, Bektesh, & Collins, 1993). While they have all shown to improve dopamine neuron survival in VM cultures, GDNF has been established as an extremely potent neurotrophic factor, significantly improving cell survival and efficacy (Apostolides, Sanford, Hong, & Mendez, 1998;Chaturvedi et al, 2003;Deng et al, 2013;Redmond et al, 2013;Rosenblad, Martinez-Serrano, & Bjorklund, 1996;Yurek, Flectcher, Kowalczyk, Padegimas, & Cooper, 2009).…”

Section: Growth Factor Provisionmentioning

confidence: 99%

“…Hydrogels from a variety of sources, both natural and synthetic, have shown to successfully deliver trophic factors to the brain in a site-specific, controlled and sustained manner (Chierchia et al, 2017;Fon et al, 2014;Li et al, 2016). Further to the enhanced delivery of GDNF in injectable hydrogels (Fon et al, 2014), many approaches have investigated the use of hollow microparticles to achieve sustained GDNF release from a single administration (Agbay, Mohtaram, & Willerth, 2014;Garbayo et al, 2016;García-Caballero et al, 2017;Lampe, Kern, Mahoney, & Bjugstad, 2011).…”

Section: F I G U R E 1 Therapeutic Concept Of Biomaterials For Brain mentioning

confidence: 99%

Primary tissue for cellular brain repair in Parkinson's disease: Promise, problems and the potential of biomaterials

Moriarty

Parish

Dowd

2018

Eur J of Neuroscience

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The dopamine precursor, levodopa, remains the "gold standard" treatment for Parkinson's disease, and, although it provides superlative efficacy in the early stages of the disease, its long-term use is limited by the development of severe motor side effects and a significant abating of therapeutic efficacy. Therefore, there remains a major unmet clinical need for the development of effective neuroprotective, neurorestorative or neuroreparatory therapies for this condition. The relatively selective loss of dopaminergic neurons from the nigrostriatal pathway makes Parkinson's disease an ideal candidate for reparative cell therapies, wherein the dopaminergic neurons that are lost in the condition are replaced through direct cell transplantation into the brain. To date, this approach has been developed, validated and clinically assessed using dopamine neuron-rich foetal ventral mesencephalon grafts which have been shown to survive and reinnervate the denervated brain after transplantation, and to restore motor function. However, despite long-term symptomatic relief in some patients, significant limitations, including poor graft survival and the impact this has on the number of foetal donors required, have prevented this therapy being more widely adopted as a restorative approach for Parkinson's disease. Injectable biomaterial scaffolds have the potential to improve the delivery, engraftment and survival of these grafts in the brain through provision of a supportive microenvironment for cell adhesion, growth and immune shielding. This article will briefly review the development of primary cell therapies for brain repair in Parkinson's disease and will consider the emerging literature which highlights the potential of using injectable biomaterial hydrogels in this context.

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Secretome released from hydrogel-embedded adipose mesenchymal stem cells protects against the Parkinson’s disease related toxin 6-hydroxydopamine

Abstract: Graphical abstract

Cited by 54 publications

References 31 publications

SIRT3 Facilitates Amniotic Fluid Stem Cells to Repair Diabetic Nephropathy Through Protecting Mitochondrial Homeostasis by Modulation of Mitophagy

SIRT3 Facilitates Amniotic Fluid Stem Cells to Repair Diabetic Nephropathy Through Protecting Mitochondrial Homeostasis by Modulation of Mitophagy

Manipulated Mesenchymal Stem Cells Applications in Neurodegenerative Diseases

Primary tissue for cellular brain repair in Parkinson's disease: Promise, problems and the potential of biomaterials

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