Adult neural precursors isolated from post mortem brain yield mostly neurons: An erythropoietin-dependent process

Marfia, Giovanni; Madaschi, Laura; Marra, Federica; Menarini, Mauro; Bottai, Daniele; Formenti, Alessandro; Bellardita, Carmelo; Giulio, Anna Maria Di; Carelli, Stephana; Gorio, Alfredo

doi:10.1016/j.nbd.2011.02.004

Cited by 49 publications

(92 citation statements)

References 59 publications

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“…Other pathways that can modulate the protective effects of EPO include mTOR [68,80,82,83], AMPK [41,96], sirtuins [72,116,117], wingless pathways [68,72,91,118,119], and forkhead transcription factors [57,113,120]. Focusing upon the specific exposure and concentration of EPO as well as the downstream signaling pathways of this entity may provide further precision in targeting the detrimental cellular events that ensue following TBI and concurrently limit the potential toxic effects that can develop during EPO administration.…”

Section: Erythropoietin and Traumatic Brain Injury: Translating Expermentioning

confidence: 99%

Charting a course for erythropoietin in traumatic brain injury

Maiese¹

2016

J Transl Sci

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Traumatic brain injury (TBI) is a severe public health problem that impacts more than four million individuals in the United States alone and is increasing in incidence on a global scale. Importantly, TBI can result in acute as well as chronic impairments for the nervous system leaving individuals with chronic disability and in instances of severe trauma, death becomes the ultimate outcome. In light of the significant negative health consequences of TBI, multiple therapeutic strategies are under investigation, but those focusing upon the cytokine and growth factor erythropoietin (EPO) have generated a great degree of enthusiasm. EPO can control cell death pathways tied to apoptosis and autophagy as well oversees processes that affect cellular longevity and aging. In vitro studies and experimental animal models of TBI have shown that EPO can restore axonal integrity, promote cellular proliferation, reduce brain edema, and preserve cellular energy homeostasis and mitochondrial function. Clinical studies for neurodegenerative disorders that involve loss of cognition or developmental brain injury support a positive role for EPO to prevent or reduce injury in the nervous system. However, recent clinical trials with EPO and TBI have not produced such clear conclusions. Further clinical studies are warranted to address the potential efficacy of EPO during TBI, the concerns with the onset, extent, and duration of EPO therapeutic strategies, and to focus upon the specific downstream pathways controlled by EPO such as protein kinase B (Akt), mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), sirtuins, wingless pathways, and forkhead transcription factors for improved precision against the detrimental effects of TBI. KeywordsAkt; Alzheimer's disease; apoptosis; autophagy; erythropoietin; forkhead; mTOR; Parkinson's disease; neurodegeneration; programmed cell death; sirtuins; traumatic brain injury; Wnt Erythropoietin and traumatic brain injury: Translating experimental success into clinical efficacyIn more than 30 million individuals throughout the world, both acute and chronic neurodegenerative disorders can result in significant disability as well as eventual death [1,2]. Chronic neurodegenerative diseases, such as Parkinson's disease (PD) [3,4], can affect approximately 4 percent of individuals over the age of sixty. In addition, the number ofThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. For the sporadic form of AD, approximately 10 percent of the global population over the age of sixty-five is affected [3,5]. Over the next two decades, it is estimated that the number of those suffering from AD will increase significantly to more than 30 million individuals [6][7][8]. HHS Public AccessFor acute neurodegenerative injury, disorders such as stroke can impact almost 800,000 individuals every year with a...

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Section: Erythropoietin and Traumatic Brain Injury: Translating Expermentioning

confidence: 99%

Charting a course for erythropoietin in traumatic brain injury

Maiese¹

2016

J Transl Sci

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“…For example, erythropoietin (EPO), a cytokine and an investigational therapeutic strategy for DM (12, 225), targets multiple cellular signal transduction pathways in the body (226, 227) and relies upon mTOR for cytoprotection (2, 32, 42, 199, 228). EPO uses mTOR to increase cell survival during oxygen-glucose deprivation (195, 229), prevent cell injury during β-amyloid exposure (230), modulate bone homeostasis (231), improve cognitive function sepsis-associated encephalopathy (232), promote retinal progenitor cell survival during oxidant stress (233), prevent retinal degeneration in models of polycystic kidney disease (62), and foster the neuronal phenotype of adult neuronal precursor cells (234). During abnormalities in cellular metabolism, EPO facilitates wound healing during DM (50), attenuates AGE-induced toxicity (235), protects endothelial cell survival during experimental models of DM (66, 67), maintains cellular mitochondrial function and energy metabolism (70), limits high glucose-induced oxidative stress in renal tubular cells (138), and reduces the detrimental effects of obesity in animal models (14).…”

Section: Mtor and Dmmentioning

confidence: 99%

Programming Apoptosis and Autophagy with Novel Approaches for Diabetes Mellitus

Maiese¹

2015

CNR

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According to the World Health Organization, diabetes mellitus (DM) in the year 2030 will be ranked the seventh leading cause of death in the world. DM impacts all systems of the body with oxidant stress controlling cell fate through endoplasmic reticulum stress, mitochondrial dysfunction, alterations in uncoupling proteins, and the induction of apoptosis and autophagy. Multiple treatment approaches are being entertained for DM with Wnt1 inducible signaling pathway protein 1 (WISP1), mechanistic target of rapamycin (mTOR), and silent mating type information regulation 2 homolog) 1 (S. cerevisiae) (SIRT1) generating significant interest as target pathways that can address maintenance of glucose homeostasis as well as prevention of cellular pathology by controlling insulin resistance, stem cell proliferation, and the programmed cell death pathways of apoptosis and autophagy. WISP1, mTOR, and SIRT1 can rely upon similar pathways such as AMP activated protein kinase as well as govern cellular metabolism through cytokines such as EPO and oral hypoglycemics such as metformin. Yet, these pathways require precise biological control to exclude potentially detrimental clinical outcomes. Further elucidation of the ability to translate the roles of WISP1, mTOR, and SIRT1 into effective clinical avenues offers compelling prospects for new therapies against DM that can benefit hundreds of millions of individuals throughout the globe.

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“…Stem cells isolated from the human inner ear or the brain from cadaver donors, on the other hand, could serve as a source without ethical constraints [16,19]. In this scenario another possibility could come from the use of human tissue removed during infrequent surgeries [46], but surgically removed tissue is usually taken from patients with diseased organs. In this way stem cells from healthy "niches" of cadaver donors could be the only answer for these circumstances [16].…”

Section: Some Other Advantages Of Cscsmentioning

confidence: 99%

Salvage of Cadaver Stem Cells (CSCs) as a Routine Procedure: History or Future for Regenerative Medicine

Mansilla¹

2013

J Transplant Technol Res

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We present a review in the different capacities and features of Cadaver Stem Cells (CSCs). CSCs could be an innovative and interesting option in the near future for Regenerative Medicine and Transplantation procedures. This provocative topic has not been fully addressed before. The isolation of viable and functional CSCs from humans up to many days post mortem is possible today. There is a real chance to obtain culture and expand viable stem cells for cell therapy from the plentiful source of cadaver donors. Therefore, it seems that it will be possible to routinely obtain CSCs from almost any human cadaver organ or tissue as desired. This could open a new universe of strategies and research in order to find out their real potential as a routine therapeutic procedure for many diseases.

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Adult neural precursors isolated from post mortem brain yield mostly neurons: An erythropoietin-dependent process

Cited by 49 publications

References 59 publications

Charting a course for erythropoietin in traumatic brain injury

Charting a course for erythropoietin in traumatic brain injury

Programming Apoptosis and Autophagy with Novel Approaches for Diabetes Mellitus

Salvage of Cadaver Stem Cells (CSCs) as a Routine Procedure: History or Future for Regenerative Medicine

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