Mucopolysaccharidosis and Autophagy: Controversies on the Contribution of the Process to the Pathogenesis and Possible Therapeutic Applications

AbstractMucopolysaccharidosis (MPS) consists of a group of 11 enzymatic defects which result in accumulation of undegraded glycosaminoglycans (GAG) in lysosomes. MPS is a severe metabolic disease for which only bone marrow/hematopoietic stem cell transplantation and enzyme replacement therapy are current therapeutic options. However, they are available for only a few of MPS types, and are ineffective in treatment of central nervous system. Recent studies indicated that the autophagy process can be impaired in MPS, but various contradictory conclusions have been published in this matter. Nevertheless, stimulation of autophagy has been proposed as a potential therapeutic option for MPS, and very recent results suggest that such approach might be effective in improving MPS symptoms. Still the mechanisms of autophagy changes in MPS are not clear, and efficiency of autophagy activation in clearing the storage material requires further investigation. These problems are summarized and discussed in this review.
Source: NeuroMolecular Medicine - Category: Neurology Source Type: research

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CONCLUSIONS Our findings show that intravitreal injection of hRPCs is effective and safe in protecting photoreceptor cells in RCS rats, but were no longer effective at 12 weeks after transplantation. Moreover, hRPCs released multiple neurotrophic factors that may be involved in treating retinal disease. PMID: 32221273 [PubMed - in process]
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
Mesenchymal stem cell therapies vary widely in their ability to influence regeneration, though they fairly reliably reduce chronic inflammation in older patients. One challenge is that there is no standard on what constitutes a mesenchymal stem cell; it is a category so broad as to be almost meaningless. Further, two clinics performing what is ostensibly the same protocol using cells from the same source can produce widely divergent outcomes. In most cases, near all transplanted cells die, and the benefits obtained for the patient derive from signaling produced by the stem cells in the short period of survival following tr...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
Researchers here identify miR-155-5p as a potential target to improve mitochondrial function. This microRNA is upregulated with age, and appears to inhibit mitochondrial fission. That in turn prevents the cellular maintenance process of mitophagy from clearing out worn and damaged mitochondria efficiently enough to prevent loss of function. Since mitochondria provide the chemical energy store molecules that power all cellular operations, this has downstream consequences on cell and tissue function, including higher levels of cellular senescence. Aging impairs the functions of human mesenchymal stem cells (MSCs), t...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
Schematics of the experimental protocol used to demonstrate the selective anti ‐tumor effect of the OSKM factors in vivo. Briefly, HSPCs from reprogrammable mice were isolated, infected in culture for 2 days with a retrovirus containing MLL‐AF9‐GFP and transplanted into sublethally irradiated mice. One week later the percentage of GFP+ cells in the bone marrow and bloo d was determined and animals treated with doxycycline (doxy) for 1 week to activate OSKM in the donor cells or left untreated (no doxy). The mice were then monitored for several months for the onset of leukemia and death. While untreated animals...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Commentary Source Type: research
In this study, we show that niche intrinsic expression of the CXCR4 chemokine receptor critically regulates HSPC maintenance during steady state, and promotes early hematopoietic regeneration after myeloablative irradiation. At steady state, chimeric mice with wild ‐type (WT) HSPC and marrow stroma that lack CXCR4 show decreased HSPC quiescence, and their repopulation capacity was markedly reduced. Mesenchymal stromal cells (MSC) were significantly reduced in the BM of CXCR4 deficient mice, which was accompanied by decreased levels of the HSPC supporting fac tors stromal cell‐derived factor‐1 (SDF‐1) and stem cell ...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Tissue ‐Specific Stem Cells Source Type: research
Journal of Proteome ResearchDOI: 10.1021/acs.jproteome.9b00639
Source: Journal of Proteome Research - Category: Biochemistry Authors: Source Type: research
Contributors : Sonata Jodele ; Nathan Luebbering ; Mario Medvedovic ; Christopher E Dandoy ; Nicholas J Gloude ; Michael B Jordan ; Daniella L Erez ; Benjamin L Laskin ; Jenny Chen ; Stella M DaviesSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensTransplant-associated thrombotic microangiopathy (TA-TMA) is a significant cause of mortality after hematopoietic stem cell transplant (HSCT). Complement blockade is an effective therapeutic strategy for TA-TMA, but some patients with severe disease lack a complete response, prompting a search for additional targetable endothelial injury pathw...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Contributor : Yogita SharmaSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensSince the pioneering studies using fetal cell transplants in Parkinson ’s disease (PD), brain repair by cell replacement has remained a long-standing and realistic goal for the treatment of neurodegenerative disorders including PD. Authentic and functional dopamine (DA) neurons can now be generated from human pluripotent stem cells (hPSCs), and these cell preparation s are both safe and functional when transplanted to animal models of PD1. However, although resulting grafts from fetal brain tissue and hPS...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Ekta Dhamija, Pankaj Meena, Vidyasagar Ramalingam, Ranjeet Sahoo, Sameer Rastogi, Sanjay ThulkarIndian Journal of Radiology and Imaging 2020 30(1):20-26 Chemotherapy while revolutionizing cancer management by improving survival and quality of life; is also associated with several adverse effects. Lung is the most common organ affected in chemotherapy-related complications, due to either drug toxicity or more commonly due to infections caused by immunosuppression and less commonly due to immune-mediated injury. Radiology, when used in combination with clinical and lab data, can help reach the specific diagnosis or narrow d...
Source: Indian Journal of Radiology and Imaging - Category: Radiology Authors: Source Type: research
This study, for the first time, shows that transplantation of non-autologous mitochondria from healthy skeletal muscle cells into normal cardiomyocytes leads to short-term improvement of bioenergetics indicating "supercharged" state. However, over time these improved effects disappear, which suggests transplantation of mitochondria may have a potential application in settings where there is an acute stress. Outlining Some of the Science Behind Partial Reprogramming at Turn.bio https://www.fightaging.org/archives/2020/03/outlining-some-of-the-science-behind-partial-reprogramming-at-turn-bio/ Tur...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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