Impact of lysosomal storage disorders on biology of mesenchymal stem cells: Evidences from in vitro silencing of glucocerebrosidase (GBA) and alpha-galactosidase A (GLA) enzymes

2017 ◽  
Vol 232 (12) ◽  
pp. 3454-3467 ◽  
Author(s):  
Tiziana Squillaro ◽  
Ivana Antonucci ◽  
Nicola Alessio ◽  
Anna Esposito ◽  
Marilena Cipollaro ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Lysosomal Storage Disorders ◽  
Lysosomal Storage ◽  
Alpha Galactosidase ◽  
Storage Disorders

scholarly journals Small–molecule therapeutics for the treatment of glycolipid lysosomal storage disorders

2003 ◽  
Vol 358 (1433) ◽  
pp. 927-945 ◽  
Author(s):  
Terry D. Butters ◽  
Howard R. Mellor ◽  
Keishi Narita ◽  
Raymond A. Dwek ◽  
Frances M. Platt
Keyword(s):  
Catalytic Activity ◽  
Lysosomal Storage Disorders ◽  
Substrate Reduction Therapy ◽  
Lysosomal Storage ◽  
Substrate Reduction ◽  
Treatment Demand ◽  
Small Molecule Therapeutics ◽  
Storage Disorders

Glycosphingolipid (GSL) lysosomal storage disorders are a small but challenging group of human diseases to treat. Although these disorders appear to be monogenic in origin, where the catalytic activity of enzymes in GSL catabolism is impaired, the clinical presentation and severity of disease are heterogeneous. Present attitudes to treatment demand individual therapeutics designed to match the specific disease–related gene defect; this is an acceptable approach for those diseases with high frequency, but it lacks viability for extremely rare conditions. An alternative therapeutic approach termed ‘substrate deprivation’ or ‘substrate reduction therapy’ (SRT) aims to balance cellular GSL biosynthesis with the impairment in catalytic activity seen in lysosomal storage disorders. The development of N–alkylated iminosugars that have inhibitory activity against the first enzyme in the pathway for glucosylating sphingolipid in eukaryotic cells, ceramide–specific glucosyltransferase, offers a generic therapeutic for the treatment of all glucosphingolipidoses. The successful use of N–alkylated iminosugars to establish SRT as an alternative therapeutic strategy has been demonstrated in in vitro , in vivo and in clinical trials for type 1 Gaucher disease. The implications of these studies and the prospects of improvement to the design of iminosugar compounds for treating Gaucher and other GSL lysosomal storage disorders will be discussed.

scholarly journals Induced pluripotent stem cells derived from mouse models of lysosomal storage disorders

2010 ◽  
Vol 107 (17) ◽  
pp. 7886-7891 ◽  
Author(s):  
Xing-Li Meng ◽  
Jin-Song Shen ◽  
Shiho Kawagoe ◽  
Toya Ohashi ◽  
Roscoe O. Brady ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Mouse Models ◽  
Pluripotent Stem Cells ◽  
Lysosomal Storage Disorders ◽  
Lysosomal Storage ◽  
Induced Pluripotent ◽  
Storage Disorders

scholarly journals Efficacy of pentosan polysulfate in in vitro models of lysosomal storage disorders: Fabry and Gaucher Disease

PLoS ONE ◽  
2019 ◽  
Vol 14 (5) ◽  
pp. e0217780 ◽  
Author(s):  
Andrea N. Crivaro ◽  
Juan M. Mucci ◽  
Constanza M. Bondar ◽  
Maximiliano E. Ormazabal ◽  
Romina Ceci ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
In Vitro Models ◽  
Lysosomal Storage Disorders ◽  
Lysosomal Storage ◽  
Pentosan Polysulfate ◽  
Storage Disorders

Effects of suramin, a polyanionic drug inducing lysosomal storage disorders on tooth germs in vitro

1994 ◽  
Vol 81 (2) ◽  
pp. 143-152 ◽  
Author(s):  
Amel Gritli-Linde ◽  
Jean-Victor Ruch ◽  
Manuel P. Mark ◽  
Sylvie Lécolle ◽  
Michel Goldberg
Keyword(s):  
Lysosomal Storage Disorders ◽  
Lysosomal Storage ◽  
Tooth Germs ◽  
Storage Disorders

Autologous transplantation of mesenchymal stem cells into the portal vein of the miniature pig; a preliminary experiment for NOTES approach

2019 ◽  
Vol 98 (9) ◽  
pp. 350-355
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Portal Vein ◽  
Liver Parenchyma ◽  
Miniature Pig ◽  
Hepatic Diseases ◽  
Study Results

Introduction: There is evidence that mesenchymal stem cells (MSCs) could trans-differentiate into the liver cells in vitro and in vivo and thus may be used as an unfailing source for stem cell therapy of liver disease. Combination of MSCs (with or without their differentiation in vitro) and minimally invasive procedures as laparoscopy or Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a chance for many patients waiting for liver transplantation in vain. Methods: Over 30 millions of autologous MSCs at passage 3 were transplanted via the portal vein in an eight months old miniature pig. The deposition of transplanted cells in liver parenchyma was evaluated histologically and the trans-differential potential of CM-DiI labeled cells was assessed by expression of pig albumin using immunofluorescence. Results: Three weeks after transplantation we detected the labeled cells (solitary, small clusters) in all 10 samples (2 samples from each lobe) but no diffuse distribution in the samples. The localization of CM-DiI+ cells was predominantly observed around the portal triads. We also detected the localization of albumin signal in CM-DiI labeled cells. Conclusion: The study results showed that the autologous MSCs (without additional hepatic differentiation in vitro) transplantation through the portal vein led to successful infiltration of intact miniature pig liver parenchyma with detectable in vivo trans-differentiation. NOTES as well as other newly developed surgical approaches in combination with cell therapy seem to be very promising for the treatment of hepatic diseases in near future.

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