Engineered Trehalose Permeable to Mammalian Cells

Abazari, Alireza; Meimetis, Labros G.; Budin, Ghyslain; Bale, Shyam Sundhar; Weissleder, Ralph; Toner, Mehmet

doi:10.1371/journal.pone.0130323

Cited by 57 publications

(74 citation statements)

References 37 publications

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“…35 for review). Little has been done to characterize the uptake of osmolytes with the exception of trehalose, 36 which appears to penetrate poorly into the cell. The results of this investigation suggest that longer incubation times may be needed for cells frozen with non-DMSO cryoprotectants to allow for penetration of larger components and elicit maximum cell recovery.…”

Section: Permeation/partitioning Of Solutesmentioning

confidence: 99%

Combinations of Osmolytes, Including Monosaccharides, Disaccharides, and Sugar Alcohols Act in Concert During Cryopreservation to Improve Mesenchymal Stromal Cell Survival

Pollock

Moller-Trane

et al. 2016

Tissue Engineering Part C: Methods

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There is demand for non-dimethyl sulfoxide (DMSO) cryoprotective agents that maintain cell viability without causing poor postthaw function or systemic toxicity. The focus of this investigation involves expanding our understanding of multicomponent osmolyte solutions and their ability to preserve cell viability during freezing. Controlled cooling rate freezing, Raman microscopy, and differential scanning calorimetry (DSC) were utilized to evaluate the differences in recovery and ice crystal formation behavior for solutions containing multiple cryoprotectants, including sugars, sugar alcohols, and small molecule additives. Postthaw recovery of mesenchymal stem cells (MSCs) in solutions containing multiple osmolytes have been shown to be comparable or better than that of MSCs frozen in 10% DMSO at 1°C/min when the solution composition is optimized. Maximum postthaw recovery was observed in these multiple osmolyte solutions with incubation times of up to 2 h before freezing. Raman images demonstrate large ice crystal formation in cryopreserved cells incubated for shorter periods of time (*30 min), suggesting that longer permeation times are needed for these solutions. Recovery was dependent upon the concentration of each component in solution, and was not strongly correlated with osmolarity. It is noteworthy that the postthaw recovery varied significantly with the composition of solutions containing the same three components and this variation exhibited an inverted U-shape behavior, indicating that there may be a ''sweet spot'' for different combinations of osmolytes. Raman images of freezing behavior in different solution compositions were consistent with the observed postthaw recovery. Phase change behavior (solidification patterns and glass-forming tendency) did not differ for solutions with similar osmolarity, but differences in postthaw recovery suggest that biological, not physical, methods of protection are at play. Lastly, molecular substitution of glucose (a monosaccharide) for sucrose (a disaccharide) resulted in a significant drop in recovery. Taken together, the information from these studies increases our understanding of non-DMSO multicomponent cryoprotective solutions and the manner by which they enhance postthaw recovery.

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Section: Permeation/partitioning Of Solutesmentioning

confidence: 99%

Combinations of Osmolytes, Including Monosaccharides, Disaccharides, and Sugar Alcohols Act in Concert During Cryopreservation to Improve Mesenchymal Stromal Cell Survival

Pollock

Moller-Trane

et al. 2016

Tissue Engineering Part C: Methods

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“…Recently, a membrane-permeable trehalose-based compound has been developed for potential application in stem cell preservation (Abazari et al, 2015). Such developments may be used in the future to better preserve lyophilised platelets.…”

Section: Alternative Platelet Storage Methodsmentioning

confidence: 99%

Alternatives to allogeneic platelet transfusion

et al. 2016

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Allogeneic platelet transfusions are widely used for the prevention and treatment of bleeding in thrombocytopenia. Recent evidence suggests platelet transfusions have limited efficacy and are associated with uncertain immunomodulatory risks and concerns about viral or bacterial transmission. Alternatives to transfusion are a well-recognised tenet of Patient Blood Management, but there has been less focus on different strategies to reduce bleeding risk by comparison to platelet transfusion. Direct alternatives to platelet transfusion include agents to stimulate endogenous platelet production (thrombopoietin mimetics), optimising platelet adhesion to endothelium by treating anaemia or increasing von Willebrand factor levels (desmopressin), increasing formation of cross-linked fibrinogen (activated recombinant factor VII, fibrinogen concentrate or recombinant factor XIII), decreasing fibrinolysis (tranexamic acid or epsilon aminocaproic acid) or using artificial or modified platelets (cryopreserved platelets, lyophilised platelets, haemostatic particles, liposomes, engineered nanoparticles or infusible platelet membranes). The evidence base to support the use of these alternatives is variable, but an area of active research. Much of the current randomised controlled trial focus is on evaluation of the use of thrombopoietin mimetics and anti-fibrinolytics. It is also recognised that one alternative strategy to platelet transfusion is choosing not to transfuse at all.

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“…148 Recently, there have been reports of acetylated versions of trehalose with increased membrane permeability, which allow for enhanced uptake by mammalian cells and subsequent deacetylation by intracellular esterases. 149 This strategy for intracellular delivery of trehalose could prove invaluable for stabilizing cell lines and other biological products. The importance of trehalose metabolism in plant growth and development 4 may provide opportunities for the development of trehalose analogues that manipulate plant signaling for agricultural applications.…”

Section: Applications Of Trehalose Analoguesmentioning

confidence: 99%

Tailoring trehalose for biomedical and biotechnological applications

O'Neill

Piligian

Olson

et al. 2017

Pure and Applied Chemistry

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Trehalose is a non-reducing sugar whose ability to stabilize biomolecules has brought about its widespread use in biological preservation applications. Trehalose is also an essential metabolite in a number of pathogens, most significantly the global pathogen Mycobacterium tuberculosis, though it is absent in humans and other mammals. Recently, there has been a surge of interest in modifying the structure of trehalose to generate analogues that have applications in biomedical research and biotechnology. Non-degradable trehalose analogues could have a number of advantages as bioprotectants and food additives. Trehalose-based imaging probes and inhibitors are already useful as research tools and may have future value in the diagnosis and treatment of tuberculosis, among other uses. Underlying the advancements made in these areas are novel synthetic methods that facilitate access to and evaluation of trehalose analogues. In this review, we focus on both aspects of the development of this class of molecules. First, we consider the chemical and chemoenzymatic methods that have been used to prepare trehalose analogues and discuss their prospects for synthesis on commercially relevant scales. Second, we describe ongoing efforts to develop and deploy detectable trehalose analogues, trehalose-based inhibitors, and non-digestible trehalose analogues. The current and potential future uses of these compounds are discussed, with an emphasis on their roles in understanding and combatting mycobacterial infection.

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Engineered Trehalose Permeable to Mammalian Cells

Cited by 57 publications

References 37 publications

Combinations of Osmolytes, Including Monosaccharides, Disaccharides, and Sugar Alcohols Act in Concert During Cryopreservation to Improve Mesenchymal Stromal Cell Survival

Combinations of Osmolytes, Including Monosaccharides, Disaccharides, and Sugar Alcohols Act in Concert During Cryopreservation to Improve Mesenchymal Stromal Cell Survival

Alternatives to allogeneic platelet transfusion

Tailoring trehalose for biomedical and biotechnological applications

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