scholarly journals Combination of Hyaluronan and Lyophilized Progenitor Cell Derivatives: Stabilization of Functional Hydrogel Products for Therapeutic Management of Tendinous Tissue Disorders

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2196
Author(s):  
Alexis Laurent ◽  
Alexandre Porcello ◽  
Paula Gonzalez Fernandez ◽  
Annick Jeannerat ◽  
Cédric Peneveyre ◽  
...  

Cultured progenitor cells and derivatives have been used in various homologous applications of cutaneous and musculoskeletal regenerative medicine. Active pharmaceutical ingredients (API) in the form of progenitor cell derivatives such as lysates and lyophilizates were shown to retain function in controlled cellular models of wound repair. On the other hand, hyaluronan-based hydrogels are widely used as functional vehicles in therapeutic products for tendon tissue disorders. The aim of this study was the experimental characterization of formulations containing progenitor tenocyte-derived APIs and hyaluronan, for the assessment of ingredient compatibility and stability in view of eventual therapeutic applications in tendinopathies. Lyophilized APIs were determined to contain relatively low quantities of proteins and growth factors, while being physicochemically stable and possessing significant intrinsic antioxidant properties. Physical and rheological quantifications of the combination formulas were performed after hydrogen peroxide challenge, outlining significantly improved evolutive viscoelasticity values in accelerated degradation settings. Thus, potent effects of physicochemical protection or stability enhancement of hyaluronan by the incorporated APIs were observed. Finally, combination formulas were found to be easily injectable into ex vivo tendon tissues, confirming their compatibility with further translational clinical approaches. Overall, this study provides the technical bases for the development of progenitor tenocyte derivative-based injectable therapeutic products or devices, to potentially be applied in tendinous tissue disorders.

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 688 ◽  
Author(s):  
Marco Micera ◽  
Alfonso Botto ◽  
Federica Geddo ◽  
Susanna Antoniotti ◽  
Cinzia Margherita Bertea ◽  
...  

Squalene (SQ) is a natural triterpene widely distributed in nature. It is a metabolic intermediate of the sterol biosynthetic pathway and represents a possible target in different metabolic and oxidative stress-related disorders. Growing interest has been focused on SQ’s antioxidant properties, derived from its chemical structure. Strong evidence provided by ex vivo models underline its scavenging activity towards free radicals, whereas only a few studies have highlighted its effect in cellular models of oxidative stress. Given the role of unbalanced free radicals in both the onset and progression of several cardiovascular diseases, an in depth evaluation of SQ’s contribution to antioxidant defense mechanisms could represent a strategic approach in dealing with these pathological conditions. At present experimental results overall show a double-edged sword role of squalene in cardiovascular diseases and its function has to be better elucidated in order to establish intervention lines focused on its features. This review aims to summarize current knowledge about endogenous and exogenous sources of SQ and to point out the controversial role of SQ in cardiovascular physiology.


2019 ◽  
Vol 45 (4) ◽  
pp. 1092-1099
Author(s):  
Roberto Cannella ◽  
Mohammed Shahait ◽  
Alessandro Furlan ◽  
Feng Zhang ◽  
Joel D. Bigley ◽  
...  

The Analyst ◽  
2020 ◽  
Vol 145 (4) ◽  
pp. 1445-1456 ◽  
Author(s):  
Fabian Placzek ◽  
Eliana Cordero Bautista ◽  
Simon Kretschmer ◽  
Lara M. Wurster ◽  
Florian Knorr ◽  
...  

Characterization of bladder biopsies, using a combined fiber optic probe-based optical coherence tomography and Raman spectroscopy imaging system that allows a large field-of-view imaging and detection and grading of cancerous bladder lesions.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1791
Author(s):  
Rosa Scala ◽  
Fatima Maqoud ◽  
Nicola Zizzo ◽  
Giuseppe Passantino ◽  
Antonietta Mele ◽  
...  

(1) Background: Cantu syndrome (CS) arises from gain-of-function (GOF) mutations in the ABCC9 and KCNJ8 genes, which encode ATP-sensitive K+ (KATP) channel subunits SUR2 and Kir6.1, respectively. Most CS patients have mutations in SUR2, the major component of skeletal muscle KATP, but the consequences of SUR2 GOF in skeletal muscle are unknown. (2) Methods: We performed in vivo and ex vivo characterization of skeletal muscle in heterozygous SUR2[A478V] (SUR2wt/AV) and homozygous SUR2[A478V] (SUR2AV/AV) CS mice. (3) Results: In SUR2wt/AV and SUR2AV/AV mice, forelimb strength and diaphragm amplitude movement were reduced; muscle echodensity was enhanced. KATP channel currents recorded in Flexor digitorum brevis fibers showed reduced MgATP-sensitivity in SUR2wt/AV, dramatically so in SUR2AV/AV mice; IC50 for MgATP inhibition of KATP currents were 1.9 ± 0.5 × 10−5 M in SUR2wt/AV and 8.6 ± 0.4 × 10−6 M in WT mice and was not measurable in SUR2AV/AV. A slight rightward shift of sensitivity to inhibition by glibenclamide was detected in SUR2AV/AV mice. Histopathological and qPCR analysis revealed atrophy of soleus and tibialis anterior muscles and up-regulation of atrogin-1 and MuRF1 mRNA in CS mice. (4) Conclusions: SUR2[A478V] “knock-in” mutation in mice impairs KATP channel modulation by MgATP, markedly so in SUR2AV/AV, with atrophy and non-inflammatory edema in different skeletal muscle phenotypes.


2021 ◽  
Vol 2 (1) ◽  
pp. 100311
Author(s):  
Daniella C. Terenzi ◽  
Ehab Bakbak ◽  
Justin Z. Trac ◽  
Mohammad Al-Omran ◽  
Adrian Quan ◽  
...  

2021 ◽  
Vol 22 (1) ◽  
pp. 424
Author(s):  
Vlad F. Avram ◽  
Imen Chamkha ◽  
Eleonor Åsander-Frostner ◽  
Johannes K. Ehinger ◽  
Romulus Z. Timar ◽  
...  

Statins are the cornerstone of lipid-lowering therapy. Although generally well tolerated, statin-associated muscle symptoms (SAMS) represent the main reason for treatment discontinuation. Mitochondrial dysfunction of complex I has been implicated in the pathophysiology of SAMS. The present study proposed to assess the concentration-dependent ex vivo effects of three statins on mitochondrial respiration in viable human platelets and to investigate whether a cell-permeable prodrug of succinate (complex II substrate) can compensate for statin-induced mitochondrial dysfunction. Mitochondrial respiration was assessed by high-resolution respirometry in human platelets, acutely exposed to statins in the presence/absence of the prodrug NV118. Statins concentration-dependently inhibited mitochondrial respiration in both intact and permeabilized cells. Further, statins caused an increase in non-ATP generating oxygen consumption (uncoupling), severely limiting the OXPHOS coupling efficiency, a measure of the ATP generating capacity. Cerivastatin (commercially withdrawn due to muscle toxicity) displayed a similar inhibitory capacity compared with the widely prescribed and tolerable atorvastatin, but did not elicit direct complex I inhibition. NV118 increased succinate-supported mitochondrial oxygen consumption in atorvastatin/cerivastatin-exposed platelets leading to normalization of coupled (ATP generating) respiration. The results acquired in isolated human platelets were validated in a limited set of experiments using atorvastatin in HepG2 cells, reinforcing the generalizability of the findings.


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