scholarly journals Insights in Behavior of Variably Formulated Alginate-Based Microcapsules for Cell Transplantation

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Pia Montanucci ◽  
Silvia Terenzi ◽  
Claudio Santi ◽  
Ilaria Pennoni ◽  
Vittorio Bini ◽  
...  

Alginate-based microencapsulation of live cells may offer the opportunity to treat chronic and degenerative disorders. So far, a thorough assessment of physical-chemical behavior of alginate-based microbeads remains cloudy. A disputed issue is which divalent cation to choose for a high performing alginate gelling process. Having selected, in our system, high mannuronic (M) enriched alginates, we studied different gelling cations and their combinations to determine their eventual influence on physical-chemical properties of the final microcapsules preparation,in vitroandin vivo. We have shown that used of ultrapure alginate allows for high biocompatibility of the formed microcapsules, regardless of gelation agents, while use of different gelling cations is associated with corresponding variable effects on the capsules’ basic architecture, as originally reported in this work. However, only the final application which the capsules are destined to will ultimately guide the selection of the ideal, specific gelling divalent cations, since in principle there are no capsules that are better than others.

2019 ◽  
Vol 7 (4) ◽  
pp. 630-639 ◽  
Author(s):  
Lai C. ◽  
S. J. Zhang ◽  
L. Y. Sheng ◽  
T. F. Xi

The aim of this study was to investigate the influence of poly(lactide-co-glycolide) (PLGA) and polydopamine (PDA) as coating materials on the tensile strength, surface performance, in vitro cell behavior and the in vivo material-tissue reaction of bacterial cellulose (BC) membranes.


10.12737/2753 ◽  
2013 ◽  
Vol 20 (4) ◽  
pp. 160-165
Author(s):  
Сергиевич ◽  
A. Sergievich ◽  
Чайка ◽  
Vladimir Chayka ◽  
Голохваст ◽  
...  

There are both in the domestic and the world science a discussion about the biological activity of water-insoluble solid microparticles technogenous and natural. These interactions are studied in the context of the professional pathology, hygiene and nanotoxicology. The purpose of this research was to study the mechanisms of action of particles of natural minerals of various sizes on biological systems. The paper is based on the applied modern methods which allow to determine the degree of interaction of microelements with the functional systems of the organism. Analysis of the results showed that the application of these methods has a number of shortcomings in the experiments in vivo and in vitro, associated with the physical and chemical features of zeolites. It is established that under cultivation in 6- and 24-hole tablets, the zeolite in a dose of 50 mg/ml covers all the cells attached to the glass. In the fields of view of the cells are practically invisible. Thus, an assessment of toxic effects or functional condition of the cells is not possible. Zeolite being water-insoluble compound wich is not subjected to the pipetting. At the delete zeolite of culture, there is practically full elimination of cells from the hole. Accumulation of the primary information about the biological effects of nano - and microparticles is extremely important. This allows the authors to make some conclusions, but the decision of a question on the mechanism of biological activity, especially the prediction of some properties of particles without the study of physical-chemical properties of the particles isn´t possible.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4796-4796
Author(s):  
Anthony Conway ◽  
Josée Laganière ◽  
David E Paschon ◽  
Katrin Hacke ◽  
Noriyuki Kasahara ◽  
...  

Abstract A current limitation in gene therapy is obtaining a sufficient number of modified cells to produce a therapeutic effect in vivo. In several diseases, correction of a mutant allele confers a selective growth advantage to the modified cells, thus enhancing efficacy with moderate initial modification. For most diseases, however, there is no selective advantage to the corrected cells. One potential strategy to address this limitation is in vivo selection of modified cells using pharmacological agents. It has previously been shown that 6-thioguanine (6-TG), an FDA-approved chemotherapeutic small molecule, is cytotoxic to cells expressing the enzyme HPRT, allowing for selective growth of HPRT knockout cells. Knockout of HPRT can be achieved by creating a nonsense mutation in an upstream exon, or by terminating splicing by introducing a large transgene into an intron. To allow for selectable transgenesis of only cells which have undergone targeted integration (TI), engineered zinc-finger nucleases (ZFNs) were used to insert a virally-delivered transgene into an HPRT intron. After two weeks of in vitro 6-TG selection following genome modification, a 95-fold increase in TI was observed in pooled K562 cell populations to a final level of 72% TI, whereas a 30-fold increase in transgene-expressing live cells was seen in peripheral blood-mobilized primary CD34+ cells resulting in 90% transgene-positive live cells. Furthermore, a 72-fold increase in transgene mRNA transcript was observed after two weeks of erythroid differentiation and 6-TG selection of CD34+ cells compared to unselected genome-modified controls. These results represent an important step in developing hematopoietic stem cell (HSC)-based gene therapies, as well as a platform technology for creating gene-modified HSC populations with high proportions of therapeutic transgene expression via precise, targeted integration of a transgene of interest. Disclosures Conway: Sangamo Biosciences: Employment. Paschon:Sangamo Biosciences: Employment. Gregory:Sangamo Biosciences: Employment. Holmes:Sangamo Biosciences: Employment. Cost:Sangamo Biosciences: Employment.


Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 229 ◽  
Author(s):  
Germain Taiwe ◽  
Jérôme Montnach ◽  
Sébastien Nicolas ◽  
Stéphan De Waard ◽  
Emmanuelle Fiore ◽  
...  

The medical staff is often powerless to treat patients affected by drug abuse or misuse and poisoning. In the case of envenomation, the treatment of choice remains horse sera administration that poses a wealth of other medical conditions and threats. Previously, we have demonstrated that DNA-based aptamers represent powerful neutralizing tools for lethal animal toxins of venomous origin. Herein, we further pursued our investigations in order to understand whether all toxin-interacting aptamers possessed equivalent potencies to neutralize αC-conotoxin PrXA in vitro and in vivo. We confirmed the high lethality in mice produced by αC-conotoxin PrXA regardless of the mode of injection and further characterized myoclonus produced by the toxin. We used high-throughput patch-clamp technology to assess the effect of αC-conotoxin PrXA on ACh-mediated responses in TE671 cells, responses that are carried by muscle-type nicotinic receptors. We show that 2 out of 4 aptamers reduce the affinity of the toxin for its receptor, most likely by interfering with the pharmacophore. In vivo, more complex responses on myoclonus and mice lethality are observed depending on the type of aptamer and mode of administration (concomitant or differed). Concomitant administration always works better than differed administration indicating the stability of the complex in vivo. The most remarkable conclusion is that an aptamer that has no or a limited efficacy in vitro may nevertheless be functional in vivo probably owing to an impact on the biodistribution or pharmacokinetics of the toxin in vivo. Overall, the results highlight that a blind selection of aptamers against toxins leads to efficient neutralizing compounds in vivo regardless of the mode of action. This opens the door to the use of aptamer mixtures as substitutes to horse sera for the neutralization of life-threatening animal venoms, an important WHO concern in tropical areas.


2018 ◽  
Vol 15 (2) ◽  
pp. 54
Author(s):  
Ririn Lispita Wulandari ◽  
Eli Mahmud ◽  
Mufrod Mufrod

ABSTRACTEthanol extract of bitter melon leaves at a concentration of 5% has been shown to have mucolytic activity. For ease of use that is made of dosage forms syrup. Thickening agent serves to increase the viscosity and resist settling process resulting in a stable syrup. Gelatin has the ability to improve settling extract better than other thickening. This study aims to determine the effect of variations in the concentration of gelatin to the physical-chemical properties and activity of ethanol extract syrup mukolitik pare leaves the cow intestine mucus in vitro. Extraction of leaf bitter melon is done by percolation. EEDP was made into three syrup formulas using 1% (FII), 2% (FIII), 3% (FIV) gelatin thickener. There is also syrup without extract and gelatin (FI) as a control. The four syrup formulas were examined for physical chemical properties (organoleptic, homogeneity, pH, viscosity), and tested their mucolytic activity. Data on the results of activity tests in the form of viscosity were analyzed by Kruskal-Wallis followed by Mann-Whitney. Data from organoleptic examination, homogeneity, Ph were analyzed descriptively, while viscosity with Linear Regression. The results showed that EEDP syrup with a gelatin concentration of 1%; 2%; 3% have mucolytic activity. The results of examination of the physico-chemical properties of FII, III, and IV syrups have the same taste and color, sweet and bitter, and are greenish black in color, while FI syrup is sweet and yellowish in color. Homogeneous FI syrup, FIII and FIV syrup are evenly distributed, while FII syrup has coarse particles. Fourth pH normal syrup formula. Increased concentration of gelatin (1%; 2%; 3%) can increase the viscosity of syrupKeywords: ethanol extract of bitter melon leaves, syrup, gelatin


2004 ◽  
Vol 14 (S3) ◽  
pp. 20-23 ◽  
Author(s):  
giorgio soldani ◽  
massimo bernabei ◽  
paola losi ◽  
adrian crucean ◽  
dante chiappino ◽  
...  

the idea underscoring our proposed development is to take advantage of the good properties of both polyurethanes (pu) and silicones (pdms). the attributes which make polyurethanes attractive as materials for biomedical applications are their excellent physical–chemical properties, and their relatively good biocompatibility. against their use is the phenomenon of biodegradation that occurs after long-term implantation. silicones, on the other end, are known to have long-term biostability and good haemocompatibility subsequent to their use in several biomedical settings.


Author(s):  
E. D. Salmon ◽  
J. C. Waters ◽  
C. Waterman-Storer

We have developed a multi-mode digital imaging system which acquires images with a cooled CCD camera (Figure 1). A multiple band pass dichromatic mirror and robotically controlled filter wheels provide wavelength selection for epi-fluorescence. Shutters select illumination either by epi-fluorescence or by transmitted light for phase contrast or DIC. Many of our experiments involve investigations of spindle assembly dynamics and chromosome movements in live cells or unfixed reconstituted preparations in vitro in which photodamage and phototoxicity are major concerns. As a consequence, a major factor in the design was optical efficiency: achieving the highest image quality with the least number of illumination photons. This principle applies to both epi-fluorescence and transmitted light imaging modes. In living cells and extracts, microtubules are visualized using X-rhodamine labeled tubulin. Photoactivation of C2CF-fluorescein labeled tubulin is used to locally mark microtubules in studies of microtubule dynamics and translocation. Chromosomes are labeled with DAPI or Hoechst DNA intercalating dyes.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Merricka C. Livingstone ◽  
Alexis A. Bitzer ◽  
Alish Giri ◽  
Kun Luo ◽  
Rajeshwer S. Sankhala ◽  
...  

AbstractPlasmodium falciparum malaria contributes to a significant global disease burden. Circumsporozoite protein (CSP), the most abundant sporozoite stage antigen, is a prime vaccine candidate. Inhibitory monoclonal antibodies (mAbs) against CSP map to either a short junctional sequence or the central (NPNA)n repeat region. We compared in vitro and in vivo activities of six CSP-specific mAbs derived from human recipients of a recombinant CSP vaccine RTS,S/AS01 (mAbs 317 and 311); an irradiated whole sporozoite vaccine PfSPZ (mAbs CIS43 and MGG4); or individuals exposed to malaria (mAbs 580 and 663). RTS,S mAb 317 that specifically binds the (NPNA)n epitope, had the highest affinity and it elicited the best sterile protection in mice. The most potent inhibitor of sporozoite invasion in vitro was mAb CIS43 which shows dual-specific binding to the junctional sequence and (NPNA)n. In vivo mouse protection was associated with the mAb reactivity to the NANPx6 peptide, the in vitro inhibition of sporozoite invasion activity, and kinetic parameters measured using intact mAbs or their Fab fragments. Buried surface area between mAb and its target epitope was also associated with in vivo protection. Association and disconnects between in vitro and in vivo readouts has important implications for the design and down-selection of the next generation of CSP based interventions.


Nanomaterials ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 745
Author(s):  
Enrico Bergamaschi ◽  
Giacomo Garzaro ◽  
Georgia Wilson Jones ◽  
Martina Buglisi ◽  
Michele Caniglia ◽  
...  

Carbon nanotubes (CNTs) and carbon nanofibers (CNFs) are erroneously considered as singular material entities. Instead, they should be regarded as a heterogeneous class of materials bearing different properties eliciting peculiar biological outcomes both in vitro and in vivo. Given the pace at which the industrial production of CNTs/CNFs is increasing, it is becoming of utmost importance to acquire comprehensive knowledge regarding their biological activity and their hazardous effects in humans. Animal studies carried out by inhalation showed that some CNTs/CNFs species can cause deleterious effects such as inflammation and lung tissue remodeling. Their physico-chemical properties, biological behavior and biopersistence make them similar to asbestos fibers. Human studies suggest some mild effects in workers handling CNT/CNF. However, owing to their cross-sectional design, researchers have been as yet unable to firmly demonstrate a causal relationship between such an exposure and the observed effects. Estimation of acceptable exposure levels should warrant a proper risk management. The aim of this review is to challenge the conception of CNTs/CNFs as a single, unified material entity and prompt the establishment of standardized hazard and exposure assessment methodologies able to properly feeding risk assessment and management frameworks.


1975 ◽  
Author(s):  
E. G. D. Tuddenham ◽  
A. L. Bloom ◽  
J. C. Giddings ◽  
C. A. Barrett

The occurrence of factor VIII inhibitor in five mild or moderately affected liaemophilic patients is described. In four patients the inhibitor inactivated endogenous factor VIII an dtemporarily converted them to severely affected haemophiliacs with factor VIII level of 0%. In the fifth patient, a brother of one of the others, the inhibitor although more potent did not inactivate the patient’s own factor VIII and did not completely inactivate normal factor VIII in vitro. This patient responded to treatment with factor-VIII concentrate but the in-vivo recovery was reduced. The patient’s plasma was tested against a panel of normal donors but it inactivated factor VIII in each to a similar extent and no evidence for normal factor-VIII groups was obtained. In the other patients the response to replacement treatment was also better than that usually seen in severely affected haemophilic patients with inhibitor. In the two related patients the inhibitors have so far persisted but in the unrelated patients the inhibitors eventually disappeared and did not always recur with subsequent therapy. The incidence of factor- VIII inhibitor in less severe haemophiliacs (factor VIII > 3% ) in this centre is 6% suggesting that the complication is more frequent in this type of patient than hitherto recognised.


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