“…Hence we propose the strategy of decapsulating the differentiated hESCs after maturation, followed by its reencapsulation in ultrapure, endotoxin-free alginate. These alginate capsules will be further modified with a polycation coating, followed by an alginate coating, 8,17 and implanted immediately.…”
Section: Discussionmentioning
confidence: 99%
“…7 A simple and commonly used method to ensure whether alginate encapsulation provides sufficient immunoisolation for many cell types is the application of a polycationic coating, followed by an alginate coating. [8][9][10] These characteristics make it an ideal encapsulation system for islet transplantation, and thus it has been utilized for this purpose for decades. [11][12][13][14][15][16][17][18][19] Although these methods of transplantation isolate the islets from the host immune response, this treatment option is plagued by shortage of donor islets.…”
The pluripotent property of human embryonic stem cells (hESCs) makes them attractive for treatment of degenerative diseases such as diabetes. We have developed a stage-wise directed differentiation protocol to produce alginate-encapsulated islet-like cells derived from hESCs, which can be directly implanted for diabetes therapy. The advantage of alginate encapsulation lies in its capability to immunoisolate, along with the added possibility of scalable culture. We have evaluated the possibility of encapsulating hESCs at different stages of differentiation. Encapsulation of predifferentiated cells resulted in insufficient cellular yield and differentiation. On the other hand, encapsulation of undifferentiated hESCs followed by differentiation induction upon encapsulation resulted in the highest viability and differentiation. More striking was that alginate encapsulation resulted in a much stronger differentiation compared to parallel two-dimensional cultures, resulting in 20-fold increase in c-peptide protein synthesis. To elucidate the mechanism contributing to encapsulation-mediated enhancement in hESC maturation, investigation of the signaling pathways revealed interesting insight. While the phospho-protein levels of all the tested signaling molecules were lower under encapsulation, the ratio of pSMAD/pAKT was significantly higher, indicating a more efficient signal transduction under encapsulation. These results clearly demonstrate that alginate encapsulation of hESCs and differentiation to islet-cell types provides a potentially translatable treatment option for type 1 diabetes.
“…Hence we propose the strategy of decapsulating the differentiated hESCs after maturation, followed by its reencapsulation in ultrapure, endotoxin-free alginate. These alginate capsules will be further modified with a polycation coating, followed by an alginate coating, 8,17 and implanted immediately.…”
Section: Discussionmentioning
confidence: 99%
“…7 A simple and commonly used method to ensure whether alginate encapsulation provides sufficient immunoisolation for many cell types is the application of a polycationic coating, followed by an alginate coating. [8][9][10] These characteristics make it an ideal encapsulation system for islet transplantation, and thus it has been utilized for this purpose for decades. [11][12][13][14][15][16][17][18][19] Although these methods of transplantation isolate the islets from the host immune response, this treatment option is plagued by shortage of donor islets.…”
The pluripotent property of human embryonic stem cells (hESCs) makes them attractive for treatment of degenerative diseases such as diabetes. We have developed a stage-wise directed differentiation protocol to produce alginate-encapsulated islet-like cells derived from hESCs, which can be directly implanted for diabetes therapy. The advantage of alginate encapsulation lies in its capability to immunoisolate, along with the added possibility of scalable culture. We have evaluated the possibility of encapsulating hESCs at different stages of differentiation. Encapsulation of predifferentiated cells resulted in insufficient cellular yield and differentiation. On the other hand, encapsulation of undifferentiated hESCs followed by differentiation induction upon encapsulation resulted in the highest viability and differentiation. More striking was that alginate encapsulation resulted in a much stronger differentiation compared to parallel two-dimensional cultures, resulting in 20-fold increase in c-peptide protein synthesis. To elucidate the mechanism contributing to encapsulation-mediated enhancement in hESC maturation, investigation of the signaling pathways revealed interesting insight. While the phospho-protein levels of all the tested signaling molecules were lower under encapsulation, the ratio of pSMAD/pAKT was significantly higher, indicating a more efficient signal transduction under encapsulation. These results clearly demonstrate that alginate encapsulation of hESCs and differentiation to islet-cell types provides a potentially translatable treatment option for type 1 diabetes.
“…178 Reviews on the role of ECM properties and mechanism of cell-ECM interactions on cell adhesion, migration, and matrix assembly have been covered by several groups. [179][180][181] The ultimate aim of tissue scaffolding strategies is to mimic the actual 3D microenvironment that is the ECM. As with all scaffolds, it is important to consider the pore structure of the native ECM of the tissue that is to be replaced or reconstructed.…”
Tissue engineering applications commonly encompass the use of three-dimensional (3D) scaffolds to provide a suitable microenvironment for the incorporation of cells or growth factors to regenerate damaged tissues or organs. These scaffolds serve to mimic the actual in vivo microenvironment where cells interact and behave according to the mechanical cues obtained from the surrounding 3D environment. Hence, the material properties of the scaffolds are vital in determining cellular response and fate. These 3D scaffolds are generally highly porous with interconnected pore networks to facilitate nutrient and oxygen diffusion and waste removal. This review focuses on the various fabrication techniques (e.g., conventional and rapid prototyping methods) that have been employed to fabricate 3D scaffolds of different pore sizes and porosity. The different pore size and porosity measurement methods will also be discussed. Scaffolds with graded porosity have also been studied for their ability to better represent the actual in vivo situation where cells are exposed to layers of different tissues with varying properties. In addition, the ability of pore size and porosity of scaffolds to direct cellular responses and alter the mechanical properties of scaffolds will be reviewed, followed by a look at nature's own scaffold, the extracellular matrix. Overall, the limitations of current scaffold fabrication approaches for tissue engineering applications and some novel and promising alternatives will be highlighted.
“…For example, there were 98 review articles reported in the general field of microencapsulation with some specific examples in pharmacology [12][13][14][15][16][17][18][19][20][21][22][23][24], food science technology [25][26][27][28][29][30][31][32], biotechnology and applied microbiology [33][34][35], medicinal chemistry [36], and interdisciplinary areas of chemistry [37]. Among the recently published 26 reviews, only one article dealt with CD-based encapsulation for its use in bioactive food components processes [29].…”
Microencapsulation is a technique devoted to entrapping core material inside one or more polymeric coatings. Cyclodextrins (CDs) and its various derivatives are used as functional building blocks because of their unique physical properties. As well CDs possess, the ability to form well-defined host/guest inclusion complexes with lipophilic guests in aqueous solution or polar organic solvents. This review covers literature over the past decade concerning the design of microcapsules containing CDs and their physiochemical properties. Various applications of CD-based microcapsules are anticipated due to their unique surface functionalization, specific morphology, and the occurrence of a complex tertiary structure. The following themes will be addressed in this review: i) the development of CD-based microcapsules, ii) the physiochemical properties of CD-based microcapsules, and iii) the complexation thermodynamics between CDs and target molecules will be examined due to the limited availability of research corresponding to microcapsule results.
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