Zwitterionically modified alginates mitigate cellular overgrowth for cell encapsulation

Liu, Qingsheng; Chiu, Alan; Wang, Long‐Hai; An, Duo; Zhong, Monica; Smink, Alexandra M.; Haan, Bart J. de; Vos, Paul de; Keane, Kevin; Vegge, Andreas; Chen, Esther Y.; Song, Wei; Liu, Wendy F.; Flanders, James A.; Rescan, Claude; Grunnet, Lars Groth; Wang, Xi; Ma, Minglin

doi:10.1038/s41467-019-13238-7

Cited by 131 publications

(117 citation statements)

References 82 publications

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“…porosity, stability and permeability were fulfilled by alginate [50]. Consistent results by several studies were reported that pancreatic islet, ESC-and iPSC-derived IPC encapsulation using alginate could maintain the viability both in vivo and in vitro [51][52][53][54][55][56]. Another study on pancreatic islet cryopreservation incorporated alginate encapsulation reported that alginate encapsulation could maintain both viability and functionality of pancreatic islets [57].…”

Section: Discussionsupporting

confidence: 62%

Alginate/Pluronic F127-based encapsulation supports viability and functionality of human dental pulp stem cell-derived insulin-producing cells

et al. 2020

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Background: Current approach for diabetes treatment remained several adverse events varied from gastrointestinal to life-threatening symptoms. Regenerative therapy regarding Edmonton protocol has been facing serious limitations involving protocol efficiency and safety. This led to the study for alternative insulin-producing cell (IPC) resource and transplantation platform. In this study, evaluation of encapsulated human dental pulp-derived stem cell (hDPSC)-derived IPCs by alginate (ALG) and pluronic F127-coated alginate (ALGPA) was performed. Results: The results showed that ALG and ALGPA preserved hDPSC viability and allowed glucose and insulin diffusion in and out. ALG and ALGPA-encapsulated hDPSC-derived IPCs maintained viability for at least 336 h and sustained pancreatic endoderm marker (NGN3), pancreatic islet markers (NKX6.1, MAF-A, ISL-1, GLUT-2 and INSULIN), and intracellular pro-insulin and insulin expressions for at least 14 days. Functional analysis revealed a glucoseresponsive C-peptide secretion of ALG-and ALGPA-encapsulated hDPSC-derived IPCs at 14 days post-encapsulation. Conclusion: ALG and ALGPA encapsulations efficiently preserved the viability and functionality of hDPSC-derived IPCs in vitro and could be the potential transplantation platform for further clinical application.

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Section: Discussionsupporting

confidence: 62%

Alginate/Pluronic F127-based encapsulation supports viability and functionality of human dental pulp stem cell-derived insulin-producing cells

et al. 2020

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“…Therefore, we thought that the amount of anti-inflammatory cytokines secreted from MSC CellSaics was not sufficient for suppression of the immune response to ALG-PLO microcapsules [26,34]. As future work, we would like to study about a method to increase the amount of anti-inflammatory cytokines from MSC CellSaics [35], or use of microcapsules with high biocompatibility [11,[26][27][28] in order to improve %NBGL.…”

Section: Discussionmentioning

confidence: 99%

“…To provide a feasible immuno-isolated environment for islets, there are three requirements, based on the literature [4][5][6]9,21]: (1) the ability to block humoral and cellular immunity; (2) allowing the permeation of small molecules such as insulin and glucose; (3) physical resistance that does not break at the transplantation site. The microencapsulation of islets has been shown to meet these requirements, and many techniques have been reported [7,11,[21][22][23][24][25][26][27][28]. As a microencapsulating material for establishing immuno-isolated environments, alginate polymer is often used because it is inexpensive, biocompatible, and can create a gel easily at room temperature in aqueous solution with divalent ions.…”

Section: Introductionmentioning

confidence: 99%

Co-Microencapsulation of Islets and MSC CellSaics, Mosaic-Like Aggregates of MSCs and Recombinant Peptide Pieces, and Therapeutic Effects of Their Subcutaneous Transplantation on Diabetes

et al. 2020

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The subcutaneous transplantation of microencapsulated islets has been extensively studied as a therapeutic approach for type I diabetes. However, due to the lower vascular density and strong inflammatory response in the subcutaneous area, there have been few reports of successfully normalized blood glucose levels. To address this issue, we developed mosaic-like aggregates comprised of mesenchymal stem cells (MSCs) and recombinant peptide pieces called MSC CellSaics, which provide a continuous release of angiogenic factors and anti-inflammatory cytokines. Our previous report revealed that the diabetes of immunodeficient diabetic model mice was reversed by the subcutaneous co-transplantation of the MSC CellSaics and rat islets. In this study, we focused on the development of immune-isolating microcapsules to co-encapsulate the MSC CellSaics and rat islets, and their therapeutic efficiency via subcutaneous transplantation into immunocompetent diabetic model mice. As blood glucose level was monitored for 28 days following transplantation, the normalization rate of the new immuno-isolating microcapsules was confirmed to be significantly higher than those of the microcapsules without the MSC CellSaics, and the MSC CellSaics transplanted outside the microcapsules (p < 0.01). Furthermore, the number of islets required for the treatment was reduced. In the stained sections, a larger number/area of blood vessels was observed around the new immuno-isolating microcapsules, which suggests that angiogenic factors secreted by the MSC CellSaics through the microcapsules function locally for their enhanced efficacy.

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“…The increased interest in islet transplantation reached its most popular level between 2010 and 2012 [54]. For the last 2 years, researchers provided detailed in vivo experiments and defined an alginate encapsulation strategy in a more enhanced way [52,60,70,71] . The vast majority of attempts have been made to treat T1DM and the critical requirements remain to be elucidated in the future.…”

Section: Clinical Applicationsmentioning

confidence: 99%

Microencapsulation for Clinical Applications and Transplantation by Using Different Alginates

Göncü¹,

Yücesan²

2021

Nano- And Microencapsulation - Techniques and Applications

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Microencapsulation has been the most frequently used technique for several different disciplines such as cell-based therapies and/or transplantation. Technology is based on the idea of combining and coating a material or isolating from an external source. Microencapsulation may be performed with different materials and, among natural biocompatible materials, alginate-based microencapsulation technique is the most appropriate material for microencapsulation. The structural components of alginate materials are the derivatives of alginic acid, which is found in brown algae as an intercellular gel matrix. This alginate is preferred for clinical applications due to its safety in human studies. Therefore, the choice and the combined system need to be carefully optimized to achieve biocompatible application through cell microencapsulation especially for long term. Specifications of alginate such as primary source, isolation process, viscosity, and purity contribute to improve its biocompatibility. Clinically, cell microencapsulation is the major contribution to the field of transplantation by its technique and additionally provides local immune isolation. This chapter discusses the potential benefits of clinically suitable alginates and their applications. This promising technology may highlight its considerable potential for patients that require transplantation and/or replacement therapy in the future.

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Zwitterionically modified alginates mitigate cellular overgrowth for cell encapsulation

Cited by 131 publications

References 82 publications

Alginate/Pluronic F127-based encapsulation supports viability and functionality of human dental pulp stem cell-derived insulin-producing cells

Alginate/Pluronic F127-based encapsulation supports viability and functionality of human dental pulp stem cell-derived insulin-producing cells

Co-Microencapsulation of Islets and MSC CellSaics, Mosaic-Like Aggregates of MSCs and Recombinant Peptide Pieces, and Therapeutic Effects of Their Subcutaneous Transplantation on Diabetes

Microencapsulation for Clinical Applications and Transplantation by Using Different Alginates

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