Microencapsulation of Hepatocytes and Mesenchymal Stem Cells for Therapeutic Applications

Meier, Raphaël; Montanari, Elisa; Morel, Philippe; Pimenta, Joel; Schuurman, Henk‐Jan; Wandrey, Christine; Gerber‐Lemaire, Sandrine; Mahou, Redouan; Bühler, Léo H.

doi:10.1007/978-1-4939-6506-9_18

Cited by 23 publications

(19 citation statements)

References 13 publications

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“…Furthermore, it has been described that PLL is a powerful inhibitor of miRNA biogenesis ( 43 ) with pronounced effects on hepatocyte function, such as alteration of the expression of miRNAs involved in the regulation of insulin sensitivity and cell proliferation ( 44 ). Meier et al developed a protocol for the co-encapsulation of hepatocytes and MSC in hybrid poly(ethylene glycol)-alginate hydrogel microbeads, which, unlike poly-L-lysine-based hydrogels, have an excellent biological acceptance ( 45 ). However, cells are able to proliferate in these microbeads, facing the same risks described above for the microbeads with depolymerized center.…”

Section: Discussionmentioning

confidence: 99%

A New High Throughput Screening Platform for Cell Encapsulation in Alginate Hydrogel Shows Improved Hepatocyte Functions by Mesenchymal Stromal Cells Co-encapsulation

et al. 2018

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Hepatocyte transplantation has emerged as an alternative to liver transplant for liver disease. Hepatocytes encapsulated in alginate microbeads have been proposed for the treatment of acute liver failure, as they are able to provide hepatic functions while the liver regenerates. Furthermore, they do not require immunosuppression, as the alginate protects the hepatocytes from the recipient's immune cells. Mesenchymal stromal cells are very attractive candidates for regenerative medicine, being able to differentiate into cells of the mesenchymal lineages and having extensive proliferative ability. When co-cultured with hepatocytes in two-dimensional cultures, they exert a trophic role, drastically improving hepatocytes survival and functions. In this study we aimed to (i) devise a high throughput system (HTS) to allow testing of a variety of different parameters for cell encapsulation and (ii) using this HTS, investigate whether mesenchymal stromal cells could have beneficial effects on the hepatocytes when co-encapsulated in alginate microbeads. Using our HTS platform, we observed some improvement of hepatocyte behavior with MSCs, subsequently confirmed in the low throughput analysis of cell function in alginate microbeads. Therefore, our study shows that mesenchymal stromal cells may be a good option to improve the function of hepatocytes microbeads. Furthermore, the platform developed may be used for HTS studies on cell encapsulation, in which several conditions (e.g., number of cells, combinations of cells, alginate modifications) could be easily compared at the same time.

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Section: Discussionmentioning

confidence: 99%

A New High Throughput Screening Platform for Cell Encapsulation in Alginate Hydrogel Shows Improved Hepatocyte Functions by Mesenchymal Stromal Cells Co-encapsulation

et al. 2018

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“…Viability and cell death of free and microencapsulated cells (0.2 × 10 6 cells/1 mL/24-well plate) were analyzed using fluorescein diacetate (FDA) and propidium iodide (PI) for the staining of viable and dead cells, respectively, as previously described [ 24 ]. Images were acquired using a fluorescent microscope and LAS V4.5 software (Leica Microsystem, Heerbrugg, Switzerland).…”

Section: Methodsmentioning

confidence: 99%

Beneficial Effects of Human Mesenchymal Stromal Cells on Porcine Hepatocyte Viability and Albumin Secretion

Montanari

Pimenta

Szabó

et al. 2018

Journal of Immunology Research

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Porcine hepatocytes transplanted during acute liver failure might support metabolic functions until the diseased liver recovers its function. Here, we isolated high numbers of viable pig hepatocytes and evaluated hepatocyte functionality after encapsulation. We further investigated whether coculture and coencapsulation of hepatocytes with human multipotent mesenchymal stromal cells (MSC) are beneficial on hepatocyte function. Livers from 10 kg pigs (n = 9) were harvested, and hepatocytes were isolated from liver suspensions for microencapsulation using alginate and poly(ethylene-glycol)- (PEG-) grafted alginate hydrogels, either alone or in combination with MSC. Viability, albumin secretion, and diazepam catabolism of hepatocytes were measured for one week. 9.2 ± 3.6 × 109 hepatocytes with 95.2 ± 3.1% viability were obtained after isolation. At day 3, free hepatocytes displayed 99% viability, whereas microencapsulation in alginate and PEG-grafted alginate decreased viability to 62% and 48%, respectively. Albumin secretion and diazepam catabolism occurred in free and microencapsulated hepatocytes. Coencapsulation of hepatocytes with MSC significantly improved viability and albumin secretion at days 4 and 8 (p < 0.05). Coculture with MSC significantly increased and prolonged albumin secretion. In conclusion, we established a protocol for isolation and microencapsulation of high numbers of viable pig hepatocytes and demonstrated that the presence of MSC is beneficial for the viability and function of porcine hepatocytes.

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“…Explanations for these mitigate results may be the inability to prevent xenorejection, insufficient IEQ numbers, or inability of neonatal pig islet to respond sufficiently to glucose challenge. Regarding the replacement of liver function for acute and chronic liver failure, another bridge strategy is the use of encapsulated pig hepatocytes and mesenchymal stem cells . In a wild‐type pig‐to‐NHP model, encapsulated pig hepatocytes allowed a higher survival rate (60% vs. 40% at one month) in NHPs subjected to a 75% hepatectomy and a 60 minutes of liver ischemia .…”

Section: Survival Of Pig Organs and Cells Xenotransplanted In Nonhumamentioning

confidence: 99%

Xenotransplantation: back to the future?

et al. 2018

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The field of xenotransplantation has fluctuated between great optimism and doubts over the last 50 years. The initial clinical attempts were extremely ambitious but faced technical and ethical issues that prompted the research community to go back to preclinical studies. Important players left the field due to perceived xenozoonotic risks and the lack of progress in pig-to-nonhuman-primate transplant models. Initial apparently unsurmountable issues appear now to be possible to overcome due to progress of genetic engineering, allowing the generation of multiple-xenoantigen knockout pigs that express human transgenes and the genomewide inactivation of porcine endogenous retroviruses. These important steps forward were made possible by new genome editing technologies, such as CRISPR/Cas9, allowing researchers to precisely remove or insert genes anywhere in the genome. An additional emerging perspective is the possibility of growing humanized organs in pigs using blastocyst complementation. This article summarizes the current advances in xenotransplantation research in nonhuman primates, and it describes the newly developed genome editing technology tools and interspecific organ generation.

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Microencapsulation of Hepatocytes and Mesenchymal Stem Cells for Therapeutic Applications

Cited by 23 publications

References 13 publications

A New High Throughput Screening Platform for Cell Encapsulation in Alginate Hydrogel Shows Improved Hepatocyte Functions by Mesenchymal Stromal Cells Co-encapsulation

A New High Throughput Screening Platform for Cell Encapsulation in Alginate Hydrogel Shows Improved Hepatocyte Functions by Mesenchymal Stromal Cells Co-encapsulation

Beneficial Effects of Human Mesenchymal Stromal Cells on Porcine Hepatocyte Viability and Albumin Secretion

Xenotransplantation: back to the future?

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