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The Influence of Stabilized Deconjugated Ursodeoxycholic Acid on Polymer-Hydrogel System of Transplantable NIT-1 Cells

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A Correction to this article was published on 27 January 2022

An Erratum to this article was published on 24 February 2016

This article has been updated

Abstract

Purpose

The encapsulation of pancreatic β-cells in biocompatible matrix has generated great interest in diabetes treatment. Our work has shown improved microcapsules when incorporating the bile acid ursodeoxycholic acid (UDCA), in terms of morphology and cell viability although cell survival remained low. Thus, the study aimed at incorporating the polyelectrolytes polyallylamine (PAA) and poly-l-ornithine (PLO), with the polymer sodium alginate (SA) and the hydrogel ultrasonic gel (USG) with UDCA and examined cell viability and functionality post microencapsulation.

Methods

Microcapsules without (control) and with UDCA (test) were produced using 1% PLO, 2.5% PAA, 1.8% SA and 4.5% USG. Pancreatic β-cells were microencapsulated and the microcapsules’ morphology, surface components, cellular and bile acid distribution, osmotic and mechanical stability as well as biocompatibilities, insulin production, bioenergetics and the inflammatory response were tested.

Results

Incorporation of UDCA at 4% into a PLO-PAA-SA formulation system increased cell survival (p < 0.01), insulin production (p < 0.01), reduced the inflammatory profile (TNF-α, IFN-ϒ, IL-6 and IL-1β; p < 0.01) and improved the microcapsule physical and mechanical strength (p < 0.01).

Conclusions

β-cell microencapsulation using 1% PLO, 2.5% PAA, 1.8% SA, 4.5% USG and the bile acid UDCA (4%) has good potential in cell transplantation and diabetes treatment.

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Change history

Abbreviations

ACMT:

Artificial cell microencapsulation technology

ATPP:

Adenosine triphosphate production

BR:

Basal respiration

CBA:

Cytokine bead array

CE:

Coupling efficiency

DM:

Diabetes mellitus

DMEM:

Dulbecco’s modified eagle’s medium

ECAR:

Extracellular acidification rate

EDXR:

Energy dispersive x-ray spectroscopy

ELISA:

Enzyme-linked immunosorbent assay

G:

Glycolysis

IFN-γ:

Interferon-γ

IL-1β:

Interleukin-1β

IL-6:

Interleukin-6

MR:

Maximal respiration

MTT:

(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)

NGD-ECAR:

Non-glucose-derived extracellular acidification rate

OCR:

Oxygen consumption rate

OM:

Optical microscopy

PAA:

Polyallylamine

PL:

Proton leak

PLO:

Poly-l-ornithine

PPR:

Proton production rate

SA:

Sodium alginate

SEM:

Scanning electron microscopy

SRC:

Spare respiratory capacity

T1D:

Type 1 diabetes mellitus

T2D:

Type 2 diabetes mellitus

TNF-α:

Tumour necrosis factor-α

TRITC:

Tetramethylrhodamine isothiocyanate

UDCA:

Ursodeoxycholic acid

USG:

Ultrasonic gel

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors acknowledge Australian Postgraduate Award (APA) + Curtin Research Scholarship (CRS) for their support. The authors acknowledge the Curtin Health Innovation Research Institute for provision of laboratory space and technology platforms utilised in this study and also acknowledge the use of laboratory equipment, scientific and technical assistance of the Curtin University, Microscopy and Microanalysis Facility, which has been partially funded by the University, State and Commonwealth Governments. The authors also acknowledge the ARC Centre of Excellence in Plant Energy Biology (University of Western Australia) for training, support and access to equipment. The NIT-1 pancreatic mouse β-cells were a generous donation from Professor Grant Morahan at the University of Western Australia. The authors declare no conflict of interest.

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Authors and Affiliations

  1. Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia

    Armin Mooranian, Rebecca Negrulj & Hani Al-Salami

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  1. Armin Mooranian
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  2. Rebecca Negrulj
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Correspondence to Hani Al-Salami.

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The original online version of this article was revised to correct Fig. 1.

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Mooranian, A., Negrulj, R. & Al-Salami, H. The Influence of Stabilized Deconjugated Ursodeoxycholic Acid on Polymer-Hydrogel System of Transplantable NIT-1 Cells. Pharm Res 33, 1182–1190 (2016). https://doi.org/10.1007/s11095-016-1863-y

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