Evaluation of Microencapsulated Islets in Agarose Gel as Bioartificial Pancreas by Studies of Hormone Secretion in Culture and by Xenotransplantation

Iwata, Hiroo; Amemiya, Hiroshi; Matsuda, Takehisa; Takano, Hisateru; Hayashi, Rumiko; Akutsu, Tetsuzo

doi:10.2337/diab.38.1.s224

Cited by 97 publications

(37 citation statements)

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“…Previous work transplanting Islet of Langerhans in agarose beads in diabetic animals has demonstrated the ability of agarose to allow diffusion of insulin, reverse the diabetic state and prevent xenotransplant rejection (Iwata et al, 1989). These animals were implanted with agarose beads intra-peritoneally.…”

Section: Discussionmentioning

confidence: 99%

Cochlear implants and ex vivo BDNF gene therapy protect spiral ganglion neurons

et al. 2007

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Spiral ganglion neurons often degenerate in the deaf ear, compromising the function of cochlear implants. Cochlear implant function can be improved by good preservation of the spiral ganglion neurons, which are the target of electrical stimulation by the implant. Brain derived neurotrophic factor (BDNF) has previously been shown to enhance spiral ganglion survival in experimentally deafened ears. Providing enhanced levels of BDNF in human ears may be accomplished by one of several different methods. The goal of these experiments was to test a modified design of the cochlear implant electrode that includes a coating of fibroblast cells transduced by a viral vector with a BDNF gene insert. To accomplish this type of ex vivo gene transfer, we transduced guinea pig fibroblasts with an adenovirus with a BDNF gene cassette insert, and determined that these cells secreted BDNF. We then attached BDNF-secreting cells to the cochlear implant electrode via an agarose gel, and implanted the electrode in the scala tympani. We determined that the BDNF expressing electrodes were able to preserve significantly more spiral ganglion neurons in the basal turns of the cochlea after 48 days of implantation when compared to control electrodes. This protective effect decreased in the higher cochlear turns. The data demonstrate the feasibility of combining cochlear implant therapy with ex vivo gene transfer for enhancing spiral ganglion neuron survival.

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Section: Discussionmentioning

confidence: 99%

Cochlear implants and ex vivo BDNF gene therapy protect spiral ganglion neurons

et al. 2007

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“…Its use for islet encapsulation started in the late 80's [85,86] and was subsequently broadened [8791] . Other natural polysaccharides used for encapsulation of cells/islets include chitosan and cellulose.…”

Section: B Amentioning

confidence: 99%

Survival of encapsulated islets: More than a membrane story

Barkai¹,

Rotem²,

Vos³

2016

WJT

116

109

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“…The encapsulation systems utilize materials that are permeable enough to allow the diffusion of glucose and other nutrients to the islets, and the diffusion of waste and insulin away from the islets, while masking the islets from the host immune response. [3][4][5][6] Alginate is a chemically inert nondegradable polymer, and most importantly it has the capability to immunoisolate encapsulated cells. 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.…”

mentioning

confidence: 99%

Alginate Encapsulation of Human Embryonic Stem Cells to Enhance Directed Differentiation to Pancreatic Islet-Like Cells

Richardson

Kumta

Banerjee

2014

Tissue Engineering Part A

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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.

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Evaluation of Microencapsulated Islets in Agarose Gel as Bioartificial Pancreas by Studies of Hormone Secretion in Culture and by Xenotransplantation

Cited by 97 publications

References 0 publications

Cochlear implants and ex vivo BDNF gene therapy protect spiral ganglion neurons

Cochlear implants and ex vivo BDNF gene therapy protect spiral ganglion neurons

Survival of encapsulated islets: More than a membrane story

Alginate Encapsulation of Human Embryonic Stem Cells to Enhance Directed Differentiation to Pancreatic Islet-Like Cells

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