Engineering Functional Islets from Cultured Cells

Kodama, Shohta; Kojima, Koji; Furuta, Shigeyuki; Chambers, Melody; Paz, Ana C.; Vacanti, Charles A.

doi:10.1089/ten.tea.2008.0459

Cited by 30 publications

(17 citation statements)

References 23 publications

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“…In future work, encapsulating the islets in a hydrogel or in microcapsules inside the device would be an alternative way to support the spherical shape of islets within the device. Nanofibers have been used to encourage aggregation of individual cells into pseudo‐islets, underscoring possible extension of nanofibers as a macroencapsulation material for stem cell‐derived islets. Local release of FTY720 may also benefit other encapsulation designs, including scaffoldless approaches and porous scaffolding techniques …”

Section: Discussionmentioning

confidence: 99%

An engineered macroencapsulation membrane releasing FTY720 to precondition pancreatic islet transplantation

et al. 2017

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Macroencapsulation is a powerful approach to increase the efficiency of extrahepatic pancreatic islet transplant. FTY720, a small molecule that activates signaling through sphingosine-1-phosphate receptors, is immunomodulatory and pro-angiogenic upon sustained delivery from biomaterials. While FTY720 (fingolimod, Gilenya) has been explored for organ transplantation, in the present work the effect of locally released FTY720 from novel nanofiber-based macroencapsulation membranes is explored for islet transplantation. We screened islet viability during culture with FTY720 and various biodegradable polymers. Islet viability is significantly reduced by the addition of high doses (≥500 ng/mL) of soluble FTY720. Among the polymers screened, islets have the highest viability when cultured with poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). Therefore, PHBV was blended with polycaprolactone (PCL) for mechanical stability and electrospun into nanofibers. Islets had no detectable function ex vivo following 5 days or 12 h of subcutaneous implantation within our engineered device. Subsequently, we explored a preconditioning scheme in which islets are transplanted 2 weeks after FTY720-loaded nanofibers are implanted. This allows FTY720 to orchestrate a local regenerative milieu while preventing premature transplantation into avascular sites that contain high concentrations of FTY720. These results provide a foundation and motivation for further investigation into the use of FTY720 in preconditioning sites for efficacious islet transplantation.

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Section: Discussionmentioning

confidence: 99%

An engineered macroencapsulation membrane releasing FTY720 to precondition pancreatic islet transplantation

et al. 2017

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“…Finally, once a bioartifi cial organ is transplanted into a living host organism, its vascular supply can be provided by local vessels, that is by natural in situ revascularization, especially when implanted inside tissue that is highly conducive to vessel formation (sub-epidermal layer, serosa, kidney capsule) (Oberpenning et al , 1999, Grikscheit et al , 2003, Kodama et al , 2009). Therefore, it should not be necessary to reproduce ex situ the intrinsic vascularization of the bioengineered organ.…”

Section: Basic Theoretical Principles For Ex Situ Bioengineering Of Bmentioning

confidence: 99%

Biomimetic materials in regenerative medicine

Sprio

Sandri

Iafisco

et al. 2013

Biomimetic Biomaterials

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“…38 Autologously derived pancreatic islet cells or alternate cell sources presenting a β-cell-like phenotype may be engineered within an appropriate gelatinous matrix or other biosynthetic scaffold. 43 Similarly, transplantation of pancreatic islets grown over a biodegradable scaffold composed of a vicryl fleece with polydioxanone backing and implanted within a canine total pancreatectomy model resulted in normo-glycemia without the requirement for exogenous insulin injection (n = 4), in one case up to five months post-implantation. 39).…”

Section: Pancreasmentioning

confidence: 99%