Reversal of Diabetes in Mice by Xenotransplantation of a Bioartificial Pancreas in a Prevascularized Subcutaneous Site1

Wang, Wenjing; Gu, Yuanjun; Tabata, Yasuhiko; Miyamoto, Masaaki; Hori, Hiroshi; Nagata, Noriyuki; Touma, Maki; Balamurugan, A. N.; Kawakami, Yoshiyuki; Nozawa, Masumi; Inoue, Kazutomo

doi:10.1097/00007890-200201150-00023

Cited by 75 publications

(44 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Male NOD/SCID mice (6)(7)(8) Figure 3B. Figure 4A, DFO treatment for 12, 24 and 72 h significantly induced HIF-1a expression in the encapsulated human islets.…”

Section: Transplantation Of Microencapsulated Human Isletsmentioning

confidence: 97%

“…These include prevascularization (6,7), heat shock (8), ischaemic preconditioning (9), stimulation of Bcl-2/Bcl-xl complex (10,11), Xlinked inhibitor of apoptosis protein (XIAP) overexpression (12), inhibition of cellular FLICE inhibitory protein (cFLIP) (13) and A20 activation (14,15). None of the above strategies has been tried with microencapsulated human islets.…”

Section: Native Human Islets Reside In a Microenvironment Supplied Wimentioning

confidence: 99%

See 1 more Smart Citation

Beneficial Effects of Desferrioxamine on Encapsulated Human Islets—In Vitro and In Vivo Study

Vaithilingam

Oberholzer

Guillemin

et al. 2010

American Journal of Transplantation

View full text Add to dashboard Cite

As many as 2000 IEQs (islet equivalent) of encapsulated human islets are required to normalize glucose levels in diabetic mice. To reduce this number, encapsulated islets were exposed to 100 lM desferrioxamine (DFO) prior to transplantation. Cell viability, glucoseinduced insulin secretion, VEGF (Vascular endothelial growth factor), HIF-1a (Hypoxia inducible factor-1 alpha), caspase-3 and caspase-8 levels were assessed after exposure to DFO for 12, 24 or 72 h. Subsequently, 1000, 750 or 500 encapsulated IEQs were infused into peritoneal cavity of diabetic mice after 24 h exposure to DFO. Neither viability nor function in vitro was affected by DFO, and levels of caspase-3 and caspase-8 were unchanged. DFO significantly enhanced VEGF secretion by 1.6-and 2.5-fold at 24 and 72 h, respectively, with a concomitant increase in HIF-1a levels. Euglycemia was achieved in 100% mice receiving 1000 preconditioned IEQs, as compared to only 36% receiving unconditioned IEQs (p < 0.001). Similarly, with 750 IEQ, euglycemia was achieved in 50% mice receiving preconditioned islets as compared to 10% receiving unconditioned islets (p = 0.049). Mice receiving preconditioned islets had lower glucose levels than those receiving unconditioned islets. In summary, DFO treatment enhances HIF-1a and VEGF expression in encapsulated human islets and improves their ability to function when transplanted.

show abstract

“…Male NOD/SCID mice (6)(7)(8) Figure 3B. Figure 4A, DFO treatment for 12, 24 and 72 h significantly induced HIF-1a expression in the encapsulated human islets.…”

Section: Transplantation Of Microencapsulated Human Isletsmentioning

confidence: 97%

Section: Native Human Islets Reside In a Microenvironment Supplied Wimentioning

confidence: 99%

Beneficial Effects of Desferrioxamine on Encapsulated Human Islets—In Vitro and In Vivo Study

Vaithilingam

Oberholzer

Guillemin

et al. 2010

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

“…Hydrogels also provide higher permeability for low molecular weight nutrients and metabolites. Hydrogel materials that have been used include alginate (Simpson et al, 2005); agarose (Xu et al, 2001;Wang et al, 2002;Balamurugan et al, 2003), polyurethane (George et al, 2002b), chitosan-PVP hydrogels (Risbud et al, 2000), cellulose (Risbud and Bhonde, 2001), cross-linked hydrophilic poly(N,N-dimethyl acrylamide) with hydrophobic di-, tri-, and octamethacrylate telechelic polyisobutylene (Isayeva et al, 2003), and a copolymer of acrylonitrile and sodium methallylsulfonate (De Vos et al, 2002). Other approaches to address the problem of biocompatibility of these devices include membrane coating with poly(ethylene oxide) to reduce surface protein adsorption and surface hydrophobization with corona discharge.…”

Section: A Immunoisolation Of Transplanted Isletsmentioning

confidence: 99%

Biological and Biomaterial Approaches for Improved Islet Transplantation

2006

View full text Add to dashboard Cite

“…In experimental studies, there are many descriptions of positive data on extrahepatic transplantation sites. The Kyoto and other groups [73] succeeded in achieving normoglycemia in diabetic mice by transplantation of encapsulated islets in muscle, subcutaneous tissue [58,[74][75][76] , renal subcapsule [77] and omentum [56] . These may be candidate transplantation sites in the near future because the loss of islets due to IBMIR, the risk of portal hypertension and portal vein thrombosis could be prevented.…”

Section: Ideal Transplantation Site For Encapsulated Isletsmentioning

confidence: 99%

Encapsulated islets transplantation: Past, present and future

Sakata

Sumi²,

Yoshimatsu³

et al. 2012

WJGP

View full text Add to dashboard Cite

Islet transplantation could become an ideal treatment for severe diabetes to prevent hypoglycemia shock and irreversible diabetic complications, once some of the major and unresolved obstacles are overcome, including limited donor supplies and side effects caused by permanent immunosuppressant use. Approximately 30 years ago, some groups succeeded in improving the blood glucose of diabetic animals by transplanting encapsulated islets with semi-permeable membranes consisting of polymer. A semi-permeable membrane protects both the inner islets from mechanical stress and the recipient's immune system (both cellular and humoral immunities), while allowing bidirectional diffusion of nutrients, oxygen, glucose, hormones and wastes, i.e., immune-isolation. This device, which enables immune-isolation, is called encapsulated islets or bio-artificial pancreas. Encapsulation with a semipermeable membrane can provide some advantages: (1) this device protects transplanted cells from the recipient's immunity even if the xenogeneic islets (from large animals such as pig) or insulin-producing cells are derived from cells that have the potential for differentiation (some kinds of stem cells). In other words, the encapsulation technique can resolve the problem of limited donor supplies; and (2) encapsulation can reduce or prevent chronic administration of immunosuppressants and, therefore, important side effects otherwise induced by immunosuppressants. And now, many novel encapsulated islet systems have been developed and are being prepared for testing in a clinical setting.

show abstract

Reversal of Diabetes in Mice by Xenotransplantation of a Bioartificial Pancreas in a Prevascularized Subcutaneous Site1

Abstract: A successfully prevascularized subcutaneous site could be constructed by a tissue bioengineering approach. Xenotransplantation of the agarose/poly (styrene sulfonic acid) mixed gel-based bioartificial pancreas in the prevascularized subcutaneous site could reverse diabetes in mice.

Cited by 75 publications

References 26 publications

Beneficial Effects of Desferrioxamine on Encapsulated Human Islets—In Vitro and In Vivo Study

Beneficial Effects of Desferrioxamine on Encapsulated Human Islets—In Vitro and In Vivo Study

Biological and Biomaterial Approaches for Improved Islet Transplantation

Encapsulated islets transplantation: Past, present and future

Contact Info

Product

Resources

About