Immunoisolation Effect of Polyvinyl Alcohol (PVA) Macroencapsulated Islets in Type 1 Diabetes Therapy

Qi, Zhi; Yamamoto, Chiyo; Naomi, Imori; Kinukawa, Ayano; Yang, Kai Chiang; Yanai, Goichi; Ikenoue, Etsuko; Shen, Yanna; Shirouzu, Yasumasa; Hiura, Akihito; Inoue, Kazutomo; Sumi, Shoichiro

doi:10.3727/096368911x605448

Cited by 29 publications

(18 citation statements)

References 35 publications

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“…Although the transplantation of single cells and pseudoislets did not cause significant difference in NFBG and body weight, a critical finding was the difference in IPGTT. In clinical practice, the AUC that represents the insulin secretion of transplanted islets is considered an indicator to monitor the grafts' function 40 . The AUC for both pseudoislets groups was markedly smaller than that of the TCPS group, and similar to that of the normal mice group.…”

Section: Discussionmentioning

confidence: 96%

Investigating the suspension culture on aggregation and function of mouse pancreatic β‐cells

Yang

et al. 2013

J Biomedical Materials Res

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The integrity and hierarchical structure of islet influence β-cells physiology dramatically. A culture substrate which can maintain or improve β-cells aggregation shall benefit cell therapy for diabetics. In this study, nontreated, type IV collagen, Lipidure, and ultralow attachment dishes were used to culture a murine β-cell line, MIN-6. The formation and biological performances of pseudoislets were investigated. Results showed that β-cells formed loose and irregular aggregates on nontreated dishes. Oppositely, pseudoislets formed on other three substrates. Most pseudoislets on Lipidure and type IV collagen dishes had a diameter between 100-150 μm with high survival rate, while large pseudoislets (>250 μm) with seriously central necrosis were found on ultralow attachment dishes. Western blot analysis revealed that pseudoislets had relatively higher connexin 36 protein productions relative to single cells. The glucose-stimulated insulin secretion test showed pseudoislets on type IV collagen have high stimulation index. Monolayers from TCPS dishes and pseudoislets from type IV collagen or Lipidure dishes were further transplanted into diabetic mice. Animals received both single cells and pseudoislets had decreasing blood glucose level and regained body weight. Histologic examination revealed that all implants successfully engrafted with positive insulin staining. Interestingly, the area under curve for the intraperitoneal glucose tolerance test showed pseudoislets had superior glucose disappearance rate. This study reveals that isolated islets or insulin-producing cells can be cultured on type IV collagen or Lipidure dishes to improve/maintain integrity prior to transplantation.

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Section: Discussionmentioning

confidence: 96%

Investigating the suspension culture on aggregation and function of mouse pancreatic β‐cells

Yang

et al. 2013

J Biomedical Materials Res

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“…Regarding the results of the animal study, the NFBG of mice decreased to euglycemia and maintained for 7 days after naked islet transplantation. However, it returned to hyperglycemia which attributed to the rejection of grafts [18]. The NFBG of mice transplanted with islets/hydrogels also decreased to euglycemia one day postoperatively indicating the transplanted islets within hydrogels quickly released insulin into diabetic mice.…”

Section: Discussionmentioning

confidence: 99%

The cytoprotection of chitosan based hydrogels in xenogeneic islet transplantation: An in vivo study in streptozotocin-induced diabetic mouse

Yang

et al. 2010

Biochemical and Biophysical Research Communications

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Immune rejection and scarcity of donor tissues are the restrictions of islets transplantation. In this study, the cytoprotection of chitosan hydrogels in xenogeneic islet transplantation was demonstrated. Wistar rat islets encapsulated in chitosan hydrogels were performed glucose challenge test and live/dead cell staining in vitro. Islets/chitosan hydrogels were transplanted into the renal subcapsular space of diabetic C57BL/6 mice. Non-fasting blood glucose level (NFBG), body weight, intraperitoneal glucose tolerance test (IPGTT), and glucose disappearance rate were determined perioperatively. The serum insulin level was analyzed, and the kidney transplanted with islets/chitosan hydrogels were retrieved for histological examination after sacrifice. The present results showed that islets encapsulated in chitosan hydrogels secreted insulin in response to the glucose stimulation as naked islets with higher cell survival. The NFBG of diabetic mice transplanted with islets/chitosan hydrogels decreased from 487+/-46 to 148+/-32 at one day postoperation and maintained in the range of 201+/-36 mg/dl for four weeks with an increase in body weight. IPGTT showed the glucose disappearance rate of mice transplanted with islets/chitosan hydrogels was significant faster than that of mice transplanted with naked islets; the serum insulin level increased from 0.29+/-0.06 to 1.69+/-0.65 microg/dl postoperatively. Histological examination revealed that the islets successfully engrafted at renal subcapsular space with positive insulin staining. The immunostain was negative for neither the T-cell lineages nor the monocyte/macrophages. This study indicates that the chitosan hydrogels deliver and protect encapsulated islets successfully in xenotransplantation.

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“…A 10-week-old male Wistar rat islets were isolated as described previously [18]. In brief, the rat pancreas was digested by type V collagenase (1 mg/ml) and then the islets were separated by a dextran gradient.…”

Section: Islet Isolationmentioning

confidence: 99%

Optimal method for short-term or long-term islet preservation: comparison of islet culture, cold preservation and cryopreservation

et al. 2014

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Islet preservation plays an important role for the success of islet transplantation. To determine the optimal method for islet preservation, we compared the outcomes of islet culture, cold preservation, and cryopreservation in this study. Isolated rat islets were divided into three groups: 37 °C group (conventional culture at 37 °C in RPMI-1640 medium), 4 °C group (cold preservation at 4 °C in University of Wisconsin (UW) solution), and -80 °C group (cryopreservation at -80 °C with dimethyl sulfoxide (DMSO)). Recovery rate, Calcein-AM/PI double staining, insulin release, mRNA level of hypoxia-inducible factor-1α (HIF-1α), and protein level of Bax in islets were examined after short-term (1 day) or long-term (7 days) preservation. After either short-term or long-term preservation, 4 °C group showed higher recovery rate of the islets number, lower percentage of PI positive area, better insulin release ability, and lower expression levels of HIF-1α and Bax in comparison to the 37 or -80 °C group. Meanwhile, islets in 37 °C group showed better function, and down-regulation of HIF-1α and Bax than those in -80 °C group on day 1; however, worse function of islets, up-regulated HIF-1α and Bax in 37 °C group were observed in comparison to -80 °C group on day 7. These results suggest that cold preservation at 4 °C in UW solution is the optimal method in comparison to the conventional culture at 37 °C or cryopreservation at -80 °C for short-term or long-term islet preservation. Furthermore, the potential mechanism may relate to, at least in part, apoptosis induced by the HIF-1α.

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Immunoisolation Effect of Polyvinyl Alcohol (PVA) Macroencapsulated Islets in Type 1 Diabetes Therapy

Cited by 29 publications

References 35 publications

Investigating the suspension culture on aggregation and function of mouse pancreatic β‐cells

Investigating the suspension culture on aggregation and function of mouse pancreatic β‐cells

The cytoprotection of chitosan based hydrogels in xenogeneic islet transplantation: An in vivo study in streptozotocin-induced diabetic mouse

Optimal method for short-term or long-term islet preservation: comparison of islet culture, cold preservation and cryopreservation

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