| 1. |
- Jia, Xiaohui, et al.
(författare)
-
Exendin-4 Increases the Expression of Hypoxia-InducibleFactor-1 in Rat Islets and Preserves the Endocrine CellVolume of Both Free and Macroencapsulated Islet Grafts
- 2012
-
Ingår i: Cell Transplantation. - 0963-6897. ; 21:6, s. 1269-1283
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, we evaluated the effects of exendin-4 on free and encapsulated islet grafts in a rodent model.We also investigated the role of a transcription factor, hypoxia-inducible factor-1 (HIF-1), in mediating thebeneficial effects of exendin-4. Diabetic athymic mice were transplanted with free rat islets under the kidneycapsule or with macroencapsulated rat islets SC with or without exendin-4, islet preculture (exendin-4 0.1nM for 20 h), and/or recipient treatment (IP 100 ng/day, day 0–7). The mice were followed for 4 weeks andthe graft function andβ-cell volume were evaluated. The effects of exendin-4 on islet HIF-1α mRNAand protein expression and on ATP content in a rat insulinoma cell line (INS-1E) were also examined.Preculture with exendin-4 followed by recipient treatment improved the outcome of both free (73% graftfunction vs. 26% in controls,p = 0.03) and macroencapsulated islet grafts (100% vs. 25% in controls, p =0.02). In macroencapsulated grafts, the exendin-4-treated group had significantly larger endocrine volume,less graft necrosis, and more blood vessels around the capsule. In rat islets cultured with exendin-4, HIF-1αmRNA and protein expression were significantly enhanced. ATP content was increased in exendin-4-treatedINS-1E cells under hypoxic conditions. The improved functional outcome after transplantation of a marginalislet mass with a brief initial treatment with exendin-4 is related to a larger surviving endocrine cell volume.Exendin-4 may improve islet graft resistance to hypoxia during the peritransplant period by increasing theexpression of HIF-1
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Blixt, Ola, et al.
(författare)
-
Anticarbohydrate antibody repertoires in patients transplanted with fetal pig islets revealed by glycan arrays
- 2009
-
Ingår i: American Journal of Transplantation. - 1600-6135 .- 1600-6143. ; 9, s. 83-90
-
Tidskriftsartikel (refereegranskat)abstract
- Ten patients with type I diabetes were transplanted with porcine fetal islet-like cell clusters (ICC) between 1990 and 1993. A significant rise in the anti-a -Gal antibody titers was seen posttransplant, but also nona -Gal-specific antibodies were detected in some patients. We have reanalyzed the carbohydrate specificity of antibodies in the sera from seven of these patients taken before transplantation, 1, 6 and 12 months posttransplantation using a glycan array with 200 structurally defined glycans. The main findings were: (i) prepig ICC transplantation patients had antibodies reactive with terminal a -GalNAc (e.g. the Forssman antigen, but not the blood group A determinant in blood group A patients), a -Gal (except blood group B determinants in B individuals), b 3-linked Gal especially Galb 1,3GlcNAc even if terminally sulfated or sialylated, b -GlcNAc except if b 1,3-linked and oligomannosyl compounds; (ii) the titers of all carbohydrate-specific antibodies detected before transplantation rose after transplantation; (iii) the kinetics of the antibody responses differed between patients; (iv) in some patients antibodies reacting with Gala 1,3Lex and several structures terminated with Neu5Gc appeared after transplantation. In conclusion, anti-a -Gal antibodies are the predominant anticarbohydrate antibodies detected after porcine ICC transplantation, with some patients also developing Neu5Gc-specific antibodies. Their clinical significance needs to be established.
|
|
| 7. |
- Brandhorst, Heide, 1962-, et al.
(författare)
-
A new oxygen carrier for improved long-term storage of human pancreata before islet isolation
- 2010
-
Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 89:2, s. 155-60
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pancreas oxygenation during cold storage has been established in islet isolation and transplantation to prevent ischemic tissue damage using perfluorodecalin (PFD) as hyperoxygen carrier. However, studies in humans and pigs provided conflicting results about the efficiency of PFD for pancreas oxygenation. The aim of this study was to compare PFD with a newly developed oxygen carrier composed of perfluorohexyloctane and polydimethylsiloxane 5 (F6H8S5) for long-term storage of human pancreata.METHODS: After 24-hr storage in preoxygenated PFD or F6H8S5, pancreata were processed using Liberase HI for pancreas dissociation and a Ficoll gradient for islet purification. Islet quality assessment was performed measuring glucose-stimulated insulin release, viability, islet ATP content, and posttransplant function in diabetic nude mice.RESULTS: Compared with PFD, F6H8S5 significantly increased the intrapancreatic partial oxygen pressure and islet ATP content. This corresponded to an increase of islet yield, recovery after culture, glucose stimulation index, viability, and improved graft function in diabetic nude mice.CONCLUSIONS: The present findings indicate clearly that F6H8S5 improves isolation outcome after prolonged ischemia compared with PFD. This observation seems to be related to the significant lipophilicity and almost pancreas-specific density of F6H8S5. Moreover, these characteristics facilitate pancreas shipment without using custom-made transport vessels as required for PFD.
|
|
| 8. |
|
|
| 9. |
- Brandhorst, Heide, 1962-, et al.
(författare)
-
The importance of tryptic-like activity in purified enzyme blends for efficient islet isolation
- 2009
-
Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 87:3, s. 370-5
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The isolation of islets from the human pancreas critically depends on an efficient enzyme blend. Previous studies have solely focused on the presence of collagenase and neutral protease/thermolysin. Despite improved characterization of these components, the lot-related variability in efficacy still persists suggesting that additional so far disregarded enzymes are required for efficient islet cleavage. METHODS: Varying activities of a tryptic-like enzyme were identified within collagenase NB1 lots, which were selected according to a matched ratio between tryptic-like and collagenase activity (TLA-ratio). Rat and human pancreata were processed with current standard procedures. RESULTS: Increasing the TLA-ratio from 1.3% to 10% reduced pancreas dissociation time in rats by 50% without affecting islet yield, viability, or posttransplant function in diabetic nude mice. Enhancing the TLA-ratio from 1.3% to 12.6% for human pancreas processing resulted in a significant reduction of recirculation time and increased incrementally human islet yield without affecting purity, in vitro function or recovery after culture. Optimized pancreas digestion correlated with a higher percentage of islet preparations fulfilling quality criteria for clinical transplantation. CONCLUSIONS: We conclude that TLA is an effective component that should be included in moderate amounts in enzyme blends for human islet isolation to optimize the efficiency and minimize the lot-related variability.
|
|
| 10. |
- Caballero-Corbalán, José, et al.
(författare)
-
No beneficial effect of two-layer storage compared with UW-storage on human islet isolation and transplantation
- 2007
-
Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337 .- 1534-6080. ; 84:7, s. 864-869
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Shipment of pancreata between distant centers is frequently associated with prolonged cold ischemia time (CIT) that leads to poorer outcomes for islet transplantation. Clinical pilot trials have indicated that oxygenation of explanted human pancreata utilizing the two-layer method (TLM) allows the use of marginal donor pancreata for islet transplantation. The present study aimed to clarify whether TLM enhances the ischemic tolerance of human pancreata. Methods. We analyzed retrospectively the outcome of 200 human islet isolations performed after TLM preservation or storage in University of Wisconsin solution (UWS). Results. Donor characteristics and digestion parameters did not vary significantly between TLM-preserved and UWS-stored pancreata. No differences were observed between experimental groups with regard to islet yield, purity, or dynamic glucose stimulation index after either short or prolonged CIT. However, CIT and stimulation index were negatively correlated in each experimental group. The isolation outcome in donors aged ≥60 years was not increased after TLM preservation when compared to UWS storage. No effect was observed regarding islet posttransplant function in recipients with established kidney grafts. Conclusions. The present study suggests that the ischemic tolerance of human pancreata cannot be extended by TLM preservation. In addition, TLM does not seem to improve the isolation outcome for pancreata from elderly donors.
|
|
