Adipose mesenchymal stem cells promote the function and survival of islet graft during co-transplantation / 中华器官移植杂志

Objective To explore the function and survival of islet grafts during co-transplantation with adipose mesenchymal stem cells (AMSCs) in diabetic mice .Methods After human AMSCs and islet cells were isolated ,purified and then subcutaneously co-transplanted into nude mice with diabetes mellitus . Four groups of AMSCs + islet co-transplantation , islet transplantation alone ,phosphate buffered solution (PBS) and normal control mice were designated . Islet cell activity and apoptosis/revascularization degree of islet grafts were observed by immunohistochemical double staining of insulin ,factor associated suicide (Fas) and CD31 antibody . The blood glucose and serum insulin levels of mice and the survival time of islet grafts were compared . Results The blood glucose and serum insulin levels of diabetic mice analyzed by multivariate analysis in AMSCs + islet co-transplantation group were better than those in islet transplantation alone group (P< 0 .05 ) . The mean survival time (MST ) of islet grafts was longer in AMSCs + islet co-transplantation group than that in islet transplantation alone group [(81 .33 ± 7 .58) vs .(58 .17 ± 6 .91) days] (P<0 .05) .At Day 7 post-transplantation ,insulin staining intensity of islet grafts was higher in AMSCs + islet co-transplantation group than that in islet transplantation alone group while Fas staining intensity of islet grafts was lower .And mean microvascular density (MVD) of islet grafts per square millimeter was higher in AMSCs + islet co-transplantation group than that in islet transplantation alone group [(21 .8 ± 5 .6 ) vs . (14 .6 ± 4 .1 )] ( P< 0 .05 ) .Conclusions Co-transplantation with AMSCs may improve the function of islet grafts ,prolong its survival and promote its revascularization .

Recent Progress in Clinical Islet Transplantation / 한양의대학술지

Allo-islet transplantation is believed to be a promising treatment for normalizing blood glucose levels without hypoglycemic episodes in patients with type 1 diabetes mellitus (T1DM). In 2000, a pioneering study by the Edmonton group showed that allo-islet transplantation could achieve insulin independence for at least 1 year post-transplantation in all seven consecutive patients. This breakthrough study excited numerous researchers, clinicians, and patients. Although longer follow-up studies did not have the same success as the first study, substantial efforts to establish successful islet transplantation have been made in the last decade. Several leading centers of islet transplantation have reported success rates of nearly 50% insulin independence at 5 years post-transplantation. However, recent advancements in transplant outcomes are limited to only a few centers and select patients; thus, we are still confronted with numerous hurdles against long-term successful islet transplantation. Herein, we review the recent advances and challenges for allo-islet transplantation to be accepted as a standard therapy for patients with T1DM.

The hepatic stellate cells protection for homotransplanted islet cells / 中华普通外科杂志

Objective To analyze the protection supplied by HSCs in vivo after islet cells homotransplantation. Method Diabetic mice were randomly divided into three groups as diabetic group,islet-transplant group and co-transplant group. 300 islets alone or mixed with HSCs were transplanted under the capsule of the kidney of the diabetic recipients respectively. Blood glucose and the length of normal blood glucose level were recorded and we collected the blood and tissue of islet graft 7 days after transplantation in each group. Blood concentration of TGF-β, TNF-α, IL-1β and IFN-γ were detected by ELISA. The infiltration of lymphocytes was observed by HE staining and immunohistochemieal examination.Result Co-transplant group had a prolonged islet allograft survival for (23.75 ± 8. 96) days, compared with the islet alone of (11.9 ± 6. 92) days. Blood concentration of TGF-β in co-transplant group was (2292.31 ± 5.87) pg/ml, significantly higher than those in simple transplant group (1246.55 ±38.91) pg/ml(P <0.05), there was no differentence in the two groups for TNF-α,IL-1β and IFN-γ.Conclusion HSCs may prolong the islet graft survival by expressing higher level of TGF-β and form a capsule around the graft.

An experimental study on improving quality of routine cryopreserved islets cultured with hyperbaric RCCS and transplantation / 中华普通外科杂志

Objective To investigate the therapeutic effect of frozen-thawed murine islets which were transplanted into diabetic rats after cultured with hyperbaric oxygenated rotary cell culture system (HORCCS). Methods The purified rat islets were divided into two groups: A. In vitro experiment groups (IvEG) : The rat islets in each subgroup were cultured in HORCCS or common medium for 30 days, then evaluated for the intracellular DNA and insulin contents of islets, and the viability and insulin secreting level of islets. B. Islet transplantation experimental groups (TxEG) : The frozen-thawed islets were cultured in HORCCS or common medium for 7 days, and then transplanted into the recipients. We observed the blood glucose level (BGL) and insulin secreting level in the recipients as well as the uhrastructure change of islets in TxEG. Results The viability and insulin secreting level of islets cultured with HORCCS at 14th day were much higher than those cultured with common medium (P <0.05). The blood glucose level in recipients transplanted with islets cultured with HORCCS recovered to normal value at the 2nd week and lasted for 8 weeks. All these recipients maintained the normal glucose tolerance curve. Electronic microscopy found microchannel outlets on the surface of the frozen-thawed islets cultured with HORCCS. Conclusions Frozen-thawed islets cultured with HORCCS could establish nutrient transmission microchannels, which were not only capable of oxygen and nutrients transmission, but also improving cryopreservation solution to diffuse inside the islet cells evenly and uniformly. So this method not only lessens islet damage from cryopreservation, but also improves the effect of transplantation.

Islet transplantation in multicenter networks:the GRAGIL example / 介入放射学杂志

Purpose of review The enthusiasm generated by the results of the Edmonton protocol of islet transplantation is inciting a great number of institutions to start such programs. However, the procedure of islet isolation and purification is costly, complex and technically challenging. In order to share costs and to avoid facing the steep learning curve of the procedure, many centers interested in islet transplantation have looked into collaborating with experienced groups serving as core islet isolation facilities. Recent findings The proof of principle that remote islet processing and shipment could be successfully implemented with obtainng the Portland/Minneapolis, Huddinge/Giessen and Houston/Miami partnerships. Moreover, in order to increase both the donor pool and the number of patients gaining access to islet transplantation, multicenter networks,such as the Swiss-French GRAGIL consortium and the 4-country Nordic Network in Scandinavia have been built. The GRAGIL group has been fully operational since 1999, allowing the transplantation of 27 islet preparations processed in Geneva, Switzerland into 20 recipients in France over the course of 4.5 years.Organizational issues in the design of such networks are discussed based on the example of the GRAGIL experience. Summary The feasibility and the efficiency of islet transplantation in multicenter networks have been demonstrated. This strategy allows to increase the donor pool and the accessibility to islet transplantation in an extended population area. (J Intervent Radiol, 2006, 15:626-631 )

Effective glycemic control achieved by transplanting non-viral cationic liposome-mediated VEGF-transfected islets in streptozotocin-induced diabetic mice

Hypoxic damage is one of the major causes of islet graft failure and VEGF is known to play a crucial role in revascularization. To address the effectiveness of a cationic lipid reagent as a VEGF gene carrier, and the beneficial effect of VEGF-transfected islets on glycemic control, we used effectene lipid reagent in a transfection experiment using mouse islets. Transfection efficiencies were highest for 4 microgram/microliter cDNA and 25 microliter effectene and cell viabilities were also satisfactory under this condition, and the overproduction of VEGF mRNA and protein were confirmed from conditioned cells. A minimal number of VEGF-transfected islets (100 IEQ/animal) were transplanted into streptozotocin (STZ)-induced diabetic mice. Hyperglycemia was not controlled in the islet transplantation (IT)-alone group (0/8) (non- diabetic glucose mice number/total recipient mice number) or in the IT-pJDK control vector group (0/8). However, hyperglycemia was completely abrogated in the IT-pJDK-VEGF transduced group (8/8), and viable islets and increased VEGF-transfected grafts vascularization were observed in renal capsules.

Blocking the CC chemokine receptor 5 pathway by antisense peptide nucleic acid prolongs islet allograft survival / 中国普通外科杂志

Objective To identify the effect of peptide nucleic acid of CC chemokine receptor 5 on acute rejection of islet allograft.Methods Mice islet transplant models were used to test the effect of PNA CCR5 by targeting CCR5 in acute allograft rejection.In vitro T cell proliferative responses were assessed by mixed lymphocyte response(MLR).RT-PCR and Western blot were used to detect the expression of mRNA and protein.Results PNA CCR5-treated recipients demonstrated statistically significant prolongation(12.00?1.75)d in functional allograft survival when compared with saline(6.50?0.58)d or PNA mismatch-treated recipients(6.50?0.50)d.The CCR5 mRNA expression level of PNA CCR5,control,and PNA mismatch treatment recipients at day 7 posttransplant was 0.56?0.05,1.68?0.07 and 1.80?0.14,respectively.The data showed that CCR5 protein was significantly down-regulated in PNA CCR5 treatment allografts compared with saline and PNA mismatch treatment allografts(P

Postoperative metabolic characteristics of islet transplantation in the treatment of type Ⅰ diabetes / 中国普通外科杂志

Objective To assess the effect of fetal islet transplantation for the treatment of Type Ⅰ diabetes. Methods The pancreatic islets from human aborted embryos were cultured and implanted into the greater omentum and omental bursa of 26 patients with type Ⅰ diabetes. The function of transplanted islets was evaluated. Results After transplantation, the exogenous insulin requirement significantly decreased (P