Bernard E. Tuch

Prof. Bernard E. Tuch


Research Focus & Metrics

Academic Career Length

36Years (1991-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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30 August 2017 in Scientific Reports
Verified
Journal Article
Open access
PDF file
VVVijayaganapathy Vaithilingam
Vijayaganapathy Vaithilingam
MEMargaret D. M. Evans
Margaret D. M. Evans
DLDenise M. Lewy
Denise M. Lewy
PBPenelope A. Bean
Penelope A. Bean
SBSumeet Bal
Sumeet Bal
BTBernard E. Tuch
Bernard E. Tuch
Pericapsular fibrotic overgrowth (PFO) is associated with poor survival of encapsulated islets. A strategy to combat PFO is the use of mesenchymal stem cells (MSC). MSC have anti-inflammatory properties and their potential can be enhanced by stimulation with proinflammatory cytokines. This study investigated whether co-encapsulation or co-transplantation of MSC with encapsulated islets would reduce PFO and improve graft survival. Stimulating MSC with a cytokine cocktail of IFN-γ and TNF-α enhanced their immunosuppressive potential by increasing nitric oxide production and secreting higher levels of immunomodulatory cytokines. In vitro, co-encapsulation with MSC did not affect islet viability but significantly enhanced glucose-induced insulin secretion. In vivo, normoglycemia was achieved in 100% mice receiving islets co-encapsulated with stimulated MSC as opposed to 71.4% receiving unstimulated MSC and only 9.1% receiving encapsulated islets alone. Microcapsules retrieved from both unstimulated and stimulated MSC groups had significantly less PFO with improved islet viability and function compared to encapsulated islets alone. Levels of peritoneal immunomodulatory cytokines IL-4, IL-6, IL-10 and G-CSF were significantly higher in MSC co-encapsulated groups. Similar results were obtained when encapsulated islets and MSC were co-transplanted. In summary, co-encapsulation or co-transplantation of MSC with encapsulated islets reduced PFO and improved the functional outcome of allotransplants.

15 June 2007 in Transplantation
Verified
Journal Article
Closed access
JFJayne L. Foster
Jayne L. Foster
GWGeorgia Williams
Georgia Williams
LWLindy J. Williams
Lindy J. Williams
BTBernard E. Tuch
Bernard E. Tuch
Background. Fetal β cells are a potential form of cell therapy for type 1 diabetes. To protect transplanted cells from cellular immune attack, microencapsulation using barium alginate can be employed. Whether microencapsulated fetal pancreatic cells will differentiate as occurs with nonencapsulated fetal pancreatic cells is presently unknown. It is suggested that such differentiation would occur in encapsulated cells, similar to previous experiments conducted using encapsulated embryonic stem cells. Methods. Streptozotocin-induced diabetic severe combined immunodeficient mice were transplanted with 5,000 to 38,000 fetal pig islet-like cell clusters (ICCs) within barium alginate microcapsules of diameter 300, 600, or 1000 μm. Viability, insulin secretion, and content of encapsulated cells were measured prior to transplantation. Blood glucose levels (BGL) were measured twice weekly and porcine C-peptide monthly. Encapsulated cells were recovered from mice at 6 months posttransplantation for analysis. Results. Encapsulated cells became glucose responsive and normalized BGL within 13 to 68 days posttransplantation, with 5,000 to 10,000 ICCs required. Microcapsule diameter did not affect the time required to achieve normoglycemia. BGL remained normal for the 6-month duration of the experiments. After removal of grafts at 25 weeks posttransplantation, glucose stimulated insulin secretion of the explants was enhanced 96-fold, insulin content was enhanced 34-fold, and the percentage of insulin and glucagon positive cells increased 10-fold and threefold, respectively, from the time of transplantation. Conclusions. This study demonstrates that fetal pancreatic cells differentiate and function normally when placed within barium alginate microcapsules and transplanted.

16 August 2022 in Journal of Cellular and Molecular Medicine
Verified
Journal Article
Open access
HDHoang Phuc Dang
Hoang Phuc Dang
Hui ChenHui Chen
Hui Chen
TDTim R. Dargaville
Tim R. Dargaville
BTBernard E. Tuch
Bernard E. Tuch
Immunoprotection and oxygen supply are vital in implementing a cell therapy for type 1 diabetes (T1D). Without these features, the transplanted islet cell clusters will be rejected by the host immune system, and necrosis will occur due to hypoxia. The use of anti‐rejection drugs can help protect the transplanted cells from the immune system; yet, they also may have severe side effects. Cell delivery systems (CDS) have been developed for islet transplantation to avoid using immunosuppressants. CDS provide physical barriers to reduce the immune response and chemical coatings to reduce host fibrotic reaction. In some CDS, there is architecture to support vascularization, which enhances oxygen exchange. In this review, we discuss the current clinical and preclinical studies using CDS without immunosuppression as a cell therapy for T1D. We find that though CDS have been demonstrated for their ability to support immunoisolation of the grafted cells, their functionality has not been fully optimized. Current advanced methods in clinical trials demonstrate the systems are partly functional, physically complicated to implement or inefficient. However, modifications are being made to overcome these issues.

27 August 2010 in American Journal of Transplantation
Verified
Journal Article
Open access
PDF file
VVV. Vaithilingam
V. Vaithilingam
JOJ. Oberholzer
J. Oberholzer
Gilles GUILLEMINGilles GUILLEMIN
Gilles GUILLEMIN
BTBernard E. Tuch
Bernard E. Tuch
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 μM desferrioxamine (DFO) prior to transplantation. Cell viability, glucose‐induced insulin secretion, VEGF (Vascular endothelial growth factor), HIF‐1α (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‐1α 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‐1α and VEGF expression in encapsulated human islets and improves their ability to function when transplanted.

27 December 2022 in Pharmaceutics
Verified
Journal Article
Open access
PDF file
Yanan HuangYanan Huang
Yanan Huang
ZDZiqing Du
Ziqing Du
Bao GuochenBao Guochen
Bao Guochen
GFGuocheng Fang
Guocheng Fang
MCMatthew Cappadona
Matthew Cappadona
Xiaoxue XuXiaoxue Xu
Xiaoxue Xu
Drug-delivery vehicles have garnered immense interest in recent years due to unparalleled progress made in material science and nanomedicine. However, the development of stimuli-responsive devices with controllable drug-release systems (DRSs) is still in its nascent stage. In this paper, we designed a two-way controlled drug-release system that can be promoted and prolonged, using the external stimulation of near-infrared light (NIR) and protein coating. A hierarchical nanostructure was fabricated using upconversion nanoparticles (UCNPs)—mesoporous silica as the core-shell structure with protein lysozyme coating. The mesoporous silica shell provides abundant pores for the loading of drug molecules and a specific type of photosensitive molecules. The morphology and the physical properties of the nanostructures were thoroughly characterized. The results exhibited the uniform core-shell nanostructures of ~four UCNPs encapsulated in one mesoporous silica nanoparticle. The core-shell nanoparticles were in the spherical shape with an average size of 200 nm, average surface area of 446.54 m2/g, and pore size of 4.6 nm. Using doxorubicin (DOX), a chemotherapy agent as the drug model, we demonstrated that a novel DRS with capacity of smart modulation to promote or inhibit the drug release under NIR light and protein coating, respectively. Further, we demonstrated the therapeutic effect of the designed DRSs using breast cancer cells. The reported novel controlled DRS with dual functionality could have a promising potential for chemotherapy treatment of solid cancers.

1 March 2022 in Tissue Engineering Part A
Verified
Journal Article
Closed access
AMAuvro R. Mridha
Auvro R. Mridha
TDTim R. Dargaville
Tim R. Dargaville
PDPaul Donald Dalton
Paul Donald Dalton
LCLuke Carroll
Luke Carroll
Michael MorrisMichael Morris
Michael Morris
BTBernard E. Tuch
Bernard E. Tuch

Replacement of pancreatic β-cells is one of the most promising treatment options for treatment of type 1 diabetes (T1D), however toxic immunosuppressive drugs are required. In this study, we aim to deliver allogeneic β-cell therapies without anti‐rejection drugs using a bioengineered hybrid device that contains microencapsulated β-cells inside 3D polycaprolactone (PCL) scaffolds printed using melt electrospin writing (MEW). Mouse β-cell (MIN6) pseudo-islets and QS-mouse islets are encapsulated in alginate microcapsules, without affecting viability and insulin secretion. Microencapsulated MIN6 cells are then seeded within 3D MEW scaffolds, and these hybrid devices implanted subcutaneously in streptozotocin-treated diabetic NOD/SCID and BALB/c mice. Similar to NOD/SCID mice, blood glucose levels (BGL) are lowered from 30.1 to 4.8 mmol/L in 25-41 days in BALB/c. In contrast, microencapsulated islets placed in pre-vascularized MEW scaffold 3 weeks after implantation in BALB/c mice normalize BGL (〈12 mmol/L) more rapidly, lasting for 60 - 105 days. The lowering of glucose levels is confirmed by an intraperitoneal glucose tolerance test. Vascularity within the implanted grafts is demonstrated and quantified by 3D-doppler ultrasound, with a linear increase over 4 weeks (r = 0.65). Examination of the device at 5 weeks shows inflammatory infiltrates of neutrophils, macrophages and B-lymphocytes on the MEW scaffolds but not on microcapsules, which have infrequent pro-fibrotic walling. In conclusion, we demonstrate the fabrication of an implantable and retrievable hybrid device for vascularization and enhancing the survival of encapsulated islets implanted subcutaneously in an allotransplantation setting without immunosuppression. This study provides proof-of-concept for the application of such devices for human use, however, will require modifications to allow translation to people with T1D.