The Experts below are selected from a list of 8103 Experts worldwide ranked by ideXlab platform
Shinichi Matsumoto - One of the best experts on this subject based on the ideXlab platform.
-
clinical benefit of islet xenotransplantation for the treatment of type 1 diabetes
EBioMedicine, 2016Co-Authors: Shinichi Matsumoto, Adrian Abalovich, Carlos Wechsler, Shaun Wynyard, Robert B ElliottAbstract:Abstract Background Allogeneic islet transplantation has become a viable option for the treatment of unstable type 1 diabetes. However, the Donor Shortage and the necessity of the immunosuppressive drugs are two major issues. To solve these issues, we performed islet xenotransplantation using encapsulated neonatal porcine islets without immunosuppressive drugs. Methods Two different doses (approximately 5000IEQ/kg and 10,000IEQ/kg) of encapsulated neonatal porcine islets were transplanted twice (total approximately 10,000IEQ/kg and 20,000IEQ/kg) into four type 1 diabetic patients in each group (total 8 patients). Findings In the higher dose group, all four patients improved HbA1c. This was maintained at a level of 600days with significant reduction of the frequency of unaware hypoglycemic events. Interpretation The clinical benefit of islet xenotransplantation with microencapsulation has been shown.
-
islet cell transplantation for type 1 diabetes
Journal of Diabetes, 2010Co-Authors: Shinichi MatsumotoAbstract:Islet transplantation is an attractive concept for the treatment of Type 1 diabetes because of its potential high efficacy and minimal invasion to patients. The treatment may effectively control blood glucose for brittle Type 1 diabetes, resulting in a marked reduction in hypoglycemic episodes and improvements in HbA1c. In addition, approximately 70% of transplanted Type 1 diabetic patients have achieved insulin independence. However, there are still important issues to be addressed before this treatment is widely applicable, including difficulty in maintaining insulin independence, low islet isolation success rate, multiple Donor requirements, and side effects associated with the use of immunosuppressants. Donor Shortage is another dilemma. To address the issue of Donor Shortage, living Donor islet transplantation and bioartificial islet transplantation using pig islets are being evaluated. Bioartificial islet transplantation could be the ultimate solution of the Donor Shortage. Currently, overcoming immunological hurdles, establishing reliable islet isolation methods, and controlling porcine endogenous retrovirus are the primary obstacles to the implementation of this treatment. If bioartificial islet transplant becomes a clinical reality, it may even be applicable in the treatment of select Type 2 diabetic patients. β-Cell regeneration from naive pancreas and β-cell generation from embryonic stem cells or induced pluripotent stem cells are the next-generation treatments for Type 1 diabetes.
-
improvement of pancreatic islet cell isolation for transplantation
Proceedings (Baylor University. Medical Center), 2007Co-Authors: Shinichi Matsumoto, Nicholas Onaca, Bashoo Naziruddin, Hirofumi Noguchi, Andrew P Jackson, Hatanaka Nobuyo, Okitsu Teru, Kobayashi Naoya, Goran B Klintmalm, Marlon F. LevyAbstract:Pancreatic islet transplantation is a promising treatment for diabetes but still faces several challenges. Poor islet isolation efficiency and poor long-term insulin independence are currently two major issues, although Donor Shortage and the need for immunosuppressants also need to be addressed. We established the Kyoto islet isolation method (KIIM), which has enabled us to isolate and transplant islets even from non–heart-beating Donors. KIIM involves 1) cooling the Donor pancreas in situ, 2) preserving the ducts with modified Kyoto solution, 3) using a modified two-layer pancreas preservation method, and 4) adjusting the density of the density gradient centrifugation and using an iodixanol-based solution for purification. KIIM has enabled us to transplant 17 islet preparations out of 21 isolations (an 81% success rate). All transplanted islets functioned, and all transplanted patients had improved glycemic control without hypoglycemic unawareness. Recently, we used KIIM for islet isolation from a brain-dead Donor at Baylor, which resulted in a very high islet yield (789,984 IE) with high viability (100% by fluorescein diacetate/propidium iodide staining and a stimulation index of 4.7). This preliminary evidence suggests that KIIM may also be promising for islet isolation from brain-dead Donors. In addition, to assess engrafted islet mass, we developed a secretory unit of islet transplant objects (SUITO) index: fasting C-peptide (ng/dL) / [fasting blood glucose (mg/dL) – 63] × 1500. This simple index has enabled us to monitor the engrafted islet mass. This index should be useful when deciding whether to perform additional islet transplantations to maintain insulin independence. Poor islet isolation efficacy and poor long-term results could be resolved with ongoing research.
-
successful islet transplantation from nonheartbeating Donor pancreata using modified ricordi islet isolation method
Transplantation, 2006Co-Authors: Shinichi Matsumoto, Hirofumi Noguchi, Teru Okitsu, Yasuhiro Iwanaga, Hideo Nagata, Yukihide Yonekawa, Yuichiro Yamada, Kazuhito Fukuda, Toshiya Shibata, Yasunari KasaiAbstract:BACKGROUND Current success of islet transplantation has led to Donor Shortage and the need for marginal Donor utilization to alleviate this Shortage. The goal of this study was to improve the efficacy of islet transplantation using nonheartbeating Donors (NHBDs). METHODS First, we used porcine pancreata for the implementation of several strategies and applied to human pancreata. These strategies included ductal injection with trypsin inhibitor for protection of pancreatic ducts, ET-Kyoto solution for pancreas preservation, and Iodixanol for islet purification. RESULTS These strategies significantly improved both porcine and human islet isolation efficacy. Average 399,469+/-36,411 IE human islets were obtained from NHBDs (n=13). All islet preparations met transplantation criteria and 11 out of 13 cases (85%) were transplanted into six type 1 diabetic patients for the first time in Japan. All islets started to secrete insulin and all patients showed better blood glucose control without hypoglycemic loss of consciousness. The average HbA1c levels of the six recipients significantly improved from 7.5+/-0.4% at transplant to 5.1+/-0.2% currently (P<0.0003). The average insulin amounts of the six recipients significantly reduced from 49.2+/-3.3 units at transplant to 11+/-4.4 units (P<0.0005) and five out of six patients reduced to less than half dose. The first patient is now insulin free, the first such case in Japan. CONCLUSION This demonstrates that our current protocol makes it feasible to use NHBDs for islet transplant into type 1 diabetic patients efficiently.
-
insulin independence after living Donor distal pancreatectomy and islet allotransplantation
The Lancet, 2005Co-Authors: Shinichi Matsumoto, Hirofumi Noguchi, Teru Okitsu, Yasuhiro Iwanaga, Hideo Nagata, Yukihide Yonekawa, Yuichiro Yamada, Kazuhito Fukuda, Katsushi Tsukiyama, Haruhiko SuzukiAbstract:Rising demand for islet transplantation will lead to severe Donor Shortage in the near future, especially in countries where cadaveric organ donation is scarce. We undertook a successful transplantation of living-Donor islets for unstable diabetes. The recipient was a 27-year-old woman who had had brittle, insulin-dependent diabetes mellitus for 12 years. The Donor, who was a healthy 56-year-old woman and mother of the recipient, underwent a distal pancreatectomy. After isolation, 408 114 islet equivalents were transplanted immediately. The transplants functioned immediately and the recipient became insulin-independent 22 days after the operation. The Donor had no complications and both women showed healthy glucose tolerance. Transplantation of living-Donor islets from the distal pancreas can be sufficient to reverse brittle diabetes.
Peter X - One of the best experts on this subject based on the ideXlab platform.
-
nano fibrous scaffolding architecture selectively enhances protein adsorption contributing to cell attachment
Journal of Biomedical Materials Research Part A, 2003Co-Authors: Kyung Mi Woo, Victor J Chen, Peter XAbstract:Tissue engineering aims at resolving problems such as Donor Shortage and immune rejection faced by transplantation. Scaffolds (artificial extracellular matrices) have critical roles in tissue engineering. Recently, we developed nano-fibrous poly(L-lactic acid) scaffolds under the hypothesis that synthetic nano-fibrous scaffolding, mimicking the structure of natural collagen fibers, could create a more favorable microenvironment for cells. This is the first report that the nano-fibrous architecture built in three-dimensional scaffolds improved the features of protein adsorption, which mediates cell interactions with scaffolds. Scaffolds with nano-fibrous pore walls adsorbed four times more serum proteins than scaffolds with solid pore walls. More interestingly, the nano-fibrous architecture selectively enhanced protein adsorption including fibronectin and vitronectin, even though both scaffolds were made from the same poly(L-lactic acid) material. Furthermore, nano-fibrous scaffolds also allowed >1.7 times of osteoblastic cell attachment than scaffolds with solid pore walls. These results demonstrate that the biomimetic nano-fibrous architecture serves as superior scaffolding for tissue engineering.
-
nano fibrous scaffolding architecture enhances protein adsorption and cell attachment
MRS Proceedings, 2002Co-Authors: Kyung Mi Woo, Victor J Chen, Peter XAbstract:Tissue engineering aims at resolving problems such as Donor Shortage and immune rejection faced in transplantation. Scaffolds (artificial extracellular matrices) play critical roles in tissue engineering. Recently, we developed nano-fibrous poly(L-lactic acid) (PLLA) scaffolds under the hypothesis that synthetic nano-fibrous scaffolding, mimicking the structure of natural collagen fibers, could create a more favorable microenvironment for cells. This is the first report that the nano-fibrous architecture built in three-dimensional scaffolds improved the features of protein adsorption, which mediates cell interactions with scaffolds. Scaffolds with nano-fibrous pore walls adsorbed 4 times more serum proteins than scaffolds with solid pore walls. More interestingly, the nano-fibrous architecture selectively enhanced protein adsorption including fibronectin and vitronectin, even though both scaffolds were made from the same PLLA material. Furthermore, nano-fibrous scaffolds also allowed more than 1.7 times of osteoblastic cell attachment than scaffolds with “solid” pore walls. These results demonstrate that the biomimetic nano-fibrous architecture serves as superior scaffolding for tissue engineering.
Byungsoo Kim - One of the best experts on this subject based on the ideXlab platform.
-
kidney tissue reconstruction by fetal kidney cell transplantation effect of gestation stage of fetal kidney cells
Stem Cells, 2007Co-Authors: Sangsoo Kim, Sojung Gwak, Joungho Han, Heung Jae Park, Moon Hyang Park, Kang Won Song, Seung Woo Cho, Yun Hee Rhee, Hyungmin Chung, Byungsoo KimAbstract:Dialysis and kidney transplantation, current therapies for kidney failure, have limitations such as severe complications, Donor Shortage, and immune-related problems. The development of an alternative treatment for kidney failure is demanded. The present study shows that the transplantation of fetal kidney cells reconstitutes functional kidney tissue, and that the gestation stage of kidney cells influences the kidney reconstitution. Fetal kidney cells were isolated from metanephroi of rat fetuses at various gestation stages and transplanted into the omentum or kidney of immunodeficient mice. Immunophenotype analysis of fetal kidney cells showed apparent expression of stem cell markers. Three weeks after transplantation, histological analyses of retrieved grafts revealed the formation of kidney structures, including fluorescently labeled transplanted cells, suggesting the potential of fetal kidney cells to reconstitute kidney tissues. The grafts retrieved from omentum contained cystic fluids with concentrated solutes. However, transplanted early fetal kidney cells had also differentiated into nonrenal tissues such as bone and cartilage. In addition, transplantation of fetal kidney cells from a later gestation stage resulted in poor kidney structure formation. Kidney-specific genes were strongly expressed in the earlier cell transplants. The cells at an earlier gestation stage had higher colony forming ability than the cells at a later stage. This study demonstrates the reconstitution of kidney tissue by transplanting fetal kidney cells and the presence of an optimal time window in which fetal kidney cells regenerate kidney tissues. Disclosure of potential conflicts of interest is found at the end of this article.
Kyung Mi Woo - One of the best experts on this subject based on the ideXlab platform.
-
nano fibrous scaffolding architecture selectively enhances protein adsorption contributing to cell attachment
Journal of Biomedical Materials Research Part A, 2003Co-Authors: Kyung Mi Woo, Victor J Chen, Peter XAbstract:Tissue engineering aims at resolving problems such as Donor Shortage and immune rejection faced by transplantation. Scaffolds (artificial extracellular matrices) have critical roles in tissue engineering. Recently, we developed nano-fibrous poly(L-lactic acid) scaffolds under the hypothesis that synthetic nano-fibrous scaffolding, mimicking the structure of natural collagen fibers, could create a more favorable microenvironment for cells. This is the first report that the nano-fibrous architecture built in three-dimensional scaffolds improved the features of protein adsorption, which mediates cell interactions with scaffolds. Scaffolds with nano-fibrous pore walls adsorbed four times more serum proteins than scaffolds with solid pore walls. More interestingly, the nano-fibrous architecture selectively enhanced protein adsorption including fibronectin and vitronectin, even though both scaffolds were made from the same poly(L-lactic acid) material. Furthermore, nano-fibrous scaffolds also allowed >1.7 times of osteoblastic cell attachment than scaffolds with solid pore walls. These results demonstrate that the biomimetic nano-fibrous architecture serves as superior scaffolding for tissue engineering.
-
nano fibrous scaffolding architecture enhances protein adsorption and cell attachment
MRS Proceedings, 2002Co-Authors: Kyung Mi Woo, Victor J Chen, Peter XAbstract:Tissue engineering aims at resolving problems such as Donor Shortage and immune rejection faced in transplantation. Scaffolds (artificial extracellular matrices) play critical roles in tissue engineering. Recently, we developed nano-fibrous poly(L-lactic acid) (PLLA) scaffolds under the hypothesis that synthetic nano-fibrous scaffolding, mimicking the structure of natural collagen fibers, could create a more favorable microenvironment for cells. This is the first report that the nano-fibrous architecture built in three-dimensional scaffolds improved the features of protein adsorption, which mediates cell interactions with scaffolds. Scaffolds with nano-fibrous pore walls adsorbed 4 times more serum proteins than scaffolds with solid pore walls. More interestingly, the nano-fibrous architecture selectively enhanced protein adsorption including fibronectin and vitronectin, even though both scaffolds were made from the same PLLA material. Furthermore, nano-fibrous scaffolds also allowed more than 1.7 times of osteoblastic cell attachment than scaffolds with “solid” pore walls. These results demonstrate that the biomimetic nano-fibrous architecture serves as superior scaffolding for tissue engineering.
Marlon F. Levy - One of the best experts on this subject based on the ideXlab platform.
-
Islet cell transplantation for the treatment of type 1 diabetes in the USA
Journal of Hepato-Biliary-Pancreatic Surgery, 2008Co-Authors: Tetsuya Ikemoto, Masayuki Shimoda, Nicholas Onaca, Bashoo Naziruddin, Andrew Jackson, Yoshiko Tamura, Yasutaka Fujita, Marlon F. LevyAbstract:Islet cell transplantation (ICTx) is one of the most effective treatments for type 1 diabetes and is less invasive compared to whole organ transplantation. The US has been the leader in the research and clinical applications of ICTx for the last 40 years. ICTx requires complex procedures, including pancreas procurement and preservation; pancreas digestion; islet purification; and transplantation. Even with the dramatic progresses in each of the procedures listed above, there are still challenges to make ICTx the standard therapy. These challenges are: (1) obtaining enough islets from a single Donor and (2) preventing graft loss due to allogenic rejection and recurrence of autoimmune islet destruction. A new preservation strategy for pancreata and pancreatic ducts using ET-Kyoto solution as well as a new islet purification method using iodixanol has substantially improved islet yields. Continuous research to improve the efficacy of islet isolation will solve the issue of obtaining enough islets from a single Donor. Immunological tolerance is an ideal solution for the issue of rejection and autoimmune recurrence and a regulatory T cell strategy seems promising. Moreover, the SUITO index is a simple and powerful tool to assess engrafted islet mass and is, therefore, useful for evaluating the efficacy of new immunosuppressant strategies. Once ICTx becomes a standard treatment, the Donor Shortage will become the next challenge. Marginal or living Donor islet transplantations could help alleviate this issue; however, bio-artificial islet transplantation with animal islets could be the ultimate solution.
-
improvement of pancreatic islet cell isolation for transplantation
Proceedings (Baylor University. Medical Center), 2007Co-Authors: Shinichi Matsumoto, Nicholas Onaca, Bashoo Naziruddin, Hirofumi Noguchi, Andrew P Jackson, Hatanaka Nobuyo, Okitsu Teru, Kobayashi Naoya, Goran B Klintmalm, Marlon F. LevyAbstract:Pancreatic islet transplantation is a promising treatment for diabetes but still faces several challenges. Poor islet isolation efficiency and poor long-term insulin independence are currently two major issues, although Donor Shortage and the need for immunosuppressants also need to be addressed. We established the Kyoto islet isolation method (KIIM), which has enabled us to isolate and transplant islets even from non–heart-beating Donors. KIIM involves 1) cooling the Donor pancreas in situ, 2) preserving the ducts with modified Kyoto solution, 3) using a modified two-layer pancreas preservation method, and 4) adjusting the density of the density gradient centrifugation and using an iodixanol-based solution for purification. KIIM has enabled us to transplant 17 islet preparations out of 21 isolations (an 81% success rate). All transplanted islets functioned, and all transplanted patients had improved glycemic control without hypoglycemic unawareness. Recently, we used KIIM for islet isolation from a brain-dead Donor at Baylor, which resulted in a very high islet yield (789,984 IE) with high viability (100% by fluorescein diacetate/propidium iodide staining and a stimulation index of 4.7). This preliminary evidence suggests that KIIM may also be promising for islet isolation from brain-dead Donors. In addition, to assess engrafted islet mass, we developed a secretory unit of islet transplant objects (SUITO) index: fasting C-peptide (ng/dL) / [fasting blood glucose (mg/dL) – 63] × 1500. This simple index has enabled us to monitor the engrafted islet mass. This index should be useful when deciding whether to perform additional islet transplantations to maintain insulin independence. Poor islet isolation efficacy and poor long-term results could be resolved with ongoing research.