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https://read.qxmd.com/read/32749728/pancreas-transplants-from-small-donors-are-the-outcomes-acceptable
#1
Talal M Al-Qaoud, Jon S Odorico, David P Al-Adra, Dixon B Kaufman, Hans W Sollinger, Glen Leverson, Bridget Welch, Robert R Redfield
Despite good organ quality, pancreata from extremely small pediatric donors (<30kg) are generally avoided by many centers due to concerns of reduced islet cell mass and early technical failure. Therefore, we sought to compare the outcomes of small pancreas grafts (<30 kg) to those from higher weight donors from transplants performed between 1994-2015 (n=1183). A total of 33 pancreata were from donors' ≤30 kg (3%), with a mean weight of 23.8 kg and mean age of 7.8 yrs. Patient survival was similar at 1, 5 and 10 years between recipients of ≤30 kg and >30 kg donors (≤30 kg: 96...
August 4, 2020: Transplant International: Official Journal of the European Society for Organ Transplantation
https://read.qxmd.com/read/32749168/engineering-of-primary-pancreatic-islet-cell-spheroids-for-three-dimensional-culture-or-transplantation-a-methodological-comparative-study
#2
Charles-Henri Wassmer, Kevin Bellofatto, Lisa Perez, Vanessa Lavallard, David Cottet-Dumoulin, Sanda Ljubicic, Géraldine Parnaud, Domenico Bosco, Ekaterine Berishvili, Fanny Lebreton
Three-dimensional (3D) cell culture by engineering spheroids has gained increasing attention in recent years because of the potential advantages of such systems over conventional two-dimensional (2D) tissue culture. Benefits include the ability of 3D to provide a more physiologically relevant environment, for the generation of uniform, size-controlled spheroids with organ-like microarchitecture and morphology. In recent years, different techniques have been described for the generation of cellular spheroids...
January 2020: Cell Transplantation
https://read.qxmd.com/read/32749162/role-of-sirtuin-1-sirt1-in-hypoxic-injury-in-pancreatic-%C3%AE-cells
#3
Ye-Jee Lee, Esder Lee, Young-Hye You, Yu-Bae Ahn, Ki-Ho Song, Ji-Won Kim, Seung-Hyun Ko
Islet transplantation (ITx) is being developed as a treatment for type 1 diabetes mellitus, but hypoxic damage to transplanted islet grafts is an important factor affecting successful transplantation. To investigate the role of sirtuin-1 (SIRT1) under hypoxic injury in INS-1 cells, one type of pancreatic β-cell line, we used SRT1720 and GW4064 for SIRT1 activation. The small interfering RNA SIRT1 (si-SIRT1) was used to suppress SIRT1 gene expression. We measured cell viability, apoptosis, and the levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and reactive oxygen species (ROS), under hypoxic conditions...
August 4, 2020: Journal of Drug Targeting
https://read.qxmd.com/read/32749147/-old-school-islet-purification-based-on-the-unit-gravity-sedimentation-as-a-rescue-technique-for-intraportal-islet-transplantation-a-case-report
#4
Justyna E Gołębiewska, Karolina Gołąb, Tomasz Gorycki, Maciej Śledziński, Jacek Gulczyński, Iwona Żygowska, Bogumił Wolnik, Michał Hoffmann, Piotr Witkowski, Camillo Ricordi, Edyta Szurowska, Zbigniew Śledziński, Alicja Dębska-Ślizień
Here, we present a case that required a supplemental "old school" islet purification for a safe intraportal infusion. Following pancreas procurement from a brain-dead 26-year-old male donor (body mass index: 21.9), 24.6 ml of islet tissue was isolated after continuous density gradient centrifugation. The islet yield was 504,000 islet equivalent (IEQ), distributed among the following three fractions: 64,161 IEQ in 0.6 ml of pellet, 182,058 IEQ in 10 ml, and 258,010 IEQ in 14 ml with 95%, 20%, and 10% purity, respectively...
January 2020: Cell Transplantation
https://read.qxmd.com/read/32743962/islet-or-pancreas-after-kidney-transplantation-is-the-whole-still-greater-than-some-of-its-parts
#5
EDITORIAL
Jonathan A Fridell, Robert J Stratta
In their landmark publication entitled Phase 3 trial of human islet-after-kidney transplantation in type 1 diabetes, Markmann and colleagues report the outcomes of the Clinical Islet Transplantation (CIT) consortium trial 06 of purified human pancreatic islets transplanted into patients with type 1 diabetes following successful kidney transplantation (1). This study was conducted at ten North American transplant centers and demonstrated that in kidney transplant recipients with diabetes on intensive insulin therapy with frequent severe hypoglycemic events and poor glycemic control, islet after kidney (IAK) transplantation can achieve improved glucose homeostasis, normalization of HBA1C levels, and freedom from severe hypoglycemic episodes in 60% of patients at one-year follow-up...
August 2, 2020: American Journal of Transplantation
https://read.qxmd.com/read/32732835/transient-mixed-chimerism-with-nonmyeloablative-conditioning-does-not-induce-liver-allograft-tolerance-in-nonhuman-primates
#6
Sulemon Chaudhry, Yojiro Kato, Joshua Weiner, Paula Alonso-Guallart, Sam Baker, David C Woodland, Jay H Lefkowitch, Raimon Duran-Struuck, Hugo P Sondermeijer, Jonah Zitsman, Mallory L Sears, Anette Wu, Brian Karolewski, Philipp J Houck, Mercedes Martinez, Tomoaki Kato, Megan Sykes, Adam D Griesemer
BACKGROUND: Although short-term outcomes for liver transplantation have improved, patient and graft survival are limited by infection, cancer, and other complications of immunosuppression. Rapid induction of tolerance after liver transplantation would decrease these complications, improving survival and quality of life. Tolerance to kidneys, but not thoracic organs or islets, has been achieved in nonhuman primates and humans through the induction of transient donor chimerism. Since the liver is considered to be tolerogenic, we tested the hypothesis that the renal transplant transient chimerism protocol would induce liver tolerance...
August 2020: Transplantation
https://read.qxmd.com/read/32731883/direct-lineage-tracing-reveals-activin-a-potential-for-improved-pancreatic-homing-of-bone-marrow-mesenchymal-stem-cells-and-efficient-%C3%A3-cell-regeneration-in-vivo
#7
Nidheesh Dadheech, Abhay Srivastava, Mitul Vakani, Paresh Shrimali, Ramesh Bhonde, Sarita Gupta
BACKGROUND: Despite the potential, bone marrow-derived mesenchymal stem cells (BMSCs) show limitations for beta (ß)-cell replacement therapy due to inefficient methods to deliver BMSCs into pancreatic lineage. In this study, we report TGF-ß family member protein, Activin-a potential to stimulate efficient pancreatic migration, enhanced homing and accelerated ß-cell differentiation. METHODS: Lineage tracing of permanent green fluorescent protein (GFP)- tagged donor murine BMSCs transplanted either alone or in combination with Activin-a in diabetic mice displayed potential ß-cell regeneration and reversed diabetes...
July 30, 2020: Stem Cell Research & Therapy
https://read.qxmd.com/read/32731817/comparative-study-of-two-different-islet-transplantation-sites-in-mice-hepatic-sinus-tract-vs-splenic-parenchyma
#8
Feng Li, Yi Lv, Xiaohang Li, Zhaoming Yang, Tingwei Guo, Jialin Zhang
Although 90% of clinical islet transplantations are performed via the portal vein approach, it is still far from the ideal transplant site. Alternative islet transplant sites are promising to reduce the islet dose required to reverse hyperglycemia, thereby improving the efficiency of islet transplantation. The aim of this study was to compare the differences in survival and metabolic function of islet grafts transplanted into the hepatic sinus tract (HST) and the splenic parenchyma (SP). Approximately 300 syngeneic mouse islets were transplanted into the HST ( n = 6) and the SP ( n = 6) of recipient diabetic mice, respectively...
January 2020: Cell Transplantation
https://read.qxmd.com/read/32722544/mcmv-dissemination-from-latently-infected-allografts-following-transplantation-into-pre-tolerized-recipients
#9
Sahil Shah, Matthew DeBerge, Andre Iovane, Shixian Yan, Longhui Qiu, Jiao-Jing Wang, Yashpal S Kanwar, Mary Hummel, Zheng J Zhang, Michael M Abecassis, Xunrong Luo, Edward B Thorp
Transplantation tolerance is achieved when recipients are unresponsive to donor alloantigen yet mobilize against third-party antigens, including virus. After transplantation, cytomegalovirus (CMV) reactivation in latently-infected transplants reduces allograft viability. To determine if pre-tolerized recipients are resistant to viral dissemination in this setting, we transfused chemically-fixed donor splenocytes (1-ethyl-3- (3'-dimethyl-aminopropyl)-carbo-diimide (ECDI)-treated splenocytes (ECDIsp)) to induce donor antigen tolerance without immunosuppression...
July 26, 2020: Pathogens
https://read.qxmd.com/read/32718230/commentary-on-some-recent-theses-relevant-to-combating-aging-august-2020
#10
Benjamin Zealley, Aubrey D N J de Grey
Theses reviewed in this issue include "Characterization and Purification of Putative Stem Cells from the Adult Murine Pancreas", "Inhibition of TLR4 Minimizes Islet Damage due to Sterile Inflammation and Improves Islet Transplant Outcomes", "Liquefaction of the Brain Following Stroke Shares Multiple Characteristics with Atherosclerosis and Mediates Secondary Neurodegeneration in an Osteopontin-Dependent Mechanism", "Manipulating the segregation of human mitochondrial DNA", "Role of Mitochondria in Plasma Membrane Repair and Pathogenesis of Muscular Dystrophy", and "The Role of Cytosolic Accumulation of Nuclear DNA in Retinal-Pigment Epithelium Dysfunction and Age-Related Macular Degeneration"...
July 27, 2020: Rejuvenation Research
https://read.qxmd.com/read/32700473/microencapsulation-for-the-cell-and-molecular-therapy-of-type-1-diabetes-mellitus-actual-state-and-future-perspectives-between-promise-and-progress
#11
REVIEW
Giuseppe Basta, Pia Montanucci, Riccardo Calafiore
The history of microencapsulation of live cells starts from an old idea of Thomas M. S. Chang in 1964, thereafter applied to isolated pancreatic islets by Anthony M. Sun in 1980. The original aim was to provide isolated cells with an immune-protective shield, to prevent physical contact between the transplanted cells and the host's immune system, with retention of the microcapsules' biocompatibility and physical-chemical properties over time. In particular, this revolutionary approach essentially applied to islet grafts, in diabetic not immunosuppressed recipients, at pre-clinical (rodents), and subsequently clinical level...
July 22, 2020: Journal of Diabetes Investigation
https://read.qxmd.com/read/32699230/insulin2-q104del-kuma-mutant-mice-develop-diabetes-with-dominant-inheritance
#12
Daisuke Sakano, Airi Inoue, Takayuki Enomoto, Mai Imasaka, Seiji Okada, Mutsumi Yokota, Masato Koike, Kimi Araki, Shoen Kume
Insulin gene mutations have been identified to cause monogenic diabetes, and most of which developed permanent neonatal diabetes at young ages before 6 months of age in humans. To establish an animal model of permanent diabetes, we performed genome editing using the CRISPR/Cas9 system. We generated a novel Kuma mutant mice with p.Q104del in the Insulin2 (Ins2) gene in a BRJ background that exhibits a severe immune deficiency. Kuma mutant mice are non-obese and developed hyperglycemia from 3 weeks after birth in both males and females, which are inherited in a dominant mode...
July 22, 2020: Scientific Reports
https://read.qxmd.com/read/32694729/in-vivo-studies-of-glucagon-secretion-by-human-islets-transplanted-in-mice
#13
Krissie Tellez, Yan Hang, Xueying Gu, Charles A Chang, Roland W Stein, Seung K Kim
Little is known about regulated glucagon secretion by human islet α-cells compared to insulin secretion from β-cells, despite conclusive evidence of dysfunction in both cell types in diabetes mellitus. Distinct insulins in humans and mice permit in vivo studies of human β-cell regulation after human islet transplantation in immunocompromised mice, whereas identical glucagon sequences prevent analogous in vivo measures of glucagon output from human α-cells. Here, we use CRISPR-Cas9 editing to remove glucagon codons 2-29 in immunocompromised NSG mice, preserving the production of other proglucagon-derived hormones...
June 2020: Nature metabolism
https://read.qxmd.com/read/32694579/mitomycin-c-treatment-improves-pancreatic-islet-graft-longevity-in-intraportal-islet-transplantation-by-suppressing-proinflammatory-response
#14
Kei Yamane, Takayuki Anazawa, Seiichiro Tada, Nanae Fujimoto, Kenta Inoguchi, Norio Emoto, Kazuyuki Nagai, Toshihiko Masui, Hideaki Okajima, Kyoichi Takaori, Shoichiro Sumi, Shinji Uemoto
The in vitro culture period prior to cell transplantation (i.e. pancreatic islet transplantation) enables cell modification and is thus advantageous. However, the islet preconditioning method has not been fully explored. Here we present a simple approach for islet preconditioning that uses the antibiotic mitomycin C (MMC), which has antitumor activity, to reduce islet immunogenicity and prevent proinflammatory events in an intraportal islet transplantation model. Freshly isolated mice islets were treated for 30 min with 10 μg/mL MMC or not, cultured for 20 h and transplanted into the livers of syngeneic or allogeneic diabetic mouse recipients...
July 21, 2020: Scientific Reports
https://read.qxmd.com/read/32691966/long-term-follow-up-for-the-microbiological-safety-of-clinical-microencapsulated-neonatal-porcine-islet-transplantation
#15
Shinichi Matsumoto, Shaun Wynyard, Mariëlla Giovannangelo, Sneha Lakshmandas Hemdev, Adrian Abalovich, Mariana E Carulla, Carlos J Wechsler
Enrollment in three clinical trials for microencapsulated neonatal porcine islet xenotransplantation to treat unstable type 1 diabetic patients concluded in November 2014. In this study, we report a long-term follow-up assessment of microbiological safety for these trials. Thirty-eight type 1 diabetic patients received microencapsulated neonatal porcine islet transplants. Islets were isolated and prepared from the pancreata of New Zealand (NZ) based designated pathogen-free (DPF) pigs under GMP conditions. Blood samples of thirty-six patients were collected from 5 to 7 years post-first transplant and were tested by real-time PCR for porcine circovirus-1 (PCV1), porcine circovirus-2 (PCV2), porcine lymphotropic herpesvirus 1 (PLHV1), porcine lymphotropic herpesvirus 2 (PLHV2), and porcine cytomegalovirus (PCMV)...
July 21, 2020: Xenotransplantation
https://read.qxmd.com/read/32659030/acute-murine-cytomegalovirus-disrupts-established-transplantation-tolerance-and-causes-recipient-allo-sensitization
#16
Shuangjin Yu, Anil Dangi, Melanie Burnette, Michael M Abecassis, Edward B Thorp, Xunrong Luo
We have previously shown that acute cytomegalovirus (CMV) infection disrupts the induction of transplantation tolerance. However, what impact acute CMV infection would have on the maintenance of established tolerance and on subsequent recipient allo-sensitization is a clinically important unanswered question. Here, we used an allogeneic murine islet transplantation tolerance model to examine the impact of acute CMV infection on: (1) disruption of established transplantation tolerance during tolerance maintenance; and (2) the possibility of recipient allo-sensitization by CMV-mediated disruption of stable tolerance...
July 13, 2020: American Journal of Transplantation
https://read.qxmd.com/read/32654450/-early-efficacy-of-islet-transplantation-in-the-treatment-of-adult-advanced-diabetes
#17
A B Hu, X C Ling, J L Duan, W W Liao, X F Zhu, X S He, F R Liu, F Bai
Objective: To evaluate the safety and efficacy of islet transplantation for patients with advanced diabetes. Methods: Five cases of islet allotransplantation were performed on 4 adult recipients. The same blood type adult brain-dead pancreas donors were selected and the islets were prepared in GMP laboratory. The prepared islet suspension was slowly injected into the liver of the recipients within 30-60 minutes. The immunosuppressive regimen was a combination of basiliximab, tacrolimus and mycophenolate mofetil and TNF-alpha monoclonal antibody was used to reduce the post-transplant inflammatory response...
July 14, 2020: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://read.qxmd.com/read/32654418/advancements-in-transplantation-therapy-for-diabetes-pancreas-islet-and-stem-cell
#18
Toshihiro Nakamura, Junji Fujikura, Nobuya Inagaki
In the hundred-year history of exogenous insulin therapy for patients with insulin-dependent diabetes mellitus (IDDM), pancreas transplantation and islet transplantation have gained wide acceptance over recent decades. In addition, research and development of human stem cell-derived cell transplantation have accelerated in recent years. Several preclinical approaches using somatic stem cells for the complications of diabetes also have been explored. This article summarizes recent developments in transplantation therapy for diabetes including ongoing trials as well as research on the use of stem cells for complications of diabetes...
July 11, 2020: Journal of Diabetes Investigation
https://read.qxmd.com/read/32641151/current-progress-in-stem-cell-therapy-for-type-1-diabetes-mellitus
#19
REVIEW
Shuai Chen, Kechen Du, Chunlin Zou
Type 1 diabetes mellitus (T1DM) is the most common chronic autoimmune disease in young patients and is characterized by the loss of pancreatic β cells; as a result, the body becomes insulin deficient and hyperglycemic. Administration or injection of exogenous insulin cannot mimic the endogenous insulin secreted by a healthy pancreas. Pancreas and islet transplantation have emerged as promising treatments for reconstructing the normal regulation of blood glucose in T1DM patients. However, a critical shortage of pancreases and islets derived from human organ donors, complications associated with transplantations, high cost, and limited procedural availability remain bottlenecks in the widespread application of these strategies...
July 8, 2020: Stem Cell Research & Therapy
https://read.qxmd.com/read/32634811/control-of-hyperglycemia-using-differentiated-and-undifferentiated-mesenchymal-stem-cells-in-rats-with-type-1-diabetes
#20
Ehsan Aali, Zahra Madjd, Neda Tekiyehmaroof, Ali Mohammad Sharifi
Due to their ability in self-renewing and differentiation into a wide variety of tissues, mesenchymal stem cells (MSCs) exhibit outstanding potential for regenerative medicine. This study was aimed at investigating different aspects of MSC therapy in controlling hyperglycemia in streptozotocin-induced diabetes rats. Using an islet cell differentiation protocol, bone marrow (BM) MSCs were differentiated into insulin-producing cells (IPCs). The differentiation process was evaluated by immunocytochemistry, reverse transcriptase PCR, and dithizone staining...
July 7, 2020: Cells, Tissues, Organs
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