Thibault Bahougne, Jérome Olagne, Marion Munch, Laura Braun-Parvez, Marie-Pierrette Chenard, Véronique Frémeaux-Bacchi, Sophie Caillard, Philippe Baltzinger, Michel Greget, Laurence Kessler, Bruno Moulin
BACKGROUND: We here report on the first observation of a C3 mutation that is related to atypical hemolytic and uremic syndrome (aHUS), which occurred in a pancreatic islet transplant patient. Immunosuppressive treatments, such as calcineurin inhibitors, have been linked to undesirable effects like nephrotoxicity. CASE PRESENTATION: A 40-year-old man with brittle diabetes, who was included in the TRIMECO trial, became insulin-independent 2 months after pancreatic islet transplantation...
September 19, 2020: BMC Nephrology
Hannah Everwien, Eriselda Keshi, Karl H Hillebrandt, Barbara Ludwig, Marie Weinhart, Peter Tang, Anika S Beierle, Hendrik Napierala, Joseph Mgv Gassner, Nicolai Seiffert, Simon Moosburner, Dominik Geisel, Anja Reutzel-Selke, Benjamin Strücker, Johann Pratschke, Nils Haep, Igor M Sauer
Islet-based recellularization of decellularized, repurposed rat livers may form a transplantable Neo-Pancreas. The aim of this study is the establishment of the necessary protocols, the evaluation of the organ structure and the analysis of the islet functionality ex vivo. After perfusion-based decellularization of rat livers, matrices were repopulated with endothelial cells and mesenchymal stromal cells, incubated for 8 days in a perfusion chamber and finally repopulated on day 9 with intact rodent islets. Integrity and quality of re-endothelialization was assessed by histology and FITC-dextran perfusion assay...
September 16, 2020: Acta Biomaterialia
Mehdi Razavi, Tanchen Ren, Fengyang Zheng, Arsenii Telichko, Jing Wang, Jeremy J Dahl, Utkan Demirci, Avnesh S Thakor
BACKGROUND: The aim of this study was to examine the effect of a three-step approach that utilizes the application of adipose tissue-derived mesenchymal stem cells (AD-MSCs), encapsulation, and pulsed focused ultrasound (pFUS) to help the engraftment and function of transplanted islets. METHODS: In step 1, islets were co-cultured with AD-MSCs to form a coating of AD-MSCs on islets: here, AD-MSCs had a cytoprotective effect on islets; in step 2, islets coated with AD-MSCs were conformally encapsulated in a thin layer of alginate using a co-axial air-flow method: here, the capsule enabled AD-MSCs to be in close proximity to islets; in step 3, encapsulated islets coated with AD-MSCs were treated with pFUS: here, pFUS enhanced the secretion of insulin from islets as well as stimulated the cytoprotective effect of AD-MSCs...
September 18, 2020: Stem Cell Research & Therapy
Paulami Mandal, Debojyoti De, Kyunghee Yun, Kyeong Kyu Kim
Diabetes mellitus (DM) is a metabolic syndrome where insulin secretion or the response to insulin produced by the body is compromised. The only available long-term treatment is the transplantation of pancreas or islet for procuring β-cells. However, due to the shortage of β-cell sources from the tissues, differentiation of pluripotent stem cells or terminally differentiated cells into β-cell is proposed as an alternative strategy. Previously, human adipose-derived stem cells (ADSCs) were reported to be converted into β-like cells by a stepwise treatment of chemicals and growth factors...
September 12, 2020: Biochemical and Biophysical Research Communications
Lingling Wei, Yanzhuo Liu, Lijie Zhang, Tianhang Feng, Chunyou Lai, Longyan Yang, Xiaolun Huang, Shaoping Deng, Dong Zhao
BACKGROUND: Islets transplanted under the ear skin would allow easy observation of the graft response and survival in vivo. This research was designed to establish an efficient mouse islet transplant model to probe the dynamic cellular interplay in vivo. METHODS: Green fluorescent protein transgenic mice and BALB/c mice were used as donors and recipients. All recipients were divided into 6 groups of 6 mice each. First, we treated the transplant recipients, including diabetes induction, autologous epididymal fat pad, and MATRIGEL transplant to the ears...
September 11, 2020: Transplantation Proceedings
Elİfcan AladaĞ Karakulak, Haluk DemİroĞlu, Umit Yavuz Malkan, Umit Akman, Hakan GÖker, Yahya BÜyÜkaŞik
BACKGROUND: Graft-versus-Host Disease (GVHD) is a crucial complication leading to significant morbidity and mortality allogeneic hematopoietic stem cell transplantation which occurs in approximately half of the transplant recipients. Suppression of tumorigenicity 2 (ST2) and Regenerating islet-derived 3-alpha (Reg3a) might be important biomarkers to predict acute GVHD. MATERIALS AND METHODS: In the present study, blood samples were collected from 17 patients with acute GVHD and 12 control patients after allogeneic stem cell transplantation...
September 15, 2020: Turkish Journal of Medical Sciences
María M Coronel, Karen E Martin, Michael D Hunckler, Graham Barber, Eric B O'Neill, Juan D Medina, Enrico Opri, Claire A McClain, Lalit Batra, Jessica D Weaver, Hong S Lim, Peng Qiu, Edward A Botchwey, Esma S Yolcu, Haval Shirwan, Andrés J García
Antibody-mediated immune checkpoint blockade is a transformative immunotherapy for cancer. These same mechanisms can be repurposed for the control of destructive alloreactive immune responses in the transplantation setting. Here, we implement a synthetic biomaterial platform for the local delivery of a chimeric streptavidin/programmed cell death-1 (SA-PD-L1) protein to direct "reprogramming" of local immune responses to transplanted pancreatic islets. Controlled presentation of SA-PD-L1 on the surface of poly(ethylene glycol) microgels improves local retention of the immunomodulatory agent over 3 weeks in vivo...
August 2020: Science Advances
Mehdi Razavi, Rosita Primavera, Bhavesh D Kevadiya, Jing Wang, Mujib Ullah, Peter Buchwald, Avnesh S Thakor
In the present study, we created a nanoscale platform that can deliver nutrients to pancreatic islets in a controlled manner. Our platform consists in mesoporous silica nanoparticle (MSNP), which can be reversibly loaded with glutamine (G: an essential amino acid required for islet survival and function). To control the release of glutamine, MSNPs were coated with a polydopamine (PD) layer. Using the optimal parameters (0.5 mg/mL and 0.5 h), MSNPs were coated with a layer of PD which resulted in a delay of glutamine release from MSNPs over 14 days (57...
September 10, 2020: Nano Letters
Rachel Gurlin, Jaime A Giraldo, Esther Latres
Type 1 diabetes (T1D) is an autoimmune disorder in which the body's own immune system selectively attacks beta cells within pancreatic islets resulting in insufficient insulin production and loss of the ability to regulate blood glucose (BG) levels. Currently the standard of care consists of BG level monitoring and insulin administration, which are essential to avoiding the consequences of hyper- and hypoglycemia and long-term complications. Although recent advances in continuous glucose monitoring and automated insulin delivery systems have resulted in improved clinical outcomes for users, nearly 80 percent of people with T1D fail to achieve their target hemoglobin A1c (HbA1c) levels defined by the American Diabetes Association...
September 10, 2020: Tissue Engineering. Part B, Reviews
Ming Yu, Divyansh Agarwal, Laxminarayana Korutla, Catherine L May, Wei Wang, Negin Noorchashm Griffith, Bernhard J Hering, Klaus H Kaestner, Omaida C Velazquez, James F Markmann, Prashanth Vallabhajosyula, Chengyang Liu, Ali Naji
The intrahepatic milieu is inhospitable to intraportal islet allografts1-3 , limiting their applicability for the treatment of type 1 diabetes. Although the subcutaneous space represents an alternate, safe and easily accessible site for pancreatic islet transplantation, lack of neovascularization and the resulting hypoxic cell death have largely limited the longevity of graft survival and function and pose a barrier to the widespread adoption of islet transplantation in the clinic. Here we report the successful subcutaneous transplantation of pancreatic islets admixed with a device-free islet viability matrix, resulting in long-term euglycaemia in diverse immune-competent and immuno-incompetent animal models...
September 7, 2020: Nature metabolism
Jelena Kolic, Leanne Beet, Peter Overby, Haoning Howard Cen, Evgeniy Panzhinskiy, Daren R Ure, Jennifer L Cross, Robert B Huizinga, James D Johnson
The incidence of new onset diabetes after transplant (NODAT) has increased over the past decade, likely due to calcineurin inhibitor-based immunosuppressants, including tacrolimus (TAC) and cyclosporin (CsA). Voclosporin (VCS), a next generation calcineurin inhibitor is reported to cause fewer incidences of NODAT but the reason is unclear. Whilst calcineurin signaling plays important roles in pancreatic β-cell survival, proliferation, and function, its effects on human β-cells remain understudied. In particular, we do not understand why some calcineurin inhibitors have more profound effects on the incidence of NODAT...
September 7, 2020: Endocrinology
S A Safley, N S Kenyon, D M Berman, G F Barber, H Cui, S Duncanson, T De Toni, M Willman, P De Vos, A A Tomei, A Sambanis, N M Kenyon, C Ricordi, C J Weber
OBJECTIVE: Our goal was to assess the efficacy of encapsulated allogeneic islets transplanted in diabetic NOD mice and streptozotocin (STZ)-diabetic nonhuman primates (NHPs). MATERIALS AND METHODS: Murine or NHP islets were microencapsulated and transplanted in non-immunosuppressed mice or NHPs given clinically-acceptable immunosuppressive regimens, respectively. Two NHPs were treated with autologous mesenchymal stem cells (MSCs) and peri-transplant oxygen therapy...
August 2020: European Review for Medical and Pharmacological Sciences
Melena D Bellin, Ty B Dunn
Whole-organ pancreas and islet transplantations are performed in a highly selected group of patients with diabetes mellitus, primarily those with type 1 diabetes mellitus, complicated by recurrent severe hypoglycaemia or renal failure requiring kidney transplantation. Clinical accessibility to pancreases or islets, and patient characteristics and therapeutic goals, may dictate choice of procedure. Pancreas transplantation is most often performed simultaneous with a kidney transplant, but patients with particularly labile type 1 diabetes may be considered for a pancreas transplant alone...
October 2020: Diabetologia
Daniel W Clough, Jessica L King, Feiran Li, Lonnie D Shea
Cell-based therapies are emerging for Type I diabetes mellitus (T1D), an autoimmune disease characterized by the destruction of insulin producing pancreatic β-cells, as a means to provide long term restoration of glycemic control. Biomaterial scaffolds provide an opportunity to enhance the manufacturing and transplantation of islets or stem cell-derived β-cells. In contrast to encapsulation strategies that prevent host contact with the graft, recent approaches aim to integrate the transplant with the host to facilitate glucose sensing and insulin distribution, while also needing to modulate the immune response...
September 7, 2020: Endocrinology
Xing Yu Li, Po Sing Leung
Ferroptosis is a newly identified and novel form of cell death, which is characterized by an iron- and reactive oxygen species (ROS)-dependent manner. Potential utility of ferroptotic cell death has been recently proposed for cancer treatment. Meanwhile, ROS generation and apoptosis are inherently consequent to cell apoptosis and dysfunction during islet cell preparation and transplantation. Whether ferroptosis induction is a regulator for cell viability and function in human pancreatic islet-cell clusters (ICCs) derived from pancreatic progenitor cells (PPCs) remains elusive...
September 7, 2020: Cell Regeneration
Hirotake Komatsu, Nelson Gonzalez, Fouad Kandeel, Yoko Mullen
PURPOSE: Subcutaneous tissue is a promising site for cell transplantation; advantages include minimally invasive procedures and easy post-transplant monitoring. However, limited vascularity is the major known challenge. To address this challenge, a prevascularized graft bed is prepared in recipients. We aimed to establish an improved, clinically applicable approach to promote prevascularization of the subcutaneous graft bed prior to cell transplantation. METHODS: We applied a conventional prevascularization approach by subcutaneously implanting nylon discs into the backs of Lewis rats...
September 2, 2020: Microvascular Research
Min Jung Kim, Eun Young Lee, Young-Hye You, Hae Kyung Yang, Kun-Ho Yoon, Ji-Won Kim
For alternative sources of β cells, patient-specific induced pluripotent stem cells (iPSCs) could be promising, as cells derived from the "self" allow autologous transplantation. However, only a few studies have investigated insulin-producing cells (IPCs) using iPSCs of patients with type 1 diabetes (T1D). In this study, we generated IPCs using iPSCs derived from patients with T1D and type 2 diabetes (T2D) and compared them with IPCs from a non-diabetic (ND) individual. To facilitate differentiation of human iPSCs into IPCs, we induced PDX-1 gene expression using Ad-PDX-1/VP16...
August 18, 2020: Stem Cell Research
Gumpei Yoshimatsu, Mazhar A Kanak, Srividya Vasu, Kenjiro Kumano, Michael Lawrence, Nicholas Onaca, Morihito Takita, Marlon F Levy, Bashoo Naziruddin
Total pancreatectomy with islet autotransplantation (TPIAT) is a promising treatment for refractory chronic pancreatitis (CP). Pathological features of CP include progressive fibrosis in pancreas parenchyma, atrophy, and/or ductal occlusion. Complete acinar atrophy (CAA) caused by chronic fibrosis and necroinflammation results in exocrine sufficiency and may influence islet isolation characteristics during TPIAT. In this analysis of patients who underwent TPIAT at our center, we compared transplant outcomes among those with CAA ( n = 5) vs non-acinar atrophy (NAA; matching controls, n = 36)...
January 2020: Cell Transplantation
Yusuke Mochizuki, Ryo Kogawa, Ryuta Takegami, Kentaro Nakamura, Akira Wakabayashi, Tadashi Ito, Yasuhiro Yoshioka
The subcutaneous transplantation of microencapsulated islets has been extensively studied as a therapeutic approach for type I diabetes. However, due to the lower vascular density and strong inflammatory response in the subcutaneous area, there have been few reports of successfully normalized blood glucose levels. To address this issue, we developed mosaic-like aggregates comprised of mesenchymal stem cells (MSCs) and recombinant peptide pieces called MSC CellSaics, which provide a continuous release of angiogenic factors and anti-inflammatory cytokines...
August 31, 2020: Biomedicines
Yu Na Lee, Hye-Jin Yi, Yang Hee Kim, Song Lee, Jooyun Oh, Teruo Okano, In Kyong Shim, Song Cheol Kim
Islet cell transplantation is considered an ideal treatment for insulin-deficient diabetes, but implantation sites are limited and show low graft survival. Cell sheet technology and adipose-derived stem cells (ADSCs) can be useful tools for improving islet cell transplantation outcomes since both can increase implantation efficacy and graft survival. Herein, the optimal transplantation site in diabetic mice was investigated using islets and stem cell sheets. We constructed multi-layered cell sheets using rat/human islets and human ADSCs...
August 31, 2020: Cells
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