Roya Karimi, Zahra Barabadi, Bagher Larijani, Gholamreza Tavoosidana, Nasrin Lotfibakhshaiesh, Moloud Absalan, Zahra Jabbarpour, Seyed Naser Ostad, Jafar Ai
Type 1 diabetes is a metabolic disorder caused by the loss or dysfunction of β-cellsin the pancreas. Organ shortage is a critical concern ofdiabetic patients in need of beta islet transplantation. Tissue engineered islets are promising alternatives to traditional organ transplantation. Recent progress in stem cell biology and gene cloning techniques hasraised hopes for the generation of insulin producing cells (IPCs) without the need of immunosuppression.The purpose of this study was to produce insulin producing cells (IPCs) using human adipose-derived stem cells (hADSCs) and human endometrial-derivedstem cells (hEnSCs) and also to compare the level of insulin secretion by these cells in 2D and 3D culture systems on fibrin scaffolding...
August 30, 2020: Journal of Biomedical Materials Research. Part A
Virginie F Coindre, Sean M Kinney, Michael V Sefton
Subcutaneous devices can be used to house therapeutic cells such as pancreatic islets so that the cells can be retrieved. However, a high number of cells may be required to reverse diabetes, since a portion of the graft can be lost after transplantation due to ischemia and therefore the right device design is important. Increasing the vascularity of the subcutaneous space prior to cell transplantation is a strategic goal for cell transplantation, as it promotes islet survival, glucose-sensing and insulin secretion...
August 15, 2020: Biomaterials
Bushra Memon, Ihab Younis, Fadhil Abubaker, Essam M Abdelalim
AIM: Beta cell replacement strategies are a promising alternative for diabetes treatment. Human pluripotent stem cells (hPSCs) serve as a scalable source for producing insulin- secreting cells for transplantation therapy. We recently generated novel hPSC-derived pancreatic progenitors, expressing high levels of the transcription factor NKX6.1, in the absence of PDX1 (PDX1- /NKX6.1+ ). Herein, our aim was to characterize this novel population and assess its ability to differentiate into insulin-secreting beta cells in vitro...
August 28, 2020: Diabetes/metabolism Research and Reviews
Suryo Kuncorojakti, Watchareewan Rodprasert, Supansa Yodmuang, Thanaphum Osathanon, Prasit Pavasant, Sayamon Srisuwatanasagul, Chenphop Sawangmake
Background: Current approach for diabetes treatment remained several adverse events varied from gastrointestinal to life-threatening symptoms. Regenerative therapy regarding Edmonton protocol has been facing serious limitations involving protocol efficiency and safety. This led to the study for alternative insulin-producing cell (IPC) resource and transplantation platform. In this study, evaluation of encapsulated human dental pulp-derived stem cell (hDPSC)-derived IPCs by alginate (ALG) and pluronic F127-coated alginate (ALGPA) was performed...
2020: Journal of Biological Engineering
Thomas Pomposelli, Ping Wang, Kazuhiro Takeuchi, Katsunori Miyake, Yuichi Ariyoshi, Hironosuke Watanabe, Chen Xiaojuan, Akira Shimizu, Neil Robertson, Kazuhiko Yamada, Anna Moore
The long-term success of pancreatic islet transplantation (Tx) as a cure for type 1 diabetes remains limited. Islet loss after Tx related to apoptosis, inflammation and other factors continues to limit its efficacy. In this project we demonstrate a novel approach aimed at protection of islets prior to Tx in non-human primates (NHP, baboons) by silencing a gene (caspase 3) responsible for induction of apoptosis. This was done using small interfering RNA (siRNA, siCas-3) conjugated to magnetic nanoparticles (MN)...
August 27, 2020: Diabetes
Charles-Henri Wassmer, Fanny Lebreton, Kevin Bellofatto, Domenico Bosco, Thierry Berney, Ekaterine Berishvili
Diabetes is a major health issue of increasing prevalence. ß-cell replacement, by pancreas or islet transplantation, is the only long-term curative option for patients with insulin-dependent diabetes. Despite good functional results, pancreas transplantation remains a major surgery with potentially severe complications. Islet transplantation is a minimally invasive alternative that can widen the indications in view of its lower morbidity. However, the islet isolation procedure disrupts their vasculature and connection to the surrounding extracellular matrix, exposing them to ischemia and anoikis...
August 27, 2020: Transplant International
Raphael P H Meier, Jeremy Meyer, Yannick D Muller, Gregory L Szot, Benoît Bédat, Axel Andres, Nathalie Massé, Sandrine Lablanche, Giacomo Puppa, Domenico Bosco, Thierry Berney
BACKGROUND: The success of pancreas islet isolation largely depends on donor characteristics, including extracellular matrix composition of which collagen is the main element. We hypothesized that isolation yields are proportional to collagen digestion percentage, and aimed to determine a threshold that predicts isolation success. METHODS: The amount of pancreas collagen (I-V) was determined prior to and after the digestion process in 52 human islet isolations. Collagen I-V and VI were assessed histologically...
August 27, 2020: Transplant International
Seiichiro Tada, Takayuki Anazawa, Takero Shindo, Kei Yamane, Kenta Inoguchi, Nanae Fujimoto, Kazuyuki Nagai, Toshihiko Masui, Hideaki Okajima, Kyoichi Takaori, Shoichiro Sumi, Shinji Uemoto
Background: Potential adverse effects, such as functional impairment of islets, render conventional immunosuppressive drugs unsuitable for use in islet transplantation. In addition, as a single therapy, they cannot prolong islet allograft survival. Here, we investigated the utility of the mitogen-activated protein kinase inhibitor trametinib and asked whether it ameliorates acute rejection of transplanted islets without the need for conventional immunosuppressants. Methods: Islets from fully major histocompatibility complex-mismatched BALB/c mice were transplanted into streptozotocin-induced diabetic C57BL/6 mice via the portal vein...
September 2020: Transplantation Direct
Punn Augsornworawat, Kristina G Maxwell, Leonardo Velazco-Cruz, Jeffrey R Millman
Human pluripotent stem cells differentiated to insulin-secreting β cells (SC-β cells) in islet organoids could provide an unlimited cell source for diabetes cell replacement therapy. However, current SC-β cells generated in vitro are transcriptionally and functionally immature compared to native adult β cells. Here, we use single-cell transcriptomic profiling to catalog changes that occur in transplanted SC-β cells. We find that transplanted SC-β cells exhibit drastic transcriptional changes and mature to more closely resemble adult β cells...
August 25, 2020: Cell Reports
Mitchell H Maloy, Matthew A Ferrer, Natesh Parashurama
Type 1 diabetes mellitus (T1DM) is an autoimmune disease that results from the loss of the pancreatic β-cells. The autoimmune destruction of the β-cells causes the loss of insulin production from the islets of the pancreas, resulting in the loss of blood glucose regulation. This loss of regulation, if not treated, can lead to a plethora of long-term complications in patients. Subsequently, T1DM patients rely on the administration of exogenous insulin sources to maintain their blood glucose levels. In this review, we summarize the history of T1DM therapy and current treatment options...
August 26, 2020: Stem cell reviews and reports
Gurvinder Kaur, Kandis Wright, Payal Mital, Taylor Hibler, Jonathan M Miranda, Lea Ann Thompson, Katelyn Halley, Jannette M Dufour
The acute cell-mediated immune response presents a significant barrier to xenotransplantation. Immune-privileged Sertoli cells (SC) can prolong the survival of co-transplanted cells including xenogeneic islets, hepatocytes, and neurons by protecting them from immune rejection. Additionally, SC survive as allo- and xenografts without the use of any immunosuppressive drugs suggesting elucidating the survival mechanism(s) of SC could be used to improve survival of xenografts. In this study, the survival and immune response generated toward neonatal pig SC (NPSC) or neonatal pig islets (NPI), nonimmune-privileged controls, was compared after xenotransplantation into naïve Lewis rats without immune suppression...
January 2020: Cell Transplantation
Hasaan Hayat, Aixia Sun, Hanaan Hayat, Sihai Liu, Nazanin Talebloo, Cody Pinger, Jack Owen Bishop, Mithil Gudi, Bennett Francis Dwan, Xiaohong Ma, Yanfeng Zhao, Anna Moore, Ping Wang
PURPOSE: Current approaches to quantification of magnetic particle imaging (MPI) for cell-based therapy are thwarted by the lack of reliable, standardized methods of segmenting the signal from background in images. This calls for the development of artificial intelligence (AI) systems for MPI analysis. PROCEDURES: We utilize a canonical algorithm in the domain of unsupervised machine learning, known as K-means++, to segment the regions of interest (ROI) of images and perform iron quantification analysis using a standard curve model...
August 24, 2020: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Kayleigh L Thirlwell, David Colligan, Joanne C Mountford, Kay Samuel, Laura Bailey, Nerea Cuesta-Gomez, Kay D Hewit, Christopher J Kelly, Christopher C West, Neil W A McGowan, John J Casey, Gerard J Graham, Marc L Turner, Shareen Forbes, John D M Campbell
BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) isolated from various tissues are under investigation as cellular therapeutics in a wide range of diseases. It is appreciated that the basic biological functions of MSCs vary depending on tissue source. However, in-depth comparative analyses between MSCs isolated from different tissue sources under Good Manufacturing Practice (GMP) conditions are lacking. Human clinical-grade low-purity islet (LPI) fractions are generated as a byproduct of islet isolation for transplantation...
August 19, 2020: Cytotherapy
Sara J Photiadis, Rebecca C Gologorsky, Deepika Sarode
Type 1 diabetes mellitus is a common and highly morbid disease for which there is no cure. Treatment primarily involves exogenous insulin administration, and, under specific circumstances, islet or pancreas transplantation. However, insulin replacement alone fails to replicate the endocrine function of the pancreas and does not provide durable euglycemia. In addition, transplantation requires lifelong use of immunosuppressive medications, which has deleterious side effects, is expensive, and is inappropriate for use in adolescents...
August 19, 2020: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
Ryo Kogawa, Kentaro Nakamura, Yusuke Mochizuki
Microencapsulated islet transplantation was widely studied as a promising treatment for type 1 diabetes mellitus. However, micro-encapsulated islet transplantation has the following problems-early dysfunction of the islets due to the inflammatory reaction at the transplantation site, and hyponutrition and hypoxia due to a lack of blood vessels around the transplantation site, and difficulty in removal of the islets. On the other hand, we proposed a cell transplantation technique called CellSaic, which was reported to enhance the vascular induction effect of mesenchymal stem cells (MSCs) in CellSaic form, and to enhance the effect of islet transplantation through co-transplantation...
August 21, 2020: Biomedicines
Rashmi K Ambasta, Krishna Adeshara, Shivangi Yadav, Pravir Kumar
AIM/HYPOTHESIS: Diabetes is a hyperglycaemic disease treated by a set of allopathic drugs and natural biomolecules along with many variety of stem cell. We aim to investigate the role of these drugs in targeting common protein molecule in diabetes and its associated disease. We also aim to investigate the organ degeneration mechanistic pathway in diabetes. METHOD: We have generated diabetes using streptozotocin injection and treated them using bone marrow transplantation and curcumin administration...
September 3, 2020: Biochemical and Biophysical Research Communications
Aaron Yl Liew, Elizabeth Holmes-Truscott, Anneliese Js Flatt, Denise Bennett, Robert Crookston, Mirka Pimkova, Linda Birtles, John Casey, Andrew Pernet, Ruth C Wood, Pratik Choudhary, Shareen Forbes, Martin K Rutter, Miranda Rosenthal, Paul Johnson, James Am Shaw, Jane Speight
The psychological burden experienced by people with diabetes prior to islet transplantation is recognized but has not been studied comprehensively, especially in relation to glycemia. Therefore, we conducted a rigorous pre-operative psychosocial profile of UK islet transplant recipients, and compared groups with higher/lower HbA1 c to test the null hypothesis that pre-transplant hypoglycemia awareness and psychosocial burden would not be related to baseline HbA1 c in this high-risk cohort. Pre-transplant, recipients (n = 44) completed validated hypoglycemia awareness questionnaires and generic/diabetes-specific measures of psychological traits and states...
August 20, 2020: Islets
Jun Kit Wang, Nicole Mein Ji Cheam, Scott Alexander Irvine, Nguan Soon Tan, Subbu Venkatraman, Chor Yong Tay
Transplantation of microencapsulated islet cells holds great potential for the treatment of type 1 diabetes mellitus. However, its clinical translation is hampered by the peri-transplantation loss of islet viability and functionality in the microcapsules. In this work, a novel islet cells biomimetic microencapsulant material that is based on the interpenetrating networks of alginate and extracellular matrix (ECM) hydrogel composite (AEC) is presented. The ECM component is derived from human lipoaspirate. In situ encapsulation of pancreatic β islet cells (MIN6 β-cells) can be achieved via ionotropic gelation of the alginate matrix and thermal-induced gelation of the pepsin-solubilized ECM pre-gel...
August 19, 2020: Macromolecular Rapid Communications
Eiji Yoshihara, Carolyn O'Connor, Emanuel Gasser, Zong Wei, Tae Gyu Oh, Tiffany W Tseng, Dan Wang, Fritz Cayabyab, Yang Dai, Ruth T Yu, Christopher Liddle, Annette R Atkins, Michael Downes, Ronald M Evans
Islets derived from stem cells hold promise as a therapy for insulin-dependent diabetes, but there remain challenges towards achieving this goal1-6 . Here we generate human islet-like organoids (HILOs) from induced pluripotent stem cells and show that non-canonical WNT4 signalling drives the metabolic maturation necessary for robust ex vivo glucose-stimulated insulin secretion. These functionally mature HILOs contain endocrine-like cell types that, upon transplantation, rapidly re-establish glucose homeostasis in diabetic NOD/SCID mice...
August 19, 2020: Nature
Xiaojie Ni, Ziqiang Xu, Jinjun Wang, Shaoling Zheng, Yong Cai
OBJECTIVES: Islet transplantation has been proved to be effective in delaying early stage of DN. This study was established to observe the mechanism of islet transplantation on early diabetic nephropathy (DN). METHOD: The diabetes mellitus (DM) rat model was established by an injection of a single-dose streptozotocin. According to the treatment, the rats were randomly divided into 4 groups: the untreated DN rats (DN group); the C-peptide treated rats (CP group); the islet transplanted rats (IT group); the normal control rats (NC group)...
August 13, 2020: Transplant Immunology
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