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encapsulated beta cell therapy

James F Markmann, Stephen T Bartlett, Paul Johnson, Olle Korsgren, Bernhard J Hering, David Scharp, Thomas W H Kay, Jonathan Bromberg, Jon S Odorico, Gordon C Weir, Nancy Bridges, Raja Kandaswamy, Peter Stock, Peter Friend, Mitsukazu Gotoh, David K C Cooper, Chung-Gyu Park, Philip J OʼConnell, Cherie Stabler, Shinichi Matsumoto, Barbara Ludwig, Pratik Choudhary, Boris Khovatchev, Michael R Rickels, Megan Sykes, Kathryn Wood, Kristy Kraemer, Albert Hwa, Edward Stanley, Camillo Ricordi, Mark Zimmerman, Julia Greenstein, Eduard Montanya, Timo Otonkoski
The International Pancreas and Islet Transplant Association (IPITA), in conjunction with the Transplantation Society (TTS), convened a workshop to consider the future of pancreas and islet transplantation in the context of potential competing technologies that are under development, including the artificial pancreas, transplantation tolerance, xenotransplantation, encapsulation, stem cell derived beta cells, beta cell proliferation, and endogenous regeneration. Separate workgroups for each topic and then the collective group reviewed the state of the art, hurdles to application, and proposed research agenda for each therapy that would allow widespread application...
July 2016: Transplantation
Stefano Focaroli, Gabriella Teti, Viviana Salvatore, Isabella Orienti, Mirella Falconi
Articular cartilage is a highly organized tissue with complex biomechanical properties. However, injuries to the cartilage usually lead to numerous health concerns and often culminate in disabling symptoms, due to the poor intrinsic capacity of this tissue for self-healing. Although various approaches are proposed for the regeneration of cartilage, its repair still represents an enormous challenge for orthopedic surgeons. The field of tissue engineering currently offers some of the most promising strategies for cartilage restoration, in which assorted biomaterials and cell-based therapies are combined to develop new therapeutic regimens for tissue replacement...
2016: Stem Cells International
Daniel Pipeleers, Bart Keymeulen
A recent study reported that encapsulation of human embryonic stem cell (hESC)-derived beta cells by a novel alginate formula protects against foreign body reactivity in immune-competent mice. Intraperitoneal implants corrected a diabetic state for at least 6 months. These observations will stimulate the development of alginate encapsulation towards novel cell therapy protocols for treating type 1 diabetes (T1DM).
May 2016: Trends in Endocrinology and Metabolism: TEM
Klearchos K Papas, Efstathios S Avgoustiniatos, Thomas M Suszynski
Beta-cell replacement therapy is a promising approach for the treatment of diabetes but is currently limited by the human islet availability and by the need for systemic immunosuppression. Tissue engineering approaches that will enable the utilization of islets or β-cells from alternative sources (such as porcine islets or human stem cell derived beta cells) and minimize or eliminate the need for immunosuppression have the potential to address these critical limitations. However, tissue engineering approaches are critically hindered by the device size (similar to the size of a large flat screen television) required for efficacy in humans...
March 2016: Panminerva Medica
Lei Yao, Xiao Gu, Qingxiang Song, Xiaolin Wang, Meng Huang, Meng Hu, Lina Hou, Ting Kang, Jun Chen, Hongzhuan Chen, Xiaoling Gao
Alzheimer's disease (AD), the most common form of dementia, is now representing one of the largest global healthcare challenges. However, an effective therapy is still lacking. Accumulation of amyloid-beta (Aβ) in the brain is supposed to trigger pathogenic cascades that eventually lead to AD. Therefore, Aβ clearance strategy is being actively pursued as a promising disease modifying therapy. Here, we found that α-mangostin (α-M), a polyphenolic xanthone derivative from mangosteen, up-regulated low density lipoprotein receptor (LDLR) expression in microglia and liver cells, and efficiently facilitated Aβ clearance...
March 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Arturo J Vegas, Omid Veiseh, Mads Gürtler, Jeffrey R Millman, Felicia W Pagliuca, Andrew R Bader, Joshua C Doloff, Jie Li, Michael Chen, Karsten Olejnik, Hok Hei Tam, Siddharth Jhunjhunwala, Erin Langan, Stephanie Aresta-Dasilva, Srujan Gandham, James J McGarrigle, Matthew A Bochenek, Jennifer Hollister-Lock, Jose Oberholzer, Dale L Greiner, Gordon C Weir, Douglas A Melton, Robert Langer, Daniel G Anderson
The transplantation of glucose-responsive, insulin-producing cells offers the potential for restoring glycemic control in individuals with diabetes. Pancreas transplantation and the infusion of cadaveric islets are currently implemented clinically, but these approaches are limited by the adverse effects of immunosuppressive therapy over the lifetime of the recipient and the limited supply of donor tissue. The latter concern may be addressed by recently described glucose-responsive mature beta cells that are derived from human embryonic stem cells (referred to as SC-β cells), which may represent an unlimited source of human cells for pancreas replacement therapy...
March 2016: Nature Medicine
Yu Guo, Jing Wang, Lu Zhang, Shunli Shen, Ruomi Guo, Yang Yang, Wenjie Chen, Yiru Wang, Guihua Chen, Xintao Shuai
UNLABELLED: Because the primary surgical treatment options for hepatocellular carcinoma (HCC)-including hepatic resection and liver transplantation-often fail due to recurrence and metastasis, identifying early prognostic biomarkers and therapeutic targets for HCC is of great importance. This study shows that transducin β-like protein 1-related protein (TBLR1) is a key HCC oncogene that plays important roles in HCC proliferation, antiapoptosis, and angiogenesis by regulating the Wnt/β-catenin pathway...
April 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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No abstract text is available yet for this article.
November 2015: Cardiovascular Journal of Africa
Seyed Jafar Hashemian, Marjan Kouhnavard, Ensieh Nasli-Esfahani
Type 1 diabetes mellitus (T1DM) is an autoimmune disorder that leads to beta cell destruction and lowered insulin production. In recent years, stem cell therapies have opened up new horizons to treatment of diabetes mellitus. Among all kinds of stem cells, mesenchymal stem cells (MSCs) have been shown to be an interesting therapeutic option based on their immunomodulatory properties and differentiation potentials confirmed in various experimental and clinical trial studies. In this review, we discuss MSCs differential potentials in differentiation into insulin-producing cells (IPCs) from various sources and also have an overview on currently understood mechanisms through which MSCs exhibit their immunomodulatory effects...
2015: Journal of Diabetes Research
R David Leslie, Jerry Palmer, Nanette C Schloot, Ake Lernmark
Diabetes is not a single homogeneous disease but composed of many diseases with hyperglycaemia as a common feature. Four factors have, historically, been used to identify this diversity: the age at onset; the severity of the disease, i.e. degree of loss of beta cell function; the degree of insulin resistance and the presence of diabetes-associated autoantibodies. Our broad understanding of the distinction between the two major types, type 1 diabetes mellitus and type 2 diabetes mellitus, are based on these factors, but it has become apparent that they do not precisely capture the different disease forms...
January 2016: Diabetologia
Stephan Lindsey, Joseph H Piatt, Peter Worthington, Cem Sönmez, Sameer Satheye, Joel P Schneider, Darrin J Pochan, Sigrid A Langhans
There is intense interest in developing novel methods for the sustained delivery of low levels of clinical therapeutics. MAX8 is a peptide-based beta-hairpin hydrogel that has unique shear thinning properties that allow for immediate rehealing after the removal of shear forces, making MAX8 an excellent candidate for injectable drug delivery at a localized injury site. The current studies examined the feasibility of using MAX8 as a delivery system for nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), two neurotrophic growth factors currently used in experimental treatments of spinal cord injuries...
September 14, 2015: Biomacromolecules
Giovanni Luca, Francesca Mancuso, Mario Calvitti, Iva Arato, Giulia Falabella, Antonello Bufalari, Valentina De Monte, Enrico Tresoldi, Claudio Nastruzzi, Giuseppe Basta, Francesca Fallarino, Cinzia Lilli, Catia Bellucci, Tiziano Baroni, Maria Chiara Aglietti, Stefano Giovagnoli, Don F Cameron, Maria Bodo, Riccardo Calafiore
BACKGROUND: Porcine Sertoli cells (pSCs) have been employed for cell therapy in pre-clinical studies for several chronic/immune diseases as they deliver molecules associated with trophic and anti-inflammatory effects. To be employed for human xenografts, pSCs products need to comply with safety and stability. To fulfill such requirements, we employed a microencapsulation technology to increase pre-transplant storage stability of specific pathogen-free pSCs (SPF-pSCs) and evaluated the in vivo long-term viability and safety of grafts...
July 2015: Xenotransplantation
Barbara Ludwig, Stefan Ludwig
BACKGROUND: Islet transplantation has become a valuable therapy for patients with diabetes mellitus type 1.However, only selected patients with exhausted insulin therapy characterized by instable metabolic control and repeated severe hypoglycemia are transplant candidates. This strict indication is mainly due to the requirement for lifelong immunosuppression and the critical shortage for donor organs. Therefore, numerous research activities address these issues in order to provide beta cell replacement therapy to a broader cohort of patients with diabetes...
July 2015: Langenbeck's Archives of Surgery
Robin M de Kruijff, Hubert T Wolterbeek, Antonia G Denkova
This review presents an overview of the successes and challenges currently faced in alpha radionuclide therapy. Alpha particles have an advantage in killing tumour cells as compared to beta or gamma radiation due to their short penetration depth and high linear energy transfer (LET). Touching briefly on the clinical successes of radionuclides emitting only one alpha particle, the main focus of this article lies on those alpha-emitting radionuclides with multiple alpha-emitting daughters in their decay chain...
2015: Pharmaceuticals
Thomas F Conway, Laura Hammer, Stacia Furtado, Edith Mathiowitz, Ferdinando Nicoletti, Katia Mangano, Nejat K Egilmez, Dominick L Auci
BACKGROUND AND AIMS: We investigated oral delivery of transforming growth factor beta 1 [TGFβ]- and all-trans retinoic acid [ATRA]-loaded microspheres as therapy for gut inflammation in murine models of inflammatory bowel disease [IBD]. METHODS: ATRA and TGFβ were separately encapsulated in poly [lactic-co-glycolic] acid or polylactic acid microspheres [respectively]. TGFβ was encapsulated using proprietary phase-inversion nanoencapsulation [PIN] technology. RESULTS: PIN particles provided sustained release of bioactive protein for at least 4 days and were stable for up to 52 weeks when stored at either 4(0)C or -20(0)C...
August 2015: Journal of Crohn's & Colitis
B R Blazar, R Flynn, R Lee, G Marcucci, M A Caliguiri, P S Heeger
Alloantibody, not primed T cells, is the major barrier to bone marrow (BM) engraftment in allosensitized mice. We have shown that a single intravenous injection of donor splenocytes, to mimic a blood transfusion, results in high, sustained levels of serum alloantibody sufficient to eliminate donor BM within 3 h, resulting in uniform mortality in lethally irradiated allogeneic recipients. Current studies focused preventing and treating allopriming. Blockade of B cell survival signals with mTACI-Ig pre- and postpriming was ineffective, as was the B cell but not plasma cell depleting anti-CD20 mAb...
April 2015: American Journal of Transplantation
Siyi Fu, Fei Wang, Yan Cao, Qi Huang, Junjie Xiao, Changqing Yang, Laurentiu M Popescu
Liver fibrosis is a wound-healing response which engages a variety of cell types to encapsulate injury. Telocyte (TC), a novel type of interstitial cell, has been identified in a variety of tissues and organs including liver. TCs have been reported to be reduced in fibrotic areas after myocardial infarction, human interstitial wall's fibrotic remodelling caused either by ulcerative colitis or Crohn's disease, and skin of systemic sclerosis. However, the role of TCs in human liver fibrosis remains unclear. Liver samples from human liver biopsy were collected...
March 2015: Journal of Cellular and Molecular Medicine
Deborah J Gorth, Katherine E Lothstein, Joseph A Chiaro, Megan J Farrell, George R Dodge, Dawn M Elliott, Neil R Malhotra, Robert L Mauck, Lachlan J Smith
Degeneration of the intervertebral discs is strongly implicated as a cause of low back pain. Since current treatments for discogenic low back pain show poor long-term efficacy, a number of new biological strategies are being pursued. For such therapies to succeed, it is critical that they be validated in conditions that mimic the unique biochemical microenvironment of the nucleus pulposus (NP), which include low oxygen tension. Therefore, the objective of this study was to investigate the effects of oxygen tension on NP cell functional extracellular matrix elaboration in 3D culture...
May 2015: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Manju Saraswathy, Gavin T Knight, Srikanth Pilla, Randolph S Ashton, Shaoqin Gong
Polyamidoamine (PAMAM) dendrimer was conjugated with both carboxymethyl-β-cyclodextrin (βCD) and poly(ethylene glycol) (PEG). Cyclic RGD peptide, used as a tumor targeting ligand, was then selectively conjugated onto the distal ends of the PEG arms. The resulting βCD-PAMAM-PEG-cRGD polymer was able to form stable and uniform nanoparticles (NPs) in aqueous solution. Doxorubicin (Dox), a model hydrophobic anticancer drug, was effectively encapsulated in the NPs via an inclusion complex formed between the drug and βCD...
February 1, 2015: Colloids and Surfaces. B, Biointerfaces
Jong-Suep Baek, Cheong-Weon Cho
Paclitaxel (PTX) has been used in the treatment of wide range of cancers but its entry into cancer cell is restricted by p-glycoprotein (p-gp). Also, it was reported that verapamil (VP) could inhibit p-gp efflux. Hence, three kinds of solid lipid nanoparticles (SLN) such as PVS (PTX and VP co-loaded SLN), PSV (PTX loaded SLN, later added VP) and PVSV (PTX and VP co-loaded SLN, later added VP) were prepared to overcome MDR by combination of PTX and VP. PVS was the SLN loaded with both PTX and VP at the same time...
January 30, 2015: International Journal of Pharmaceutics
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