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Li M, Itoh A, Xi J, Yu C, Wu Y, Ridgway WM, Liu H. Enhancing Antigen Presentation and Inducing Antigen-Specific Immune Tolerance with Amphiphilic Peptides. THE JOURNAL OF IMMUNOLOGY 2021; 207:2051-2059. [PMID: 34526376 DOI: 10.4049/jimmunol.1901301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 08/06/2021] [Indexed: 11/19/2022]
Abstract
Ag-specific immunotherapy to restore immune tolerance to self-antigens, without global immune suppression, is a long-standing goal in the treatment of autoimmune disorders such as type 1 diabetes (T1D). However, vaccination with autoantigens such as insulin or glutamic acid decarboxylase have largely failed in human T1D trials. Induction and maintenance of peripheral tolerance by vaccination requires efficient autoantigen presentation by APCs. In this study, we show that a lipophilic modification at the N-terminal end of CD4+ epitopes (lipo-peptides) dramatically improves peptide Ag presentation. We designed amphiphilic lipo-peptides to efficiently target APCs in the lymph nodes by binding and trafficking with endogenous albumin. Additionally, we show that lipophilic modification anchors the peptide into the membranes of APCs, enabling a bivalent cell-surface Ag presentation. The s.c. injected lipo-peptide accumulates in the APCs in the lymph node, enhances the potency and duration of peptide Ag presentation by APCs, and induces Ag-specific immune tolerance that controls both T cell- and B cell-mediated immunity. Immunization with an amphiphilic insulin B chain 9-23 peptide, an immunodominant CD4+ T cell epitope in NOD mice, significantly suppresses the activation of T cells, increases inhibitory cytokine production, induces regulatory T cells, and delays the onset and lowers the incidence of T1D. Importantly, treatment with a lipophilic β-cell peptide mixture delays progression to end-stage diabetes in acutely diabetic NOD mice, whereas the same doses of standard soluble peptides were not effective. Amphiphilic modification effectively enhances Ag presentation for peptide-based immune regulation of autoimmune diseases.
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Affiliation(s)
- Meng Li
- Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI
| | - Arata Itoh
- Division of Rheumatology, Allergy, and Clinical Immunology, University of California, Davis, Davis, CA
| | - Jingchao Xi
- Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI
| | - Chunsong Yu
- Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI
| | - Yuehong Wu
- Division of Rheumatology, Allergy, and Clinical Immunology, University of California, Davis, Davis, CA
| | - William M Ridgway
- Division of Rheumatology, Allergy, and Clinical Immunology, University of California, Davis, Davis, CA
| | - Haipeng Liu
- Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI; .,Department of Oncology, Wayne State University, Detroit, MI; and.,Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, MI
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2
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Forget A, Rojas D, Waibel M, Pencko D, Gunenthiran S, Ninan N, Loudovaris T, Drogemuller C, Coates PT, Voelcker NH, Blencowe A. Facile preparation of tissue engineering scaffolds with pore size gradients using the muesli effect and their application to cell spheroid encapsulation. J Biomed Mater Res B Appl Biomater 2020; 108:2495-2504. [DOI: 10.1002/jbm.b.34581] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 10/14/2019] [Accepted: 01/25/2020] [Indexed: 12/20/2022]
Affiliation(s)
- Aurelien Forget
- School of Pharmacy and Medical ScienceUniversity of South Australia Adelaide South Australia Australia
- Institute for Macromolecular ChemistryUniversity of Freiburg Freiburg Germany
| | - Darling Rojas
- The Centre for Clinical and Experimental Transplantation (CCET)The Royal Adelaide Hospital Adelaide South Australia Australia
| | - Michaela Waibel
- Immunology and Diabetes UnitSt Vincent's Institute of Medical Research Fitzroy Victoria Australia
| | - Daniella Pencko
- The Centre for Clinical and Experimental Transplantation (CCET)The Royal Adelaide Hospital Adelaide South Australia Australia
- Faculty of Health and Medical Sciences, School of MedicineThe University of Adelaide Adelaide South Australia Australia
| | - Satyathiran Gunenthiran
- School of Pharmacy and Medical ScienceUniversity of South Australia Adelaide South Australia Australia
- Future Industries InstituteUniversity of South Australia Mawson Lakes South Australia Australia
| | - Neethu Ninan
- School of Pharmacy and Medical ScienceUniversity of South Australia Adelaide South Australia Australia
- Future Industries InstituteUniversity of South Australia Mawson Lakes South Australia Australia
| | - Thomas Loudovaris
- Immunology and Diabetes UnitSt Vincent's Institute of Medical Research Fitzroy Victoria Australia
| | - Chris Drogemuller
- The Centre for Clinical and Experimental Transplantation (CCET)The Royal Adelaide Hospital Adelaide South Australia Australia
- Faculty of Health and Medical Sciences, School of MedicineThe University of Adelaide Adelaide South Australia Australia
| | - Patrick T. Coates
- The Centre for Clinical and Experimental Transplantation (CCET)The Royal Adelaide Hospital Adelaide South Australia Australia
- Faculty of Health and Medical Sciences, School of MedicineThe University of Adelaide Adelaide South Australia Australia
| | - Nicolas H. Voelcker
- Future Industries InstituteUniversity of South Australia Mawson Lakes South Australia Australia
- CSIRO Manufacturing Clayton Victoria Australia
- Monash Institute of Pharmaceutical SciencesMonash University Parkville Victoria Australia
| | - Anton Blencowe
- School of Pharmacy and Medical ScienceUniversity of South Australia Adelaide South Australia Australia
- Future Industries InstituteUniversity of South Australia Mawson Lakes South Australia Australia
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3
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Paving the way for successful islet encapsulation. Drug Discov Today 2019; 24:737-748. [PMID: 30738185 DOI: 10.1016/j.drudis.2019.01.020] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 12/13/2018] [Accepted: 01/29/2019] [Indexed: 01/02/2023]
Abstract
Type 1 diabetes mellitus (T1DM) is a disorder that decimates pancreatic β-cells which produce insulin. Direct pancreatic islet transplantation cannot serve as a widespread therapeutic modality owing to the need for lifelong immunosuppression and donor shortage. Therefore, several encapsulation techniques have been developed to enclose the islets in semipermeable vehicles that will allow oxygen and nutrient input as well as insulin, other metabolites and waste output, while accomplishing immunoisolation. Although encapsulation technology continues to face significant obstacles, recent advances in material science, stem cell biology and immunology potentially serve as pathways to success. This review summarizes the accomplishments of the past 5 years.
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4
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Numerical investigation of selective withdrawal in a pancreatic cell islet encapsulation apparatus. Comput Chem Eng 2018. [DOI: 10.1016/j.compchemeng.2018.09.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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5
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Rojas-Canales DM, Waibel M, Forget A, Penko D, Nitschke J, Harding FJ, Delalat B, Blencowe A, Loudovaris T, Grey ST, Thomas HE, Kay TWH, Drogemuller CJ, Voelcker NH, Coates PT. Oxygen-permeable microwell device maintains islet mass and integrity during shipping. Endocr Connect 2018; 7:490-503. [PMID: 29483160 PMCID: PMC5861371 DOI: 10.1530/ec-17-0349] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Accepted: 02/26/2018] [Indexed: 01/05/2023]
Abstract
Islet transplantation is currently the only minimally invasive therapy available for patients with type 1 diabetes that can lead to insulin independence; however, it is limited to only a small number of patients. Although clinical procedures have improved in the isolation and culture of islets, a large number of islets are still lost in the pre-transplant period, limiting the success of this treatment. Moreover, current practice includes islets being prepared at specialized centers, which are sometimes remote to the transplant location. Thus, a critical point of intervention to maintain the quality and quantity of isolated islets is during transportation between isolation centers and the transplanting hospitals, during which 20-40% of functional islets can be lost. The current study investigated the use of an oxygen-permeable PDMS microwell device for long-distance transportation of isolated islets. We demonstrate that the microwell device protected islets from aggregation during transport, maintaining viability and average islet size during shipping.
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Affiliation(s)
- Darling M Rojas-Canales
- The Centre for Clinical and Experimental Transplantation (CCET) The Royal Adelaide HospitalAdelaide, South Australia, Australia
- Cooperative Research Centre for Cell Therapy Manufacturing (CRC-CTM)Adelaide, South Australia, Australia
- Department of MedicineFaculty of Health and Medical Sciences, University of Adelaide, South Australia, Australia
| | - Michaela Waibel
- Cooperative Research Centre for Cell Therapy Manufacturing (CRC-CTM)Adelaide, South Australia, Australia
- St Vincent's Institute of Medical ResearchFitzroy, Victoria, Australia
- The University of MelbourneDepartment of Medicine, St. Vincent's Hospital, Fitzroy, Victoria, Australia
| | - Aurelien Forget
- Science and Engineering FacultyQueensland University of Technology, Brisbane, Queensland, Australia
| | - Daniella Penko
- The Centre for Clinical and Experimental Transplantation (CCET) The Royal Adelaide HospitalAdelaide, South Australia, Australia
- Cooperative Research Centre for Cell Therapy Manufacturing (CRC-CTM)Adelaide, South Australia, Australia
- Department of MedicineFaculty of Health and Medical Sciences, University of Adelaide, South Australia, Australia
| | - Jodie Nitschke
- The Centre for Clinical and Experimental Transplantation (CCET) The Royal Adelaide HospitalAdelaide, South Australia, Australia
- Cooperative Research Centre for Cell Therapy Manufacturing (CRC-CTM)Adelaide, South Australia, Australia
- Department of MedicineFaculty of Health and Medical Sciences, University of Adelaide, South Australia, Australia
| | - Fran J Harding
- Cooperative Research Centre for Cell Therapy Manufacturing (CRC-CTM)Adelaide, South Australia, Australia
- Future Industries InstituteUniversity of South Australia, Mawson Lakes, South Australia, Australia
| | - Bahman Delalat
- Cooperative Research Centre for Cell Therapy Manufacturing (CRC-CTM)Adelaide, South Australia, Australia
- Future Industries InstituteUniversity of South Australia, Mawson Lakes, South Australia, Australia
| | - Anton Blencowe
- Cooperative Research Centre for Cell Therapy Manufacturing (CRC-CTM)Adelaide, South Australia, Australia
- Future Industries InstituteUniversity of South Australia, Mawson Lakes, South Australia, Australia
- School of Pharmacy and Medical SciencesUniversity of South Australia, Adelaide, South Australia, Australia
| | - Thomas Loudovaris
- Cooperative Research Centre for Cell Therapy Manufacturing (CRC-CTM)Adelaide, South Australia, Australia
- St Vincent's Institute of Medical ResearchFitzroy, Victoria, Australia
| | - Shane T Grey
- The Centre for Clinical and Experimental Transplantation (CCET) The Royal Adelaide HospitalAdelaide, South Australia, Australia
- Transplantation Immunology GroupGarvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
| | - Helen E Thomas
- Cooperative Research Centre for Cell Therapy Manufacturing (CRC-CTM)Adelaide, South Australia, Australia
- St Vincent's Institute of Medical ResearchFitzroy, Victoria, Australia
- The University of MelbourneDepartment of Medicine, St. Vincent's Hospital, Fitzroy, Victoria, Australia
| | - Thomas W H Kay
- Cooperative Research Centre for Cell Therapy Manufacturing (CRC-CTM)Adelaide, South Australia, Australia
- St Vincent's Institute of Medical ResearchFitzroy, Victoria, Australia
- The University of MelbourneDepartment of Medicine, St. Vincent's Hospital, Fitzroy, Victoria, Australia
| | - Chris J Drogemuller
- The Centre for Clinical and Experimental Transplantation (CCET) The Royal Adelaide HospitalAdelaide, South Australia, Australia
- Cooperative Research Centre for Cell Therapy Manufacturing (CRC-CTM)Adelaide, South Australia, Australia
- Department of MedicineFaculty of Health and Medical Sciences, University of Adelaide, South Australia, Australia
| | - Nicolas H Voelcker
- Future Industries InstituteUniversity of South Australia, Mawson Lakes, South Australia, Australia
- Monash Institute of Pharmaceutical SciencesMonash University, Parkville, Victoria, Australia
| | - Patrick T Coates
- The Centre for Clinical and Experimental Transplantation (CCET) The Royal Adelaide HospitalAdelaide, South Australia, Australia
- Cooperative Research Centre for Cell Therapy Manufacturing (CRC-CTM)Adelaide, South Australia, Australia
- Department of MedicineFaculty of Health and Medical Sciences, University of Adelaide, South Australia, Australia
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Abstract
The promise of pancreatic islet transplantation is hindered by organ shortage, and the need for immunosuppression of transplant recipient in order to prevent rejection. Alginate microencapsulation can overcome these hurdles; however further optimization of this technique is required. Among the critical factors to be optimized is the durability of alginate microcapsules, which can be determined by their mechanical strength tests. Here we describe several simple and reliable methods to assist in assessing the mechanical strength of alginate beads.
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Wiles K, Fishman JM, De Coppi P, Birchall MA. The Host Immune Response to Tissue-Engineered Organs: Current Problems and Future Directions. TISSUE ENGINEERING PART B-REVIEWS 2016; 22:208-19. [DOI: 10.1089/ten.teb.2015.0376] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
| | | | | | - Martin A. Birchall
- UCL Ear Institute & Royal National Throat, Nose and Ear Hospital, London, United Kingdom
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8
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Zhu HT, Lu L, Liu XY, Yu L, Lyu Y, Wang B. Treatment of diabetes with encapsulated pig islets: an update on current developments. J Zhejiang Univ Sci B 2016; 16:329-43. [PMID: 25990050 DOI: 10.1631/jzus.b1400310] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
The potential use of allogeneic islet transplantation in curing type 1 diabetes mellitus has been adequately demonstrated, but its large-scale application is limited by the short supply of donor islets and the need for sustained and heavy immunosuppressive therapy. Encapsulation of pig islets was therefore suggested with a view to providing a possible alternative source of islet grafts and avoiding chronic immunosuppression and associated adverse or toxic effects. Nevertheless, several vital elements should be taken into account before this therapy becomes a clinical reality, including cell sources, encapsulation approaches, and implantation sites. This paper provides a comprehensive review of xenotransplantation of encapsulated pig islets for the treatment of type 1 diabetes mellitus, including current research findings and suggestions for future studies.
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Affiliation(s)
- Hai-tao Zhu
- Heart Center, Northwest Women's and Children's Hospital, Xi'an 710061, China; Department of Hepatobiliary Surgery, the First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an 710061, China; Department of Hand Surgery, China-Japan Union Hospital, Norman Bethune Health Science Center, Jilin University, Changchun 130033, China; Institute of Advanced Surgical Technology and Engineering, Xi'an Jiaotong University, Xi'an 710061, China
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Zhu H, Yu L, He Y, Lyu Y, Wang B. Microencapsulated Pig Islet Xenotransplantation as an Alternative Treatment of Diabetes. TISSUE ENGINEERING PART B-REVIEWS 2015; 21:474-89. [PMID: 26028249 DOI: 10.1089/ten.teb.2014.0499] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Haitao Zhu
- Department of Hepatobiliary Surgery, First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an, China
- Heart Center, Northwest Women's and Children's Hospital, Xi'an, China
| | - Liang Yu
- Department of Hepatobiliary Surgery, First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an, China
| | - Yayi He
- Department of Endocrinology, First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an, China
| | - Yi Lyu
- Department of Hepatobiliary Surgery, First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an, China
- Institute of Advanced Surgical Technology and Engineering, Xi'an Jiaotong University, Xi'an, China
| | - Bo Wang
- Department of Hepatobiliary Surgery, First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an, China
- Institute of Advanced Surgical Technology and Engineering, Xi'an Jiaotong University, Xi'an, China
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10
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Nyitray CE, Chang R, Faleo G, Lance KD, Bernards DA, Tang Q, Desai T. Polycaprolactone Thin-Film Micro- and Nanoporous Cell-Encapsulation Devices. ACS NANO 2015; 9:5675-82. [PMID: 25950860 PMCID: PMC4628825 DOI: 10.1021/acsnano.5b00679] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
Cell-encapsulating devices can play an important role in advancing the types of tissue available for transplantation and further improving transplant success rates. To have an effective device, encapsulated cells must remain viable, respond to external stimulus, and be protected from immune responses, and the device itself must elicit a minimal foreign body response. To address these challenges, we developed a micro- and a nanoporous thin-film cell encapsulation device from polycaprolactone (PCL), a material previously used in FDA-approved biomedical devices. The thin-film device construct allows long-term bioluminescent transfer imaging, which can be used for monitoring cell viability and device tracking. The ability to tune the microporous and nanoporous membrane allows selective protection from immune cell invasion and cytokine-mediated cell death in vitro, all while maintaining typical cell function, as demonstrated by encapsulated cells' insulin production in response to glucose stimulation. To demonstrate the ability to track, visualize, and monitor the viability of cells encapsulated in implanted thin-film devices, we encapsulated and implanted luciferase-positive MIN6 cells in allogeneic mouse models for up to 90 days. Lack of foreign body response in combination with rapid neovascularization around the device shows promise in using this technology for cell encapsulation. These devices can help elucidate the metrics required for cell encapsulation success and direct future immune-isolation therapies.
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Affiliation(s)
- Crystal E. Nyitray
- Program in Chemistry and Chemical Biology, University of California, San Francisco, 1700 4th Street, Byers Hall, Box 2520, San Francisco, California 94158, United States
| | - Ryan Chang
- UCB/UCSF Joint Program in Bioengineering, University of California, San Francisco, 1700 4th Street, Byers Hall, Box 2520, San Francisco, California 94158, United States
| | - Gaetano Faleo
- Department of Surgery, University of California, San Francisco, 513 Parnassus Avenue HSE520 Box 0780, San Francisco, California 94143, United States
| | - Kevin D. Lance
- UCB/UCSF Joint Program in Bioengineering, University of California, San Francisco, 1700 4th Street, Byers Hall, Box 2520, San Francisco, California 94158, United States
| | - Daniel A. Bernards
- Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, 1700 4th Street, Byers Hall, Box 2520, San Francisco, California 94158, United States
| | - Qizhi Tang
- Department of Surgery, University of California, San Francisco, 513 Parnassus Avenue HSE520 Box 0780, San Francisco, California 94143, United States
| | - TejalA Desai
- Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, 1700 4th Street, Byers Hall, Box 2520, San Francisco, California 94158, United States
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11
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Copelan A, George D, Kapoor B, Nghiem HV, Lorenz JM, Erly B, Wang W. Iatrogenic-related transplant injuries: the role of the interventional radiologist. Semin Intervent Radiol 2015; 32:133-55. [PMID: 26038621 DOI: 10.1055/s-0035-1549842] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
As advances in surgical techniques and postoperative care continue to improve outcomes, the use of solid organ transplants as a treatment for end-stage organ disease is increasing. With the growing population of transplant patients, there is an increasing need for radiologic diagnosis and minimally invasive procedures for the management of posttransplant complications. Typical complications may be vascular or nonvascular. Vascular complications include arterial stenosis, graft thrombosis, and development of fistulae. Common nonvascular complications consist of leaks, abscess formation, and stricture development. The use of interventional radiology in the management of these problems has led to better graft survival and lower patient morbidity and mortality. An understanding of surgical techniques, postoperative anatomy, radiologic findings, and management options for complications is critical for proficient management of complex transplant cases. This article reviews these factors for kidney, liver, pancreas, islet cell, lung, and small bowel transplants.
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Affiliation(s)
- Alexander Copelan
- Department of Diagnostic Radiology, William Beaumont Hospital, Royal Oak, Michigan
| | - Daniel George
- Department of Diagnostic Radiology, William Beaumont Hospital, Royal Oak, Michigan
| | - Baljendra Kapoor
- Section of Interventional Radiology, Imaging Institute, Cleveland Clinic, Cleveland, Ohio
| | - Hahn Vu Nghiem
- Department of Diagnostic Radiology, William Beaumont Hospital, Royal Oak, Michigan
| | - Jonathan M Lorenz
- Section of Interventional Radiology, The University of Chicago, Chicago, Illinois
| | - Brian Erly
- Section of Interventional Radiology, Imaging Institute, Cleveland Clinic, Cleveland, Ohio ; Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Weiping Wang
- Section of Interventional Radiology, Imaging Institute, Cleveland Clinic, Cleveland, Ohio
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12
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Pancreatic Epithelial Cells Form Islet-Like Clusters in the Absence of Directed Migration. Cell Mol Bioeng 2015. [DOI: 10.1007/s12195-015-0396-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
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13
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Katuchova J, Harvanova D, Spakova T, Kalanin R, Farkas D, Durny P, Rosocha J, Radonak J, Petrovic D, Siniscalco D, Qi M, Novak M, Kruzliak P. Mesenchymal stem cells in the treatment of type 1 diabetes mellitus. Endocr Pathol 2015; 26:95-103. [PMID: 25762503 DOI: 10.1007/s12022-015-9362-y] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Diabetes mellitus type 1 is a form of diabetes mellitus that results from the autoimmune destruction of insulin-producing beta cells in the pancreas. The current gold standard therapy for pancreas transplantation has limitations because of the long list of waiting patients and the limited supply of donor pancreas. Mesenchymal stem cells (MSCs), a relatively new potential therapy in various fields, have already made their mark in the young field of regenerative medicine. Recent studies have shown that the implantation of MSCs decreases glucose levels through paracrine influences rather than through direct transdifferentiation into insulin-producing cells. Therefore, these cells may use pro-angiogenic and immunomodulatory effects to control diabetes following the cotransplantation with pancreatic islets. In this review, we present and discuss new approaches of using MSCs in the treatment of diabetes mellitus type 1.
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Affiliation(s)
- Jana Katuchova
- 1st Department of Surgery, Faculty of Medicine, Pavol Jozef Safarik University and University Hospital, Kosice, Slovak Republic
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14
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Sun B, Liu R, Xiao ZD. Induction of insulin-producing cells from umbilical cord blood-derived stromal cells by activation of the c-Met/HGF axis. Dev Growth Differ 2015; 57:353-361. [DOI: 10.1111/dgd.12214] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2015] [Revised: 03/18/2015] [Accepted: 03/22/2015] [Indexed: 12/27/2022]
Affiliation(s)
- Bo Sun
- State Key Laboratory of Bioelectronics; School of Biological Science and Medical Engineering; Southeast University; Nanjing 210096 China
- Institute of Microbiology; Seoul National University; 151-742 Seoul South Korea
| | - Rui Liu
- Laboratory of Biophysics; School of Biological Sciences; Seoul National University; 151-742 Seoul South Korea
| | - Zhong-Dang Xiao
- State Key Laboratory of Bioelectronics; School of Biological Science and Medical Engineering; Southeast University; Nanjing 210096 China
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16
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Figliuzzi M, Bonandrini B, Silvani S, Remuzzi A. Mesenchymal stem cells help pancreatic islet transplantation to control type 1 diabetes. World J Stem Cells 2014; 6:163-172. [PMID: 24772243 PMCID: PMC3999774 DOI: 10.4252/wjsc.v6.i2.163] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 12/20/2013] [Accepted: 03/04/2014] [Indexed: 02/06/2023] Open
Abstract
Islet cell transplantation has therapeutic potential to treat type 1 diabetes, which is characterized by autoimmune destruction of insulin-producing pancreatic islet β cells. It represents a minimal invasive approach for β cell replacement, but long-term blood control is still largely unachievable. This phenomenon can be attributed to the lack of islet vasculature and hypoxic environment in the immediate post-transplantation period that contributes to the acute loss of islets by ischemia. Moreover, graft failures continue to occur because of immunological rejection, despite the use of potent immunosuppressive agents. Mesenchymal stem cells (MSCs) have the potential to enhance islet transplantation by suppressing inflammatory damage and immune mediated rejection. In this review we discuss the impact of MSCs on islet transplantation and focus on the potential role of MSCs in protecting islet grafts from early graft failure and from autoimmune attack.
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17
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Jiang L, Liu J, Wang K, Gu X, Luo Y. Investigating design principles of micropatterned encapsulation systems containing high-density microtissue arrays. SCIENCE CHINA-LIFE SCIENCES 2014; 57:221-31. [PMID: 24435251 DOI: 10.1007/s11427-014-4609-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/20/2013] [Accepted: 10/12/2013] [Indexed: 12/24/2022]
Abstract
Immunoisolation is an important strategy to protect transplanted cells from rejection by the host immune system. Recently, microfabrication techniques have been used to create hydrogel membranes to encapsulate microtissue in an arrayed organization. The method illustrates a new macroencapsulation paradigm that may allow transplantation of a large number of cells with microscale spatial control, while maintaining an encapsulation device that is easily maneuverable and remaining integrated following transplantation. This study aims to investigate the design principles that relate to the translational application of micropatterned encapsulation membranes, namely, the control over the transplantation density/quantity of arrayed microtissues and the fidelity of pre-formed microtissues to micropatterns. Agarose hydrogel membranes with microwell patterns were used as a model encapsulation system to exemplify these principles. Our results show that high-density micropatterns can be generated in hydrogel membranes, which can potentially maximize the percentage volume of cellular content and thereby the transplantation efficiency of the encapsulation device. Direct seeding of microtissues demonstrates that microwell structures can efficiently position and organize pre-formed microtissues, suggesting the capability of micropatterned devices for manipulation of cellular transplants at multicellular or tissue levels. Detailed theoretical analysis was performed to provide insights into the relationship between micropatterns and the transplantation capacity of membrane-based encapsulation. Our study lays the ground for developing new macroencapsulation systems with microscale cellular/tissue patterns for regenerative transplantation.
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Affiliation(s)
- LiYang Jiang
- Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, 100871, China
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18
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Li W, Zhao R, Liu J, Tian M, Lu Y, He T, Cheng M, Liang K, Li X, Wang X, Sun Y, Chen L. Small islets transplantation superiority to large ones: implications from islet microcirculation and revascularization. J Diabetes Res 2014; 2014:192093. [PMID: 24829922 PMCID: PMC4009214 DOI: 10.1155/2014/192093] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2013] [Accepted: 03/01/2014] [Indexed: 12/30/2022] Open
Abstract
Pancreatic islet transplantation is a promising therapy to regain glycemic control in diabetic patients. The selection of ideal grafts is the basis to guarantee short-term effectivity and longevity of the transplanted islets. Contradictory to the traditional notion, recent findings implied the superiority of small islets for better transplantation outcomes rather than the large and intact ones. However, the mechanisms remain to be elucidated. Recent evidences emphasized the major impact of microcirculation on islet β -cell mass and function. And potentials in islet graft revascularization are crucial for their survival and preserved function in the recipient. In this study, we verified the distinct histological phenotype and functionality of small islets versus large ones both in vitro and in vivo. With efforts to exploring the differences in microcirculation and revascularization of islet grafts, we further evaluated local expressions of angiotensin and vascular endothelial growth factor A (VEGF-A) at different levels. Our findings reveal that, apart from the higher density of insulin-producing β -cells, small islets express less angiotensin and more angiotrophic VEGF-A. We therefore hypothesized a logical explanation of the small islet superiority for transplantation outcome from the aspects of facilitated microcirculation and revascularization intrinsically in small islets.
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Affiliation(s)
- Wenjuan Li
- Department of Endocrinology, Qilu Hospital of Shandong University, Institute of Endocrinology and Metabolism, No. 107 West Wenhua Road, Jinan, Shandong 250012, China
| | - Ruxing Zhao
- Department of Endocrinology, Qilu Hospital of Shandong University, Institute of Endocrinology and Metabolism, No. 107 West Wenhua Road, Jinan, Shandong 250012, China
| | - Jidong Liu
- Department of Poisoning and Occupational Disease, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Meng Tian
- Department of Endocrinology, Qilu Hospital of Shandong University, Institute of Endocrinology and Metabolism, No. 107 West Wenhua Road, Jinan, Shandong 250012, China
| | - Yiran Lu
- Department of Endocrinology, Qilu Hospital of Shandong University, Institute of Endocrinology and Metabolism, No. 107 West Wenhua Road, Jinan, Shandong 250012, China
| | - Tianyi He
- Department of Endocrinology, Qilu Hospital of Shandong University, Institute of Endocrinology and Metabolism, No. 107 West Wenhua Road, Jinan, Shandong 250012, China
| | - Meng Cheng
- Department of Endocrinology, Qilu Hospital of Shandong University, Institute of Endocrinology and Metabolism, No. 107 West Wenhua Road, Jinan, Shandong 250012, China
| | - Kai Liang
- Department of Endocrinology, Qilu Hospital of Shandong University, Institute of Endocrinology and Metabolism, No. 107 West Wenhua Road, Jinan, Shandong 250012, China
| | - Xia Li
- Institute of Cell Biology, Shandong University School of Medicine, Jinan 250012, China
| | - Xiangdong Wang
- Institute of Cell Biology, Shandong University School of Medicine, Jinan 250012, China
| | - Yu Sun
- Department of Endocrinology, Qilu Hospital of Shandong University, Institute of Endocrinology and Metabolism, No. 107 West Wenhua Road, Jinan, Shandong 250012, China
- *Yu Sun: and
| | - Li Chen
- Department of Endocrinology, Qilu Hospital of Shandong University, Institute of Endocrinology and Metabolism, No. 107 West Wenhua Road, Jinan, Shandong 250012, China
- *Li Chen:
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