uu.seUppsala University Publications
Change search
Refine search result
1 - 8 of 8
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 1.
    Friberg, Andrew S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Standardization of Islet Isolation and Transplantation Variables2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Currently, the transplantation of islets of Langerhans is a viable means to maintain control of blood sugar levels and reduce the risk of hypoglycemia in defined populations with brittle type I diabetes mellitus or those requiring pancreatectomy. However, the process of islet isolation is highly variable and not all isolations result in islet numbers or quality suitable for transplantation.

    This thesis aimed to improve transplantation success through optimization and standardization of the isolation process and to identify pretransplant variables associated with early islet engraftment.

    A previously disregarded enzyme activity, tryptic-like activity (TLA), has been identified to influence pancreas digestion efficiency and islet isolation success in both the preclinical and clinical situations. For human pancreases, islet isolation success rates improved from 0% in the lowest TLA group to over 50% in the highest TLA groups without affecting islet quality. These findings should help standardize evaluation of enzymes for clinical islet isolation.

    A closed, automated, pump-made gradient system was compared to the open, manual method for islet separation. No differences were observed in expected gradient volumes, islet yields or total purities between the two methods. The pump-made gradient system successfully removed manual influences on density gradient production while fulfilling regulatory requirements for closed system processing.

    Islet quantification was evaluated with computer-assisted digital imaging analysis (DIA) and a semi-closed assessment system. By using the DIA system method, which measures islet purity and pellet volume instead of manual counting methods, variation in islet counts and purity reduced by almost half.

    By using a transplant outcome measurement of C-peptide adjusted by blood glucose and creatinine, we identified four pretransplant factors that affect early transplant outcome. Of the four factors, one was related to the organ transport time, one to function of the islets, and two to the transplanted tissue volume. When these four factors were put into a predictive model, it accounted for about 40% of the transplant outcome.

    The work contained in this thesis identifies and optimizes a number of critical elements related to islet isolation and transplantation protocols.

     

    List of papers
    1. The importance of tryptic-like activity in purified enzyme blends for efficient islet isolation
    Open this publication in new window or tab >>The importance of tryptic-like activity in purified enzyme blends for efficient islet isolation
    Show others...
    2009 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 87, no 3, 370-5 p.Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: The isolation of islets from the human pancreas critically depends on an efficient enzyme blend. Previous studies have solely focused on the presence of collagenase and neutral protease/thermolysin. Despite improved characterization of these components, the lot-related variability in efficacy still persists suggesting that additional so far disregarded enzymes are required for efficient islet cleavage. METHODS: Varying activities of a tryptic-like enzyme were identified within collagenase NB1 lots, which were selected according to a matched ratio between tryptic-like and collagenase activity (TLA-ratio). Rat and human pancreata were processed with current standard procedures. RESULTS: Increasing the TLA-ratio from 1.3% to 10% reduced pancreas dissociation time in rats by 50% without affecting islet yield, viability, or posttransplant function in diabetic nude mice. Enhancing the TLA-ratio from 1.3% to 12.6% for human pancreas processing resulted in a significant reduction of recirculation time and increased incrementally human islet yield without affecting purity, in vitro function or recovery after culture. Optimized pancreas digestion correlated with a higher percentage of islet preparations fulfilling quality criteria for clinical transplantation. CONCLUSIONS: We conclude that TLA is an effective component that should be included in moderate amounts in enzyme blends for human islet isolation to optimize the efficiency and minimize the lot-related variability.

    Keyword
    human islet transplantation, human islet isolation, collagenase, enzymes
    National Category
    Surgery
    Research subject
    Medical Science
    Identifiers
    urn:nbn:se:uu:diva-103604 (URN)10.1097/TP.0b013e31819499f0 (DOI)000263397400010 ()19202441 (PubMedID)
    Available from: 2009-05-20 Created: 2009-05-20 Last updated: 2017-12-13Bibliographically approved
    2. Human islet separation utilizing a closed automated purification system
    Open this publication in new window or tab >>Human islet separation utilizing a closed automated purification system
    Show others...
    2008 (English)In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 17, no 12, 1305-1313 p.Article in journal (Refereed) Published
    Abstract [en]

    A central step within the human islet isolation process is the separation of islets from contaminating exocrine tissue utilizing linear, continuous density gradients manufactured by means of manually controlled standard gradient makers (SGM). The present study was performed to develop a closed, automated purification system (APS) that customizes density gradient profiles aiming to standardize and optimize human islet purification. Digested human pancreata were pooled, split evenly, and incubated in UW solution according to our standard protocol (n = 11). Continuous density gradient centrifugation was performed in parallel in two refrigerated COBE 2991 cell separators loaded with light (1.076 g/ml) and heavy (1.097 g/ml) Ficoll utilizing either an SGM or two computer-controlled pumps connected to Ficoll-containing bags. Quality control included islet equivalent (IE) yield, purity, in vitro function, and islet cytokine expression. Gradient profiles demonstrated that the APS readily customizes linear and nonlinear gradients. In comparison to the SGM, the APS recovered a higher percentage of the expected volume of continuous gradients (90.0 +/- 1.1% vs. 98.2 +/- 2.0%, p < 0.05). Islet yield (120,468 +/- 15,970 vs. 114,570 +/- 15,313 IE, NS) and purity (51.7 +/- 4.8% vs. 54.4 +/- 4.9%, NS) were nearly identical utilizing the SGM or APS. Decreased MCP-1, IL-6, and IL-8 expression indicated that APS-purified islets were possibly exposed to less proinflammatory stress. Compared to standard procedures, similar success and gentle continuous density gradient separation of human islets is feasible utilizing the APS. The APS facilitates the standardization of this complex procedure according to cGMP standards.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-105000 (URN)10.3727/096368908787648100 (DOI)000264577900003 ()19364068 (PubMedID)
    Available from: 2009-05-31 Created: 2009-05-31 Last updated: 2017-12-13Bibliographically approved
    3. Quantification of the Islet Product: Presentation of a Standardized Current Good Manufacturing Practices Compliant System With Minimal Variability
    Open this publication in new window or tab >>Quantification of the Islet Product: Presentation of a Standardized Current Good Manufacturing Practices Compliant System With Minimal Variability
    Show others...
    2011 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 91, no 6, 677-683 p.Article in journal (Refereed) Published
    Abstract [en]

    Background. Accurate islet quantification has proven difficult to standardize in a good manufacturing practices (GMP) approved manner. Methods. The influence of assessment variables from both manual and computer-assisted digital image analysis (DIA) methods were compared using calibrated, standardized microspheres or islets alone. Additionally, a mixture of microspheres and exocrine tissue was used to evaluate the variability of both the current, internationally recognized, manual method and a novel GMP-friendly purity-and volume-based method (PV) evaluated by DIA in a semiclosed, culture bag system. Results. Computer-assisted DIA recorded known microsphere size distribution and quantities accurately. By using DIA to evaluate islets, the interindividual manually evaluated percent coefficients of variation (CV%; n = 14) were reduced by almost half for both islet equivalents (IEs; 31% vs. 17%, P = 0.002) and purity (20% vs. 13%, P = 0.033). The microsphere pool mixed with exocrine tissue did not differ from expected IE with either method. However, manual IE resulted in a total CV% of 44.3% and a range spanning 258 kIE, whereas PV resulted in CV% of 10.7% and range of 60 k IE. Purity CV% for each method were similar approximating 10.5% and differed from expected by +7% for the manual method and +3% for PV. Conclusion. The variability of standard counting methods for islet samples and clinical quantities of microspheres mixed with exocrine tissue were reduced with DIA. They were reduced even further by use of a semiclosed bag system compared with standard manual counting, thereby facilitating the standardization of islet evaluation according to GMP standards.

    Keyword
    Islet evaluation, Digital imaging analysis, Purity, Volume, GMP
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-149562 (URN)10.1097/TP.0b013e31820ae48e (DOI)000288115800023 ()21248660 (PubMedID)
    Available from: 2011-03-22 Created: 2011-03-21 Last updated: 2017-12-11Bibliographically approved
    4. Transplantable functional islet mass – predictive biomarkers of graft function in islet after kidney transplanted patients
    Open this publication in new window or tab >>Transplantable functional islet mass – predictive biomarkers of graft function in islet after kidney transplanted patients
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    The ability to predict clinical function of a specific islet batch released for clinical transplantation using standardized variables remains an elusive goal. Analysis of donor, islet isolation, quality control and recipient variables was undertaken in 110 islet after kidney (IAK) transplants and correlated to the pre- to 28-day posttransplant change in C-peptide to glucose and creatinine ratio (ΔCP/GCr). Using backward multiple regression the variables positively associated to ΔCP/GCr were islet volume transplanted (p<0.001) and glucose stimulated insulin secretion (SI) (p=0.009). Factors negatively associated to ΔCP/GCr were cold ischemia time (CIT) (p=0.002) and total tissue volume (p=0.009). Donor age, donor body mass index, number of retrieved organs from the donor, preservation solution, islet insulin content, body weight of the recipient of the islets had no influence on transplant function. The transplantable functional islet mass (TFIM), accounting for islet volume transplanted, SI, CIT, and total tissue volume explained 39% of the variance of the clinical outcome in the IAK data set. Therefore, the TFIM provides a straightforward and potent tool to guide the decision to utilize a specific islet preparation for clinical transplantation.

    Keyword
    Islet transplantation, kidney function, predict outcome, transplantable islet mass
    National Category
    Surgery
    Research subject
    Medicine
    Identifiers
    urn:nbn:se:uu:diva-150243 (URN)
    Available from: 2011-03-28 Created: 2011-03-28 Last updated: 2015-06-16
  • 2.
    Friberg, Andrew S.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Lundgren, Torbjörn
    Malm, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Felldin, M
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Jenssen, T
    Kyllonen, L
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Tibell, Annika
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Transplanted functional islet mass: donor islet preparation, and recipitent factors influence early graft function in islet-after-kidney patients2012In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 93, no 6, 632-638 p.Article in journal (Refereed)
    Abstract [en]

    Background.

    The ability to predict clinical function of a specific islet batch released for clinical transplantation using standardized variables remains an elusive goal.

    Methods.

    Analysis of 10 donor, 7 islet isolation, 3 quality control, and 6 recipient variables was undertaken in 110 islet-after-kidney transplants and correlated to the pre- to 28-day posttransplant change in C-peptide to glucose and creatinine ratio ([DELTA]CP/GCr).

    Results.

    Univariate analysis yielded islet volume transplanted (Spearman r=0.360, P<0.001) and increment of insulin secretion (r=0.377, P<0.001) as variables positively associated to [DELTA]CP/GCr. A negative association to [DELTA]CP/GCr was cold ischemia time (r=-0.330, P<0.001). A linear, backward-selection multiple regression was used to obtain a model for the transplanted functional islet mass (TFIM). The TFIM model, composed of islet volume transplanted, increment of insulin secretion, cold ischemia time, and exocrine tissue volume transplanted, accounted for 43% of the variance of the clinical outcome in the islet-after-kidney data set.

    Conclusion.

    The TFIM provides a straightforward and potent tool to guide the decision to use a specific islet preparation for clinical transplantation.

  • 3.
    Friberg, Andrew S
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Lundgren, Torbjörn
    Karolinska Institutet.
    Malm, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Felldin, Marie
    Sahlgrenska University Hospital.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Jensson, Trond
    Oslo University Hospital, Rikshospitalet.
    Kyllönen, Lauri
    Helsinki University.
    Tufveson, Gunnar
    Uppsala University Hospital.
    Tibell, Annika
    Karolinska Institutet.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Transplantable functional islet mass – predictive biomarkers of graft function in islet after kidney transplanted patientsManuscript (preprint) (Other academic)
    Abstract [en]

    The ability to predict clinical function of a specific islet batch released for clinical transplantation using standardized variables remains an elusive goal. Analysis of donor, islet isolation, quality control and recipient variables was undertaken in 110 islet after kidney (IAK) transplants and correlated to the pre- to 28-day posttransplant change in C-peptide to glucose and creatinine ratio (ΔCP/GCr). Using backward multiple regression the variables positively associated to ΔCP/GCr were islet volume transplanted (p<0.001) and glucose stimulated insulin secretion (SI) (p=0.009). Factors negatively associated to ΔCP/GCr were cold ischemia time (CIT) (p=0.002) and total tissue volume (p=0.009). Donor age, donor body mass index, number of retrieved organs from the donor, preservation solution, islet insulin content, body weight of the recipient of the islets had no influence on transplant function. The transplantable functional islet mass (TFIM), accounting for islet volume transplanted, SI, CIT, and total tissue volume explained 39% of the variance of the clinical outcome in the IAK data set. Therefore, the TFIM provides a straightforward and potent tool to guide the decision to utilize a specific islet preparation for clinical transplantation.

  • 4.
    Goto, Masafumi
    et al.
    Tohoku Univ, New Ind Creat Hatchery Ctr, Sendai, Miyagi 980, Japan.;Tohoku Univ, Div Adv Surg Sci & Technol, Sendai, Miyagi 980, Japan..
    Friberg, Andrew
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Ståhle, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Imura, Takehiro
    Tohoku Univ, New Ind Creat Hatchery Ctr, Sendai, Miyagi 980, Japan..
    Yamagata, Youhei
    Tokyo Univ Agr & Technol, Dept Appl Biol Chem, Tokyo, Japan..
    Watanabe, Kimiko
    Tohoku Univ, New Ind Creat Hatchery Ctr, Sendai, Miyagi 980, Japan..
    Murayama, Kazutaka
    Tohoku Univ, Div Biomed Measurements & Diagnost, Sendai, Miyagi 980, Japan..
    Inagaki, Akiko
    Tohoku Univ, New Ind Creat Hatchery Ctr, Sendai, Miyagi 980, Japan..
    Igarashi, Yasuhiro
    Tohoku Univ, New Ind Creat Hatchery Ctr, Sendai, Miyagi 980, Japan..
    Satomi, Susumu
    Tohoku Univ, Div Adv Surg Sci & Technol, Sendai, Miyagi 980, Japan..
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Proof of concept for the clinical application of animal component free recombinant collagenase for isolating pancreatic islets2015In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 22, S50-S50 p.Article in journal (Other academic)
  • 5.
    Goto, Masafumi
    et al.
    Tohoku Univ, New Ind Creat Hatchery Ctr, Sendai, Miyagi 980, Japan.;Tohoku Univ, Div Adv Surg Sci & Technol, Sendai, Miyagi 980, Japan..
    Friberg, Andrew
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Ståhle, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Imura, Takehiro
    Tohoku Univ, New Ind Creat Hatchery Ctr, Sendai, Miyagi 980, Japan..
    Yamagata, Youhei
    Tokyo Univ Agr & Technol, Dept Appl Biol Chem, Tokyo, Japan..
    Watanabe, Kimiko
    Tohoku Univ, New Ind Creat Hatchery Ctr, Sendai, Miyagi 980, Japan..
    Murayama, Kazutaka
    Tohoku Univ, Div Biomed Measurements & Diagnost, Sendai, Miyagi 980, Japan..
    Inagaki, Akiko
    Tohoku Univ, New Ind Creat Hatchery Ctr, Sendai, Miyagi 980, Japan..
    Igarashi, Yasuhiro
    Tohoku Univ, New Ind Creat Hatchery Ctr, Sendai, Miyagi 980, Japan..
    Satomi, Susumu
    Tohoku Univ, Div Adv Surg Sci & Technol, Sendai, Miyagi 980, Japan..
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Proof Of Concept For The Clinical Application Of Animal Component Free Recombinant Collagenase For Isolating Pancreatic Islets2015In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 99, no 11, S80-S80 p.Article in journal (Other academic)
  • 6.
    Ricordi, Camillo
    et al.
    Univ Miami, Miller Sch Med, Diabet Res Inst, Miami, FL 33136 USA..
    Goldstein, Julia S.
    NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA..
    Balamurugan, A. N.
    Univ Minnesota, Schulze Diabet Inst, Minneapolis, MN USA.;Univ Minnesota, Dept Surg, Box 242 UMHC, Minneapolis, MN 55455 USA.;Univ Louisville, Dept Surg, Islet Cell Lab, Cardiovasc Innovat Inst, Louisville, KY 40292 USA..
    Szot, Gregory L.
    Univ Calif San Francisco, Dept Surg, San Francisco, CA USA..
    Kin, Tatsuya
    Univ Alberta, Clin Islet Transplant Program, Edmonton, AB, Canada.;Univ Alberta, Fac Med & Dent, Edmonton, AB, Canada..
    Liu, Chengyang
    Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.;Univ Penn, Dept Surg, Perelman Sch Med, Philadelphia, PA 19104 USA.;Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA..
    Czarniecki, Christine W.
    NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA..
    Barbaro, Barbara
    Univ Illinois Hosp & Hlth Sci Syst, Div Transplantat, Chicago, IL USA..
    Bridges, Nancy D.
    NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA..
    Cano, Jose
    Emory Univ, Dept Surg, Emory Transplant Ctr, Div Transplantat, Atlanta, GA 30322 USA..
    Clarke, William R.
    Univ Iowa, Clin Trials Stat & Data Management Ctr, Iowa City, IA USA..
    Eggerman, Thomas L.
    NIDDK, NIH, Bethesda, MD 20892 USA..
    Hunsicker, Lawrence G.
    Univ Iowa, Clin Trials Stat & Data Management Ctr, Iowa City, IA USA..
    Kaufman, Dixon B.
    Northwestern Univ, Feinberg Sch Med, Comprehens Transplant Ctr, Chicago, IL 60611 USA.;Univ Wisconsin, Madison, WI USA..
    Khan, Aisha
    Univ Miami, Miller Sch Med, Diabet Res Inst, Miami, FL 33136 USA..
    Lafontant, David-Erick
    Univ Iowa, Clin Trials Stat & Data Management Ctr, Iowa City, IA USA..
    Linetsky, Elina
    Univ Miami, Miller Sch Med, Diabet Res Inst, Miami, FL 33136 USA..
    Luo, Xunrong
    Northwestern Univ, Feinberg Sch Med, Comprehens Transplant Ctr, Chicago, IL 60611 USA..
    Markmann, James F.
    Harvard Med Sch, Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA USA..
    Naji, Ali
    Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.;Univ Penn, Dept Surg, Perelman Sch Med, Philadelphia, PA 19104 USA.;Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA..
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Oberholzer, Jose
    Univ Illinois Hosp & Hlth Sci Syst, Div Transplantat, Chicago, IL USA..
    Turgeon, Nicole A.
    Emory Univ, Dept Surg, Emory Transplant Ctr, Div Transplantat, Atlanta, GA 30322 USA..
    Brandhorst, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Friberg, Andrew S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Lei, Ji
    Harvard Med Sch, Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA USA..
    Wang, Ling-jia
    Northwestern Univ, Feinberg Sch Med, Comprehens Transplant Ctr, Chicago, IL 60611 USA..
    Wilhelm, Joshua J.
    Univ Minnesota, Schulze Diabet Inst, Minneapolis, MN USA.;Univ Minnesota, Dept Surg, Box 242 UMHC, Minneapolis, MN 55455 USA..
    Willits, Jamie
    Univ Iowa, Clin Trials Stat & Data Management Ctr, Iowa City, IA USA..
    Zhang, Xiaomin
    Northwestern Univ, Feinberg Sch Med, Comprehens Transplant Ctr, Chicago, IL 60611 USA..
    Hering, Bernhard J.
    Univ Minnesota, Schulze Diabet Inst, Minneapolis, MN USA.;Univ Minnesota, Dept Surg, Box 242 UMHC, Minneapolis, MN 55455 USA..
    Posselt, Andrew M.
    Univ Calif San Francisco, Dept Surg, San Francisco, CA USA..
    Stock, Peter G.
    Univ Calif San Francisco, Dept Surg, San Francisco, CA USA..
    Shapiro, A. M. James
    Univ Alberta, Clin Islet Transplant Program, Edmonton, AB, Canada.;Univ Alberta, Fac Med & Dent, Edmonton, AB, Canada..
    National Institutes of Health-Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial: Manufacture of a Complex Cellular Product at Eight Processing Facilities2016In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, no 11, 3418-3428 p.Article in journal (Refereed)
    Abstract [en]

    Eight manufacturing facilities participating in the National Institutes of Health-sponsored Clinical Islet Transplantation (CIT) Consortium jointly developed and implemented a harmonized process for the manufacture of allogeneic purified human pancreatic islet (PHPI) product evaluated in a phase 3 trial in subjects with type 1 diabetes. Manufacturing was controlled by a common master production batch record, standard operating procedures that included acceptance criteria for deceased donor organ pancreata and critical raw materials, PHPI product specifications, certificate of analysis, and test methods. The process was compliant with Current Good Manufacturing Practices and Current Good Tissue Practices. This report describes the manufacturing process for 75 PHPI clinical lots and summarizes the results, including lot release. The results demonstrate the feasibility of implementing a harmonized process at multiple facilities for the manufacture of a complex cellular product. The quality systems and regulatory and operational strategies developed by the CIT Consortium yielded product lots that met the prespecified characteristics of safety, purity, potency, and identity and were successfully transplanted into 48 subjects. No adverse events attributable to the product and no cases of primary nonfunction were observed.

  • 7.
    Ståhle, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Foss, Aksel
    Radiumhosp Med Ctr, Rikshosp, Dept Transplantat Surg, Oslo, Norway..
    Gustafsson, Bengt
    Univ Hosp, Dept Transplantat, Gothenburg, Sweden..
    Lempinen, Marko
    Univ Helsinki, Surg Hosp, Div Transplantat, Helsinki, Finland..
    Lundgren, Torbjorn
    Karolinska Inst, CLINTEC, Div Transplantat Surg, Stockholm, Sweden..
    Rafael, Ehab
    Univ Hosp, Dept Nephrol & Transplantat, Malmo, Sweden..
    Tufveson, Gunnar
    Univ Uppsala Hosp, Div Transplantat Surg, Dept Surg Sci, Uppsala, Sweden..
    Theisinger, Bastian
    Novaliq GmbH, Heidelberg, Germany..
    Brandhorst, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Friberg, Andrew
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Evaluation of Perfluorohexyloctane/Polydimethylsiloxane for Pancreas Preservation for Clinical Islet Isolation and Transplantation2016In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 25, no 12, 2269-2276 p.Article in journal (Refereed)
    Abstract [en]

    This study aimed to evaluate a 50:50 mix of perfluorohexyloctane/polydimethylsiloxane 5 (F6H8S5) preservation of pancreases in a clinical setting compared with standard solutions for 1) cold ischemia time (CIT) <10 h and 2) an extended CIT >20 h. Procured clinical-grade pancreases were shipped in either F6H8S5 or in standard preservation solutions, that is, University of Wisconsin (UW) or Custodiol. F6H5S5 was preoxygenated for at least 15 min. Included clinical-grade pancreases were procured in UW or Custodiol. Upon arrival at the islet isolation laboratory, the duodenum was removed followed by rough trimming while F6H8S5 was oxygenated for 15-20 min. Trimmed pancreases were immersed into oxygenated F6H8S5 and stored at 4 C overnight followed by subsequent islet isolation. Pancreas preservation using F6H8S5 proved as effective as UW and Custadiol when used within CIT up to 10 h, in terms of both isolation outcome and islet functionality. Preservation in F6H8S5 of pancreases with extended CIT gave results similar to controls with CIT <10 h for both isolated islet functionality and isolation outcome. This study of clinically obtained pancreases indicates a clear benefit of using F6H8S5 on pancreases with extended CIT as it seems to allow extended cold ischemic time without affecting islet function and islet numbers.

  • 8.
    Ståhle, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Honkanen-Scott, Minna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Ingvast, Sofie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Friberg, Andrew S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Human islet isolation processing times shortened by one hour: minimized incubation time between tissue harvest and islet purification2013In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 96, no 12, e91-e93 p.Article in journal (Refereed)
1 - 8 of 8
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf