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Christoffersson, Gustaf
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Publications (10 of 34) Show all publications
von Herrath, M., Pagni, P. P., Grove, K., Christoffersson, G., Tang-Christensen, M., Karlsen, A. E. & Petersen, J. S. (2019). Case Reports of Pre-clinical Replication Studies in Metabolism and Diabetes. Cell Metabolism, 29(4), 795-802
Open this publication in new window or tab >>Case Reports of Pre-clinical Replication Studies in Metabolism and Diabetes
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2019 (English)In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 29, no 4, p. 795-802Article, review/survey (Refereed) Published
Abstract [en]

Recent articles have highlighted the lack of reproducibility of data from scientific publications. Here we would argue that a better way to describe and also tackle this matter is to use the term "lack of robustness," since it points toward potential solutions. Presenting several case reports, we highlight examples with common underlying issues from Novo Nordisk's experience: animal model variability, reagent quality, and inter-lao variability. We discuss means to prevent these issues and argue for increased collaborative work and transparent manuscript revision procedures. Collectively, we believe these measures will help promote a more rapid and efficient self-corrective process in diabetes drug target research.

Place, publisher, year, edition, pages
CELL PRESS, 2019
National Category
Cell Biology Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-382768 (URN)10.1016/j.cmet.2019.02.004 (DOI)000463015800005 ()30879984 (PubMedID)
Available from: 2019-05-03 Created: 2019-05-03 Last updated: 2019-05-03Bibliographically approved
Christoffersson, G. & von Herrath, M. (2019). Regulatory Immune Mechanisms beyond Regulatory T Cells. Trends in immunology, 40(6), 482-491
Open this publication in new window or tab >>Regulatory Immune Mechanisms beyond Regulatory T Cells
2019 (English)In: Trends in immunology, ISSN 1471-4906, E-ISSN 1471-4981, Vol. 40, no 6, p. 482-491Article, review/survey (Refereed) Published
Abstract [en]

In autoimmunity, aggressive immune responses are counteracted by suppressive rejoinders. For instance, FOXP3-expressing regulatory T cells (Tregs), have shown remarkable effects in limiting autoimmunity in preclinical models. However, early results from human Treg trials have not been as positive. Here, we highlight questions surrounding Treg transfers as putative treatments for autoimmunity. We discuss whether lack of antigenic recognition might be key to shifting cells from contributing to an aggressive autoresponse, to being part of a regulatory network. Moreover, we argue that identifying the physiological range of immunosuppression of Tregs might help potentiate their efficacy. We propose widening the view on immunoregulation by considering the participation of CD8(+) Tregs in this process, which could have major implications in autoimmunity.

National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-387529 (URN)10.1016/j.it.2019.04.005 (DOI)000469353000006 ()31101537 (PubMedID)
Funder
Swedish Research CouncilSwedish Society for Medical Research (SSMF)
Available from: 2019-06-24 Created: 2019-06-24 Last updated: 2019-06-24Bibliographically approved
Ahl, D., Eriksson, O., Sedin, J., Seignez, C., Schwan, E., Kreuger, J., . . . Phillipson, M. (2019). Turning Up the Heat: Local Temperature Control During in vivo Imaging of Immune Cells. Frontiers in Immunology, 10, Article ID 2036.
Open this publication in new window or tab >>Turning Up the Heat: Local Temperature Control During in vivo Imaging of Immune Cells
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2019 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, article id 2036Article in journal (Refereed) Published
Abstract [en]

Intravital imaging is an invaluable tool for studying the expanding range of immune cell functions. Only in vivo can the complex and dynamic behavior of leukocytes and their interactions with their natural microenvironment be observed and quantified. While the capabilities of high-speed, high-resolution confocal and multiphoton microscopes are well-documented and steadily improving, other crucial hardware required for intravital imaging is often developed in-house and less commonly published in detail. In this report, we describe a low-cost, multipurpose, and tissue-stabilizing in vivo imaging platform that enables sensing and regulation of local tissue temperature. The effect of tissue temperature on local blood flow and leukocyte migration is demonstrated in muscle and skin. Two different models of vacuum windows are described in this report, however, the design of the vacuum window can easily be adapted to fit different organs and tissues.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2019
Keywords
intravital microscopy, skin, blood flow, leukocytes, vacuum window, confocal microscopy
National Category
Immunology Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-398848 (URN)10.3389/fimmu.2019.02036 (DOI)000482819900001 ()31507619 (PubMedID)
Funder
Swedish Research Council, 2018-02552Knut and Alice Wallenberg FoundationRagnar Söderbergs stiftelseSwedish Society for Medical Research (SSMF)Göran Gustafsson Foundation for promotion of scientific research at Uppala University and Royal Institute of TechnologyNovo Nordisk
Available from: 2019-12-18 Created: 2019-12-18 Last updated: 2019-12-18Bibliographically approved
Grapensparr, L., Christoffersson, G. & Carlsson, P.-O. (2018). Bioengineering with Endothelial Progenitor Cells Improves the Vascular Engraftment of Transplanted Human Islets. Cell Transplantation, 27(6), 948-956
Open this publication in new window or tab >>Bioengineering with Endothelial Progenitor Cells Improves the Vascular Engraftment of Transplanted Human Islets
2018 (English)In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 27, no 6, p. 948-956Article in journal (Refereed) Published
Abstract [en]

Pancreatic islets isolated for transplantation are disconnected from their vascular supply and need to establish a new functional network posttransplantation. Due to poor revascularization, prevailing hypoxia with correlating increased apoptosis rates in experimental studies can be observed for months posttransplantation. Endothelial progenitor cells (EPCs) are bone marrow-derived cells that promote neovascularization. The present study tested the hypothesis that EPCs, isolated from human umbilical cord blood, could be coated to human islet surfaces and be used to promote islet vascular engraftment. Control or EPC bioengineered human islets were transplanted into the renal subcapsular space of nonobese diabetic/severe combined immunodeficiency mice. Four weeks posttransplantation, graft blood perfusion and oxygen tension were measured using laser Doppler flowmetry and Clark microelectrodes, respectively. Vessel functionality was also assessed by in vivo confocal imaging. The vascular density and the respective contribution of human and recipient endothelium were assessed immunohistochemically by staining for human and mouse CD31. Islet grafts with EPCs had substantially higher blood perfusion and oxygen tension than control transplants. Furthermore, analysis of the vascular network of the grafts revealed that grafts containing EPC bioengineered islets had a superior vascular density compared with control grafts, with functional chimeric blood vessels. We conclude that a simple procedure of surface coating with EPCs provides a possibility to improve the vascular engraftment of transplanted human islets. Established protocols are also easily applicable for intraportal islet transplantation in order to obtain a novel directed cellular therapy at the site of implantation in the liver.

National Category
Surgery Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-327311 (URN)10.1177/0963689718759474 (DOI)000438945100009 ()29862837 (PubMedID)
Funder
Swedish Research CouncilEXODIAB - Excellence of Diabetes Research in SwedenTorsten Söderbergs stiftelseNovo NordiskSwedish Diabetes AssociationSwedish Child Diabetes FoundationStiftelsen Olle Engkvist Byggmästare
Available from: 2017-08-09 Created: 2017-08-09 Last updated: 2020-05-18Bibliographically approved
Parv, K., Christoffersson, G., Herrera Hidalgo, C., Seignez, C. & Phillipson, M. (2018). Elucidating the dynamics and role of peri-vascular macrophages. Paper presented at 52nd Annual Scientific Meeting of the European Society for Clinical Investigation “Precision medicine for healthy ageing”, 30th May – 1st June 2018, Barcelona, Spain.. European Journal of Clinical Investigation, 48(S1), 82-83
Open this publication in new window or tab >>Elucidating the dynamics and role of peri-vascular macrophages
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2018 (English)In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 48, no S1, p. 82-83Article in journal, Meeting abstract (Other academic) Published
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-366627 (URN)10.1111/eci.12926 (DOI)000434100200184 ()
Conference
52nd Annual Scientific Meeting of the European Society for Clinical Investigation “Precision medicine for healthy ageing”, 30th May – 1st June 2018, Barcelona, Spain.
Note

Meeting Abstract: P031-T

Available from: 2018-11-23 Created: 2018-11-23 Last updated: 2018-12-10Bibliographically approved
Vågesjö, E., Seignez, C., Christoffersson, G., Herrera Hidalgo, C., Giraud, A., Korsgren, O., . . . Phillipson, M. (2018). Perivascular macrophages regulate blood flow following tissue damage. Paper presented at 52nd Annual Scientific Meeting of the European Society for Clinical Investigation “Precision medicine for healthy ageing”, 30th May – 1st June 2018, Barcelona, Spain.. European Journal of Clinical Investigation, 48(S1), 44-45
Open this publication in new window or tab >>Perivascular macrophages regulate blood flow following tissue damage
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2018 (English)In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 48, no S1, p. 44-45Article in journal, Meeting abstract (Other academic) Published
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-366622 (URN)10.1111/eci.12923 (DOI)000434100200105 ()
Conference
52nd Annual Scientific Meeting of the European Society for Clinical Investigation “Precision medicine for healthy ageing”, 30th May – 1st June 2018, Barcelona, Spain.
Note

Meeting Abstract: W1-O2

Available from: 2018-11-23 Created: 2018-11-23 Last updated: 2018-12-10Bibliographically approved
Christoffersson, G. & Phillipson, M. (2018). The neutrophil: one cell on many missions or many cells with different agendas?. Cell and Tissue Research, 371(3), 415-423
Open this publication in new window or tab >>The neutrophil: one cell on many missions or many cells with different agendas?
2018 (English)In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 371, no 3, p. 415-423Article, review/survey (Refereed) Published
Abstract [en]

The unique role of neutrophils in host defense is not only based on their abilities to kill bacteria but is also due to their abundance in circulation and their ability to quickly migrate and accumulate in great numbers at afflicted sites. The high number of circulating neutrophils is the result of regulated release of new neutrophils from bone marrow as well as from marginated pools to balance their recruitment to tissue. Marginated pools, such as the spleen and lung, have previously been attributed to passively delay neutrophil transit time due to their large capillary network, but recent reports demonstrate that they are comprised of neutrophils with specific functions. The spleen, for instance, holds neutrophil subpopulations at different anatomical locations with distinct functions important for, e.g., bacterial eradication, and the lung was recently shown to re-educate neutrophils that had trafficked from a site of sterile injury to home back to bone marrow for elimination. Further, recent reports demonstrate subpopulations of neutrophils with different actions during homeostasis, infection, tissue restitution and cancer. It is becoming increasingly clear that this cannot be due to different stages of neutrophil activation during their life span but instead points towards distinct subpopulations of neutrophils with different effector functions. Whether these cellular distinctions are due to different education or origin is, however, not yet known. Together, the accumulating information about the heterogeneous neutrophils presents important insights into their role in development of pathologies, as well as revealing novel targets in the form of certain subpopulations to treat disease.

Place, publisher, year, edition, pages
Springer, 2018
Keywords
Subpopulations, Marginated pools, Development, Spleen, Lung
National Category
Cell Biology
Identifiers
urn:nbn:se:uu:diva-350683 (URN)10.1007/s00441-017-2780-z (DOI)000425596800004 ()29435651 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer SocietyNovo NordiskSwedish Heart Lung FoundationSwedish Diabetes AssociationRagnar Söderbergs stiftelseKnut and Alice Wallenberg Foundation
Available from: 2018-05-21 Created: 2018-05-21 Last updated: 2018-05-21Bibliographically approved
Christoffersson, G., Lomei, J., O'Callaghan, P., Kreuger, J., Engblom, S. & Phillipson, M. (2017). Vascular sprouts induce local attraction of proangiogenic neutrophils. Journal of Leukocyte Biology, 102, 741-751
Open this publication in new window or tab >>Vascular sprouts induce local attraction of proangiogenic neutrophils
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2017 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 102, p. 741-751Article in journal (Refereed) Published
National Category
Physiology Bioinformatics (Computational Biology)
Identifiers
urn:nbn:se:uu:diva-196483 (URN)10.1189/jlb.1MA0117-018R (DOI)000413395700019 ()
Projects
eSSENCE
Available from: 2017-06-05 Created: 2013-03-10 Last updated: 2018-11-12Bibliographically approved
Espes, D., Lau, J., Quach, M., Ullsten, S., Christoffersson, G. & Carlsson, P.-O. (2016). Rapid Restoration of Vascularity and Oxygenation in Mouse and Human Islets Transplanted to Omentum May Contribute to Their Superior Function Compared to Intraportally Transplanted Islets. American Journal of Transplantation, 16(11), 3246-3254
Open this publication in new window or tab >>Rapid Restoration of Vascularity and Oxygenation in Mouse and Human Islets Transplanted to Omentum May Contribute to Their Superior Function Compared to Intraportally Transplanted Islets
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2016 (English)In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 16, no 11, p. 3246-3254Article in journal (Refereed) Published
Abstract [en]

Transplantation of islets into the liver confers several site-specific challenges, including a delayed vascularization and prevailing hypoxia. The greater omentum has in several experimental studies been suggested as an alternative implantation site for clinical use, but there has been no direct functional comparison to the liver. In this experimental study in mice, we characterized the engraftment of mouse and human islets in the omentum and compared engraftment and functional outcome with those in the intraportal site. The vascularization and innervation of the islets transplanted into the omentum were restored within the first month by paralleled ingrowth of capillaries and nerves. The hypoxic conditions in the islets early posttransplantation were transient and restricted to the first days. Newly formed blood vessels were fully functional, and the blood perfusion and oxygenation of the islets became similar to that of endogenous islets. Furthermore, islet grafts in the omentum showed at 1 month posttransplantation functional superiority to intraportally transplanted grafts. We conclude that in contrast to the liver the omentum provides excellent engraftment conditions for transplanted islets. Future studies in humans will be of great interest to investigate the capability of this site to also harbor larger grafts without interfering with islet functionality.

National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-311198 (URN)10.1111/ajt.13927 (DOI)000388204600023 ()27321369 (PubMedID)
Funder
Swedish Research Council, 55X-15043Swedish Child Diabetes FoundationSwedish Diabetes AssociationNovo Nordisk
Available from: 2016-12-22 Created: 2016-12-22 Last updated: 2017-11-29Bibliographically approved
Espes, D., Lau, J., Quach, M., Christoffersson, G. & Carlsson, P.-O. (2016). Restoration of Islet Vascularity and Oxygenation in Mouse and Human Islets Experimentally Transplanted to the Omentum: A Basis for Superior Function when Compared to Intraportally Transplanted Islets. American Journal of Transplantation
Open this publication in new window or tab >>Restoration of Islet Vascularity and Oxygenation in Mouse and Human Islets Experimentally Transplanted to the Omentum: A Basis for Superior Function when Compared to Intraportally Transplanted Islets
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2016 (English)In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143Article in journal (Refereed) Submitted
Keywords
Islet transplantation, omentum, engraftment
National Category
Cell and Molecular Biology
Research subject
Medical Cell Biology
Identifiers
urn:nbn:se:uu:diva-282948 (URN)
Funder
Swedish Research Council, 55X-15043
Available from: 2016-04-08 Created: 2016-04-08 Last updated: 2018-01-10Bibliographically approved
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