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Eriksson, Maria
Publications (10 of 14) Show all publications
Hahn, M., Nord, C., Eriksson, M., Morini, F., Alanentalo, T., Korsgren, O. & Ahlgren, U. (2021). 3D imaging of human organs with micrometer resolution - applied to the endocrine pancreas. Communications Biology, 4(1), Article ID 1063.
Open this publication in new window or tab >>3D imaging of human organs with micrometer resolution - applied to the endocrine pancreas
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2021 (English)In: Communications Biology, E-ISSN 2399-3642, Vol. 4, no 1, article id 1063Article in journal (Refereed) Published
Abstract [en]

The possibility to quantitatively study specific molecular/cellular features of complete human organs with preserved spatial 3D context would have widespread implications for pre-clinical and clinical medicine. Whereas optical 3D imaging approaches have experienced a formidable revolution, they have remained limited due to current incapacities in obtaining specific labelling within large tissue volumes. We present a simple approach enabling reconstruction of antibody labeled cells within entire human organs with preserved organ context. We demonstrate the utility of the approach by providing volumetric data and 3D distribution of hundreds of thousands of islets of Langerhans within the human pancreas. By assessments of pancreata from non-diabetic and type 2 diabetic individuals, we display previously unrecognized features of the human islet mass distribution and pathology. As such, this method may contribute not only in unraveling new information of the pancreatic anatomy/pathophysiology, but it may be translated to essentially any antibody marker or organ system.

Place, publisher, year, edition, pages
Springer Nature, 2021
National Category
Cell and Molecular Biology Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-187770 (URN)10.1038/s42003-021-02589-x (DOI)000694906000003 ()2-s2.0-85114856810 (Scopus ID)
Available from: 2021-09-22 Created: 2021-09-22 Last updated: 2023-03-24Bibliographically approved
Eriksson, M., Litwak, S. A., Yun, Y., Stanley, W. J., Thorn, P., Ahlgren, U. & Gurzov, E. N. (2021). Insulin-Binding Peptide Probes Provide a Novel Strategy for Pancreatic β-Cell Imaging. Molecular Pharmaceutics, 18(12), 4428-4436
Open this publication in new window or tab >>Insulin-Binding Peptide Probes Provide a Novel Strategy for Pancreatic β-Cell Imaging
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2021 (English)In: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 18, no 12, p. 4428-4436Article in journal (Refereed) Published
Abstract [en]

Type 1 diabetes develops in childhood and adolescence, with peak incidence in the early teenage years. There is an urgent need for an accurate method to detect insulin-producing β-cells in patients that is not affected by alterations in β-cell function. As part of our research program to design specific probes to measure β-cell mass, we recently developed a novel insulin-binding peptide probe (IBPP) for the detection of β-cells in vivo. Here, we applied our innovative method to show specific labeling of this IBPP to human and mouse fixed β-cells in pancreatic islets. Importantly, we showed staining of human and mouse islets in culture without any negative functional or cell viability impact. Moreover, the IBPP-stained mouse islets after tail vein injection in vivo, albeit with batch differences in staining efficiency. In conclusion, we provide evidence showing that the IBPP can be used for future accurate detection of β-cell mass in a variety of preclinical models of diabetes.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2021
Keywords
glucose-stimulated insulin secretion, insulin-binding peptide, pancreatic islets, type 1 diabetes, β-cell imaging
National Category
Endocrinology and Diabetes Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-189219 (URN)10.1021/acs.molpharmaceut.1c00616 (DOI)000755047200018 ()2-s2.0-85118183928 (Scopus ID)
Funder
EU, FP7, Seventh Framework Programme, 289932Swedish Research CouncilNovo Nordisk
Available from: 2021-11-10 Created: 2021-11-10 Last updated: 2023-09-05Bibliographically approved
Hahn, M., Nord, C., Franklin, O., Alanentalo, T., Isaksson Mettävainio, M., Morini, F., . . . Ahlgren, U. (2020). Mesoscopic 3D imaging of pancreatic cancer and Langerhans islets based on tissue autofluorescence. Scientific Reports, 10(1), Article ID 18246.
Open this publication in new window or tab >>Mesoscopic 3D imaging of pancreatic cancer and Langerhans islets based on tissue autofluorescence
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2020 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 18246Article in journal (Refereed) Published
Abstract [en]

The possibility to assess pancreatic anatomy with microscopic resolution in three dimensions (3D) would significantly add to pathological analyses of disease processes. Pancreatic ductal adenocarcinoma (PDAC) has a bleak prognosis with over 90% of the patients dying within 5 years after diagnosis. Cure can be achieved by surgical resection, but the efficiency remains drearily low. Here we demonstrate a method that without prior immunohistochemical labelling provides insight into the 3D microenvironment and spread of PDAC and premalignant cysts in intact surgical biopsies. The method is based solely on the autofluorescent properties of the investigated tissues using optical projection tomography and/or light-sheet fluorescence microscopy. It does not interfere with subsequent histopathological analysis and may facilitate identification of tumor-free resection margins within hours. We further demonstrate how the developed approach can be used to assess individual volumes and numbers of the islets of Langerhans in unprecedently large biopsies of human pancreatic tissue, thus providing a new means by which remaining islet mass may be assessed in settings of diabetes. Generally, the method may provide a fast approach to provide new anatomical insight into pancreatic pathophysiology.

Place, publisher, year, edition, pages
Springer Nature, 2020
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-180639 (URN)10.1038/s41598-020-74616-6 (DOI)000615370300001 ()33106532 (PubMedID)2-s2.0-85094218464 (Scopus ID)
Available from: 2021-02-25 Created: 2021-02-25 Last updated: 2022-09-15Bibliographically approved
Hahn, M., van Krieken, P. P., Nord, C., Alanentalo, T., Morini, F., Xiong, Y., . . . Ahlgren, U. (2020). Topologically selective islet vulnerability and self-sustained downregulation of markers for β-cell maturity in streptozotocin-induced diabetes. Communications Biology, 3(1), Article ID 541.
Open this publication in new window or tab >>Topologically selective islet vulnerability and self-sustained downregulation of markers for β-cell maturity in streptozotocin-induced diabetes
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2020 (English)In: Communications Biology, E-ISSN 2399-3642, Vol. 3, no 1, article id 541Article in journal (Refereed) Published
Abstract [en]

Mouse models of Streptozotocin (STZ) induced diabetes represent the most widely used preclinical diabetes research systems. We applied state of the art optical imaging schemes, spanning from single islet resolution to the whole organ, providing a first longitudinal, 3D-spatial and quantitative account of β-cell mass (BCM) dynamics and islet longevity in STZ-treated mice. We demonstrate that STZ-induced β-cell destruction predominantly affects large islets in the pancreatic core. Further, we show that hyperglycemic STZ-treated mice still harbor a large pool of remaining β-cells but display pancreas-wide downregulation of glucose transporter type 2 (GLUT2). Islet gene expression studies confirmed this downregulation and revealed impaired β-cell maturity. Reversing hyperglycemia by islet transplantation partially restored the expression of markers for islet function, but not BCM. Jointly our results indicate that STZ-induced hyperglycemia results from β-cell dysfunction rather than β-cell ablation and that hyperglycemia in itself sustains a negative feedback loop restraining islet function recovery.

Place, publisher, year, edition, pages
Nature Publishing Group, 2020
National Category
Endocrinology and Diabetes Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-176312 (URN)10.1038/s42003-020-01243-2 (DOI)000576947100003 ()32999405 (PubMedID)2-s2.0-85091723089 (Scopus ID)
Available from: 2020-10-29 Created: 2020-10-29 Last updated: 2023-03-24Bibliographically approved
Nord, C., Eriksson, M., Dicker, A., Eriksson, A., Grong, E., Ilegems, E., . . . Ahlgren, U. (2017). Biochemical profiling of diabetes disease progression by multivariate vibrational microspectroscopy of the pancreas. Scientific Reports, 7, Article ID 6646.
Open this publication in new window or tab >>Biochemical profiling of diabetes disease progression by multivariate vibrational microspectroscopy of the pancreas
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2017 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 6646Article in journal (Refereed) Published
Abstract [en]

Despite the dramatic increase in the prevalence of diabetes, techniques for in situ studies of the underlying pancreatic biochemistry are lacking. Such methods would facilitate obtaining mechanistic understanding of diabetes pathophysiology and aid in prognostic and/or diagnostic assessments. In this report we demonstrate how a multivariate imaging approach (orthogonal projections to latent structures - discriminant analysis) can be applied to generate full vibrational microspectroscopic profiles of pancreatic tissues. These profiles enable extraction of known and previously unrecorded biochemical alterations in models of diabetes, and allow for classification of the investigated tissue with regards to tissue type, strain and stage of disease progression. Most significantly, the approach provided evidence for dramatic alterations of the pancreatic biochemistry at the initial onset of immune-infiltration in the Non Obese Diabetic model for type 1 diabetes. Further, it enabled detection of a previously undocumented accumulation of collagen fibrils in the leptin deficient ob/ob mouse islets. By generating high quality spectral profiles through the tissue capsule of hydrated human pancreata and by in vivo Raman imaging of pancreatic islets transplanted to the anterior chamber of the eye, we provide critical feasibility studies for the translation of this technique to diagnostic assessments of pancreatic biochemistry in vivo.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-138420 (URN)10.1038/s41598-017-07015-z (DOI)000406366000004 ()2-s2.0-85026213692 (Scopus ID)
Available from: 2017-08-23 Created: 2017-08-23 Last updated: 2023-03-23Bibliographically approved
Parween, S., Eriksson, M., Nord, C., Kostromina, E. & Ahlgren, U. (2017). Spatial and quantitative datasets of the pancreatic beta-cell mass distribution in lean and obese mice. Scientific Data, 4, Article ID 170031.
Open this publication in new window or tab >>Spatial and quantitative datasets of the pancreatic beta-cell mass distribution in lean and obese mice
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2017 (English)In: Scientific Data, E-ISSN 2052-4463, Vol. 4, article id 170031Article in journal (Refereed) Published
Abstract [en]

A detailed understanding of pancreatic β-cell mass distribution is a key element to fully appreciate the pathophysiology of models of diabetes and metabolic stress. Commonly, such assessments have been performed by stereological approaches that rely on the extrapolation of two-dimensional data and provide very limited topological information. We present ex vivo optical tomographic data sets of the full β-cell mass distribution in cohorts of obese ob/ob mice and their lean controls, together with information about individual islet β-cell volumes, their three-dimensional coordinates and shape throughout the volume of the pancreas between 4 and 52 weeks of age. These data sets offer the currently most comprehensive public record of the β-cell mass distribution in the mouse. As such, they may serve as a quantitative and topological reference for the planning of a variety of in vivo or ex vivo experiments including computational modelling and statistical analyses. By shedding light on intra- and inter-lobular variations in β-cell mass distribution, they further provide a powerful tool for the planning of stereological sampling assessments.

National Category
Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:umu:diva-133764 (URN)10.1038/sdata.2017.31 (DOI)000396109500001 ()2-s2.0-85015444491 (Scopus ID)
Available from: 2017-05-03 Created: 2017-05-03 Last updated: 2023-03-24Bibliographically approved
Parween, S., Kostromina, E., Nord, C., Eriksson, M., Lindström, P. & Ahlgren, U. (2016). Intra-islet lesions and lobular variations in β-cell mass expansion in ob/ob mice revealed by 3D imaging of intact pancreas. Scientific Reports, 6, Article ID 34885.
Open this publication in new window or tab >>Intra-islet lesions and lobular variations in β-cell mass expansion in ob/ob mice revealed by 3D imaging of intact pancreas
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2016 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 6, article id 34885Article in journal (Refereed) Published
Abstract [en]

The leptin deficient ob/ob mouse is a widely used model for studies on initial aspects of metabolic disturbances leading to type 2 diabetes, including insulin resistance and obesity. Although it is generally accepted that ob/ob mice display a dramatic increase in β-cell mass to compensate for increased insulin demand, the spatial and quantitative dynamics of β-cell mass distribution in this model has not been assessed by modern optical 3D imaging techniques. We applied optical projection tomography and ultramicroscopy imaging to extract information about individual islet β-cell volumes throughout the volume of ob/ob pancreas between 4 and 52 weeks of age. Our data show that cystic lesions constitute a significant volume of the hyperplastic ob/ob islets. We propose that these lesions are formed by a mechanism involving extravasation of red blood cells/plasma due to increased islet vessel blood flow and vessel instability. Further, our data indicate that the primary lobular compartments of the ob/ob pancreas have different potentials for expanding their β-cell population. Unawareness of the characteristics of β-cell expansion in ob/ob mice presented in this report may significantly influence ex vivo and in vivo assessments of this model in studies of β-cell adaptation and function.

Place, publisher, year, edition, pages
Nature Publishing Group, 2016
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-127539 (URN)10.1038/srep34885 (DOI)000392007800001 ()27713548 (PubMedID)2-s2.0-84990210699 (Scopus ID)
Funder
EU, FP7, Seventh Framework Programme, 289932Swedish Research Council
Available from: 2016-11-15 Created: 2016-11-15 Last updated: 2022-09-15Bibliographically approved
Grong, E., Kulseng, B., Arbo, I. B., Nord, C., Eriksson, M., Ahlgren, U. & Mårvik, R. (2016). Sleeve gastrectomy, but not duodenojejunostomy, preserves total beta-cell mass in Goto-Kakizaki rats evaluated by three-dimensional optical projection tomography. Surgical Endoscopy, 30(2), 532-542
Open this publication in new window or tab >>Sleeve gastrectomy, but not duodenojejunostomy, preserves total beta-cell mass in Goto-Kakizaki rats evaluated by three-dimensional optical projection tomography
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2016 (English)In: Surgical Endoscopy, ISSN 0930-2794, E-ISSN 1432-2218, Vol. 30, no 2, p. 532-542Article in journal (Refereed) Published
Abstract [en]

Background In type 2 diabetes mellitus, there is a progressive loss of beta-cell mass. Bariatric surgery has in recent investigations showed promising results in terms of diabetes remission, but little is established regarding the effect of surgery on the survival or regeneration of pancreatic beta-cells. In this study, we aim to explore how bariatric surgery with its subsequent hormonal alterations affects the islets of Langerhans.

Methods Twenty-four Goto-Kakizaki rats were operated with duodenojejunostomy (DJ), sleeve gastrectomy (SG) or sham operation. From the 38th week after surgery, body weight, fasting blood glucose, glycosylated hemoglobin, mixed meal tolerance with repeated measures of insulin, glucagon-like peptide 1, gastrin and total ghrelin were evaluated. Forty-six weeks after surgery, the animals were euthanized and the total beta-cell mass in all animals was examined by three-dimensional volume quantification by optical projection tomography based on the signal from insulin-specific antibody staining.

Results Body weight did not differ between groups (Pg = 0.37). SG showed lower fasting blood glucose compared to DJ and sham (Pg = 0.037); HbA1c levels in SG were lower compared to DJ only (p\0.05). GLP-1 levels were elevated for DJ compared to SG and sham (Pg = 0.001), whereas gastrin levels were higher in SG compared to the two other groups (Pg = 0.002). Beta-cell mass was significantly greater in animals operated with SG compared to both DJ and sham (p = 0.036).

Conclusion Sleeve gastrectomy is superior to duodenojejunostomy and sham operation when comparing the preservation of beta-cell mass 46 weeks after surgery in Goto-Kakizaki rats. This could be related to both the increased gastrin levels and the long-term improvement in glycemic parameters observed after this procedure.

Keywords
Duodenojejunostomy, Sleeve gastrectomy, Gastrin, Glucagon-like peptide 1, Beta-cell mass, Optical projection tomography, Goto-Kakizaki rats, Type 2 diabetes mellitus
National Category
Cell and Molecular Biology Endocrinology and Diabetes Surgery
Identifiers
urn:nbn:se:umu:diva-117395 (URN)10.1007/s00464-015-4236-4 (DOI)000369335900018 ()26065537 (PubMedID)2-s2.0-84957845031 (Scopus ID)
Available from: 2016-03-30 Created: 2016-02-29 Last updated: 2023-03-23Bibliographically approved
Eter, W. A., Parween, S., Joosten, L., Frielink, C., Eriksson, M., Brom, M., . . . Gotthardt, M. (2016). SPECT-OPT multimodal imaging enables accurate evaluation of radiotracers for beta-cell mass assessments. Scientific Reports, 6, Article ID 24576.
Open this publication in new window or tab >>SPECT-OPT multimodal imaging enables accurate evaluation of radiotracers for beta-cell mass assessments
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2016 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 6, article id 24576Article in journal (Refereed) Published
Abstract [en]

Single Photon Emission Computed Tomography (SPECT) has become a promising experimental approach to monitor changes in beta-cell mass (BCM) during diabetes progression. SPECT imaging of pancreatic islets is most commonly cross-validated by stereological analysis of histological pancreatic sections after insulin staining. Typically, stereological methods do not accurately determine the total beta-cell volume, which is inconvenient when correlating total pancreatic tracer uptake with BCM. Alternative methods are therefore warranted to cross-validate beta-cell imaging using radiotracers. In this study, we introduce multimodal SPECT - optical projection tomography (OPT) imaging as an accurate approach to cross-validate radionuclide-based imaging of beta-cells. Uptake of a promising radiotracer for beta-cell imaging by SPECT, In-111-exendin-3, was measured by ex vivo-SPECT and cross evaluated by 3D quantitative OPT imaging as well as with histology within healthy and alloxan-treated Brown Norway rat pancreata. SPECT signal was in excellent linear correlation with OPT data as compared to histology. While histological determination of islet spatial distribution was challenging, SPECT and OPT revealed similar distribution patterns of In-111-exendin-3 and insulin positive beta-cell volumes between different pancreatic lobes, both visually and quantitatively. We propose ex vivo SPECT-OPT multimodal imaging as a highly accurate strategy for validating the performance of beta-cell radiotracers.

Keywords
Diabetes Mellitus, Pancreas, Radioisotopes, SPECT
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-120360 (URN)10.1038/srep24576 (DOI)000374221700001 ()27080529 (PubMedID)2-s2.0-84964497676 (Scopus ID)
Available from: 2016-05-23 Created: 2016-05-16 Last updated: 2023-03-24Bibliographically approved
Ilegems, E., van Krieken, P. P., Edlund, P. K., Dicker, A., Alanentalo, T., Eriksson, M., . . . Berggren, P.-O. -. (2015). Light scattering as an intrinsic indicator for pancreatic islet cell mass and secretion. Scientific Reports, 5, Article ID 10740.
Open this publication in new window or tab >>Light scattering as an intrinsic indicator for pancreatic islet cell mass and secretion
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2015 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 5, article id 10740Article in journal (Refereed) Published
Abstract [en]

The pancreatic islet of Langerhans is composed of endocrine cells producing and releasing hormones from secretory granules in response to various stimuli for maintenance of blood glucose homeostasis. In order to adapt to a variation in functional demands, these islets are capable of modulating their hormone secretion by increasing the number of endocrine cells as well as the functional response of individual cells. A failure in adaptive mechanisms will lead to inadequate blood glucose regulation and thereby to the development of diabetes. It is therefore necessary to develop tools for the assessment of both pancreatic islet mass and function, with the aim of understanding cellular regulatory mechanisms and factors guiding islet plasticity. Although most of the existing techniques rely on the use of artificial indicators, we present an imaging methodology based on intrinsic optical properties originating from mature insulin secretory granules within endocrine cells that reveals both pancreatic islet mass and function. We demonstrate the advantage of using this imaging strategy by monitoring in vivo scattering signal from pancreatic islets engrafted into the anterior chamber of the mouse eye, and how this versatile and noninvasive methodology permits the characterization of islet morphology and plasticity as well as hormone secretory status.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-106501 (URN)10.1038/srep10740 (DOI)000355603100002 ()26030284 (PubMedID)2-s2.0-84934881048 (Scopus ID)
Available from: 2015-07-16 Created: 2015-07-14 Last updated: 2023-03-24Bibliographically approved
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