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143 results on '"Korevaar, Sander S."'

1. Human kidney organoids produce functional renin

Author

Shankar, Anusha S., Du, Zhaoyu, Mora, Hector Tejeda, van den Bosch, Thierry P.P., Korevaar, Sander S., Van den Berg-Garrelds, Ingrid M., Bindels, Eric, Lopez-Iglesias, Carmen, Clahsen-van Groningen, Marian C., Gribnau, Joost, Baan, Carla C., Danser, A.H. Jan, Hoorn, Ewout J., and Hoogduijn, Martin J.

Published
2021
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2. Interactions of the Immune System with Human Kidney Organoids.

Author

Shankar, Anusha S., Tejeda-Mora, Hector, Zhaoyu Du, Nlandu, Quincy, Palomares-Cabeza, Virginia, van den Bosch, Thierry P. P., Korevaar, Sander S., Da Costa Gonçalves, Fabiany, Bindels, Eric M. J., Kramann, R., Reinders, Marlies E. J., Clahsen-van Groningen, Marian C., Hoorn, Ewout J., Gribnau, Joost, Baan, Carla C., and Hoogduijn, Martin J.

Subjects
MONONUCLEAR leukocytes, ORGANOIDS, IMMUNE system, KIDNEYS
Abstract

Kidney organoids are an innovative tool in transplantation research. The aim of the present study was to investigate whether kidney organoids are susceptible for allo-immune attack and whether they can be used as a model to study allo-immunity in kidney transplantation. Human induced pluripotent stem cell-derived kidney organoids were co-cultured with human peripheral blood mononuclear cells (PBMC), which resulted in invasion of allogeneic T-cells around nephron structures and macrophages in the stromal cell compartment of the organoids. This process was associated with the induction of fibrosis. Subcutaneous implantation of kidney organoids in immune-deficient mice followed by adoptive transfer of human PBMC led to the invasion of diverse T-cell subsets. Single cell transcriptomic analysis revealed that stromal cells in the organoids upregulated expression of immune response genes upon immune cell invasion. Moreover, immune regulatory PD-L1 protein was elevated in epithelial cells while genes related to nephron differentiation and function were downregulated. This study characterized the interaction between immune cells and kidney organoids, which will advance the use of kidney organoids for transplantation research. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Kidney Organoids Are Capable of Forming Tumors, but Not Teratomas

Author

Shankar, Anusha S, Du, Zhaoyu, Tejeda Mora, Hector, Boers, Ruben, Cao, Wanlu, van den Bosch, Thierry P P, Korevaar, Sander S, Boers, Joachim, van IJcken, Wilfred F J, Bindels, Eric M J, Eussen, Bert, de Klein, Annelies, Pan, Qiuwei, Oudijk, Lindsey, Clahsen-van Groningen, Marian C, Hoorn, Ewout J, Baan, Carla C, Gribnau, Joost, Hoogduijn, Martin J, Shankar, Anusha S, Du, Zhaoyu, Tejeda Mora, Hector, Boers, Ruben, Cao, Wanlu, van den Bosch, Thierry P P, Korevaar, Sander S, Boers, Joachim, van IJcken, Wilfred F J, Bindels, Eric M J, Eussen, Bert, de Klein, Annelies, Pan, Qiuwei, Oudijk, Lindsey, Clahsen-van Groningen, Marian C, Hoorn, Ewout J, Baan, Carla C, Gribnau, Joost, and Hoogduijn, Martin J

Abstract

Induced pluripotent stem cell (iPSC)-derived kidney organoids are a potential tool for the regeneration of kidney tissue. They represent an early stage of nephrogenesis and have been shown to successfsully vascularize and mature further in vivo. However, there are concerns regarding the long-term safety and stability of iPSC derivatives. Specifically, the potential for tumorigenesis may impede the road to clinical application. To study safety and stability of kidney organoids, we analyzed their potential for malignant transformation in a teratoma assay and following long-term subcutaneous implantation in an immune-deficient mouse model. We did not detect fully functional residual iPSCs in the kidney organoids as analyzed by gene expression analysis, single-cell sequencing and immunohistochemistry. Accordingly, kidney organoids failed to form teratoma. Upon long-term subcutaneous implantation of whole organoids in immunodeficient IL2Ry-/-RAG2-/- mice, we observed tumor formation in 5 out of 103 implanted kidney organoids. These tumors were composed of WT1+CD56+ immature blastemal cells and showed histological resemblance with Wilms tumor. No genetic changes were identified that contributed to the occurrence of tumorigenic cells within the kidney organoids. However, assessment of epigenetic changes revealed a unique cluster of differentially methylated genes that were also present in undifferentiated iPSCs. We discovered that kidney organoids have the capacity to form tumors upon long-term implantation. The presence of epigenetic modifications combined with the lack of environmental cues may have caused an arrest in terminal differentiation. Our results indicate that the safe implementation of kidney organoids should exclude the presence of pro-tumorigenic methylation in kidney organoids.

Published
2022

6. Identification of predictive markers for the generation of well-differentiated human induced pluripotent stem cell-derived kidney organoids

Author

Du, Zhaoyu, primary, Shankar, Anusha, additional, van den Bosch, Thierry, additional, Korevaar, Sander S, additional, clahsen-van Groningen, Marian, additional, Hoorn, Ewout J., additional, Gribnau, Joost, additional, Reinders, Marlies, additional, Baan, Carla C, additional, and Hoogduijn, Martin J, additional

Published
2021
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7. Vitamin D metabolism in human kidney organoids

Author

Shankar, Anusha S, primary, van den Berg, Sjoerd A A, additional, Tejeda Mora, Hector, additional, Du, Zhaoyu, additional, Lin, Hui, additional, Korevaar, Sander S, additional, van der Wal, Ronald, additional, van den Bosch, Thierry P P, additional, Clahsen-van Groningen, Marian C, additional, Gribnau, Joost, additional, Hoorn, Ewout J, additional, Baan, Carla C, additional, and Hoogduijn, Martin J, additional

Published
2021
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8. Membrane particles from mesenchymal stromal cells reduce the expression of fibrotic markers on pulmonary cells

Author

Merino, Ana, Hoogduijn, Martin J., Molina-Molina, Maria, Arias-Salgado, Elena G., Korevaar, Sander S., Baan, Carla C., Montes-Worboys, Ana, Merino, Ana, Hoogduijn, Martin J., Molina-Molina, Maria, Arias-Salgado, Elena G., Korevaar, Sander S., Baan, Carla C., and Montes-Worboys, Ana

Abstract

Background Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with limited treatment options in which the telomere shortening is a strong predictive factor of poor prognosis. Mesenchymal stromal cells (MSC) administration is probed in several experimental induced lung pathologies; however, MSC might stimulate fibrotic processes. A therapy that avoids MSC side effects of transformation would be an alternative to the use of living cells. Membranes particles (MP) are nanovesicles artificially generated from the membranes of MSC containing active enzymes involved in ECM regeneration. We aimed to investigate the anti-fibrotic role of MP derived from MSC in an in vitro model of pulmonary fibrosis. Methods Epithelial cells (A549) and lung fibroblasts, from IPF patients with different telomere length, were co-cultured with MP and TGF-ß for 48h and gene expression of major pro-fibrotic markers were analyzed. Results About 90% of both types of cells effectively took up MP without cytotoxic effects. MP decreased the expression of profibrotic proteins such as Col1A1, Fibronectin and PAI-1, in A549 cells. In fibroblasts culture, there was a different response in the inhibitory effect of MP on some pro-fibrotic markers when comparing fibroblast from normal telomere length patients (FN) versus short telomere length (FS), but both types showed an inhibition of Col1A1, Tenascin-c, PAI-1 and MMP-1 gene expression after MP treatment. Conclusions MP conserve some of the properties attributed to the living MSC. This study shows that MP target lung cells, via which they may have a broad anti-fibrotic effect.

Published
2021

13. Differential effects of heat-inactivated, secretome-deficient MSC and metabolically active MSC in sepsis and allogenic heart transplantation

Author

Weiss, Andreas R. R., primary, Lee, Olivia, additional, Eggenhofer, Elke, additional, Geissler, Elisabeth, additional, Korevaar, Sander S., additional, Soeder, Yorick, additional, Schlitt, Hans J., additional, Geissler, Edward K., additional, Hoogduijn, Martin J., additional, and Dahlke, Marc H., additional

Published
2020
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17. Vitamin D metabolism in human kidney organoids.

Author

Shankar, Anusha S, Berg, Sjoerd A A van den, Mora, Hector Tejeda, Du, Zhaoyu, Lin, Hui, Korevaar, Sander S, van der Wal, Ronald, Bosch, Thierry P P van den, Groningen, Marian C Clahsen-van, Gribnau, Joost, Hoorn, Ewout J, Baan, Carla C, and Hoogduijn, Martin J

Subjects
VITAMIN D metabolism, ORGANOIDS, ERGOCALCIFEROL, KIDNEYS, CHOLECALCIFEROL, VITAMIN D receptors
Published
2022
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19. Immunomodulation By Therapeutic Mesenchymal Stromal Cells (MSC) Is Triggered Through Phagocytosis of MSC By Monocytic Cells

Author

de Witte, Samantha F.H., primary, Luk, Franka, additional, Sierra Parraga, Jesus M., additional, Gargesha, Madhu, additional, Merino, Ana, additional, Korevaar, Sander S., additional, Shankar, Anusha S., additional, O'Flynn, Lisa, additional, Elliman, Steve J., additional, Roy, Debashish, additional, Betjes, Michiel G.H., additional, Newsome, Philip N., additional, Baan, Carla C., additional, and Hoogduijn, Martin J., additional

Published
2018
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22. Cytokine treatment optimises the immunotherapeutic effects of umbilical cord-derived MSC for treatment of inflammatory liver disease

Author

de Witte, Samantha F. H., primary, Merino, Ana M., additional, Franquesa, Marcella, additional, Strini, Tanja, additional, van Zoggel, Johanna A. A., additional, Korevaar, Sander S., additional, Luk, Franka, additional, Gargesha, Madhu, additional, O’Flynn, Lisa, additional, Roy, Debashish, additional, Elliman, Steve J., additional, Newsome, Philip N., additional, Baan, Carla C., additional, and Hoogduijn, Martin J., additional

Published
2017
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25. Human Bone Marrow- and Adipose Tissue-derived Mesenchymal Stromal Cells are Immunosuppressive In vitro and in a Humanized Allograft Rejection Model

Author

Roemeling-van Rhijn, Marieke, Khairoun, Meriem, Korevaar, Sander S, Lievers, Ellen, Leuning, Danielle G, Ijzermans, Jan Nm, Betjes, Michiel Gh, Genever, Paul G, van Kooten, Cees, de Fijter, Hans Jw, Rabelink, Ton J, Baan, Carla C, Weimar, Willem, Roelofs, Helene, Hoogduijn, Martin J, Reinders, Marlies E, Internal Medicine, and Surgery

Subjects
business.industry, Mesenchymal stem cell, Mesenchymal stromal cells, Adipose tissue, Human skin, hemic and immune systems, Article, Transplantation, Allograft rejection, Immunomodulation, medicine.anatomical_structure, In vivo, Immunology, Humanized mouse, Medicine, Bone marrow, business, CD8
Abstract

BACKGROUND: Recent studies with bone marrow (BM)-derived Mesenchymal Stromal Cells (MSC) in transplant recipients demonstrate that treatment with MSC is safe and clinically feasible. While BM is currently the preferred source of MSC, adipose tissue is emerging as an alternative. To develop efficient therapies, there is a need for preclinical efficacy studies in transplantation. We used a unique humanized transplantation model to study the in vivo immunosuppressive effect of human BM-MSC and adipose tissue-derived MSC (ASC).METHODS: Gene expression of BM-MSC and ASC and their capacity to inhibit activated PBMC proliferation was evaluated. The in vivo immunosuppressive effect of BM-MSC and ASC was studied in a humanized mouse model. SCID mice were transplanted with human skin grafts and injected with human allogeneic PBMC with or without administration of BM-MSC or ASC. The effect of MSC on skin graft rejection was studied by immunohistochemistry and PCR.RESULTS: BM-MSC and ASC expressed TGFβ, CXCL-10 and IDO. IDO expression and acitivity increased significantly in BM-MSC and ASC upon IFN-γ stimulation. IFN-γ stimulated BM-MSC and ASC inhibited the proliferation of activated PBMC in a significant and dose dependent manner. In our humanized mouse model, alloreactivity was marked by pronounced CD45+ T-cell infiltrates consisting of CD4+ and CD8+ T cells and increased IFN-γ expression in the skin grafts which were all significantly inhibited by both BM-MSC and ASC.CONCLUSION: BM-MSC and ASC are immunosuppressive in vitro and suppress alloreactivity in a preclinical humanized transplantation model.

Published
2013

26. Inactivated Mesenchymal Stem Cells Maintain Immunomodulatory Capacity

Author

Luk, Franka, primary, de Witte, Samantha F.H., additional, Korevaar, Sander S., additional, Roemeling-van Rhijn, Marieke, additional, Franquesa, Marcella, additional, Strini, Tanja, additional, van den Engel, Sandra, additional, Gargesha, Madhusudhana, additional, Roy, Debashish, additional, Dor, Frank J.M.F., additional, Horwitz, Edwin M., additional, de Bruin, Ron W.F., additional, Betjes, Michiel G.H., additional, Baan, Carla C., additional, and Hoogduijn, Martin J., additional

Published
2016
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27. Effects of Freeze–Thawing and Intravenous Infusion on Mesenchymal Stromal Cell Gene Expression

Author

Hoogduijn, Martin J., primary, de Witte, Samantha F.H., additional, Luk, Franka, additional, van den Hout-van Vroonhoven, Mirjam C.G.N., additional, Ignatowicz, Lech, additional, Catar, Rusan, additional, Strini, Tanja, additional, Korevaar, Sander S., additional, van IJcken, Wilfred F.J., additional, Betjes, Michiel G.H., additional, Franquesa, Marcella, additional, Moll, Guido, additional, and Baan, Carla C., additional

Published
2016
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28. No Evidence for Circulating Mesenchymal Stem Cells in Patients with Organ Injury

Author

Hoogduijn, Martin J., primary, Verstegen, Monique M.A., additional, Engela, Anja U., additional, Korevaar, Sander S., additional, Roemeling-van Rhijn, Marieke, additional, Merino, Ana, additional, Franquesa, Marcella, additional, de Jonge, Jeroen, additional, Ijzermans, Jan N., additional, Weimar, Willem, additional, Betjes, Michiel G.H., additional, Baan, Carla C., additional, and van der Laan, Luc J.W., additional

Published
2014
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32. Mesenchymal stem cells derived from adipose tissue are not affected by renal disease

Author

Roemeling-van Rhijn, Marieke, primary, Reinders, Marlies E.J., additional, de Klein, Annelies, additional, Douben, Hannie, additional, Korevaar, Sander S., additional, Mensah, Fane K.F., additional, Dor, Frank J.M.F., additional, IJzermans, Jan N.M., additional, Betjes, Michiel G.H., additional, Baan, Carla C., additional, Weimar, Willem, additional, and Hoogduijn, Martin J., additional

Published
2012
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42. Interleukin-21: An Interleukin-2 Dependent Player in Rejection Processes

Author

Baan, Carla C., primary, Balk, Aggie H. M. M., additional, Dijke, I Esmé, additional, Korevaar, Sander S., additional, Peeters, Annemiek M. A., additional, de Kuiper, Ronella P., additional, Klepper, Mariska, additional, Zondervan, Pieter E., additional, Maat, Lex A. P. W. M., additional, and Weimar, Willem, additional

Published
2007
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47. Human Mesenchymal Stem Cells Are Susceptible to Lysis by CD8+T Cells and NK Cells

Author

Crop, Meindert J., Korevaar, Sander S., De Kuiper, Ronella, Ijzermans, Jan N. M., Van Besouw, Nicole M., Baan, Carla C., Weimar, Willem, and Hoogduijn, Martin J.

Abstract

There is growing interest in the use of mesenchymal stem cells (MSCs) to improve the outcome of organ transplantation. The immunogenicity of MSCs is, however, unclear and is important for the efficacy of MSC therapy and for potential sensitization against donor antigens. We investigated the susceptibility of autologous and allogeneic MSCs for lysis by CD8+T-lymphocytes and NK cells in a kidney transplant setting. MSCs were derived from adipose tissue of human kidney donors and were CD90+, CD105+, CD166+, and HLA class I+. They showed differentiation ability and immunosuppressive capacity. Lysis of MSCs by peripheral blood mononuclear cells (PBMCs), FACS-sorted CD8+T cells, and NK cells was measured by europium release assay. Allogeneic MSCs were susceptible for lysis by cytotoxic CD8+T cells and NK cells, while autologous MSCs were lysed by NK cells only. NK cell-mediated lysis was inversely correlated with the expression of HLA class I on MSCs. Lysis of autologous MSCs was not dependent on culturing of MSCs in FBS, and MSCs in suspension as well as adherent to plastic were lysed by NK cells. Pretransplant recipient PBMCs did not lyse donor MSCs, but PBMCs isolated 3, 6, and 12 months after transplantation showed increasing lysing ability. After 12 months, CD8+T-cell-mediated lysis of donor MSCs persisted, indicating there was no evidence for desensitization against donor MSCs. Lysis of MSCs is important to take into account when MSCs are considered for clinical application. Our results suggest that the HLA background of MSCs and timing of MSC administration are important for the efficacy of MSC therapy.

Published
2011
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48. Characterization of Rabbit Antithymocyte Globulins-Induced CD25Regulatory T Cells From Cells of Patients With End-Stage Renal Disease

Author

Sewgobind, Varsha D. K. D., Laan, Luc J. W. van der, Kho, Marcia M. L., Kraaijeveld, Rens, Korevaar, Sander S., van Dam, Thea, Ijzermans, Jan N. M., Weimar, Willem, and Baan, Carla C.

Abstract

Rabbit antithymocyte globulins (rATGs) are known to convert CD4CD25−FoxP3−T cells from healthy individuals to CD4CD25FoxP3T cells. In this study, we investigated the effect of rATG on the induction of regulatory T cells (Tregs) from blood cells of patients with end-stage renal disease who are candidates for transplantation and rATG-induction therapy. The induced Tregs were analyzed and compared with naturally occurring CD4CD25FoxP3T cells.

Published
2010
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49. Inadequate Immune Regulatory Function of CD4CD25brightFoxP3T Cells in Heart Transplant Patients who Experience Acute Cellular Rejection

Author

Dijke, I Esmé, Korevaar, Sander S., Caliskan, Kadir, Balk, Aggie H.M.M., Maat, Alex P.W.M., Weimar, Willem, and Baan, Carla C.

Abstract

CD4CD25brightFoxP3regulatory T cells are suppressors of antigen-activated immune reactivity. Here, we assessed the clinically relevant role of these cells in the control of immune responses directed to a transplanted heart.

Published
2009
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50. The Effect of the JAK Inhibitor CP-690,550 on Peripheral Immune Parameters in Stable Kidney Allograft Patients

Author

Gurp, Evelien A. F. J. van, Schoordijk-Verschoor, Wenda, Klepper, Mariska, Korevaar, Sander S., Chan, Gary, Weimar, Willem, and Baan, Carla C.

Abstract

CP-690,550 inhibits Janus kinase 3 (JAK3) which mediates signal transduction of receptors of the common γ-chain cytokines. These cytokines play key roles in lymphocyte function and homeostasis. As part of a phase 1 trial, we evaluated the effect of CP-690,550 on immune parameters.

Published
2009
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