دورية أكاديمية
Generation of human ILC3 from allogeneic and autologous CD34 + hematopoietic progenitors toward adoptive transfer.
العنوان: | Generation of human ILC3 from allogeneic and autologous CD34 + hematopoietic progenitors toward adoptive transfer. |
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المؤلفون: | Van der Meer JMR; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands., Bulder I; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands; Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands., Kuijk C; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands., Kleijer M; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands., Verheij MW; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands; Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands., Omar SZ; Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, University of Amsterdam, Amsterdam, The Netherlands., Haverkate NJE; Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, University of Amsterdam, Amsterdam, The Netherlands., Dolstra H; Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands., Blom B; Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, University of Amsterdam, Amsterdam, The Netherlands., Hazenberg MD; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands; Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, University of Amsterdam, Amsterdam, The Netherlands; Cancer Center Amsterdam, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Department of Hematology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands., Voermans C; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands; Department of Hematology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: c.voermans@sanquin.nl. |
المصدر: | Cytotherapy [Cytotherapy] 2024 Feb; Vol. 26 (2), pp. 136-144. Date of Electronic Publication: 2023 Dec 25. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Country of Publication: England NLM ID: 100895309 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-2566 (Electronic) Linking ISSN: 14653249 NLM ISO Abbreviation: Cytotherapy Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2013- : London : Elsevier Original Publication: Oxford, England : ISIS Medical Media, c1999- |
مواضيع طبية MeSH: | Hematopoietic Stem Cell Transplantation*/methods , Graft vs Host Disease*/prevention & control , Benzamides* , Indazoles* , Piperazines* , Pyridones*, Adult ; Infant, Newborn ; Humans ; Immunity, Innate ; Lymphocytes/chemistry ; Antigens, CD34/analysis ; Granulocyte Colony-Stimulating Factor/pharmacology ; Inflammation ; Adoptive Transfer |
مستخلص: | Type 3 innate lymphoid cells (ILC3) are important in tissue homeostasis. In the gut, ILC3 repair damaged epithelium and suppress inflammation. In allogeneic hematopoietic cell transplantation (HCT), ILC3 protect against graft-versus-host disease (GvHD), most likely by restoring tissue damage and preventing inflammation. We hypothesize that supplementing HCT grafts with interleukin-22 (IL-22)-producing ILC3 may prevent acute GvHD. We therefore explored ex vivo generation of human IL-22-producing ILC3 from hematopoietic stem and progenitor cells (HSPC) obtained from adult, neonatal and fetal sources. We established a stroma-free system culturing human cord blood-derived CD34 + HSPC with successive cytokine mixes for 5 weeks. We analyzed the presence of phenotypically defined ILC, their viability, proliferation and IL-22 production (after stimulation) by flow cytometry and enzyme-linked immunosorbent assay (ELISA). We found that the addition of recombinant human IL-15 and the enhancer of zeste homolog 1/2 inhibitor UNC1999 promoted ILC3 generation. Similar results were demonstrated when UNC1999 was added to CD34 + HSPC derived from healthy adult granulocyte colony-stimulating factor mobilized peripheral blood and bone marrow, but not fetal liver. UNC1999 did not negatively impact IL-22 production in any of the HSPC sources. Finally, we observed that autologous HSPC mobilized from the blood of adults with hematological malignancies also developed into ILC3, albeit with a significantly lower capacity. Together, we developed a stroma-free protocol to generate large quantities of IL-22-producing ILC3 from healthy adult human HSPC that can be applied for adoptive transfer to prevent GvHD after allogeneic HCT. Competing Interests: Declaration of Competing Interest The authors declare no competing interests. (Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.) |
فهرسة مساهمة: | Keywords: adoptive transfer; hematopoietic stem and progenitor cells; human; interleukin-22; stroma-free; type 3 innate lymphoid cells |
المشرفين على المادة: | 0 (UNC1999) 0 (Antigens, CD34) 143011-72-7 (Granulocyte Colony-Stimulating Factor) 0 (Benzamides) 0 (Indazoles) 0 (Piperazines) 0 (Pyridones) |
تواريخ الأحداث: | Date Created: 20231227 Date Completed: 20240205 Latest Revision: 20240605 |
رمز التحديث: | 20240606 |
DOI: | 10.1016/j.jcyt.2023.11.011 |
PMID: | 38149947 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1477-2566 |
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DOI: | 10.1016/j.jcyt.2023.11.011 |