publication . Article . Other literature type . 2017

Intrathymic injection of hematopoietic progenitor cells establishes functional T cell development in a mouse model of severe combined immunodeficiency

Marcel R.M. van den Brink; Andrea Z. Tuckett; Richard J. O'Reilly; Johannes L. Zakrzewski; Raymond H. Thornton;
Open Access English
  • Published: 16 May 2017 Journal: Journal of Hematology & Oncology, volume 10 (eissn: 1756-8722, Copyright policy)
  • Publisher: BioMed Central
Background Even though hematopoietic stem cell transplantation can be curative in patients with severe combined immunodeficiency, there is a need for additional strategies boosting T cell immunity in individuals suffering from genetic disorders of lymphoid development. Here we show that image-guided intrathymic injection of hematopoietic stem and progenitor cells in NOD-scid IL2rγnull mice is feasible and facilitates the generation of functional T cells conferring protective immunity. Methods Hematopoietic stem and progenitor cells were isolated from the bone marrow of healthy C57BL/6 mice (wild-type, Luciferase+, CD45.1+) and injected intravenously or intrathym...
free text keywords: Research, SCID, NSG mouse, Thymus, Cell therapy, Hematopoietic stem cell, Cancer Research, Oncology, Molecular Biology, Hematology, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Hematopoietic stem cell transplantation, medicine.medical_treatment, medicine, T cell, medicine.anatomical_structure, Immunology, Progenitor cell, Interleukin 3, CXCR4, Severe combined immunodeficiency, medicine.disease, Biology
Related Organizations
Funded by
NIH| Mucosal Immunity and Microbiota in Intestinal Graft-versus-Host Disease
  • Funder: National Institutes of Health (NIH)
  • Project Code: 9R01AI100288-06A1
  • Funder: National Institutes of Health (NIH)
  • Project Code: 2P30CA008748-43
NIH| The role of autophagy gene Atg16L1 in allogeneic hematopoietic stem cell transplantation - Resubmission - 1
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1R01HL123340-01A1
NIH| Strategies to enhance thymus-independent T cell development in cancer patients
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1K08CA160659-01
Development of Stem Cell Based Therapy for Thymic Regeneration
  • Funder: European Commission (EC)
  • Project Code: 602587
  • Funding stream: FP7 | SP1 | HEALTH
25 references, page 1 of 2

Anderson, G, Jenkinson, EJ. Lymphostromal interactions in thymic development and function. Nat Rev Immunol. 2001; 1: 31-40 [OpenAIRE] [PubMed] [DOI]

Marrella, V, Poliani, PL, Notarangelo, LD, Grassi, F, Villa, A. Rag defects and thymic stroma: lessons from animal models. Front Immunol. 2014; 5: 259 [OpenAIRE] [PubMed]

Pai, SY, Logan, BR, Griffith, LM, Buckley, RH, Parrott, RE, Dvorak, CC, Kapoor, N, Hanson, IC, Filipovich, AH, Jyonouchi, S. Transplantation outcomes for severe combined immunodeficiency, 2000-2009. N Engl J Med. 2014; 371: 434-446 [OpenAIRE] [PubMed] [DOI]

Adjali, O, Vicente, RR, Ferrand, C, Jacquet, C, Mongellaz, C, Tiberghien, P, Chebli, K, Zimmermann, VS, Taylor, N. Intrathymic administration of hematopoietic progenitor cells enhances T cell reconstitution in ZAP-70 severe combined immunodeficiency. Proc Natl Acad Sci U S A. 2005; 102: 13586-13591 [OpenAIRE] [PubMed] [DOI]

Vicente, R, Adjali, O, Jacquet, C, Zimmermann, VS, Taylor, N. Intrathymic transplantation of bone marrow-derived progenitors provides long-term thymopoiesis. Blood. 2010; 115: 1913-1920 [OpenAIRE] [PubMed] [DOI]

de Barros, SC, Vicente, R, Chebli, K, Jacquet, C, Zimmermann, VS, Taylor, N. Intrathymic progenitor cell transplantation across histocompatibility barriers results in the persistence of early thymic progenitors and T-cell differentiation. Blood. 2013; 121: 2144-2153 [OpenAIRE] [PubMed] [DOI]

Chan, AC, Kadlecek, TA, Elder, ME, Filipovich, AH, Kuo, WL, Iwashima, M, Parslow, TG, Weiss, A. ZAP-70 deficiency in an autosomal recessive form of severe combined immunodeficiency. Science. 1994; 264: 1599-1601 [OpenAIRE] [PubMed] [DOI]

Picard, C, Al-Herz, W, Bousfiha, A, Casanova, JL, Chatila, T, Conley, ME, Cunningham-Rundles, C, Etzioni, A, Holland, SM, Klein, C. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J Clin Immunol. 2015; 35: 696-726 [OpenAIRE] [PubMed] [DOI]

Shultz, LD, Lyons, BL, Burzenski, LM, Gott, B, Chen, X, Chaleff, S, Kotb, M, Gillies, SD, King, M, Mangada, J. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J Immunol. 2005; 174: 6477-6489 [OpenAIRE] [PubMed] [DOI]

Rodewald, HR, Brocker, T, Haller, C. Developmental dissociation of thymic dendritic cell and thymocyte lineages revealed in growth factor receptor mutant mice. Proc Natl Acad Sci U S A. 1999; 96: 15068-15073 [OpenAIRE] [PubMed] [DOI]

Tuckett, AZ, Zakrzewski, JL, Li, D, van den Brink, MR, Thornton, RH. Free-hand ultrasound guidance permits safe and efficient minimally invasive intrathymic injections in both young and aged mice. Ultrasound Med Biol. 2015; 41: 1105-1111 [OpenAIRE] [PubMed] [DOI]

Tuckett, AZ, Thornton, RH, Shono, Y, Smith, OM, Levy, ER, Kreines, FM, van den Brink, MR, Zakrzewski, JL. Image-guided intrathymic injection of multipotent stem cells supports lifelong T-cell immunity and facilitates targeted immunotherapy. Blood. 2014; 123: 2797-2805 [OpenAIRE] [PubMed] [DOI]

Makino, S, Kunimoto, K, Muraoka, Y, Mizushima, Y, Katagiri, K, Tochino, Y. Breeding of a non-obese, diabetic strain of mice. Jikken Dobutsu. 1980; 29: 1-13 [OpenAIRE] [PubMed]

Cao, YA, Wagers, AJ, Beilhack, A, Dusich, J, Bachmann, MH, Negrin, RS, Weissman, IL, Contag, CH. Shifting foci of hematopoiesis during reconstitution from single stem cells. Proc Natl Acad Sci U S A. 2004; 101: 221-226 [OpenAIRE] [PubMed] [DOI]

Anderson, MS, Bluestone, JA. The NOD mouse: a model of immune dysregulation. Annu Rev Immunol. 2005; 23: 447-485 [OpenAIRE] [PubMed] [DOI]

25 references, page 1 of 2
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