Werner-Klein, Melanie and Proske, Judith and Werno, Christian and Schneider, Katharina and Hofmann, Hans-Stefan and Rack, Brigitte and Buchholz, Stefan and Ganzer, Roman and Blana, Andreas and Seelbach-Goebel, Birgit and Nitsche, Ulrich and Maennel, Daniela N. and Klein, Christoph A. (2014) Immune Humanization of Immunodeficient Mice Using Diagnostic Bone Marrow Aspirates from Carcinoma Patients. PLOS ONE, 9 (5): e97860. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
Tumor xenografts in immunodeficient mice, while routinely used in cancer research, preclude studying interactions of immune and cancer cells or, if humanized by allogeneic immune cells, are of limited use for tumor-immunological questions. Here, we explore a novel way to generate cancer models with an autologous humanized immune system. We demonstrate that hematopoietic stem and progenitor cells (HSPCs) from bone marrow aspirates of non-metastasized carcinoma patients, which are taken at specialized centers for diagnostic purposes, can be used to generate a human immune system in NOD-scid IL2r gamma(null) (NSG) and HLA-I expressing NSG mice (NSG-HLA-A2/HHD) comprising both, lymphoid and myeloid cell lineages. Using NSG-HLA-A2/HHD mice, we show that responsive and self-tolerant human T cells develop and human antigen presenting cells can activate human T cells. As critical factors we identified the low potential of bone marrow HSPCs to engraft, generally low HSPC numbers in patient-derived bone marrow samples, cryopreservation and routes of cell administration. We provide here an optimized protocol that uses a minimum number of HSPCs, preselects high-quality bone marrow samples defined by the number of initially isolated leukocytes and intra-femoral or intra-venous injection. In conclusion, the use of diagnostic bone marrow aspirates from non-metastasized carcinoma patients for the immunological humanization of immunodeficient mice is feasible and opens the chance for individualized analyses of anti-tumoral T cell responses.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEMATOPOIETIC STEM-CELLS; LYMPHOID-SYSTEM MICE; BREAST-CANCER; TUMOR-CELLS; CLINICAL-SIGNIFICANCE; PERIPHERAL-BLOOD; CHALLENGES; MODEL; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Geburtshilfe) Medicine > Abteilung für Thoraxchirurgie Medicine > Lehrstuhl für Immunologie Medicine > Lehrstuhl für experimentelle Medizin und Therapieverfahren |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Nov 2019 13:11 |
| Last Modified: | 08 Nov 2019 13:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/10179 |
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