Methods comprising apoptosis inhibitors for the generation of transgenic pigs

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Stem Cell Related Patent Number US6455756

Title:Long term xenogeneic myeloid and lymphoid cell production in chimeric immunocompromised mice
Inventors:Chen, Benjamin P.; Fremont, CA, USA
Fraser, Christopher C.; Los Altos, CA, USA
Summary:Described herein are novel chimeric hosts which produce human myeloid and lymphoid cells. The invention relates to a mouse host lacking functional syngeneic B-cells and T-cells due to a genetic defect that results in an inability to undergo germline DNA rearrangement at the loci encoding immunoglobulins and T-cell antigen receptors. Further disclosed are methods by which immunocompromsed mammalian hosts are sub-cutaneously implanted with a combination of human fetal bone and spleen, resulting in chimeric animals that can produce human B-cells, myeloid cells and T-cells for up to 9 months in vivo when supplied with an allogeneic human fetal thymic fragment at the same site. Claims of the invention include grafts containing cell populations expressing CD4 and CD8, CD19 or CD33, CD14 and CD15, all of which also express the HLA type of the fetal bone/spleen. The T-cells herein are described as being derived from progenitors in the fetal bone/spleen containing both mature single positive CD4+CD8-, CD8+CD4- as well as a high percentage of immature double positive CD4+CD8+ populations. Applications in studying the pathogenesis of various diseases are included.
Abstract:Immunocompromised mammalian hosts are sub-cutaneously implanted with a combination of human fetal bone and spleen. The chimeric animals can produce human B-cells, myeloid cells and T-cells for up to 9 months in vivo when supplied with an allogeneic human fetal thymic fragment at the same site. Grafts contain cell populations expressing CD4 and CD8, CD19 or CD33, CD14 and CD15, all of which also express the HLA type of the fetal bone/spleen. T-cells derived from progenitors in the fetal bone/spleen contain both mature single positive CD4+CD8-, CD8+CD4- as well as a high percentage of immature double positive CD4+CD8+ populations.
US Patent Website:Click Here for Full Text of Patent
Title Number:US6455756
Application Number:US1994000290038
Date Filed:12/08/1994
Date Published:24/09/2002
Assignee:Novartis AG, Basel, Switzerland


 
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