Systemix, Inc.

Hideto Kaneshima

Joseph M McCune

Reiko Namikawa

Mark L Bonyhadi

Seishi Kyoizumi

Brian Ford

Susan K Mayo

Lishan Su

A human hematopoietic system is provided in an immunocompromised mammalian host, where the hematopoietic system is functional for extended periods of time. Particularly, human fetal liver tissue and human fetal thymus is introduced into an appropriate site of a young immunocompromised mouse at a site supplied with a vascular system, whereby the fetal tissue results in novel formation of functional human bone marrow tissue.

Extended human hematopoiesis in a heterologous host

The invention provides methods for screening agents for potential anti-viral effects by assessing the ability of the agents to suppress viral replication and/or pathology in thymic cells grown in thymic organ culture in vitro. Also provided are methods to study viral pathology and infectivity.

Method for screening potential therapeutically effective antiviral agents

Chimeric immunocompromised hosts are provided, comprising human bone marrow of at least 4 weeks from the time of implantation. The bone marrow is found to assume the normal population of bone marrow except for erythrocytes. The bone marrow may be used to study the effect of various agents on the proliferation and differentiation of hematopoietic cells.

In vivo use of human bone marrow for investigation and production

A method is provided for screening compounds for the ability to supress thymocyte depletion in thymuses of HIV-infected individuals, particularly enhancing the CD4.sup.+ -expressing population as compared to an untreated individual. Particularly, drugs are provided which allow for this result, cyclosporine A being exemplary.

Drug screening and treatment for HIV thymocyte depletion

Immunocompromised hosts comprising xenogeneic fetal lymph node tissue implanted in the ear pinna are provided. The chimeric hosts are prepared by inserting the xenogeneic lymph node tissue into the ear pinna and closing the incision. The tissue is found to be rapidly vascularized and can be productively infected with HIV.

Xenogeneic tissue implant in ear pinna

Human lymphoid tissue is introduced into an immunocompromised host to provide opportunities to investigate the effect of stimuli on the human immune system and obtain information and products from the stimulus. Particularly, methodology is provided for the production of human monoclonal antibodies by introducing lymphoid tissue into an immunocompromised host, stimulating the B-lymphocytes with an appropriate immunogen, harvesting the tissue and immortalizing and/or cloning the B-lymphocytes under conditions to obtain a stable supply of monoclonal antibodies.

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Palo Alto, CA, United States of America

Hideto Kaneshima