Engraftment and Development of Human T and B Cells in Mice After Bone Marrow Transplantation

Lubin, Ido; Faktorowich, Yifat; Lapidot, Tsvee; Gan, Yehudit; Eshhar, Zelig; Gazit, Ephraim; Levite, Mia; Reisner, Yair

doi:10.1126/science.1826797

Cited by 83 publications

(46 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Transfer of autoimmune disease has been accomplished by the transfer of lymphocytes from patients with primary biliary cirrhosis into severe combined immunodeficient mice (8). Human antibody response to dinitrophenol has been observed by Lubin et al (4) after primary and secondary immunization (4).…”

Section: Forward Light Scattermentioning

confidence: 99%

“…(4)(5)(6)(7)(8)(9)(10). Both irradiated mice (4) and genetically immunodeficient mice (5-10) have served as recipients.…”

Section: Forward Light Scattermentioning

confidence: 99%

“…HLA matching and T cell depletion ofthe donor graft are also useful adjuncts to mitigate development of life-threatening graft versus host disease (GVHD) which may occur during graft rejection (1,2). When applied appropriately, these procedures have been used to achieve chimerism between different species including humanmouse (4)(5)(6)(7)(8)(9)(10). Xenogeneic transplantation ofhuman HSC has also been reported in genetically deficient mice (5)(6)(7)(8)(9)(10) and in normal mice rendered tolerant by lethal irradiation (4).…”

mentioning

confidence: 99%

“…Tolerance oftransplanted allogeneic cells in clinical settings can be achieved using genetically immunodeficient donors/recipients (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). Alternatively, immunocompetent recipients can be rendered immunotolerant by using immunosuppressive and/or cytoablative procedures, which may also serve to promote engraftment by donor HSC by eliminating recipient HSC which may compete for homing sites within the bone marrow (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). HLA matching and T cell depletion ofthe donor graft are also useful adjuncts to mitigate development of life-threatening graft versus host disease (GVHD) which may occur during graft rejection (1,2).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Engraftment and long-term expression of human fetal hemopoietic stem cells in sheep following transplantation in utero.

Zanjani

Pallavicini²,

Ascensāo³

et al. 1992

J. Clin. Invest.

229

153

View full text Add to dashboard Cite

Hemopoietic stem cells from human fetal liver were transplanted in utero into preimmune fetal sheep (48-54 days of gestation). The fate ofdonor cells was followed using karyotype analysis, by immunofluorescence labelingwith anti-CD antibodies, and by fluorescent in situ hybridization using human-specific DNA probes. Engrftment occurred in 13 of 33 recipients. Of five live born sheep that exhibited chimerism, all expressed human cells in the marrow, whereas three expressed them in blood as well.Engraftment was multilineage (erythroid, myeloid, and lymphoid) and human hemopoietic progenitors (multipotent colony-forming units, colony-forming units-granulocyte, macrophage, and erythroid burst-forming units) capable of forming colonies in vitro were detected in all five lambs for > 2 yr. These progenitors responded to human-specific growth-factors both in vitro and in vivo. Thus the administration of recombinanthumanIL-3andgranulocytemacrophage-colony-stimulating factor to chimeric sheep resulted in a 2.1-3.4-fold increase in the relative expression of donor (human) cells. These results demonstrate that the permissive environment ofthe preimmune fetal sheep provides suitable conditions for the engraftment and long-term multilineage expression of human hemopoietic stem cells in a large animal model. In this model, donor human cells appear to retain certain phenotypic and functional characteristics that can be used to manipulate the size of donor cell pool.

show abstract

Section: Forward Light Scattermentioning

confidence: 99%

“…(4)(5)(6)(7)(8)(9)(10). Both irradiated mice (4) and genetically immunodeficient mice (5-10) have served as recipients.…”

Section: Forward Light Scattermentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Engraftment and long-term expression of human fetal hemopoietic stem cells in sheep following transplantation in utero.

Zanjani

Pallavicini²,

Ascensāo³

et al. 1992

J. Clin. Invest.

229

153

View full text Add to dashboard Cite

show abstract

“…[12][13][14][15][16] This resulting humanmouse model that comprises three genetically disparate sources of tissue is therefore termed ''Trimera.'' The Trimera mouse, engrafted with human peripheral blood lymphocytes, has been adapted successfully to generate human monoclonal antibodies.…”

mentioning

confidence: 99%

The Hepatitis B Virus-Trimera Mouse: A Model for Human Hbv Infection and Evaluation of Anti–Hbv Therapeutic Agents

et al. 1999

Self Cite

View full text Add to dashboard Cite

Previous studies have demonstrated the feasibility of implantation of human blood cells or tissues in lethally irradiated mice or rats, radioprotected with SCID mouse bone marrow cells: The Trimera system. In the present study, we describe the development of a mouse Trimera model for human hepatitis B virus (HBV) infection. In this model, viremia is induced by transplantation of ex vivo HBV-infected human liver fragments. Engraftment of the human liver fragments, evaluated by hematoxylin-eosin staining and human serum albumin mRNA expression, was observed in 85% of the transplanted animals 1 month postimplantation. Viremia levels were determined in these mice by measuring serum HBV DNA using polymerase chain reaction (PCR), followed by dot-blot hybridization. HBV DNA is first detected 8 days after liver transplantation. Viremia attains a peak between days 18 and 25 when HBV infection is observed in 85% of the transplanted animals. Hepatitis B virus (HBV) infection is a major public health problem affecting millions of people worldwide. 1 Following acute HBV infection, 5% to 10% of the adult patients will develop persistent infection that may lead to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. 2-4 Whereas considerable progress has been achieved regarding the identification and characterization of the virus, the development of new, effective therapies has been impeded because of the lack of a practical small HBV animal model. Attempts to establish animal models to study HBV infection in rats, 5 nude mice, 6 and transgenic mice 7-9 have been described. Other animal models, based on HBV-related hepadnaviruses that infect nonprimates, were developed and successfully used for assessment of antiviral drugs. These models, however, involve relatively large animals that are difficult to handle in most laboratories. In addition, testing of antiviral agents such as nucleoside analogs could produce aberrant results as a consequence of virus-specific differential susceptibility of the viral polymerase. 10 Chimpanzees provide a good HBV animal model in which effects of vaccines and therapeutic agents can be evaluated. 11 Nonetheless, the limited availability and the high cost of these primates severely restrict their use for such purposes.Recently, we have developed a human-mouse radiation chimera in which normal mice, preconditioned by lethal total body irradiation and radioprotected with SCID mouse bone marrow cells, are permissive for engraftment of human hematopoietic cells and tissues. [12][13][14][15][16] This resulting humanmouse model that comprises three genetically disparate sources of tissue is therefore termed ''Trimera.'' The Trimera mouse, engrafted with human peripheral blood lymphocytes, has been adapted successfully to generate human monoclonal antibodies. 17 Likewise, transplantation of Trimera mice with hepatitis C virus-infected human liver tissue was used for the development of an hepatitis C virus infection model. 14 In the present study, we describe in detail the development of an HBV ani...

show abstract

Construction of Human‐SCID Chimeric Mice

Roncarolo

Carballido

1998

CP in Immunology

View full text Add to dashboard Cite

Until recently, testing of new therapeutic agents has relied extensively upon the use of mice and nonhuman primates for in vivo preclinical studies. Unfortunately, these animal models do not always mimic the physiological and pathophysiological processes that occur in humans. The finding that C.B-17 severe combined immunodeficiency (SCID) mice lack a competent immune system, and therefore are unable to mount effective cellular and humoral responses to foreign antigens, has led to their use as recipients for xenografts of human tissues. This unit is focused on the construction of human-SCID chimeric through the surgical implantation of human fetal hematolymphoid tissues into SCID mice (SCID-hu mice). The Basic Protocol describes the surgical implantation of human fetal thymus and liver under the kidney capsules of SCID mice (SCID-hu Thy/Liv model). Subcutaneous transplantation of human fetal bone marrow and thymus (SCID-hu Bm/Thy mice) is described in the Alternate Protocol. Additional support protocols provide procedures to analyze human lymphocyte populations in the peripheral blood and grafted organs of SCID-hu mice. The advantages and disadvantages of each protocol and potential applications are discussed in the Commentary.

show abstract

Engraftment and Development of Human T and B Cells in Mice After Bone Marrow Transplantation

Cited by 83 publications

References 17 publications

Engraftment and long-term expression of human fetal hemopoietic stem cells in sheep following transplantation in utero.

Engraftment and long-term expression of human fetal hemopoietic stem cells in sheep following transplantation in utero.

The Hepatitis B Virus-Trimera Mouse: A Model for Human Hbv Infection and Evaluation of Anti–Hbv Therapeutic Agents

Construction of Human‐SCID Chimeric Mice

Contact Info

Product

Resources

About