Basic study towords reconstitution of normal and leukemic human hemopoiesis in small monkey of common marmoset

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For the purpose of constructing preclinical monkey models with normal and leukemic human hematopoiesis, we have introduced small monkey of common marmoset. The followings are the progress in this year.1) Construction of normal and leukemic human hematopoiesis in marmoset :We transplanted CD34 positive human umbilical cord blood cells intraperitoneally to marmoset fetus under the guide of ultrasonograph. We have so far transplanted the CD34 positive human cord blood cells to 16 fetuses in 8 mother marmosets. We have also transplanted human leukemia cells of BV173, IMS-BC1 or Meg-01 to 14 fetuses in 7 mother marmosets. In the beginning abortions followed by the transplantations were experienced but the techniques have been improved using highly sensitive ultrasonography. Now we are following up carefully the in vivo constitution of human/marmoset chimera hematopoiesis in newborn marmosets.2) Characterization of common marmoset lymphocytes : We have isolated marmoset lymphocyte fractions which were positive for human CD4, CD8 or CD56 monoclonal antibodies. The lymphocytes positive for human CD4 or CD8 antibody were considered also to be functional in marmosets. CD56 positive lymphocytes should furthermore be characterized to elucidate its characters.We have so far demonstrated the similar characters of hematopoietic cells and lymphocytes between human and common marmosets. These findings support the possibility of constructing marmoset with human/marmoset hematopoietic chimera. Such marmosets would be very beneficial to study the safety and efficacy of newly developed gene transfer vectors as well as biological modifiers at preclinical levels. Although we have not successfully constructed such chimera marmosets yet, we have developed several new strategies which would make the xenografting more safely and efficiently. Further experiment is required to construct marmoset preclinical model system to study normal and leukemic human hematopoiesis.