Experimental model for the development of the artificial bone marrow

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The bone marrow microenvironment has been suggested to play a important role in hematopoietic phenomenon. Stromal cells has been emphasized to be a essential component of this microenvironment, however, the complexity of the stromal cell populations makes it difficult to study the nature of their interaction with hematopoietic cells. To elucidate the hematopoietic supportive function of stromal cells, cloned stromal cell line from bone marrow was eatablished and the specific character of stromal cell was analyzed.1. When purified bone marrow hematopoietic stem cells (CD34+) were cocultivated with cloned stromal cell (in vitro bone marrow cell culture system ; LTMC system), CD34+cells were increased one-hundred higher than that of stromal cell free control and these cells were maintained for more than 8 weeks. Further study showed that the stromal cells support the hematopoietic stem cell proliferation and differentiation by the mechanisms of ; 1)production of soluble hematopoietic regu … More latory factors and 2)physical cell-to-cell interactions through the adherent molecules expressed on the surface of stromal cells. It was found that the production of hematopoietic factors from stromal cells was regulated by not only various cytokines but also neurotransmitters. A novel Kd35 protein, which involved in the proliferation and differentiation of hematopoietic stem cells was detected on the surface of stromal cells by cell blotting technique and a study for cloning of this protein is now on going.2. By using the LTMC system, a role of stromal cell in hematopoietic disorders was studied. First, it was clarified that vesnarinone, an oral therapeutic agent for cardiac failure, caused agranulocytosis through the impairment of the production of hematopoietic growth factors from stromal cells. Second, a lack of hematopoietic supportive function of stromal cells was found in the patients with myelodysplastic syndrome. All these findings suggest that LTMC system provides an essential tool for studying the hematopoietic phenomenon in vitro. Less