The overall objectives of this project is to establish a hemopoietic stem cell model which can be tested to study and understand the mechanism of self renewal and/or commitment to differentiated cell types by a primitive cell. A high incidence of lineage, undifferentiated cells was identified in the spleens of female NZB mice. Phenotypic, morphological, histochemical, genomic and functional characterization of the purified population suggested that these may be very primitive cells of the hemopoietic system. In Vitro, these cells were found to differentiate in response to a few early-acting lymphokines and a bone marrow stromal cell conditioned medium. In that culture system, both myeloid (adherent Mac- 1+), and lymphoid (CD3+, surface Ig+) cell types were detectable. In vivo, these cells reconstitute immunodeficient SCID mice into fully functional immunocompetent mice. Similar splenic stem cells from BALB/c mice also. In the present reporting period (October 1992 thru september 1993), the comparative reconstituting potentials of bone marrow vs spleen derived stem cells was examined in neonatal NFS X NZBF1 mice model. Neonates were bred in house and were injected with in 24 hrs of their birth with graded dose of splenic stem cells and bone marrow cells. The recipient F1 mice were being typed for all the lineages of the donor origin by two-color FMF analyses. A dose dependant reconstitution of stem cells of donor origin was observed. Both marrow-derived and splenic stem cells exhibited similar reconstituting abilities. Further, marrow derived and splenic stem cells from SCID mice reconstituted primarily (either with the marrow-derived or splenic stem cells) successfully reconstituted the secondary SCID mice, confirming the self renewal potential of splenic stem cells. The SCID-NZB mice reconstituted with marrow derived and splenic stem cells were examined for the development of antierythrocytic antibodies and proteinurea, the indicators of Lupus disease. At the that time results were negative, suggesting the splenic or marrow derived stem cells in a non-autoimmune microenvironment develop into functional normal immune cells.

National Institute of Health (NIH)
Food and Drug Administration (FDA)
Intramural Research (Z01)
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