Kinetics Of Donor-deirved Hematopoietic Stem And Porgenitor Cells In A Haplo-identical Acute Graft-versus-host Disease Model

In this study, we have established the haplo-MHC matched BM transplantation (BMT)animal model to quantitatively study the alteration of donor-derived hematopoiesis inaGVHD environment. Methods We took the approaches of quantitative clonal assay invitro and flowcytometry to analyze HSC/HPC frequencies and their properties of cell cycleand apoptosis, with no aGVHD but irradiated transplantation model as control group.Results1.Haplo-MHC matched bone marrow transplantation induced aGVHD with100%.2. Hematopoietic suppression at both stem and progenitor cell levels in theaGVHD-bearing mice.3. Increased quiescence but no difference in homing process orapoptosis of the donor-derived hematopoietic cells in aGVHD marrow.4. Functionalpreservation of HSC in the aGVHD marrow.5. In aGVHD environment, there was adifferentiation bias of donor-derived hematopoietic progenitor cells in the egress fromCMP to GMP.6.CsA-administration can rescue the frequency decrease of CMP/MEP inaGVHD hosts.Conclusions Our current study demonstrates for the first time that pan-scalerepression of hematopoietic cells in aGVHD environment which displayed in a specificway that the absolute numbers declined dramatically while the relative frequencies indonor-derived CD45.1+cells stayed higher as compare to control group. Our data suggest the donor-derived stem cell candidates were kept in the dormant status with reservation ofself-renewal potential. It is the first report suggesting that sereve oligocythemia andthrombocytopenia during aGVHD result from the differentiation bias in the egress fromCMP to GMP. While CsA can rescue the alteration of hematopoiesis in aGVHD hosts.