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Allogeneic non-adherent bone marrow cells do not lead to allogeneic engraftment but facilitate hematopoietic recovery

: Sack, U.; Ackermann, M.; Stolzing, A.; Hilger, N.; Schimmelpfennig, C.; Jahns, J.; Hildebrandt, G.; Emmrich, F.; Boltze, J.; Kamprad, M.; Fricke, S.

Cytometry. Part B, Clinical cytometry 76 (2009), Nr.6, S.431
ISSN: 1552-4949
ISSN: 0196-4763
ISSN: 1552-4957
Euroconference on Clinical Cell Analysis <9, 2009, St. Etienne>
Fraunhofer IZI ()

Non-adherent bone marrow derived cells (naBMCs) have recently been described to give rise to multiple mesenchymal phenotypes and to have an impact in tissue regeneration. Therefore, the effects of murine bone marrow derived non-adherent cells were investigated with regard to engraftment capacities in allogeneic and syngeneic stem cell transplantation using transgenic, human CD4þ, murine CD4-/-, HLA-DR3þ mice. Bone marrow cells were harvested from C57Bl/6 and Balb/c wild-type mice, expanded to naBMCs for 4 days and characterized by flow cytometry and CFU-f before transplantation in lethally irradiated recipient mice. Chimerism was detected at day 40, using flow cytometry (MHC-I (H-2D[b], H-2K[d]), CD4), quantitative PCR, and histology of the gut. Culturing of bone marrow cells in dexamethasone-containing DMEM medium induced expansion of non-adherent cells expressing CD11b, CD45, and CD90. Analysis of the CD45þ cells showed depletion of CD4þ, CD8þ, CD19þ, and CD117þ cells. Expanded syngeneic and allogeneic naBMCs were transplanted into triple transgenic mice. Syngeneic naBMCs protected 83% of mice from death (n 5 8, hematopoietic CD4þ donor chimerism of 5.862.4% [day 40], P .001). Allogeneic naBMCs preserved 62.5% (n 5 8) of mice from death without detectable hematopoietic donor chimerism. naBMCs triggered endogenous hematopoiesis and induced faster recovery compared to bone marrow controls. To our knowledge, this is the first report describing such effects of naBMCs in mice. These findings might have an impact on clinical transplantation settings, namely for the explanation of relapses of leukemia.