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Controversy persists about mixed chimerism (mCh) occurring in the hearts of patients after orthotopic cardiac transplantation in comparison with allogeneic bone marrow (BM) and peripheral blood stem-cell (PBSC) transplants. Cadaver hearts were examined after sex-mismatched transplantation by immunophenotyping combined with dual color fluorescence in situ hybridization (X and Y chromosome-specific probes). A striking disparity in the extent of mCh depending on the different transplantation procedures was recognizable. After allografting with PBSCs, 1.7% chimeric cardiomyocytes were detectable contrasting 5.4% of donor cells after full BM transplantation. In cardiac transplants, host-type endothelial cells (16.2%) and myocytes (14.3%) of the vessel walls were more often encountered than after BM and PBSC allografting. A sprouting of vascular structures into the donor heart after orthotopic cardiac transplantation has to be assumed, as does a pivotal role of the mesenchymal stem cells of the BM in the development of mCh.

BackgroundIn this study we evaluated the interactions of human adipose tissue-derived stem cells (ADSCs) and different human breast cancer cell lines (BRCAs) with regard to the safety of cell-assisted lipotransfers for breast reconstruction and a thereby unintended co-localization of ADSCs and BRCAs.MethodsADSCs were co-cultured with five different human BRCAs (MCF-7, MDA-MB-231, SK-BR-3, ZR-75-30, and EVSA-T) and primary BRCAs from one patient in a transwell system, and cell-cell-interactions were analyzed by assessing doubling time, migration and invasion, angiogenesis, quantitative real-time polymerase chain reaction (PCR) of more than 300 tumor-associated genes, and multiplex protein assays of 20 chemokines and growth factors and eight matrix metalloproteinases (MMPs). Results of co-culture were compared to those of the respective monoculture.ResultsQuantitative real-time PCR revealed remarkable changes in the expression of multiple tumor-associated genes in co-culture compared to monocultures of both ADSCs and BRCAs. Concomitantly, the concentration of several tumor-associated proteins, such as cytokines and MMPs, were strongly increased in co-culture. Furthermore, exclusively in co-culture with ADSCs, the different BRCAs were exposed to several important tumor-modulating proteins, such as CCL2, HGF, or interleukins.Co-culture did not significantly affect cellular proliferation of either ADSCs or BRCAs (p > 0.05). The migration of MCF-7 and MDA-MB-231 BRCAs was significantly increased in co-culture with ADSCs by a mean of 11% and 23%, respectively (p = 0.04 and 0.012), as well as that of ADSCs in co-culture with MDA-MB-231, ZR-75-30, and EVSA-T (+11–15%, p = 0.035–0.045). Co-culture with MDA-MB-231, SK-BR-3, and EVSA-T BRCAs significantly increased the invasive behavior of ADSCs by a mean of 24–41% (p = 0.014–0.039). There were no significant differences in the in vitro invasive properties of BRCAs in co-culture compared to monoculture. An in vitro angiogenesis assay revealed an increased tube formation of conditioned media from co-cultured BRCAs and ADSCs compared to the respective monocultures.ConclusionThis study further elucidates the possible interactions of primary human ADSCs with human BRCAs, pointing towards a potential increased oncological risk which should not be neglected when considering a clinical use of cell-assisted lipoaspirates in breast reconstruction.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0579-1) contains supplementary material, which is available to authorized users.

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