Stromal Stem Cell Therapy for Prophylaxis of Acute GVHD: Preliminary Results From a Phase 1 Trial

R.T. Maziarz, C. Bachier, S. Goldstein, S. Devine, J. Leis, K. Cooke, R. Perry, W. Van't Hof, R. Deans, H.M. Lazarus
2011 Biology of Blood and Marrow Transplantation  
Bone marrow is a frequent metastatic site for neuroblastoma, a common form of childhood cancer with poor prognosis. The SDF-1/CXCR4 axis has been proposed as an important pathway during metastasis of neuroblastoma. But the role of mesenchymal stromal cells (MSCs) and CXCR7, the other known receptor for SDF-1, in metastatic neuroblastoma is yet to be clarified. Materials & Methods: In this study, we investigated the chemotactic effects of human bone marrow derived MSCs on the migration of
more » ... astma cells, with specific emphasis on the SDF-1/ CXCR4 and SDF-1/CXCR7 axes. To determine the contribution of SDF-1 released by MSCs, we collected serum poor conditioned media from three different MSC cultures and estimated their SDF-1 levels by ELISA. We then examined the cell surface expression of CXCR4 and CXCR7 on five known neuroblastoma cell lines (BE2C, BE2M17, IMR32, SK-N-LP and SY5Y) with metastatic potential by flow cytometer. The metastatic functional assessment was performed by transwell migration and invasion assay. Results: SDF-1 can be identified from the MSCs culture medium. The migration and invasion of neuroblastoma was enhanced by either MSCs co-culture or SDF-1 under transwell migration and invasion assay. Flow cytometry analysis revealed that all of the five cell lines expressed CXCR7, and four of them expressed CXCR4. The migration efficiency of neuroblastoma cells in response to either MSCs conditioned media or SDF-1 treatments was considerably higher than that to control medium (n 5 3, p \ 0.01), and such effect could be significantly blocked by AMD3100, an inhibitor of CXCR4. Conclusion: Our preliminary data suggested that MSCs enhanced neuroblastoma cells migration and invasion and this is probably acting through the SDF-1/CXCR4 and SDF-1/CXCR7 axes. Background: Bone marrow derived mesenchymal cells and stem cells are potential to differentiate into mature cells of various organs. Here we describe the initial results of study which suggests that these cells transformed to hepatocytes. Methods: In this prospective, single-center study during 18 months, liver biopsy were obtained from 9 patients who had undergone Co-Transplantation of Mesenchymal and Hematopoietic Stem Cell for beta thalassemia major class III. Five female patients and 4 male patients had received transplant from their sex mismatch donors. The biopsies were studied for the presence of donor-derived hepatocytes with the use of fluorescence in situ hybridization (FISH) and immunohistochemical staining (IHC) for CD45 (leukocyte common antigen), and a hepatocyte-specific antigen. Results: According to sex mismatch transplantation, mixed donorrecipient XY-positive hepatocytes in liver specimen means that new chimer stem cells were originated from donor cells. These cells accounted for 8 to 70 percent of the cells on FISH slides and their hepatocyte properities were shown by IHC methods. Conclusions: Co-transplantation of Mesenchymal and Hematopoietic Stem Cell can enhance regeneration of mature hepatocytes in liver tissue.
doi:10.1016/j.bbmt.2010.12.214 fatcat:gousxlvtmvb4dg6a5dbmuovyie