Serum after Autologous Transplantation Stimulates Proliferation and Expansion of Human Hematopoietic Progenitor Cells

Regeneration after hematopoietic stem cell transplantation (HSCT) depends on enormous activation of the stem cell pool. So far, it is hardly understood how these cells are recruited into proliferation and self-renewal. In this study, we have addressed the question if systemically released factors are involved in activation of hematopoietic stem and progenitor cells (HPC) after autologous HSCT. Serum was taken from patients before chemotherapy, during neutropenia and after hematopoietic recovery. Subsequently, it was used as supplement for in vitro culture of CD34+ cord blood HPC. Serum taken under hematopoietic stress (4 to 11 days after HSCT) significantly enhanced proliferation, maintained primitive immunophenotype (CD34+, CD133+, CD45−) for more cell divisions and increased colony forming units (CFU) as well as the number of cobblestone area-forming cells (CAFC). The stimulatory effect decays to normal levels after hematopoietic recovery (more than 2 weeks after HSCT). Chemokine profiling revealed a decline of several growth-factors during neutropenia, including platelet-derived growth factors PDGF-AA, PDGF-AB and PDGF-BB, whereas expression of monocyte chemotactic protein-1 (MCP-1) increased. These results demonstrate that systemically released factors play an important role for stimulation of hematopoietic regeneration after autologous HSCT. This feedback mechanism opens new perspectives for in vivo stimulation of the stem cell pool

Mathematical Modelling as a Proof of Concept for MPNs as a Human Inflammation Model for Cancer Development

<p><b>Left:</b> Typical development in stem cells (top panel A) and mature cells (bottom panel B). Healthy hematopoietic cells (full blue curves) dominate in the early phase where the number of malignant cells (stipulated red curves) are few. The total number of cells is also shown (dotted green curves). When a stem cell mutates without repairing mechanisms, a slowly increasing exponential growth starts. At a certain stage, the malignant cells become dominant, and the healthy hematopoietic cells begin to show a visible decline. Finally, the composition between the cell types results in a takeover by the malignant cells, leading to an exponential decline in hematopoietic cells and ultimately their extinction. The development is driven by an approximately exponential increase in the MPN stem cells, and the development is closely followed by the mature MPN cells. <b>Right:</b> B)The corresponding allele burden (7%, 33% and 67% corresponding to ET, PV, and PMF, respectively) defined as the ratio of MPN mature cells to the total number of mature cells.</p

Modeling SDF-1-induced mobilization in leukemia cell lines

The stromal cell-derived factor 1 (SDF-1) is essential for circulation, homing, and retention of hematopoietic stem cells in the bone marrow. Present evidence indicates that this factor might play an important role in leukemia cells as well. The aim of this study is to present a model of SDF-1-induced mobilization using leukemia cell lines. CXCR4 expression was compared in Kasumi-1, Jurkat, HL-60, KG-1a, and K562 cells by flow cytometry and Western blot. Migration was analyzed with Transwell assays, and adhesive cell-cell interaction was quantified with a standardized adhesion assay and flow cytometry. CXCR4 was expressed by all leukemic cell lines analyzed, although surface expression of this receptor was found in Kasumi-1 and Jurkat cells only. Correspondingly, SDF-1? effects on migration and cell-cell adhesion were observed in Kasumi-1 and Jurkat cells only, and this could be blocked by AMD3100 in a reversible manner. We have provided evidence that SDF-1? acts as a chemotactic and chemokinetic agent. In addition, surface expression of integrin-?2, activated leukocyte cell adhesion molecule and N-cadherin decreased after stimulation with SDF-1?. SDF-1? affects cell-cell adhesion and migration only in leukemia cells on which the CXCR4 receptor is present on the surface. An SDF-1 gradient is not necessarily required to induce migration, as chemokinesis can also occur. Upon stimulation with SDF-1, CXCR4 promotes modifications on the surface pattern of adhesion molecules, which have an influence on adhesion and migration. � 2012 ISEH - Society for Hematology and Stem Cells