Cotransplantation of CD34+ hematopoietic stem and progenitor cells (HSPCs) with mesenchymal stromal cells (MSCs) enhances HSPC engraftment. For these applications, MSCs are mostly obtained from bone marrow (BM). However, MSCs can also be isolated from the Wharton's jelly (WJ) of the human umbilical cord. This source, regarded to be a waste product, enables a relatively low-cost MSC acquisition without any burden to the donor. In this study, we evaluated the ability of WJ MSCs to enhance HSPC engraftment. First, we compared cultured human WJ MSCs with human BM-derived MSCs (BM MSCs) for in vitro marker expression, immunomodulatory capacity, and differentiation into three mesenchymal lineages. Although we confirmed that WJ MSCs have a more restricted differentiation capacity, both WJ MSCs and BM MSCs expressed similar levels of surface markers and exhibited similar immune inhibitory capacities. Most importantly, cotransplantation of either WJ MSCs or BM MSCs with CB CD34 + cells into NOD SCID mice showed similar enhanced recovery of human platelets and CD45 + cells in the peripheral blood and a 3-fold higher engraftment in the BM, blood, and spleen 6 weeks after transplantation when compared to transplantation of CD34 + cells alone. Upon coincubation, both MSC sources increased the expression of adhesion molecules on CD34 + cells, although stromal cell-derived factor-1 (SDF-1)-induced migration of CD34 + cells remained unaltered. Interestingly, there was an increase in CFU-GEMM when CB CD34 + cells were cultured on monolayers of WJ MSCs in the presence of exogenous thrombopoietin, and an increase in BFU-E when BM MSCs replaced WJ MSCs in such cultures. Our results suggest that WJ MSC is likely to be a practical alternative for BM MSC to enhance CB CD34 + cell engraftment.

Although TPO expansion before cryopreservation would yield higher nucleated cell and clonogenic myeloid and megakaryocyte cell numbers and enable earlier availability, CB TPO expansion after cryopreservation is likely to be clinically more effective, despite the lower number of cells obtained after expansion. Moreover, the latter strategy is logistically more feasible.

Objections Development of acute lung injury after cardiac surgery is associated with an unfavourable outcome. Acute respiratory distress syndrome in general is, besides cytokine- and interleukin activation, associated with activation of platelets, monocytes and neutrophils. In relation to pulmonary outcome after cardiac surgery, leucocyte- and platelet-activation is described in animal studies, only. Therefore, we explored the peri-operative time course of platelet- and leucocyte- activation in cardiac surgery and related these findings to acute lung injury assessed via PaO2/FiO2 (P/F) ratio measurements. Methods a prospective cohort study was performed, including 80 cardiac surgery patients. At five timepoints, blood samples were directly assessed by flowcytometry. For time course analyses in low (<200) versus high (>/=200) P/F ratio groups repeated measurements techniques with linear mixed models were used. Results Already before the start of surgery platelet activatability (p = 0.003 for Trombine Receptor Activator Peptide and p = 0.017 for Adenosine Di Phosphate) was higher, and expression of neutrophil activation markers was lower (CD18/CD11; p = 0.001, CD62L; p = 0.013) in the low P/F group. After correction for these baseline differences, the peri-and postoperative Trombine Receptor Activator Peptide induced thrombocyte activatability was decreased in the low P/F ratio group (p 0.008), and a changed pattern of neutrophil activation markers was observed. Conclusions Prior to surgery, an upregulated inflammatory state with higher platelet- activatability, and indications for higher neutrophil turnover was demonstrated in cardiac surgery patients that developed lung injury. It is difficult to distinguish whether these factors are mediators, or also etiologically related to development of lung injury after cardiac surgery and further research is warranted. Trial registration Clinical Registration number: ICTRP: NTR 5314, 26-05-2015