Reactive oxygen species (ROS) are generated following ligand-receptor interactions and function as specific second messengers in signaling cascades involved in cell proliferation and differentiation. Although ROS are generated intracellularly by several sources, including mitochondria, the primary sources of ROS involved in receptor-mediated signaling cascades are plasma membrane oxidases, preferentially NADPH oxidases, with a rapid kinetics of activation and inactivation. This allows a tight up- and downregulation of intracellular ROS levels within the short time required for the transduction of signals from the plasma membrane to the cell nucleus. The mode of action of ROS may involve direct interaction with specific receptors, and/or redox-activation of members of signaling pathways such as protein kinases, protein phosphatases, and transcription factors. Furthermore, ROS act in concert with intracellular Ca²⁺ in signaling pathways which regulate the balance of cell proliferation versus cell cycle arrest and cell death. The delicate intracellular interplay between oxidizing and reducing equivalents allows ROS to function as second messengers in the control of cell proliferation and differentiation.

Cellular replacement therapy has emerged as a novel strategy for the treatment of heart failure. The aim of our study was to determine the fate of injected mesenchymal stem cells (MSCs) and whole bone marrow (BM) cells in the infarcted heart. MSCs were purified from BM of transgenic mice and characterized using flow cytometry and in vitro differentiation assays. Myocardial infarctions were generated in mice and different cell populations including transgenic MSCs, unfractionated BM cells, or purified hematopoietic progenitors were injected. Encapsulated structures were found in the infarcted areas of a large fraction of hearts after injecting MSCs (22 of 43, 51.2%) and unfractionated BM cells (6 of 46, 13.0%). These formations contained calcifications and/or ossifications. In contrast, no pathological abnormalities were found after injection of purified hematopoietic progenitors ( IntroductionSevere heart failure is caused by an irreversible loss of cardiomyocytes and has a poor prognosis regardless of the underlying disease. 1 Since medical treatment is of only limited help, solid organ transplantation was considered until recently the only effective therapy. However, as organ availability decreases, there is an urgent need for alternative treatments. Studies in mice have suggested that myocardial infarctions can be repaired following transplantation of bone marrow (BM)-derived cells into the lesioned myocardium, either through generation of cardiomyocytes or angiogenesis. 2 An underlying assumption of this approach is that the environment will instruct as well as restrict the developmental fate of adult stem cells after their transplantation (for review see Laflamme and Murry 3 or Murry et al 4 ). However, the original findings in mice have recently been put into question, since we and others have demonstrated that BM-derived hematopoietic cells do not transdifferentiate into cardiomyocytes in the infarcted myocardium. [5][6][7] In this study, we focused on the potential of an enriched population of mesenchymal stem cells (MSCs) that are known to be present in the BM and are multipotent. 8 In contrast to hematopoietic progenitors, MSCs are easy to obtain and to expand in vitro and have therefore emerged as attractive candidates for cellular therapies in heart and other organs. 9,10 However, recent reports have questioned their "transdifferentiation" potential after injection into the myocardium and rather propose benefits via paracrine mechanisms. 11,12 Herein, we investigated and provide novel insights with regard to the fate of enriched populations of BM-derived MSCs as well as whole BM cells comprising both hematopoietic and mesenchymal progenitors after transplantation into the infarcted heart. Materials and methodsAll experiments were approved by the local ethics care committees at Bonn, Cologne, and Lund Universities. Cells for transplantation were isolated from transgenic C57Bl/6 mice expressing enhanced green fluorescent protein (EGFP) under control of the ␤-actin promoter. 13 Cell isolation and cultu...

Background-The recent breakthrough in the generation of induced pluripotent stem (iPS) cells, which are almost indistinguishable from embryonic stem (ES) cells, facilitates the generation of murine disease-and human patientspecific stem cell lines. The aim of this study was to characterize the cardiac differentiation potential of a murine iPS cell clone in comparison to a well-established murine ES cell line.

A mutation in the centrosomal‐P4.1‐associated protein (CPAP) causes Seckel syndrome with microcephaly, which is suggested to arise from a decline in neural progenitor cells (NPCs) during development. However, mechanisms of NPCs maintenance remain unclear. Here, we report an unexpected role for the cilium in NPCs maintenance and identify CPAP as a negative regulator of ciliary length independent of its role in centrosome biogenesis. At the onset of cilium disassembly, CPAP provides a scaffold for the cilium disassembly complex (CDC), which includes Nde1, Aurora A, and OFD1, recruited to the ciliary base for timely cilium disassembly. In contrast, mutated CPAP fails to localize at the ciliary base associated with inefficient CDC recruitment, long cilia, retarded cilium disassembly, and delayed cell cycle re‐entry leading to premature differentiation of patient iPS‐derived NPCs. Aberrant CDC function also promotes premature differentiation of NPCs in Seckel iPS‐derived organoids. Thus, our results suggest a role for cilia in microcephaly and its involvement during neurogenesis and brain size control.