Stem cell therapy can help repair damaged heart tissue. Yet many of the suitable cells currently identified for human use are difficult to obtain and involve invasive procedures. In our search for novel stem cells with a higher cardiomyogenic potential than those available from bone marrow, we discovered that potent cardiac precursor-like cells can be harvested from human menstrual blood. This represents a new, noninvasive, and potent source of cardiac stem cell therapeutic material. We demonstrate that menstrual blood-derived mesenchymal cells (

Next‐generation sequencing ( NGS ) of tumor tissue (ie, clinical sequencing) can guide clinical management by providing information about actionable gene aberrations that have diagnostic and therapeutic significance. Here, we undertook a hospital‐based prospective study ( TOP ‐ GEAR project, 2nd stage) to investigate the feasibility and utility of NGS ‐based analysis of 114 cancer‐associated genes (the NCC Oncopanel test). We examined 230 cases (comprising more than 30 tumor types) of advanced solid tumors, all of which were matched with nontumor samples. Gene profiling data were obtained for 187 cases (81.3%), 111 (59.4%) of which harbored actionable gene aberrations according to the Clinical Practice Guidelines for Next Generation Sequencing in Cancer Diagnosis and Treatment (Edition 1.0) issued by 3 major Japanese cancer‐related societies. Twenty‐five (13.3%) cases have since received molecular‐targeted therapy according to their gene aberrations. These results indicate the utility of tumor‐profiling multiplex gene panel testing in a clinical setting in Japan. This study is registered with UMIN Clinical Trials Registry ( UMIN 000011141).

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Key Words: cardiomyogenesis Ⅲ human mesenchymal stem cell Ⅲ immunologic tolerance Ⅲ myocardial infarction Ⅲ cell-based therapy A lthough embryonic stem cells 1 and induced pluripotent stem (iPS) cells 2 can be differentiated into cells of various organs, including cardiomyocytes, there are many underlining problems to overcome before clinical applications can be used, eg, tumorigenicity. 3 Autografts of iPS cells may not cause immunologic rejection; ironically, however, possible neoplasm formation would cause a serious problem because the neoplasm would not be rejected by the withdrawal of immunosuppressive agents. On the other hand, mesenchymal stem cells (MSCs) have recently been used for clinical application, and their safety and feasibility in cardiac stem cell-based therapy have been demonstrated. 4 Thus, MSCs are a more important cellular source for stem cell-based therapy from a practical point of view.The efficacy of human bone marrow-derived MSCs (BMMSCs) was still limited, 5 however, because of low efficiency for cardiomyogenic transdifferentiation. 6 We previously reported that non-marrow-derived mesenchymal cells had higher cardiomyogenic transdifferentiation efficiency, eg, menstrual blood-derived mesenchymal cells (MMCs), 7 umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs), 8 and placental chorionic plate-derived mesenchymal cells (PCPCs). 9 These cells are thought to be used by an allograft; therefore, problems of immunologic rejection arise. However, an allograft may be superior to an autograft in several ways. Taking into account the background condition of the patient (eg, metabolic disease or age), Original received July 16, 2009; revision received April 14, 2010; accepted April 22, 2010 16 reported significant recovery of cardiac function by the rat amnion-derived cell transplantation in rat myocardial infarction (MI) model, however, they failed to show clear evidence of cardiomyogenic differentiation in vivo. Therefore, in the present study, we attempted to show: (1) the powerful cardiomyogenic transdifferentiation potential of our isolated hAMCs, and the beneficial effect of transplantation of hAMCs on cardiac function in vivo; (2) the induction of immunologic tolerance so that hAMCs can be a powerful allograftable stem cell source without either the administration of immunosuppressive agents or matching of MHC typing; (3) the mechanism of induction of tolerance; and (4) the close relationship between the cardiomyogenic transdifferentiation of mesenchymal cells and the process of immunologic tolerance. MethodsAn expanded Methods section is available in the Online Data Supplement at http://circres.ahajournals.org. Isolation and Culture of Human Amniotic Membrane-Derived Mesenchymal CellsHuman amniotic membrane was collected, with informed consent from individual patients, after delivery of a male neonate. The study was approved by the ethics committee of Keio University School of Medicine. The precise methods for culture have been described previously. 9,17 Detail is shown in...

Murine bone marrow stromal cells differentiate not only into mesodermal derivatives, such as osteocytes, chondrocytes, adipocytes, skeletal myocytes, and cardiomyocytes, but also into neuroectodermal cells in vitro.Human bone marrow stromal cells are easy to isolate but difficult to study because of their limited life span. To overcome this problem, we attempted to prolong the life span of bone marrow stromal cells and investigated whether bone marrow stromal cells modified with bmi-1, hTERT, E6, and E7 retained their differentiated capability, or multipotency. In this study, we demonstrated that the life span of bone marrow stromal cells derived from a 91-year-old donor could be extended and that the stromal cells with an extended life span differentiated into neuronal cells in vitro. We examined the neuronally differentiated cells morphologically, physiologically, and biologically and compared the gene profiles of undifferentiated and differentiated cells. The neuronally differentiated cells exhibited characteristics similar to those of midbrain neuronal progenitors. Thus, the results of this study support the possible use of autologous-cell graft systems to treat central nervous system diseases in geriatric patients.Murine and human bone marrow stromal cells differentiate into osteoblasts (2), chondrocytes (13), skeletal myocytes, adipocytes, and cardiomyocytes (24) in vitro and thus are a useful cell source for bone regeneration (26) and in vivo cardiovasculogenesis (11). However, recent studies suggest that bone marrow stromal cells can also differentiate into a neuronal lineage (22), and murine bone marrow-derived multipotent adult progenitor cells differentiate into dopaminergic neuronal cells (16). Since the use of bone marrow stromal cells entails no ethical or immunological problems, and bone marrow aspiration is an established routine procedure, they may be a useful source of cells for transplantation.Large numbers of cells may be necessary for repairing damaged human tissues to restore function. However, there have been no reports of a sufficient number of differentiated neurons ever having been obtained from human marrow stromal cells. One reason is that normal human cells undergo a limited number of divisions in culture and then enter a nondividing state referred to as "senescence." Senescence is classified into two categories: "stress-induced premature senescence," or "telomere-independent senescence," and "replicative senescence," or "telomere-dependent senescence" (3, 5, 38). p16 Ink4a (p16), a cyclin-dependent kinase (CDK) inhibitor, is induced by certain oncogenes and other damage or stress signals and is required for "premature senescence" in human mammary epithelial cells and keratinocytes. p16 inhibits dephosphorylation of pRb by Cdk4/6-cyclin D, and hypophosphorylated pRb actively represses the genes required for the S phase by sequestering the E2F transcription factors. "Replicative senescence" is caused by telomere size reduction during successive cell divisions because of the chromosome...