Safety and antitumor activity of copanlisib in Japanese patients with relapsed/refractory indolent non-Hodgkin lymphoma: a phase Ib/II study.

The safety, efficacy, and pharmacokinetics of copanlisib were evaluated in this phase Ib/II study in Japanese patients with relapsed/refractory indolent non-Hodgkin lymphoma (NHL). The primary endpoint was safety at the recommended dose; efficacy endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival. In phase Ib, patients received copanlisib 45 mg intravenously on days 1, 8, and 15 of a 28-day cycle, and when tolerated, consecutive patients received copanlisib 60 mg.

Pivotal Role of Non-cardiomyocytes in Electromechanical and Therapeutic Potential of Induced Pluripotent Stem Cell-Derived Engineered Cardiac Tissue.

Although engineered cardiac tissues (ECTs) derived from induced pluripotent stem cells (iPSCs) are promising for myocardial regenerative therapy, the appropriate ratio of cardiomyocytes to non-cardiomyocytes is not fully understood. Here, we determined whether ECT-cell content is a key determinant of its structure/function, thereby affecting ECT therapeutic potential for advanced heart failure. Scaffold-free ECTs containing different ratios (25%, 50%, 70%, or 90%) of iPSC-derived cardiomyocytes were generated by magnetic-activated cell sorting by using cardiac-specific markers.

Building A New Treatment For Heart Failure-Transplantation of Induced Pluripotent Stem Cell-derived Cells into the Heart.

Advanced cardiac failure is a progressive intractable disease and is the main cause of mortality and morbidity worldwide. Since this pathology is represented by a definite decrease in cardiomyocyte number, supplementation of functional cardiomyocytes into the heart would hypothetically be an ideal therapeutic option. Recently, unlimited in vitro production of human functional cardiomyocytes was established by using induced pluripotent stem cell (iPSC) technology, which avoids the use of human embryos.

Teratocarcinomas Arising from Allogeneic Induced Pluripotent Stem Cell-Derived Cardiac Tissue Constructs Provoked Host Immune Rejection in Mice.

Transplantation of induced pluripotent stem cell-derived cardiac tissue constructs is a promising regenerative treatment for cardiac failure: however, its tumourigenic potential is concerning. We hypothesised that the tumourigenic potential may be eliminated by the host immune response after allogeneic cell transplantation. Scaffold-free iPSC-derived cardaic tissue sheets of C57BL/6 mouse origin were transplanted into the cardiac surface of syngeneic C57BL/6 mice and allogeneic BALB/c mice with or without tacrolimus injection.

Modelling Fanconi anemia pathogenesis and therapeutics using integration-free patient-derived iPSCs.

Fanconi anaemia (FA) is a recessive disorder characterized by genomic instability, congenital abnormalities, cancer predisposition and bone marrow (BM) failure. However, the pathogenesis of FA is not fully understood partly due to the limitations of current disease models. Here, we derive integration free-induced pluripotent stem cells (iPSCs) from an FA patient without genetic complementation and report in situ gene correction in FA-iPSCs as well as the generation of isogenic FANCA-deficient human embryonic stem cell (ESC) lines.

Chemically induced pluripotent stem cells (CiPSCs): a transgene-free approach.

Induced pluripotent stem cells (iPSCs) could be generated by a single gene Oct4 and chemical compounds, in which exogenous expression of Oct4 was indispensable for reprogramming. Recent advances in chemical-mediated cellular reprogramming suggest that small molecules alone (i.e.

Niche-less maintenance of HSCs by 2i.

Maintenance of hematopoietic stem cells (HSCs) in vitro has been believed to be difficult due to a lack of complete understanding of HSC quiescence maintained by the niche. Recent evidence suggests that in vitro maintenance of human and mouse long-term HSCs (LT-HSCs) is possible through dual inhibition (2i) of both GSK-3 and mTOR in the absence of cytokines, serum, or feeder cells.

In vitro generation of platelets through direct conversion: first report in My Knowledge (iMK).

Blood transfusion medicine requires a constant supply of platelets, which is now totally donor dependent. Recent advances in the generation of platelets in vitro through megakaryocytes (MKs) may provide protocols not only via pluripotent stem cells, including induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), but also via induced MKs (iMKs). For the first time, mouse and human fibroblasts are successfully transdifferentiated into iMKs by the introduction of three factors, p45NF-E2, Maf G, and Maf K.

A Simplified In Vitro Teratoma Assay for Pluripotent Stem Cells Injected Into Rodent Fetal Organs.

Teratoma formation assays are established methods for evaluating the pluripotency of embryonic stem (ES) cells and induced pluripotent stem (iPS) cells. Teratoma formation in immunodeficient mice takes approximately 2 months. Here, we have developed a novel assay system for developing teratomas in vitro from ES cells and iPS cells in a short period.