A phase I/IIa clinical trial of third-generation autologous chondrocyte implantation (IK-01) for focal cartilage injury of the knee.

Background/objective: The purpose of this study was to report the outcomes of a clinical trial conducted in Japan to assess the safety and effectiveness of third-generation autologous chondrocyte implantation (ACI) using IK-01 (CaReS™), which does not require flap coverage, in the treatment of patients with focal cartilage injury of the knee.

Methods: This was an open label, exploratory clinical trial. Patients were enrolled between June 2012 and September 2016.

Autologous Induced Stem-Cell-Derived Retinal Cells for Macular Degeneration.

We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing.

Design of a Tumorigenicity Test for Induced Pluripotent Stem Cell (iPSC)-Derived Cell Products.

Human Pluripotent Stem Cell (PSC)-derived cell therapy holds enormous promise because of the cells' "unlimited" proliferative capacity and the potential to differentiate into any type of cell. However, these features of PSC-derived cell products are associated with concerns regarding the generation of iatrogenic teratomas or tumors from residual immature or non-terminally differentiated cells in the final cell product. This concern has become a major hurdle to the introduction of this therapy into the clinic.

Tumorigenicity studies of induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration.

Basic studies of human pluripotential stem cells have advanced rapidly and stem cell products are now seeing therapeutic applications. However, questions remain regarding the tumorigenic potential of such cells. Here, we report the tumorigenic potential of induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) for the treatment of wet-type, age-related macular degeneration (AMD).

Pigment epithelium-derived factor secreted from retinal pigment epithelium facilitates apoptotic cell death of iPSC.

We show that pigment epithelium-derived factor (PEDF), which is secreted from primary or iPSC-derived retinal pigment epithelium (RPE), dramatically inhibits the growth of iPSCs. PEDF is detected abundantly in culture supernatants of primary or iPSC-derived RPE. Apoptotic cell death is induced in iPSC when co-cultured with RPE, a process that is significantly blocked by addition of antibody against PEDF.

Forced expression of Sox2 or Nanog in human bone marrow derived mesenchymal stem cells maintains their expansion and differentiation capabilities.

Mesenchymal stem cells (MSCs) derived from human bone marrow have capability to differentiate into cells of mesenchymal lineage. The cells have already been applied in various clinical situations because of their expansion and differentiation capabilities. The cells lose their capabilities after several passages, however.

Multipotent cells from the human third molar: feasibility of cell-based therapy for liver disease.

Adult stem cells have been reported to exist in various tissues. The isolation of high-quality human stem cells that can be used for regeneration of fatal deseases from accessible resources is an important advance in stem cell research. In the present study, we identified a novel stem cell, which we named tooth germ progenitor cells (TGPCs), from discarded third molar, commonly called as wisdom teeth.

Effect of forced expression of basic fibroblast growth factor in human bone marrow-derived mesenchymal stromal cells.

Mesenchymal stromal cells (MSCs) derived from human bone marrow are expected to be utilized for the purpose of tissue engineering, because of their extensive self-renewal or proliferation capability. The capability decreases after several passages, however. Basic fibroblast growth factor (bFGF) is commonly used for culture of various cells including bone marrow-derived MSCs.

Activation of Rac1 or Cdc42 during early morphogenesis of eye discs induces ectopic antennae in Drosophila.

The Rho family small guanosine triphosphatases (GTPases) play important roles in many cellular processes, especially in regulation of cytoskeletal organization. In this study, I examined the functions of Rac1 and Cdc42 for disc morphogenesis in Drosophila. I expressed either a constitutively active form or a dominant negative form of each protein during early morphogenesis of eye discs.

Drosophila deltex mediates suppressor of Hairless-independent and late-endosomal activation of Notch signaling.

Notch (N) signaling is an evolutionarily conserved mechanism that regulates many cell-fate decisions. deltex (dx) encodes an E3-ubiquitin ligase that binds to the intracellular domain of N and positively regulates N signaling. However, the precise mechanism of Dx action is unknown.

EphA receptor tyrosine kinases interact with co-expressed ephrin-A ligands in cis.

Eph receptor tyrosine kinases have been implicated in various developmental processes, including axonal guidance, angiogenesis and morphogenesis. In general, Eph receptors and their ligands, ephrins, are reciprocally compartmentalized during embryogenesis. However, they are expressed in an overlapping fashion in some developing neural and non-neural tissues.

Distinct functions of Rac1 and Cdc42 during axon guidance and growth cone morphogenesis in Drosophila.

Rho family small GTPases are thought to be key molecules in the regulation of cytoskeletal organization, especially for actin filaments. In order to examine the functions of Rac1 and Cdc42 in axon guidance at the midline of the central nervous system in Drosophila embryos, we either activated or inactivated Rac1 and Cdc42 in all postmitotic neurons. We found that the phenotypes of Cdc42 activation and Rac1 inactivation were similar to those of roundabout mutants, in that many extra axons crossed the midline.