Treating Age related Macular Degeneration Using Human iPS

Treating Age-related Macular Degeneration Using Human iPS Cells Age-related macular degeneration (AMD) is a medical condition of the eye that results in blurred vision and/or a loss of central vision. The wet form of AMD – caused by abnormal blood vessel growth – is often treated using anti-VEGF medication. This approach can slow deterioration but is unable to treat the cause, or reverse the effects of, retinal pigment epithelium (RPE) atrophy. A regenerative medicine strategy currently being explored is the possibility that healthy RPE tissue could replace defective RPE. Masayo Takahashi from the RIKEN Center for Developmental Biology (Kobe, Japan) presented data on the creation and utilization of RPE src inhibitors from inducible pluripotent stem cells (iPSCs) to treat wet AMD. In 2014, Takahashi led a pilot study of the first transplant of human iPSC-derived tissue into a human being. Skin cells taken from a patient suffering from wet-AMD were converted into iPSCs, differentiated into RPE cells and transplanted back into the patient\'s eye. Importantly, transplanted cells were not rejected and resulted in the stabilization of visual acuity. However, using autologous cells is a costly option and is of limited use to patients with acute ocular diseases. To address these points, Takahashi has explored the therapeutic use of RPE cells from iPSCs derived from human leukocyte antigen (HLA)-matched homozygote donors. When tested in a monkey model, no rejection signs were observed in monkey iPSC-RPE allografts of MHC-matched animal models, whereas immune attacks around the graft were detected in the MHC-mismatched situation. Using an in vitro assay to assess the immune response in a quasi-human context, T cells were unable to respond to human iPSC-RPE cells derived from HLA homozygous donors. This encouraging result indicates that the allogeneic option is viable and should be tested in future clinical trials if the donor and recipient are HLA matched.
Remuscularization of Injured Hearts with Human ESC-Derived Cardiomyocytes
First Application of Gene-edited ‘Universal’ T Cells for Leukemia Chemotherapy has been used with great success to treat patients with leukemia. Unfortunately, this approach is not always effective, especially when cancerous cells become refractory through resistance mechanisms. Until recently, palliative care has been the only option left for patients suffering from aggressive drug-resistant leukemia. However, developments in the field of immunology are revolutionizing the way hematological cancers are tackled. Waseem Qasim (University College, London) presented one such strategy that is being used with great success to treat CD19-positive B-cell Acute Lymphoblastic Leukemia (B-ALL). Essentially, T cells derived from healthy donors were molecularly tweaked using genome editing technology. These so-called UCART19 cells express chimeric antigen receptors (CARs) that target surface CD19 proteins found on leukemic cells, and kill them. CART19 cells were initially tested in two extremely sick children with relapsed B-ALL. Using a special license allowing application of unlicensed medical products, CART19 cells were administered. This was a landmark experiment in which gene-edited therapeutic T cells were being tested in humans for the first time. Both patients responded remarkably well to the treatment, showing robust abolition of leukemic cells. This pioneering study informed the dosing and schedule of a Phase 1 trial to evaluate the safety and ability to induce molecular remission in pediatric patients with relapsed/refractory CD19-positive B-ALL, taking place at Great Ormond Street hospital (NCT02808442). This trial is currently recruiting participants and hopes to prove the effectiveness of UCART19 cells in larger groups of patients. Similar studies are needed to test if this therapeutic approach can be expanded to treat other aggressive forms of chemotherapy-resistant cancer.
Generating a Kidney From Human Pluripotent Stem Cells: Where to From here?