Fujifilm (United States)

Background Hematopoietic progenitor cells are a multipotent cell type with the ability to differentiate into various blood lineages.Using directed differentiation following the correct developmental pathway, iCell Hematopoietic Progenitor Cells 2.0 are induced pluripotent stem cell (iPSC)-derived CD34+/ CD43+ cells capable of producing progeny of myeloid, erythroid, and lymphoid lineages.iCell Hematopoietic Progenitor Cells 2.0 are a consistent source of a readily available and easy to use intermediate cell type that can serve as a gateway to immunology.Methods iCell Hematopoietic Progenitor Cells 2.0 can be used directly out of thaw or plated and maintained in culture for extended periods of time.Cell identity was confirmed by flow cytometry of specific markers such as CD34, CD43, CD45, and CD31.Colony Forming Units were assessed and quantified by methylcellulose gel to establish multipotency.Downstream directed differentiation was performed for multiple cell types, including macrophages, microglia, dendritic cells, natural killer cells, mesenchymal stem cells, and erythrocytes.Results Hematopoietic markers such as CD34, CD43, CD45, and CD31 were expressed at high levels (>90%) consistently across lots.These multipotent cells demonstrate consistent CFU activity down the myeloid, granulocyte, erythroid, and megakaryocyte lineages as measured by Colony Forming Unit counts.Differentiation of this intermediate cell type was performed to generate CD68+ macrophages, IBA+ microglia, CD53+ NK cells, CD71+ erythroid cells, and CD105+ mesenchymal stem cells.Some of these products were characterized further in functional assays.Conclusions CD34+/CD43+ iPSC-derived hematopoietic progenitor cells provide a constant, reproducible source of biologically relevant material for use in immunology and oncology.iCell Hematopoietic Progenitor Cells 2.0 are multipotent and able to generate multiple blood cell lineages.Functionally, iCell Hematopoietic Progenitor Cells 2.0 display consistent, quantifiable CFU potential with the capacity to generate downstream cells, such as macrophages, NK cells, and erythrocytes.This overall profile of iCell Hematopoietic Progenitor Cells 2.0 demonstrates its suitability as a continuing source of human multipotent hematopoietic cells.

Yttrium-90 FF-21101 (90Y-FF-21101) is a radiopharmaceutical that targets P-cadherin as a therapy against solid tumors. A previously reported, first-in-human study determined that a dose of 25 mCi/m2 was safe, and a patient with clear cell carcinoma of the ovary achieved a complete response. In this article, the authors report the results of 90Y-FF-21101 treatment in an ovarian carcinoma expansion cohort and in patients with selected solid tumors who had known high P-cadherin expression. The trial was conducted as an open-label study in patients with advanced/metastatic disease. Radiologic response and safety were evaluated in patients who received 25 mCi/m2 intravenously once every three cycles of 28 days until they developed progressive disease. Evaluation of the ovarian cohort was conducted in a Simon two-stage manner to determine further enrollment. Fifty-seven patients (20 with ovarian carcinoma) were enrolled and treated. Patients who had ovarian and solid tumors had received a median of five and three prior therapies, respectively. No complete or partial responses were observed, so the trial was ended. The median progression-free survival was 118 days for the ovarian cohort and 55 days for the solid-tumor cohort. The most common treatment-related adverse events were thrombocytopenia (40%) and neutropenia (54%). One patient each developed fatal veno-occlusive disease and intracranial hemorrhage. Patients with higher P-cadherin levels remained on the study longer. 90Y-FF-21101 did not meet the predefined efficacy criteria, and adverse events were consistent with 90Y agents. These data may assist in the development of other P-cadherin-directed therapies (ClinicalTrials.gov identifier NCT02454010).

This paper describes performance characteristics of a photoimageable dielectric organic polymer. Dielectric material used in this study is a preimidized polyimide (PID). Preimidized polymer cured in the temperature range of 170 ℃ to 230 ℃ shows excellent thermal stability and stable thermomechanical properties in a broad cure temperature range compared to its precursor analog (polyamic acid; PAA). PID also demonstrates excellent adhesion on different substrate types. PID retains good peel strength on copper even after 96 hours of HAST. PID has excellent stability against ion migration under multiple reliability test conditions.

Chemotherapy-induced peripheral neuropathy (CIPN) is widely recognized as a potentially severe toxicity that often leads to dose reduction or discontinuation of cancer treatment. Symptoms may persist despite discontinuation of chemotherapy and quality of life can be severely compromised. The clinical symptoms of CIPN, and the cellular and molecular targets involved in CIPN, are just as diverse as the wide variety of anticancer agents that cause peripheral neurotoxicity. There is an urgent need for extensive molecular and functional investigations aimed at understanding the mechanisms of CIPN. Furthermore, a reliable human cell culture system that recapitulates the diversity of neuronal modalities found in vivo and the pathophysiological changes that underlie CIPN would serve to advance the understanding of the pathogenesis of CIPN. The demonstration of experimental reproducibility in a human peripheral neuronal cell system will increase confidence that such an in vitro model is clinically useful, ultimately resulting in deeper exploration for the prevention and treatment of CIPN. Herein, we review current in vitro models with a focus on key characteristics and attributes desirable for an ideal human cell culture model relevant for CIPN investigations.

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by an expanded polyglutamine repeat in the huntingtin gene. The neuropathology of HD is characterized by the decline of a specific neuronal population within the brain, the striatal medium spiny neurons (MSNs). The origins of this extreme vulnerability remain unknown. Human induced pluripotent stem cell (hiPS cell)-derived MSNs represent a powerful tool to study this genetic disease. However, the differentiation protocols published so far show a high heterogeneity of neuronal populations in vitro. Here, we compared two previously published protocols to obtain hiPS cell-derived striatal neurons from both healthy donors and HD patients. Patch-clamp experiments, immunostaining and RT-qPCR were performed to characterize the neurons in culture. While the neurons were mature enough to fire action potentials, a majority failed to express markers typical for MSNs. Voltage-clamp experiments on voltage-gated sodium (Nav) channels revealed a large variability between the two differentiation protocols. Action potential analysis did not reveal changes induced by the HD mutation. This study attempts to demonstrate the current challenges in reproducing data of previously published differentiation protocols and in generating hiPS cell-derived striatal MSNs to model a genetic neurodegenerative disorder in vitro.

Nongenetic methodologies to reduce undesirable proliferation would be valuable when generating dopamine neurons from stem cells for transplantation in Parkinson's disease (PD). To this end, we modified an established method for controlled differentiation of human induced pluripotent stem cells (iPSCs) into midbrain dopamine neurons using two distinct methods: omission of FGF8 or the in‐process use of the DNA cross‐linker mitomycin‐C (MMC). We transplanted the cells to athymic rats with unilateral 6‐hydroxydopamine lesions and monitored long‐term survival and function of the grafts. Transplants of cells manufactured using MMC had low proliferation while still permitting robust survival and function comparable to that seen with transplanted dopamine neurons derived using genetic drug selection. Conversely, cells manufactured without FGF8 survived transplantation but exhibited poor in vivo function. Our results suggest that MMC can be used to reduce the number of proliferative cells in stem cell‐derived postmitotic neuron preparations for use in PD cell therapy.