Deep learning predicts function of live retinal pigment epithelium from quantitative microscopy

Increases in the number of cell therapies in the preclinical and clinical phases have prompted the need for reliable and noninvasive assays to validate transplant function in clinical biomanufacturing. We developed a robust characterization methodology composed of quantitative bright-field absorbance microscopy (QBAM) and deep neural networks (DNNs) to noninvasively predict tissue function and cellular donor identity. The methodology was validated using clinical-grade induced pluripotent stem cell–derived retinal pigment epithelial cells (iPSC-RPE). QBAM images of iPSC-RPE were used to train DNNs that predicted iPSC-RPE monolayer transepithelial resistance, predicted polarized vascular endothelial growth factor (VEGF) secretion, and matched iPSC-RPE monolayers to the stem cell donors. DNN predictions were supplemented with traditional machine-learning algorithms that identified shape and texture features of single cells that were used to predict tissue function and iPSC donor identity. These results demonstrate noninvasive cell therapy characterization can be achieved with QBAM and machine learning.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

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Bargou Andreas Rosenwald Thorsten Stühmer Ellen Leich Approximately 20% of multiple myeloma (MM) cases harbor a point mutation in KRAS. However, there is still no final consent on whether KRAS-mutations are associated with disease outcome. Specifically, no data exist on whether KRAS-mutations have an impact on survival of MM patients at diagnosis in the era of novel agents. Direct blockade of KRAS for therapeutic purposes is mostly impossible, but recently a mutation-specific covalent inhibitor targeting KRASp.G12C entered into clinical trials. However, other KRAS hotspot-mutations exist in MM patients, incl...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes syndrome are currently treated with therapeutic options for multiple myeloma, and this disease is a treatable disease. Accurate diagnosis and proper treatment in the early stage of the disease are essential to further improve prognosis. This review focuses on diagnosis, treatment and the current status of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes syndrome in Japan. AbstractPolyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome is a rare ...
Source: Clinical and Experimental Neuroimmunology - Category: Neurology Authors: Tags: REVIEW ARTICLE Source Type: research
We have identified a transcortical perivascular osteoprogenitor (TPC) located within cortical bone channels under basal conditions. When cortical bone was isolated from iDMP/T;ColGFP reporter mice and transplanted into recipient mice, TPCs migrate out of the bone into the newly forming bone marrow cavity where they continue to proliferate and differentiate to form new trabecular bone. AbstractBone remodeling and regeneration are dependent on resident stem/progenitor cells with the capability to replenish mature osteoblasts and repair the skeleton. Using lineage tracing approaches, we identified a population of Dmp1+ cells ...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Tissue ‐Specific Stem Cells Source Type: research
This study determined the dose-dependent effects of tetramethylpyrazine (TMP) on the characteristics of ucMSCs in vitro. The effect on proliferation was determined with Cell Counting kit-8 assays. Cell migration was analyzed with Transwell assays and western blot analysis. Differentiation of ucMSCs was evaluated according to markers and the expression of relevant proteins and genes. Secretion capacity was detected by ELISA analysis. TMP protected ucMSCs against H2O2 induced-oxidative damage but had no influence on ucMSC activity at a low concentration. Furthermore, ucMSC migration was improved by TMP via the SDF-1/CXCR4 ax...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research
ConclusionsIn this study, theAspergillus azole resistance rate was 1% (3/292). In addition to A. fumigatus sensu stricto, A. lentulus and A. awamori azole resistant were identified. Therefore, it is important a correct identification at species level to better address a rapid therapy, to understand quickly the shift towards cryptic species and to have an updated knowledge of the local epidemiology.
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
Publication date: Available online 13 February 2020Source: Autoimmunity ReviewsAuthor(s): Johann Sellner, Paulus S. RommerAbstractImmune reconstitution therapy (IRT) is an emerging concept for the treatment of multiple sclerosis (MS) that is given intermittently and can induce long-term remission of MS that is sustained in treatment-free periods. A systematic literature review was performed to identify and summarize current knowledge regarding the short- and long-term immunological consequences of different IRTs and CD20 depleting therapies on the cellular level in patients with MS. A total of 586 articles published betwee...
Source: Autoimmunity Reviews - Category: Allergy & Immunology Source Type: research
Publication date: Available online 13 February 2020Source: Autoimmunity ReviewsAuthor(s): Dana Yehudai-Ofir, Israel Henig, Tsila ZuckermanAbstractChronic graft-versus-host disease (cGVHD) remains the main complication of allogeneic hematopoietic stem cell transplantation, limiting its chances for a successful outcome. The over-activity of CD4+ effector T cells and the excessive production of pro-inflammatory cytokines are followed by the development of immune-mediated inflammation and fibrosis of multiple organs. This is the reason for adopting T cell targeting therapies such as cyclosporine A, tacrolimus and mycophenolate...
Source: Autoimmunity Reviews - Category: Allergy & Immunology Source Type: research
In this study we describe a two dimensional extended culture system that promotes proliferation of specified hPGCLCs, without reversion to a pluripotent state. We demonstrate that hPGCLCs in extended culture undergo partial epigenetic reprogramming, mirroring events described in hPGCs in vivo, including a genome-wide reduction in DNA methylation and maintenance of depleted H3K9me2. This extended culture system provides a new approach for expanding the number of hPGCLCs for downstream technologies, including transplantation, molecular screening, or possibly the differentiation of hPGCLCs into gametes by in vitro g...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research
AbstractBone marrowWT1 mRNA levels assessed by the ELN method are useful to establish prognostic correlations in myeloid malignancies treated with chemotherapy or hematopoietic stem cell transplantation (HCT). Those patients withWT1 levels below ten copies have a good outcome. However, some of these patients relapse. To further characterize this group of cases, we applied a new and sensitive digital (ddPCR)WT1 method. A consecutive series of 49 patients with treated myeloid malignancies and with an ELNWT1 quantitation of
Source: Annals of Hematology - Category: Hematology Source Type: research
AbstractAutologous stem cell transplant (ASCT) is a widely used and safe procedure to treat mostly hematologic diseases. These patients are at risk of infectious complications, which represents a major cause of morbidity and it is the second cause of mortality. This retrospective 12-year analysis of the incidence, type, and severity of infections in 266 consecutive unselected ASCT patients at our institution provides novel information addressing this issue. We included 266 ASCT procedures. Patients included in the 2006 –2013 period are referred to as group 1 (ciprofloxacin prophylaxis and ceftazidime-amikacin as empi...
Source: Annals of Hematology - Category: Hematology Source Type: research
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