Background Disease modeling with patient-derived induced pluripotent stem cells (iPSCs) is a powerful tool for elucidating the mechanisms underlying disease pathogenesis and developing safe and effective treatments. Patient peripheral blood (PB) cells are used for iPSC generation in many cases since they can be collected with minimum invasiveness. To derive iPSCs that lack immunoreceptor gene rearrangements, hematopoietic stem and progenitor cells (HSPCs) are often targeted as the reprogramming source. However, the current protocols generally require HSPC mobilization and/or ex vivo expansion owing to their sparsity at the steady state and low reprogramming efficiencies, making the overall procedure costly, laborious, and time-consuming. Methods We have established a highly efficient method for generating iPSCs from non-mobilized PB-derived CD34 + HSPCs. The source PB mononuclear cells were obtained from 1 healthy donor and 15 patients and were kept frozen until the scheduled iPSC generation. CD34 + HSPC enrichment was done using immunomagnetic beads, with no ex vivo expansion culture. To reprogram the CD34 + -rich cells to pluripotency, the Sendai virus vector SeVdp-302L was used to transfer four transcription factors: KLF4 , OCT4 , SOX2 , and c-MYC . In this iPSC generation series, the reprogramming efficiencies, success rates of iPSC line establishment, and progression time were recorded. After generating the iPSC frozen stocks, the cell recovery and their residual transgenes, karyotypes, T cell receptor gene rearrangement, pluripotency markers, and differentiation capability were examined. Results We succeeded in establishing 223 iPSC lines with high reprogramming efficiencies from 15 patients with 8 different disease types. Our method allowed the rapid appearance of primary colonies (~ 8 days), all of which were expandable under feeder-free conditions, enabling robust establishment steps with less workload. After thawing, the established iPSC lines were verified to be pluripotency marker-positive and of non-T cell origin. A majority of the iPSC lines were confirmed to be transgene-free, with normal karyotypes. Their trilineage differentiation capability was also verified in a defined in vitro assay. Conclusion This robust and highly efficient method enables the rapid and cost-effective establishment of transgene-free iPSC lines from a small volume of PB, thus facilitating the biobanking of patient-derived iPSCs and their use for the modeling of various diseases. Electronic supplementary material The online version of this article (10.1186/s13287-019-1273-2) contains supplementary material, which is available to authorized users.

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Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease characterized by stiffness and aching mainly in the shoulders, neck and hip girdles. The underlying pathogenesis of PMR involves myeloid lineage activation with a high expression of pattern recognition receptors. In addition, vaccination against SARS-CoV-2 with mRNA-1273 functions as both an immunogen and intrinsic adjuvant. It leads to the activation of innate immunity, resulting in antibody production. We herein report the first case of PMR-like syndrome seven days after mRNA-1273 vaccination. Reassuringly, the symptoms, such as pain of the neck, shoulder girdle and pelvic girdle, as well as elevated inflammatory markers were resolved within a month without glucocorticoid or immunosuppressant administration.

The discovery of induced pluripotent stem cells (iPSCs) has diversified approaches to studies of human diseases. iPSCs can be used in regenerative medicine and for the analysis of the pathogenesis of hereditary diseases. They can also be applied to research on immune disorders, including the influence of genetic factors on autoimmune diseases in the human system. Some immune cells, such as dendritic cells and macrophages, can be differentiated from iPSCs. Thus, immune disorders caused by defects in the innate immune system can be studied with that approach. We propose that biological mechanisms of genetic risks could be examined by mutating or modifying disease-susceptibility genes in iPSCs by genome editing. Studies using human iPSCs are also expected to elucidate the underlying pathogenesis of immunological diseases and new approaches to drug discovery. ARTICLE HISTORY

Objective The immature platelet fraction (IPF) represents recently produced platelets in bone marrow and this parameter is increased in patient with primary immune thrombocytopenia (ITP). We investigated the associations between IPF and absolute immature platelet count (AIPC), and clinical parameters in systemic lupus erythematosus (SLE), which has more complex pathological mechanisms than in primary ITP. Methods Patients with SLE were retrospectively reviewed at the University of Tokyo Hospital from May, 2012 to January, 2021. The correlations between clinical parameters and the number of immature platelets were assessed with Spearman’s rank correlation coefficients. A multiple logistic regression model was used to identify the independent clinical parameters for IPF and AIPC. The difference in the distribution of time for a complete response (CR) after prednisolone (PSL) administration was also evaluated by log-rank test. Results A total of 282 SLE patients were enrolled, and 12.41% of those patients showed thrombocytopenia. IPF correlated with clinical parameters such as platelet count (r = −0.58), AIPC (r = 0.64) and systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) (r = 0.24). SLEDAI-2K [odds ratio (OR) (per unit increase), 1.07; 95% CI, 1.013 - 1.13] and thrombocytopenia (OR, 32.23; 95% CI, 11.072 - 93.80) were independent clinical parameters to account for IPF increase. IPF correlated with the number of bone marrow megakaryocytes (n = 19, r = 0.57). Notably, the probability of CR in response to PSL in AIPC-high patients was higher than in AIPC-low patients (hazard ratio, 4.62; 95% CI, 1.07 - 20.02). Conclusion IPF correlated with disease activity of SLE and represented platelet production in the bone marrow, whereas AIPC predicted a rapid response to steroids in thrombocytopenic patients with SLE.