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We have successively constructed several induced pluripotent stem cell (iPSC) lines of middle-aged and elderly male, but cell samples from young donors are still scarce. In this project, we recruited a healthy 29-year-old Chinese Han male, obtained his skin fibroblasts and successfully established iPSC line using non-integrated reprogramming technology. The iPSC line showed normal karyotype, expressed pluripotency markers and differentiated into three germ layers in vivo. The cell line will serve as an available control in the research of pathological mechanisms of early-onset neurological diseases.

Ataxia Telangiectasia is a rare autosomal recessive disorder caused by a mutated ATM gene. The most debilitating symptom of Ataxia Telangiectasia is the progressive neurodegeneration of the cerebellum, though the molecular mechanisms driving this degeneration remains unclear. Here we describe the generation and validation of an induced pluripotent stem cell (iPSC) line from an olfactory biopsy from a patient with Ataxia Telangiectasia. Sequencing identified two previously unreported disease-causing mutations in the ATM gene. This line can be used to generate 2D and 3D patient-specific neuronal models enabling investigations into the mechanisms underlying neurodegeneration.

We have generated MLi004-A, a new induced pluripotent stem cell (iPSC) line derived from skin fibroblasts of a female patient with recessive dystrophic epidermolysis bullosa (RDEB). This iPSC line may be used as a model system for studies on skin integrity, the extracellular matrix and skin barrier function. The characterization of the MLi004-A cell line consisted of molecular karyotyping, next-generation sequencing of the COL7A1 alleles, plu-ripotency and differentiation potentials testing by immunofluorescence of associated markers in vitro. The MLi004-A line has been also tested for ability to differentiate into fibroblasts.

Induced pluripotent stem cells (iPSCs) hold great potential to generate novel, curative cell therapy products. However, current methods to generate these novel therapies lack scalability, are labor‐intensive, require a large footprint, and are not suited to meet clinical and commercial demands. Therefore, it is necessary to develop scalable manufacturing processes to accommodate the generation of high‐quality iPSC derivatives under controlled conditions. The current scale‐up methods used in cell therapy processes are based on empirical, geometry‐dependent methods that do not accurately represent the hydrodynamics of 3D bioreactors. These methods require multiple iterations of scale‐up studies, resulting in increased development cost and time. Here we show a novel approach using computational fluid dynamics modeling to effectively scale‐up cell therapy manufacturing processes in 3D bioreactors. Using a GMP‐compatible iPSC line, we translated and scaled‐up a small‐scale cardiomyocyte differentiation process to a 3‐L computer‐controlled bioreactor in an efficient manner, showing comparability in both systems., Induced pluripotent stem cells (iPSCs) hold great potential to generate novel, curative cell therapy products. However, current methods to generate these novel therapies lack scalability, are labor‐intensive, require a large footprint, and are not suited to meet clinical and commercial demands. Therefore, it is necessary to develop scalable manufacturing processes to accommodate the generation of high‐quality iPSC derivatives under controlled conditions.

Bardet-Biedl syndrome (BBS) is primarily a multisystem nonmotile ciliopathy. In this study, we describe the successful establishment and characterization of an iPSC line from a patient diagnosed with BBS who was compound heterozygous for the BBS7 variants c.849 + 1G > C (splicing) and c.754G > A (p.D252N).

Variants in FBN1 are associated with Marfan Syndrome, an autosomal dominant disorder with clinical features that involve the musculoskeletal, cardiovascular and ocular systems. We generated a human iPSC line QDMHi001-A from a patient with Marfan syndrome and a heterozygous c.6772 T > C (p.Cys2258Arg) variant in FBN1. This line will be a valuable resource for in vitro disease modeling and drug testing for Marfan syndrome.

Mutation in STING1 gene, which encodes stimulator of type I IFN gene (STING) leads to its constitutive activation and thereby to a severe vasculopathy and sometimes a lupus-like disease. We generated induced pluripotent stem cells (iPSCs) from a patient carrying a rare heterozygous variant c.463G > A (resulting in a p.V155M substitution) in STING1. Cells from this patient, which were reprogrammed by non-integrative viral transduction, had normal karyotype, expressed pluripotency markers and were able to differentiate into the three germ cell layers.

Summary Melanocytes, derived from neural crest cells, are involved in melanin production. This protocol describes a method to generate induced melanocytes (iMelanocytes) from human induced pluripotent stem cells (iPSCs) using a suspension culture system, which considerably improves the differentiation efficiency. The most critical parts of this protocol are the selection of a reliable iPSC line with strong potential to differentiate into melanocytes and their stemness maintenance. For complete information on the use and generation of this protocol, please refer to our Cell Reports article, Liu el al. (2019)., Graphical Abstract, Highlights • Selection of reliable iPSC lines and their stemness maintenance is critical • EB-based suspensive system enhances efficiency of iMelanocytes generation • EBs characterized by smooth borders and dark centers without cavities are preferred • Quality control is performed through morphology checks and melanocyte markers, Melanocytes, derived from neural crest cells, are involved in melanin production. This protocol describes a method to generate induced melanocytes (iMelanocytes) from human induced pluripotent stem cells (iPSCs) using a suspension culture system, which considerably improves the differentiation efficiency. The most critical parts of this protocol are the selection of a reliable iPSC line with strong potential to differentiate into melanocytes and their stemness maintenance.

miR-26b has been implicated in a wide range of human diseases, including cancer, diabetes, heart disease, Alzheimer’s disease and osteoarthritis. To provide a tool to explore the importance of miR-26b in this broad context, we have generated and characterized a homozygous miR-26b stem-loop knockout human iPSC line. This gene-edited line exhibited a normal karyotype, expressed pluripotency markers and differentiated into cells representative of the three embryonic germ layers. This iPSC line will be valuable for studies investigating disease mechanisms and testing therapeutic strategies in vitro.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that is the major cause of dementia in older people. Here, we report the derivation of human induced pluripotent stem cells (iPSCs) from an AD patient at age of 80 who has the APOE e4/e4 genotype and is resilient to cognitive decline for 10 years. The iPSCs reprogrammed from the blood cells of this patient by transient expression of pluripotency genes maintain the e4/e4 genotype, are karyotypically normal and display typical iPSC characteristics. Upon differentiation, the iPSCs are able to differentiate into cells of the three germ layers, confirming their pluripotency.

Long QT syndrome (LQTS), an inherited cardiac ion channelopathy, is associated with ventricular arrhythmias and risk of sudden death. LQTS sub-type 2 (LQT2) is caused by pathogenic variants in KCNH2 encoding the α-subunit of Kv11.1, thus affecting the rapid component of delayed rectifier K+ current (IKr) channel during the action potential. In this study, non-integrational Sendai reprogramming method was used to generate an induced-pluripotent-stem-cell (iPSC) line carrying the KCNH2 c.2464G>A (p.Val822Met) pathogenic variant from a LQT2 patient. This patient-specific iPSC line NUIGi003-A harbouring the c.2464G>A variant expressed pluripotency markers and demonstrated the differentiation potential to all three germ layers.

Hypertrophic cardiomyopathy (HCM) is a disease in which the heart muscle becomes abnormally thick making it difficult for the heart to pump blood. In this study an induced pluripotent stem cells (iPSC) line was derived from peripheral blood mononuclear cells of a 62-year-old male hypertrophic cardiomyopathy (HCM) patient with the mutation of heterozygous pathogenic myosin binding protein C (MYBPC3) c.3369-3370 insC using an episomal method. The generated iPSC line presented normal 46, XY male karyotypes, expressed pluripotent markers and could spontaneously differentiate into triblast cells. This HCM-specific iPSC line could act as a useful tool for studying and modeling hypertrophic cardiomyopathy.

Dermal fibroblasts isolated from an apparently healthy 50-year-old man were successfully transformed into induced pluripotent stem cells (iPSCs) by using the integration-free CytoTune-iPS Sendai Reprogramming method. The generated iPSC line has been expanded under feeder-free conditions and displayed all hallmarks of a standard pluripotent stem cell line such as a normal karyotype, expression of pluripotent factors and differentiation capacity into the three germ layers.

β-thalassemia is mostly caused by homozygous or compound heterozygous variants in HBB. We generated a human iPSC line CIBi008-A from amniotic fluid-derived cells of a fetus with β-thalassemia major, carrying compound heterozygous −28A > G and IVS-II-654C > T variants in HBB gene. This line will be a valuable resource for disease modeling and testing gene therapies for β-thalassemia.

Parkinson's disease (PD) is a devastating movement disorder with an unknown etiology. Multiplications of the SNCA gene cause the autosomal dominant form of familial PD as well as missense mutations of the gene. We established and characterized a human induced pluripotent stem cell (iPSC) line from a PD patient carrying SNCA duplication. The iPSC line displayed a capacity to differentiate into midbrain dopaminergic neurons affected in PD. The iPSC line will be useful for disease modeling applications.

Age-related macular degeneration (AMD) is a late-onset progressive blinding disease. We established human induced pluripotent stem cells (iPSCs) from an AMD patient. The generated iPSC line showed pluripotency markers and three-germ layer differentiation ability in vitro. This iPSC line will be useful for elucidating the pathomechanisms of and drug discovery for AMD.

Arrhythmogenic Cardiomyopathy (ACM) is an inherited cardiac disease characterized by arrhythmias and fibro-fatty replacement in the ventricular myocardium. Causative mutations are mainly reported in desmosomal genes, especially in plakophilin2 (PKP2). Here, using a virus-free reprogramming approach, we generated induced pluripotent stem cells (iPSCs) from skin fibroblasts of one ACM patient carrying the frameshift heterozygous PKP2 mutation c.2569_3018del50. The iPSC line (EURACi004-A) showed the typical morphology of pluripotent cells, possessed normal karyotype and exhibited pluripotency markers and trilineage differentiation potential, including cardiomyogenic capability. Thus, this line can represent a human in vitro model to study the molecular basis of ACM.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with the loss of upper motor neurons in the cortex and lower motor neurons in the brain stem and spinal cord regressively. The vast majority of ALS cases have no familial history are apparently sporadic (SALS), making the modeling of SALS essential to the development of ALS therapeutics. Therefore, human induced pluripotent stem cell (iPSC) from peripheral blood mononuclear cells of a 64-year-old SALS patient were produced using a virus-free protocol and characterized using standard validate methods. This generated iPSC line could be useful to reveal SALS mechanisms and screen drug development. Keywords: induced pluripotent stem cell, sporadic amyotrophic lateral sclerosis, reprogramming, differentiation

A human induced pluripotent stem cell (hiPSC) line (WMUi001-A) was generated from the aortic tissue of a 47-year-old donor with aortic dissection and normal blood pressure. Integration-free episomal vector-mediated reprogramming was used for the generation of this iPSC line. The established iPSC line was found to express pluripotency markers, exhibit a differentiation potential in vitro, as well as display a normal karyotype. We further identified that this iPSC line contained a mutation in collagen type IV (COL4A2, R131M), which may serve as a useful tool for the disease modeling of aortic dissection.

Astrotactin-2, encoded by ASTN2, is implicated in neuronal migration. Although genetic studies of schizophrenia (SCZ) patients have suggested that exonic deletions of ASTN2 are associated with neurodevelopmental and psychiatric disorders, their biological significance remains unclear. Herein, we generated human induced pluripotent stem cells (iPSCs) from a SCZ patient with an exonic deletion of ASTN2. The generated iPSCs carried ASTN2 deletion and showed typical iPSC morphology, pluripotency marker expression, normal chromosomal aneuploidy, and the capacity to differentiate into three germ layers. This iPSC line may be suitable for evaluating Astrotactin-2 function relevant for SCZ onset in the human brain.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of hereditary stroke disorder. It is caused by mutations in NOTCH3 that lead to progressive degeneration of the smooth muscle cells in blood vessels. There is currently no treatment for this disorder. We reprogrammed to pluripotency blood mononuclear cells isolated from a patient carrying a NOTCH3 mutation by using a commercially available non-integrating system. The success in the generation of this iPSC line (IDISi001-A) suggests that the NOTCH3 mutation did not limit cell reprogramming and offers an unprecedented opportunity for studying and modeling CADASIL pathology.

Bain type X-linked mental retardation syndrome is an X-linked dominant neurodevelopmental disorder characterized by psychomotor developmental delay and intellectual disability. The rare syndrome is caused by HNRNPH2 gene mutation. In this study, the iPSC cell line (SMCPGi001-A) was acquired by Sendai virus-mediated iPSC reprogramming from the peripheral blood mononuclear cells (PBMCs) obtained from a 1-year-old girl with de novo p.R206W mutation in the HNRNPH2 gene. The identification experiments of stemness and differentiation potential of three germ layers showed that the cell line had pluripotent stem cell characteristics and the potential of tridermal differentiation.

Moyamoya disease (MMD) is an idiopathic and chronic steno-occlusive cerebrovascular disease. Genetic studies identified RNF213 as a principal susceptibility gene of MMD. In this study, peripheral blood mononuclear cells (PBMCs) were obtained from an MMD patient with RNF213 p. R4810K mutations, and the PBMCs were then reprogrammed to induced pluripotent stem cells (iPSCs) by the transfection of non-integrated episomal vectors. The iPSC line shows pluripotency markers and has the potential for in vitro differentiation into three germ layers, and will be valuable for elucidating the underlying cellular mechanisms of MMD, selecting therapeutic targets, and developing drugs.

Robertsonian translocation between chromosomes 13 and 14 is reported to be a cause of male infertility. Here, we established an iPSC line (HRMSDUi001-A) from an azoospermic patient with 45,XY,der(13;14)(q10;q10) karyotype. Peripheral blood mononuclear cells were reprogrammed to generate hiPSCs by non-integrating delivery of OCT4, SOX2, KFL4 and MYC. The iPSC line expressed pluripotency markers, could differentiate into cells of three germ layers in vitro, and carried 45,XY,der(13;14)(q10;q10) karyotype.

Human iPSC line IISHDOi001-A was generated from fibroblasts of a patient with McArdle disease harbouring the mutation, c.148C > T; p.Arg50Ter, in the PYGM gene. Reprogramming factors Oct3/4, Sox2, Klf4, and c-Myc were delivered using Sendai virus., This work was supported by grants from: 1) the “Fondo de Investigación Sanitaria, Instituto de Salud Carlos III”: PI10/0703, PI13/00556 and PI16/00789 to RG and PI15/00484 to MEG cofunded by FEDER, 2) from the “Centro de Investigación Biomédica en Red en Enfermedades Raras” (CIBERER): grants 13-717/132.05 and ER16P3AC717 to RG and 3) “Comunidad Autónoma de Madrid” (grant number S2010/BMD-2402 to RG). MDCOC receives grant support from CIBERER and FZD from the Ministerio de Educación, Cultura y Deporte (FPU13/00544). MEG is supported by a “Miguel Servet contract” (CP16/00046) from ISCIII-MINECO-Spain/FEDER-EU.

Peripheral blood mononuclear cells (PBMCs) were collected from a 6-year-old female child who was clinically diagnosed as primary nephrotic syndrome (NS) with hormone resistance. An iPSC line was successfully established by the Sendai-virus (SeV) delivery system. The iPS-19 (GSPHi001-A) expressed pluripotent markers, exhibited a normal karyotype and differentiated towards three germ layers. The iPSC line might offer a potentially useful tool for investigating mechanisms of primary NS, drug testing and gene therapy studies.

7541 Background: FT516 is an investigational, NK cell cancer immunotherapy derived from a clonal master iPSC line. FT516 is engineered with a novel hnCD16 Fc receptor, demonstrated preclinically to maximize antibody-dependent cellular cytotoxicity (Zhu et al. Blood 2020). FT516 can be mass produced and made available off-the-shelf for broad pt access and multi-dose administration. Methods: This is a Phase I trial of FT516 combined with rituximab (R) in pts with R/R BCL. Treatment consists of 2 cycles, each with 3 days lympho-conditioning (fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2) and 1 dose of R followed by 3 weekly infusions of FT516 (planned doses 30-900 million/dose) with IL-2 (6 MIU after each FT516 dose). The primary objective is to identify the incidence of dose-limiting toxicity (DLT)/dose cohort and the recommended Phase II dose using a standard 3+3 design. Additional objectives include safety, tolerability, preliminary activity, pharmacokinetics, and immunogenicity. Results: Six pts (5 DLBCL, 1 FL, median age 65.5 y) have completed (5) or discontinued (1) study treatment after the DLT period (data cutoff 9 Dec 2020): 2 received 30 million cells/dose, 3 received 90 million cells/dose, and 1 received 300 million cells/dose. All pts received > 1 prior R-containing regimen, and median number of prior therapies was 3 (range 2-6), including CAR-T in 3 pts. FT516 was primarily administered in the outpatient setting. No FT516-related Grade ≥3 adverse events (AEs) or serious AEs, and no events of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GvHD) of any grade were reported. DLT (Grade 4 neutrophil count decreased, not recovered to baseline by D29) was reported in the first pt at 30 million cells/dose and R dosing of 375 mg/m2 weekly x 4/cycle, resulting in modification of R dosing to once/cycle; no DLTs were observed with modified R dosing. Most common all grade AEs in ≥3 pts: fatigue (4 pts) and decreased appetite, nausea, neutrophil count decreased, and headache (3 pts each). Grade ≥3 AEs in ≥2 pts: neutrophil count decreased (3 pts) and febrile neutropenia and platelet count decreased (2 pts each); none considered related to FT516. Host anti-product B- or T-cell immunogenicity was not observed. Three of 4 pts treated at ≥90 million cells/dose achieved objective response (2 complete responses [CRs] and 1 partial response). Conclusions: Administration of up to 6 doses of FT516 cells, including up to 300 million cells/dose, appears to be safe and tolerable, without CRS, ICANS, or GvHD. Activity was observed, including CRs, in heavily pretreated pts. Dose escalation is ongoing. Updated clinical and translational data will be presented. Clinical trial information: NCT04023071.

Patients with familial hypercholesterolemia (FH) are susceptible to premature coronary artery disease. We generated a human iPSC line CIBi009-A from a patient with FH who carried variants of LDLR c.T1241G and APOB c.G1618T. This line will be a valuable resource for investigating novel therapeutic approaches to FH.

The deletions of the long arm of chromosome 14 involving the 14q24-q32 region have been identified as deletion 14q (del 14q) syndrome, but were rarely reported. The patients with del 14q syndrome are observed a peculiar facial appearance and neurological defects, but the molecular mechanisms were not clear. Here we generated a human iPSC line from the patient’s amniotic fluid cells with 24 Mb deletion in 14q24.3q32.31 which will serve as useful tools for studying the mechanism of del 14q syndrome and the genes involved, which will provide useful basic theory of prenatal diagnosis.

Mutations in TRAF7 cause developmental delay and cardiac, facial, digital anomalies. c.1964G > A variant was most recurrent, suggesting its essentiality of pathogenicity. Further studies to determine the underlying mechanism of c.1964G > A variant are warranted. But no patient-specific cellular models have been generated. Here, we generated an iPSC line with c.1964G > A variant (SHCMDLi001-A) and a line from healthy individual (SHCMDLi002-A). Characterization of SHCMDLi001-A and SHCMDLi002-A demonstrated these iPSCs are free of exogenous reprogramming genes, expressed pluripotency markers, exhibited a normal karyotype and were potential of three germ layer differentiation. These lines provide a valuable resource for studying disease-causing mechanism of TRAF7 variant.

Human induced pluripotent stem cells with indefinite propagation in vitro provide a potential donor source of cells including erythroid cells for human therapy. Since group O D-negative (RhD−) blood cells are considered as universal donors for transfusion, it is compelling to derive iPSC line from group O/RhD− sample as a new cellular source to generate universal RBCs. The resulting iPSC line derived from group O/RhD− somatic source showed typical features of pluripotent stem cells and could provide an unprecedented cellular tool to develop universal therapeutics for blood transfusion.

A non-integrated induced pluripotent stem cell (iPSC) line was established using urine cells (UCs) derived from a healthy 32-year-old male. The patient-derived iPSC line SMBCi006-A exhibited a normal karyotype, expressed pluripotency markers and possessed trilineage differentiation potential. This cell line may serve as a basis for disease modeling, and help explore the molecular pathogenesis further.

The CHOPWT4 iPSC line was generated as a control for applications such as differentiation analyses to the three germ layers and derivative tissues. Human foreskin fibroblasts were reprogrammed using the non-integrating Sendai virus expressing Oct3/4, Sox2, c-myc, and Klf4.

Cancer-derived iPSCs have provided valuable insight into oncogenesis, but human cancer cells can often be difficult to reprogram, especially in cases of complex genetic abnormalities. Here we report, to our knowledge, the first successful generation of an iPSC line from a human immortalized acute myeloid leukemia (AML) cell line, the cell line HL-60. This iPSC line retains a majority of the leukemic genotype and displays defects in myeloid differentiation, thus providing a tool for modeling and studying AML.

Human induced pluripotent stem cell line (JUCTCi011-A) was generated from skin fibroblasts obtained from a 34-year-old healthy male subject from Jordan. The generated iPSCs showed typical embryonic-like characteristics. They retained their normal karyotype similar to their parental dermal fibroblast cells, expressed pluripotency markers and showed a differentiation potential into three germ layers as demonstrated by immunostaining and flow cytometry. This generated cell line can be used in disease modeling studies, to serve as a healthy control line and to help in developing novel therapeutic strategies for patients with hereditary neuromuscular diseases.

Variations in PRKN or HTRA2 are associated with Parkinson’s disease. We generated a human induced pluripotent stem cell (iPSC) line CIBi007-A from a patient with young-onset Parkinson’s disease (YOPD) who carried variants in PRKN and HTRA2. The generated iPSCs resembled human embryonic stem cells, expressed pluripotency markers, exhibited a normal karyotype, and could be differentiated into three germ layers in vitro. This line will be valuable for investigating disease mechanisms of YOPD and screening candidate drugs.

Using a non-integrative reprogramming method, a human iPSC Line, ZZUNEUi002-A, was generated from a 22-year-old male patient with spinocerebellar ataxia type 3 /Machado-Joseph disease (SCA3/MJD). This cell line shows pluripotency both in vitro and vivo, and has a normal karyotype. The iPSC line could be used as a tool for mechanism researching and drug screening.

We have generated MLi003-A, a new induced pluripotent stem cell (iPSC) line derived from hair follicle keratinocytes of a healthy male characterized with a maximum number of filaggrin tandem repeats, making this iPSC line the best control for studies on skin barrier function. The characterization of the MLi003-A cell line consisted of molecular karyotyping, high-throughput array-based sequencing composed of Fluidigm microfluidics technology and next-generation sequencing of the filaggrin alleles, and pluripotency and differentiation potentials testing by immunofluorescence of associated markers both in vitro and in vivo. The MLi-003A line has been also tested for ability to differentiate into keratinocytes.

Best Disease is an inherited retinal dystrophy that results in progressive and irreversible central vision loss caused by mutations of BESTROPHIN1 (BEST1). We established human induced pluripotent stem cells (iPSCs) from a Best disease patient with mutations R218H and A357V in the BEST1 gene. The generated iPSCs showed pluripotency markers and three-germ layer differentiation ability in vitro. A genetic analysis revealed mutations of R218H and A357V in the iPSCs. This iPSC line will be useful for elucidating the pathomechanisms of and drug discovery for Best disease.

Human iPSC Line, ZZUNEUi001-A, was generated from a healthy 38-year-old male individual, using non-integrating reprogramming methods. The resulting iPSCs were integration-free, expressed pluripotency stem cell markers, exhibited the potential for tri-lineage differentiation both in vitro and vivo, and maintained the normal karyotype. This cell line can be used as a control line for disease modelling.

Intellectual disability (ID) is a highly inherited neurodevelopmental disorder. A human induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells (PBMCs) in a patient with intellectual disability and carrying a haploinsufficiency for PLPPR4. This iPSC line offers a useful resource to investigate the pathogenesis and molecular mechanisms involved in PLPPR4-related ID.

Cystic Fibrosis (CF) is a genetic disease caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene which encodes for a chloride ion channel regulating the balance of salt and water across secretory epithelia. Here we generated an iPSC line from a CF patient homozygous for the p.Asn1303Lys mutation, a Class II folding defect mutation. This iPSC line provides a useful resource for disease modeling and to investigate the pharmacological response to CFTR modulators in iPSC derived epithelia.

Chronic mucocutaneous candidiasis (CMC) is a disease that is characterized by susceptibility to chronic or recurrent infections with Candida spp. due to mutations affecting mainly the IL-17 signaling of T-Cells. The most common etiologies of CMC are gain-of-function (GOF) mutations in the STAT1 gene. In this paper we report the generation of a hiPSC line from a patient suffering from CMC due to a heterozygous GOF STAT1 p.R274Q mutation which can be used for disease modeling purposes.

Use of clinical-grade human induced pluripotent stem cell (iPSC) lines as a starting material for the generation of cellular therapeutics requires demonstration of comparability of lines derived from different individuals and in different facilities. This requires agreement on the critical quality attributes of such lines and the assays that should be used. Working from established recommendations and guidance from the International Stem Cell Banking Initiative for human embryonic stem cell banking, and concentrating on those issues more relevant to iPSCs, a series of consensus workshops has made initial recommendations on the minimum dataset required to consider an iPSC line of clinical grade, which are outlined in this report. Continued evolution of this field will likely lead to revision of these guidelines on a regular basis.

Human-induced pluripotent stem cells (iPSCs) hold considerable promise for future biomedical applications. However, the generation, isolation, and establishment of an iPSC line still presents many challenges. In this study, we describe a simple yet highly efficient two-step method for the isolation, purification, and passaging of human iPSC lines that utilizes commercially available reagents. The first step adapts iPSCs to single cell culture and passage, promoting survival and self-renewal; the second step enables the isolation and purification of bona fide iPSCs from a mixed population using column-based positive selection of cells expressing pluripotency markers such as TRA-1-60. Using this method, we were able to purify iPSCs from cell preparations containing differentiated or unreprogrammed cells, and even to isolate iPSC lines directly from derivation plates. The iPSC lines generated by this method maintained their pluripotency and genomic stability, as demonstrated by trilineage differentiation and karyotype analysis. The method presented here could be adopted for high-throughput isolation and expansion of iPSC lines and facilitate the widespread use of iPSCs in future applications.

We have generated a human iPSC line, IISHDOi002-A, from commercial primary normal human dermal fibroblasts belonging to an African mitochondrial haplogroup (L3), and with a 46, XY/47, XYY mosaicism. For this purpose, reprogramming factors Oct3/4, Sox2, Klf4 and cMyc were delivered using a non-integrative methodology that involves the use of Sendai virus., This work was supported by grants from: 1) the “Fondo de Investigación Sanitaria, Instituto de Salud Carlos III”: PI10/0703, PI13/00556 and PI16/00789 to RG and PI15/00484 to MEG cofunded by FEDER, 2) from the “Centro de Investigación Biomédica en Red en Enfermedades Raras” (CIBERER): grants 13-717/132.05 and ER16P3AC717 to RG and 3) “Comunidad Autónoma de Madrid” (grant number S2010/BMD-2402 to RG). MDCOC receives grant support from the Ministerio de Educación, Cultura y Deporte, grant number FPU16/03895 and MEG is supported by the “Miguel Servet Program” (CP16/00046) from Instituto de Salud Carlos III (Spanish Ministry of Health).

Heterozygous activating mutation (p.Glu227Lys) in KCNJ11 leads to maturity-onset diabetes of the young (MODY) type 13, that is a subtype of dominant inherited young-onset non-autoimmune diabetes due to a primary defect in pancreatic beta cells. We generated induced pluripotent stem cells (iPSCs) from a patient with KCNJ11p.Glu227Lys mutation who developed MODY at 13 years old. KCNJ11p.Glu227Lys-mutated cells that were reprogrammed by non-integrative viral transduction had normal karyotype, harboured the KCNJ11p.Glu227Lys mutation, expressed pluripotency hallmarks and had the differentiation capacity into the three germ layers.