Publications by authors named "Huai-En Lu"

38 Publications

Generation of IBMS-iPSC-015, -016, -017 human induced pluripotent stem cells (IBMSi013-A, IBMSi014-A, and IBMSi015-A) derived from patients with atrial fibrillation.

Stem Cell Res 2021 07 10;54:102419. Epub 2021 Jun 10.

Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Atrial fibrillation is the most common heart disease in the world, with around 35 million patients in 2020. Here we reported the generation of IBMS-iPSC-015-06, IBMS-iPSC-016-06, and IBMS-iPSC-017-02 as human induced pluripotent stem cell (iPSC) lines from patients' peripheral blood mononuclear cells (PBMCs) with atrial fibrillation. The cell lines expressed properties of pluripotent stem cells, including pluripotent markers and the ability to differentiate into three germ layers. These cell lines served as suitable models for studying alternative therapies of atrial fibrillation.
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http://dx.doi.org/10.1016/j.scr.2021.102419DOI Listing
July 2021

Generation of IBMS-iPSC-021, -022, -023 human induced pluripotent stem cells (IBMSi016-A, IBMSi017-A, and IBMSi018-A) derived from patients with the ALDH2 rs671 polymorphism.

Stem Cell Res 2021 07 10;54:102416. Epub 2021 Jun 10.

Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

ALDH2 gene is coded for the aldehyde dehydrogenase (ALDH), which is an enzyme involved in alcohol metabolism. Compared to normal aldehyde dehydrogenases, a homozygous point mutation on exon 12 from G to A significantly reduces its efficiency. In this study, we have reported the generation of IBMS-iPSC-021-04, IBMS-iPSC-022-01, and IBMS-iPSC-023-03 as induced pluripotent stem cell (iPSC) lines carrying the homozygous form of ALDH2 with the rs671 genetic polymorphism (E487K mutation). These cell lines were characterized in terms of pluripotency and differentiation potential. They serve as useful platforms to study alcohol metabolism and other chronic diseases associated with alcohol consumption.
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http://dx.doi.org/10.1016/j.scr.2021.102416DOI Listing
July 2021

4D spatiotemporal modulation of biomolecules distribution in anisotropic corrugated microwrinkles via electrically manipulated microcapsules within hierarchical hydrogel for spinal cord regeneration.

Biomaterials 2021 04 20;271:120762. Epub 2021 Mar 20.

Department of Materials Science and Engineering, National Chiao Tung University, No. 1001 Ta-Hsueh Rd., Hsinchu, 300, Taiwan, ROC; Department of Materials Science and Engineering, National Yang Ming Chiao Tung University, No. 1001 Ta-Hsueh Rd., Hsinchu, 300, Taiwan, ROC; Frontier Research Centre on Fundamental and Applied Sciences of Matters, National Tsing Hua University, No. 101-1, Sec. 2, Guangfu Rd., Hsinchu, 300, Taiwan, ROC; School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, No.100, Shih-Chuan 1st Rd., Kaohsiung, 807, Taiwan, ROC; Graduate Institute of Biomedical Science, China Medical University, No. 100, Sec. 1, Jingmao Rd., Taichung, 406, Taiwan, ROC. Electronic address:

Although traditional 3D scaffolds or biomimetic hydrogels have been used for tissue engineering and regenerative medicine, soft tissue microenvironment usually has a highly anisotropic structure and a dynamically controllable deformation with various biomolecule distribution. In this study, we developed a hierarchical hybrid gelatin methacrylate-microcapsule hydrogel (HGMH) with Neurotrophin-3(NT-3)-loaded PLGA microcapsules to fabricate anisotropic structure with patterned NT-3 distribution (demonstrated as striped and triangular patterns) by dielectrophoresis (DEP). The HGMH provides a dynamic biomimetic sinuate-microwrinkles change with NT-3 spatial gradient and 2-stage time-dependent distribution, which was further simulated using a 3D finite element model. As demonstrated, in comparison with striped-patterned hydrogel, the triangular-patterned HGMH with highly anisotropic array of microcapsules exhibits remarkably spatial NT-3 gradient distributions that can not only guide neural stem cells (NSCs) migration but also facilitate spinal cord injury regeneration. This approach to construct hierarchical 4D hydrogel system via an electromicrofluidic platform demonstrates the potential for building various biomimetic soft scaffolds in vitro tailed to real soft tissues.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120762DOI Listing
April 2021

Generation of induced pluripotent stem cells FIRDIi001-A from a Taiwanese subject carrying ALDH2 pE487K mutation.

Stem Cell Res 2021 04 11;52:102229. Epub 2021 Feb 11.

Institute of Biomedical Sciences, Mackay Medical College, New Taipei City, Taiwan. Electronic address:

The ALDH2 mutation (ALDH2*2) is caused by an amino acid substitution ALDH2 rs671 G>A (pE487K) which reduces ALDH2 enzyme activity. When individuals with the ALDH2 mutation consume alcohol, accumulating acetaldehyde in the blood can cause reddened face, headache, nausea, and palpitations; symptoms referred to as Alcohol Flushing Reaction. We report the production of an induced pluripotent stem cell (iPSC) line, FIRDIi001-A, developed from peripheral blood mononuclear cells of a 39-year-old male subject with the ALDH2*2 mutation. The ALDH2-pE487K iPSCs will be valuable in investigating pathogenic mechanisms involved in the link between the ALDH2 polymorphism and alcohol-related diseases.
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http://dx.doi.org/10.1016/j.scr.2021.102229DOI Listing
April 2021

Copy number variant hotspots in Han Taiwanese population induced pluripotent stem cell lines - lessons from establishing the Taiwan human disease iPSC Consortium Bank.

J Biomed Sci 2020 Sep 4;27(1):92. Epub 2020 Sep 4.

Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan.

Background: The Taiwan Human Disease iPSC Service Consortium was established to accelerate Taiwan's growing stem cell research initiatives and provide a platform for researchers interested in utilizing induced pluripotent stem cell (iPSC) technology. The consortium has generated and characterized 83 iPSC lines: 11 normal and 72 disease iPSC lines covering 21 different diseases, several of which are of high incidence in Taiwan. Whether there are any reprogramming-induced recurrent copy number variant (CNV) hotspots in iPSCs is still largely unknown.

Methods: We performed genome-wide copy number variant screening of 83 Han Taiwanese iPSC lines and compared them with 1093 control subjects using an Affymetrix genome-wide human SNP array.

Results: In the iPSCs, we identified ten specific CNV loci and seven "polymorphic" CNV regions that are associated with the reprogramming process. Additionally, we established several differentiation protocols for our iPSC lines. We demonstrated that our iPSC-derived cardiomyocytes respond to pharmacological agents and were successfully engrafted into the mouse myocardium demonstrating their potential application in cell therapy.

Conclusions: The CNV hotspots induced by cell reprogramming have successfully been identified in the current study. This finding may be used as a reference index for evaluating iPSC quality for future clinical applications. Our aim was to establish a national iPSC resource center generating iPSCs, made available to researchers, to benefit the stem cell community in Taiwan and throughout the world.
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http://dx.doi.org/10.1186/s12929-020-00682-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487458PMC
September 2020

Organ-on-a-Chip: Opportunities for Assessing the Toxicity of Particulate Matter.

Front Bioeng Biotechnol 2020 29;8:519. Epub 2020 May 29.

Department of Electrical and Computer Engineering, College of Electrical and Computer Engineering National Chiao Tung University, Hsinchu, Taiwan.

Recent developments in epidemiology have confirmed that airborne particulates are directly associated with respiratory pathology and mortality. Although clinical studies have yielded evidence of the effects of many types of fine particulates on human health, it still does not have a complete understanding of how physiological reactions are caused nor to the changes and damages associated with cellular and molecular mechanisms. Currently, most health assessment studies of particulate matter (PM) are conducted through cell culture or animal experiments. The results of such experiments often do not correlate with clinical findings or actual human reactions, and they also cause difficulty when investigating the causes of air pollution and associated human health hazards, the analysis of biomarkers, and the development of future pollution control strategies. Microfluidic-based cell culture technology has considerable potential to expand the capabilities of conventional cell culture by providing high-precision measurement, considerably increasing the potential for the parallelization of cellular assays, ensuring inexpensive automation, and improving the response of the overall cell culture in a more physiologically relevant context. This review paper focuses on integrating the important respiratory health problems caused by air pollution today, as well as the development and application of biomimetic organ-on-a-chip technology. This more precise experimental model is expected to accelerate studies elucidating the effect of PM on the human body and to reveal new opportunities for breakthroughs in disease research and drug development.
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http://dx.doi.org/10.3389/fbioe.2020.00519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272695PMC
May 2020

Generation of a gene corrected human isogenic IBMS-iPSC-014-C from polycystic-kidney-disease induced pluripotent stem cell line using CRISPR/Cas9.

Stem Cell Res 2020 05 20;45:101784. Epub 2020 Apr 20.

Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:

We report the engendering an isogenic iPSC line from the IBMS-iPSC-014-05 with homozygous correction of the R803X, Chr4: 88989098C > T in PKD2, using CRISPR/Cas9 technology. The results from the isogenic control, IBMS-iPSC-014-05C, showed that mutation had been corrected, while maintaining normal morphology, pluripotency, and differentiation capacity into three germ layers.
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http://dx.doi.org/10.1016/j.scr.2020.101784DOI Listing
May 2020

Generation of a human induced pluripotent stem cell (iPSC) line (IBMS-iPSC-048-05) from a patient with ALS and parkinsonism having a hexanucleotide repeat expansion mutation in C9orf72 gene.

Stem Cell Res 2020 04 27;44:101734. Epub 2020 Feb 27.

Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan. Electronic address:

A hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72) gene causes a heterogeneous neurodegenerative disorder that includes amyotrophic lateral sclerosis (ALS), frontotemporal degeneration (FTD), and parkinsonism. Here, we used the Sendai virus delivery system to generate induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells of a male patient with an increased hexanucleotide repeat expansion in C9orf72. The resulting iPSCs exhibited pluripotency, confirmed by immunofluorescent staining for pluripotency markers, and differentiated into three germ layers in vivo. This cellular model will provide a useful platform for further pathophysiological studies of C9orf72-related neurodegeneration.
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http://dx.doi.org/10.1016/j.scr.2020.101734DOI Listing
April 2020

Generation of induced pluripotent stem cells MMCi001-A from a Taiwanese hearing loss patient carrying GJB2 pV37I mutation.

Stem Cell Res 2020 01 18;42:101692. Epub 2019 Dec 18.

Institute of Biomedical Sciences, Mackay Medical College, New Taipei City, Taiwan. Electronic address:

Hearing loss is the most common disorder in the sensory system. Mutations in GJB2 have been reported to be very common in sensorineural hearing loss patients. In this report, we generated an induced pluripotent stem cell (iPSC) line, MMCi001-A, from the peripheral blood mononuclear cells of a 4-year-old male hearing loss patient carrying GJB2 pV37I mutation by using the Sendai virus delivery system. The generated iPSCs were demonstrated to express pluripotent markers and be differentiated into three germ layers in vitro and in vivo. This GJB2-pV37I iPSCs is valuable for studying the pathogenic mechanisms and drug discovery of hearing loss.
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http://dx.doi.org/10.1016/j.scr.2019.101692DOI Listing
January 2020

The Development of Controllable Magnetic Driven Microphysiological System.

Front Cell Dev Biol 2019 7;7:275. Epub 2019 Nov 7.

Institute of Biomedical Engineering, College of Electrical and Computer Engineering, National Chiao Tung University, Hsinchu, Taiwan.

Current research has enabled the use of microphysiological systems and creation of models for alveolar and pulmonary diseases. However, bottlenecks remain in terms of medium- and long-term regulation of cell cultures and their functions in microchannel systems, as well as in the enhancement of representation of alveolar models and reference values of the data. Currently used systems also require on-chip manufacturing of complex units, such as pumps, tubes, and other cumbersome structures for maintaining cells in culture. In addition, system simplification and minimization of all external and human factors major challenges facing the establishment of alveolar models. In this study, a magnetically driven dynamic alveolus cell-culture system has been developed to use controlled magnetic force to drive a magnetic film on the chip, thereby directing the fluid within it to produce a circulating flow. The system has been confirmed to be conducive with regard to facilitating uniform attachment of human alveolar epithelial cells and long-term culture. The cell structure has been recapitulated, and differentiation functions have been maintained. Subsequently, reactions between silica nanoparticles and human alveolar epithelial cells have been used to validate the effects and advantages of the proposed dynamic chip-based system compared to a static environment. The innovative concept of use of a magnetic drive has been successfully employed in this study to create a simple and controllable yet dynamic alveolus cell-culture system to realize its functions and advantages with regard to tissue construction.
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http://dx.doi.org/10.3389/fcell.2019.00275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853840PMC
November 2019

Generation of induced pluripotent stem cells (IBMSi011-A) from a patient with Parkinson's disease carrying LRRK2 p.I1371V mutation.

Stem Cell Res 2019 05 22;37:101447. Epub 2019 Apr 22.

Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan. Electronic address:

Leucine rich repeat kinase 2 (LRRK2) is the causative gene for autosomal-dominant familial forms of Parkinson's disease (PD). Here, we generated induced pluripotent stem cells (iPSCs) from the peripheral blood mononuclear cells of a female patient with LRRK2 c.4111A > G (p.I1371V) mutation by using the Sendai-virus delivery system. The resulting iPSCs had a normal karyotype. The iPSCs also showed pluripotency confirmed by immunofluorescent staining and differentiated into the three germ layers in vivo. This cellular model will provide a platform for studying the role of LRRK2 in the disease process.
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http://dx.doi.org/10.1016/j.scr.2019.101447DOI Listing
May 2019

Generation of induced pluripotent stem cell line-NTUHi001-A from a premature ovarian failure patient with Turner's syndrome mosaicism.

Stem Cell Res 2019 05 2;37:101422. Epub 2019 Apr 2.

Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University, Taipei, Taiwan. Electronic address:

Turner's syndrome (TS) is one of the main causes of premature ovarian failure (POF). However, the mechanisms underlying POF are difficult to study due to the lack of suitable disease models. Herein, we have generated a human induced pluripotent stem cell (hiPSC) line derived from the peripheral blood mononuclear cells of a female patient with Turner's syndrome mosaicism via integration-free Sendai-virus system. The hiPSCs were confirmed with a 45, X karyotype and the acquisition of pluripotency. It's likely that hiPSCs can serve as a feasible cellular model for further pathophysiological studies of POF cases, especially for those originating in TS.
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http://dx.doi.org/10.1016/j.scr.2019.101422DOI Listing
May 2019

Reprogramming of a human induced pluripotent stem cell (iPSC) line (IBMSi012-A) from an early-onset Parkinson's disease patient harboring a homozygous p.D331Y mutation in the PLA2G6 gene.

Stem Cell Res 2019 05 5;37:101432. Epub 2019 Apr 5.

Institute of Molecular Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address:

A recessive mutation in PLA2G6, which is known to cause a heterogeneous neurodegenerative clinical spectrum, has recently been shown to be responsible for autosomal-recessive familial forms of Parkinson's disease (PD). Here, we generated induced pluripotent stem cells (iPSCs) from the peripheral blood mononuclear cells of a female patient with a homozygous PLA2G6 c.991G > T (p.D331Y) mutation by using the Sendai-virus delivery system. The resulting iPSCs showed pluripotency confirmed by immunofluorescent staining for pluripotency markers and differentiated into the 3 germ layers in vivo. This cellular model will provide a good resource for further pathophysiological studies of PD.
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http://dx.doi.org/10.1016/j.scr.2019.101432DOI Listing
May 2019

Corrigendum to "Generation of induced pluripotent stem cells from a patient with X-linked juvenile retinoschisis" [Stem Cell Res. 29(2018): 152-156].

Stem Cell Res 2019 01;34:101388

Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Genomic Research Center, Academia Sinica, Taipei, Taiwan; Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan. Electronic address:

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http://dx.doi.org/10.1016/j.scr.2019.101388DOI Listing
January 2019

Generation of induced pluripotent stem cells from a patient with X-linked juvenile retinoschisis.

Stem Cell Res 2018 05 11;29:152-156. Epub 2018 Apr 11.

Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Genomic Research Center, Academia Sinica, Taipei, Taiwan; Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan. Electronic address:

X-linked juvenile retinoschisis (XLRS) is a hereditary retinal dystrophy manifested as splitting of anatomical layers of retina. In this report, we generated a patient-specific induced pluripotent stem cell (iPSC) line, TVGH-iPSC-013-05, from the peripheral blood mononuclear cells of a male patient with XLRS by using the Sendai-virus delivery system. We believe that XLRS patient-specific iPSCs provide a powerful in vitro model for evaluating the pathological phenotypes of the disease.
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http://dx.doi.org/10.1016/j.scr.2018.04.005DOI Listing
May 2018

Generation of induced pluripotent stem cells from a patient with Best Dystrophy carrying 11q12.3 (BEST1 (VMD2)) mutation.

Stem Cell Res 2018 05 3;29:134-138. Epub 2018 Apr 3.

Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.

Best disease (BD), also termed Best vitelliform macular dystrophy (BVMD), is a juvenile-onset form of macular degeneration and central visual loss. In this report, we generated an induced pluripotent stem cell (iPSC) line, TVGH-iPSC-012-04, from the peripheral blood mononuclear cells of a female patient with BD by using the Sendai virus delivery system. The resulting iPSCs retained the disease-causing DNA mutation, expressed pluripotent markers and could differentiate into three germ layers. We believe that BD patient-specific iPSCs provide a powerful in vitro model for evaluating the pathological phenotypes of the disease.
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http://dx.doi.org/10.1016/j.scr.2018.03.019DOI Listing
May 2018

Generation of patient-specific induced pluripotent stem cells from Leber's hereditary optic neuropathy.

Stem Cell Res 2018 04 31;28:56-60. Epub 2018 Jan 31.

Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Genomic Research Center, Academia Sinica, Taipei, Taiwan. Electronic address:

Leber's hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disease caused by homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. In this report, we generated an induced pluripotent stem cell (iPSCs) line, TVGH-iPSC-010-09, from the peripheral blood mononuclear cells of a female patient with Leber's hereditary optic neuropathy (LHON) by using the Sendai-virus delivery system. The resulting iPSCs retained the disease-causing mitochondrial DNA mutation, expressed pluripotent markers and could differentiate into the three germ layers. We believe LHON patient-specific iPSCs provide a powerful in vitro model for evaluating the pathological phenotypes of the disease.
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http://dx.doi.org/10.1016/j.scr.2018.01.029DOI Listing
April 2018

Generation of novel induced pluripotent stem cell (iPSC) line from a 16-year-old sialidosis patient with NEU-1 gene mutation.

Stem Cell Res 2018 04 31;28:39-43. Epub 2018 Jan 31.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Electronic address:

Sialidosis is a rare autosomal recessive disorder that affects the intralysosomal catabolism of sialylated glycoconjugates and is involved in cellular immune response. Mutations in NEU1, which encodes the sialidase enzyme, result in sialidosis. Sialidosis is characterized by the progressive lysosomal storage of sialylated glycopeptides and oligosaccharides. In this study, we used Sendai virus reprogramming to generate an induced pluripotent stem cell (iPSC) line carrying the A544G mutation combined with the 667-679 deletion of the NEU1 gene from a sialidosis patient. The patient-specific iPSCs expressed pluripotent markers, possessed a normal karyotype, and displayed the capability to differentiate into three germ layers.
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http://dx.doi.org/10.1016/j.scr.2018.01.024DOI Listing
April 2018

Generation of 2 induced pluripotent stem cell lines derived from patients with Parkinson's disease carrying LRRK2 G2385R variant.

Stem Cell Res 2018 04 28;28:1-5. Epub 2018 Feb 28.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Electronic address:

Leucine rich repeat kinase (LRRK2) is the most prevalent genetic cause for Parkinson's disease. LRRK2 p.G2385R is an Asian specific genetic risk factor for sporadic Parkinson's disease. We generated two induced pluripotent stem cells (iPSCs), IBMS-iPSC-018-09 and IBMS-iPSC-020-01, from the peripheral blood mononuclear cells of two patients carrying LRRK2 p.G2385R variant by using the Sendai-virus delivery system. These iPSCs had a normal karyotype and exhibited pluripotency, such as an embryonic stem cell-like morphology, expression of pluripotent markers, and capacity to differentiate into three germ layers. This cellular model will provide a platform for pathophysiological studies of neurodegeneration in Parkinson's disease.
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http://dx.doi.org/10.1016/j.scr.2018.01.034DOI Listing
April 2018

Generation of an induced pluripotent stem cell (iPSC) line from a 40-year-old patient with the A8344G mutation of mitochondrial DNA and MERRF (myoclonic epilepsy with ragged red fibers) syndrome.

Stem Cell Res 2018 03 19;27:10-14. Epub 2017 Dec 19.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Electronic address:

Mitochondrial defects are associated with clinical manifestations from common diseases to rare genetic disorders. Myoclonus epilepsy associated with ragged-red fibers (MERRF) syndrome results from an A to G transition at nucleotide position 8344 in the tRNA gene of mitochondrial DNA (mtDNA) and is characterized by myoclonus, myopathy and severe neurological symptoms. In this study, Sendai reprogramming method was used to generate an iPS cell line carrying the A8344G mutation of mtDNA from a MERRF patient. This patient-specific iPSC line expressed pluripotent stem cell markers, possessed normal karyotype, and displayed the capability to differentiate into mature cells in three germ layers.
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http://dx.doi.org/10.1016/j.scr.2017.12.013DOI Listing
March 2018

Generation of an induced pluripotent stem cell line from a 39-year-old female patient with severe-to-profound non-syndromic sensorineural hearing loss and a A1555G mutation in the mitochondrial MTRNR1 gene.

Stem Cell Res 2017 12 8;25:245-249. Epub 2017 Nov 8.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Electronic address:

Sensorineural hearing loss (SNHL) is a prevalent form of deafness commonly arising from damage to the cochlear sensory hair cells and degeneration of the spiral ganglion neurons. In this study, Sendai virus was used to generate an induced pluripotent stem cell (iPSC) line from a 39-year-old female patient diagnosed with severe-to-profound, non-syndromic SNHL. The patient also carries a A1555G mutation in the mitochondrial 12S ribosome RNA gene (MTRNR1). This iPSC line was verified to express pluripotent markers, possess normal karyotype, harbor the specific mutation and demonstrated the capacity to differentiate into three germ layers.
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http://dx.doi.org/10.1016/j.scr.2017.10.024DOI Listing
December 2017

Generation of induced pluripotent stem cells from a patient with Parkinson's disease carrying LRRK2 p.I2012T mutation.

Stem Cell Res 2017 12 31;25:123-127. Epub 2017 Oct 31.

Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan. Electronic address:

Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by interactions between genetic and environmental factors. Leucine rich repeat kinase (LRRK2) is the most prevalent mutation in autosomal-dominant inheritance of PD. Here, we generated induced pluripotent stem cells (iPSCs) from the peripheral blood mononuclear cells of a female patient with p.I2012T mutation in LRRK2 gene by using the Sendai-virus delivery system. The resulting iPSCs had a normal karyotype. The iPSCs also showed pluripotency confirmed by immunofluorescent staining and differentiated into the 3 germ layers in vivo. This cellular model will provide a useful platform for further pathophysiological studies of PD.
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http://dx.doi.org/10.1016/j.scr.2017.10.020DOI Listing
December 2017

Induced pluripotent stem cells derived from an autosomal dominant polycystic kidney disease patient carrying a PKD1 Q533X mutation.

Stem Cell Res 2017 12 28;25:83-87. Epub 2017 Oct 28.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Electronic address:

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most prevalent monogenic kidney disorder leading to kidney failure. We generated induced pluripotent stem cells (iPSCs) from a 37-year-old man carrying a PKD1 Q533X mutation who suffered from kidney failure and a myocardial infarction. The iPSCs were reprogrammed from the patient's peripheral blood mononuclear cells using the Sendai virus system, and were confirmed to possess the specific PKD1 Q533X mutation and normal karyotype. Pluripotency was confirmed using in vitro and in vivo assays. This iPSC line will be useful for studying the mechanisms driving the complicated pathophysiology of ADPKD.
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http://dx.doi.org/10.1016/j.scr.2017.10.026DOI Listing
December 2017

Generation of an induced pluripotent stem cell line, IBMS-iPSC-014-05, from a female autosomal dominant polycystic kidney disease patient carrying a common mutation of R803X in PKD2.

Stem Cell Res 2017 12 10;25:38-41. Epub 2017 Oct 10.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Electronic address:

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most commonly inherited forms of polycystic kidney disease, and is characterized by the growth of numerous cysts in both kidneys. Here we generated an induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells (PBMCs) of a 63-year-old female ADPKD patient carrying an R803X mutation in the PKD2 gene using the Sendai-virus delivery system. Downstream characterization of these iPSCs showed that they possessed normal karyotyping, were free of genomic integration, retained the disease-causing PKD2 mutation, expressed pluripotency markers and could differentiate into three germ layers.
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http://dx.doi.org/10.1016/j.scr.2017.10.005DOI Listing
December 2017

Generation of induced pluripotent stem cells derived from an autosomal dominant polycystic kidney disease patient with a p.Ser1457fs mutation in PKD1.

Stem Cell Res 2017 10 15;24:139-143. Epub 2017 Sep 15.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Electronic address:

Autosomal dominant polycystic kidney disease is one of the most prevalent forms of inherited cystic kidney disease, and can be characterized by kidney cyst formation and enlargement. Here we report the generation of a Type 1 ADPKD disease iPS cell line, IBMS-iPSC-012-12, which retains the conserved deletion of PKD1, normal karyotype and exhibits the properties of pluripotent stem cells such as ES-like morphology, expression of pluripotent markers and capacity to differentiate into all three germ layers. Our results show that we have successfully generated a patient-specific iPS cell line with a mutation in PKD1 for study of renal disease pathophysiology.
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http://dx.doi.org/10.1016/j.scr.2017.09.004DOI Listing
October 2017

Direct Reprogramming of Human Suspension Cells into Mesodermal Cell Lineages via Combined Magnetic Targeting and Photothermal Stimulation by Magnetic Graphene Oxide Complexes.

Small 2017 08 30;13(32). Epub 2017 Jun 30.

Department of Materials Science and Engineering, National Chiao Tung University, Hsinchu, 30010, Taiwan, ROC.

Suspension cells can provide a source of cells for cellular reprogramming, but they are difficult to transfect by nonviral vectors. An efficient and safe nonviral vector (GO-Fe O -PEI complexes) based on iron oxide nanoparticle (Fe O )-decorated graphene oxide (GO) complexed with polyethylenimine (PEI) for the first time is developed for delivering three individual episomal plasmids (pCXLE-hOCT3/4-shp53, pCXLE-hSK, and pCXLE-hUL) encoding pluripotent-related factors of Oct3/4, shRNA against p53, Sox2, Klf4, L-Myc, and Lin28 into human peripheral blood mononuclear cells (PBMCs) simultaneously. The combined treatment of magnetic stirring and near-infrared (NIR)-laser irradiation, which can promote contact between the complexes and floating cells and increase the cell membrane permeability, respectively, is used to conduct multiple physical stimulations for suspension PBMCs transfection. The PCR analysis shows that the combinatorial effect of magnetic targeting and photothermal stimulation obviously promoted the transfection efficiency of suspension cells. The transfected cells show positive expression of the pluripotency markers, including Nanog, Oct4, and Sox2, and have potential to differentiate into mesoderm and ectoderm cells. The results demonstrate that the GO-Fe O -PEI complex provides a safe, convenient, and efficient tool for reprogramming PBMCs into partially induced pluripotent stem cells, which are able to rapidly transdifferentiate into mesodermal lineages without full reprogramming.
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http://dx.doi.org/10.1002/smll.201700703DOI Listing
August 2017

Generation of induced pluripotent stem cells from a patient with spinocerebellar ataxia type 3.

Stem Cell Res 2017 01 9;18:29-32. Epub 2016 Dec 9.

Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan. Electronic address:

Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited neurodegenerative disease caused by a trinucleotide repeat (CAG) expansion in the coding region of ATXN3 gene resulting in production of ataxin-3 with an elongated polyglutamine tract. Here, we generated induced pluripotent stem cells (iPSCs) from the peripheral blood mononuclear cells of a male patient with SCA3 by using the Sendai-virus delivery system. The resulting iPSCs had a normal karyotype, retained the disease-causing ATXN3 mutation, expressed pluripotent markers and could differentiate into the three germ layers. Potentially, the iPSCs could be a useful tool for the investigation of disease mechanisms of SCA3.
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http://dx.doi.org/10.1016/j.scr.2016.12.017DOI Listing
January 2017

Early Administration of Glutamine Protects Cardiomyocytes from Post-Cardiac Arrest Acidosis.

Biomed Res Int 2016 12;2016:2106342. Epub 2016 Dec 12.

Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.

Postcardiac arrest acidosis can decrease survival. Effective medications without adverse side effects are still not well characterized. We aimed to analyze whether early administration of glutamine could improve survival and protect cardiomyocytes from postcardiac arrest acidosis using animal and cell models. Forty Wistar rats with postcardiac arrest acidosis (blood pH < 7.2) were included. They were divided into study (500 mg/kg L-alanyl-L-glutamine, = 20) and control (normal saline, = 20) groups. Each of the rats received resuscitation. The outcomes were compared between the two groups. In addition, cardiomyocytes derived from human induced pluripotent stem cells were exposed to HBSS with different pH levels (7.3 or 6.5) or to culture medium (control). Apoptosis-related markers and beating function were analyzed. We found that the duration of survival was significantly longer in the study group ( < 0.05). In addition, in pH 6.5 or pH 7.3 HBSS buffer, the expression levels of cell stress (p53) and apoptosis (caspase-3, Bcl-xL) markers were significantly lower in cardiomyocytes treated with 50 mM L-glutamine than those without L-glutamine (RT-PCR). L-glutamine also increased the beating function of cardiomyocytes, especially at the lower pH level (6.5). More importantly, glutamine decreased cardiomyocyte apoptosis and increased these cells' beating function at a low pH level.
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http://dx.doi.org/10.1155/2016/2106342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5183754PMC
January 2017

Impact of Different Initial Epinephrine Treatment Time Points on the Early Postresuscitative Hemodynamic Status of Children With Traumatic Out-of-hospital Cardiac Arrest.

Medicine (Baltimore) 2016 Mar;95(12):e3195

From the Department of Emergency Medicine (Y-RL, C-FC, C-YC, CHC), Changhua Christian Hospital, Changhua, Taiwan; School of Medicine (Y-RL), Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine (Y-RL), Chung Shan Medical University, Taichung, Taiwan; Department of Anesthesiology (Y-JS), Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Biological Science and Technology (WB, C-YC, W-LC), National Chiao Tung University, Hsinchu, Taiwan; Interdisciplinary Graduate Program in Genetic Engineering (WB), Graduate School, Kasetsart University, Bangkhen campus, Bangkok, Thailand; Bioresource Collection and Research Center (H-EL), Food Industry Research and Development Institute, Hsinchu, Taiwan; Department of Emergency Medicine (C-JL), Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; and Department of Public Health (C-JL), College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan.

The postresuscitative hemodynamic status of children with traumatic out-of-hospital cardiac arrest (OHCA) might be impacted by the early administration of epinephrine, but this topic has not been well addressed. The aim of this study was to analyze the early postresuscitative hemodynamics, survival, and neurologic outcome according to different time points of first epinephrine treatment among children with traumatic OHCA.Information on 388 children who presented to the emergency departments of 3 medical centers and who were treated with epinephrine for traumatic OHCA during the study period (2003-2012) was retrospectively collected. The early postresuscitative hemodynamic features (cardiac functions, end-organ perfusion, and consciousness), survival, and neurologic outcome according to different time points of first epinephrine treatment (early: <15, intermediate: 15-30, and late: >30 minutes after collapse) were analyzed.Among 165 children who achieved sustained return of spontaneous circulation, 38 children (9.8%) survived to discharge and 12 children (3.1%) had good neurologic outcomes. Early epinephrine increased the postresuscitative heart rate and blood pressure in the first 30 minutes, but ultimately impaired end-organ perfusion (decreased urine output and initial creatinine clearance) (all P < 0.05). Early epinephrine treatment increased the chance of achieving sustained return of spontaneous circulation, but did not increase the rates of survival and good neurologic outcome.Early epinephrine temporarily increased heart rate and blood pressure in the first 30 minutes of the postresuscitative period, but impaired end-organ perfusion. Most importantly, the rates of survival and good neurologic outcome were not significantly increased by early epinephrine administration.
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http://dx.doi.org/10.1097/MD.0000000000003195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998412PMC
March 2016

N-butylidenephthalide attenuates Alzheimer's disease-like cytopathy in Down syndrome induced pluripotent stem cell-derived neurons.

Sci Rep 2015 Mar 4;5:8744. Epub 2015 Mar 4.

1] Program in Tissue Engineering and Regenerative Medicine, Agricultural Biotechnology Center, National Chung-Hsing University, Taichung, Taiwan [2] Department of Life Sciences, Agricultural Biotechnology Center, National Chung-Hsing University, Taichung, Taiwan.

Down syndrome (DS) patients with early-onset dementia share similar neurodegenerative features with Alzheimer's disease (AD). To recapitulate the AD cell model, DS induced pluripotent stem cells (DS-iPSCs), reprogrammed from mesenchymal stem cells in amniotic fluid, were directed toward a neuronal lineage. Neuroepithelial precursor cells with high purity and forebrain characteristics were robustly generated on day 10 (D10) of differentiation. Accumulated amyloid deposits, Tau protein hyperphosphorylation and Tau intracellular redistribution emerged rapidly in DS neurons within 45 days but not in normal embryonic stem cell-derived neurons. N-butylidenephthalide (Bdph), a major phthalide ingredient of Angelica sinensis, was emulsified by pluronic F127 to reduce its cellular toxicity and promote canonical Wnt signaling. Interestingly, we found that F127-Bdph showed significant therapeutic effects in reducing secreted Aβ40 deposits, the total Tau level and the hyperphosphorylated status of Tau in DS neurons. Taken together, DS-iPSC derived neural cells can serve as an ideal cellular model of DS and AD and have potential for high-throughput screening of candidate drugs. We also suggest that Bdph may benefit DS or AD treatment by scavenging Aβ aggregates and neurofibrillary tangles.
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http://dx.doi.org/10.1038/srep08744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4348654PMC
March 2015
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