1.Inducing Pluripotency in Somatic Cells:Historical Perspective and Recent Advances
Junmyeong PARK ; Jueun KIM ; Borami SHIN ; Hans R SCHÖLER ; Johnny KIM ; Kee-Pyo KIM
International Journal of Stem Cells 2024;17(4):353-373
Inducing pluripotency in somatic cells is mediated by the Yamanaka factors Oct4, Sox2, Klf4, and c-Myc. The resulting induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine by virtue of their ability to differentiate into different types of functional cells. Specifically, iPSCs derived directly from patients offer a powerful platform for creating in vitro disease models. This facilitates elucidation of pathological mechanisms underlying human diseases and development of new therapeutic agents mitigating disease phenotypes. Furthermore, genetically and phenotypically corrected patient-derived iPSCs by gene-editing technology or the supply of specific pharmaceutical agents can be used for preclinical and clinical trials to investigate their therapeutic potential. Despite great advances in developing reprogramming methods, the efficiency of iPSC generation remains still low and varies between donor cell types, hampering the potential application of iPSC technology. This paper reviews histological timeline showing important discoveries that have led to iPSC generation and discusses recent advances in iPSC technology by highlighting donor cell types employed for iPSC generation.
2.Inducing Pluripotency in Somatic Cells:Historical Perspective and Recent Advances
Junmyeong PARK ; Jueun KIM ; Borami SHIN ; Hans R SCHÖLER ; Johnny KIM ; Kee-Pyo KIM
International Journal of Stem Cells 2024;17(4):353-373
Inducing pluripotency in somatic cells is mediated by the Yamanaka factors Oct4, Sox2, Klf4, and c-Myc. The resulting induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine by virtue of their ability to differentiate into different types of functional cells. Specifically, iPSCs derived directly from patients offer a powerful platform for creating in vitro disease models. This facilitates elucidation of pathological mechanisms underlying human diseases and development of new therapeutic agents mitigating disease phenotypes. Furthermore, genetically and phenotypically corrected patient-derived iPSCs by gene-editing technology or the supply of specific pharmaceutical agents can be used for preclinical and clinical trials to investigate their therapeutic potential. Despite great advances in developing reprogramming methods, the efficiency of iPSC generation remains still low and varies between donor cell types, hampering the potential application of iPSC technology. This paper reviews histological timeline showing important discoveries that have led to iPSC generation and discusses recent advances in iPSC technology by highlighting donor cell types employed for iPSC generation.
3.Inducing Pluripotency in Somatic Cells:Historical Perspective and Recent Advances
Junmyeong PARK ; Jueun KIM ; Borami SHIN ; Hans R SCHÖLER ; Johnny KIM ; Kee-Pyo KIM
International Journal of Stem Cells 2024;17(4):353-373
Inducing pluripotency in somatic cells is mediated by the Yamanaka factors Oct4, Sox2, Klf4, and c-Myc. The resulting induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine by virtue of their ability to differentiate into different types of functional cells. Specifically, iPSCs derived directly from patients offer a powerful platform for creating in vitro disease models. This facilitates elucidation of pathological mechanisms underlying human diseases and development of new therapeutic agents mitigating disease phenotypes. Furthermore, genetically and phenotypically corrected patient-derived iPSCs by gene-editing technology or the supply of specific pharmaceutical agents can be used for preclinical and clinical trials to investigate their therapeutic potential. Despite great advances in developing reprogramming methods, the efficiency of iPSC generation remains still low and varies between donor cell types, hampering the potential application of iPSC technology. This paper reviews histological timeline showing important discoveries that have led to iPSC generation and discusses recent advances in iPSC technology by highlighting donor cell types employed for iPSC generation.
4.Generation of Induced Pluripotent Stem Cells from Lymphoblastoid Cell Lines by Electroporation of Episomal Vectors
Myunghyun KIM ; Junmyeong PARK ; Sujin KIM ; Dong Wook HAN ; Borami SHIN ; Hans Robert SCHÖLER ; Johnny KIM ; Kee-Pyo KIM
International Journal of Stem Cells 2023;16(1):36-43
Background and Objectives:
Lymphoblastoid cell lines (LCLs) deposited from disease-affected individuals could be a valuable donor cell source for generating disease-specific induced pluripotent stem cells (iPSCs). However, generation of iPSCs from the LCLs is still challenging, as yet no effective gene delivery strategy has been developed.
Methods:
and Results: Here, we reveal an effective gene delivery method specifically for LCLs. We found that LCLs appear to be refractory toward retroviral and lentiviral transduction. Consequently, lentiviral and retroviral transduction of OCT4, SOX2, KFL4 and c-MYC into LCLs does not elicit iPSC colony formation. Interestingly, however we found that transfection of oriP/EBNA-1-based episomal vectors by electroporation is an efficient gene delivery system into LCLs, enabling iPSC generation from LCLs. These iPSCs expressed pluripotency makers (OCT4, NANOG, SSEA4, SALL4) and could form embryoid bodies.
Conclusions
Our data show that electroporation is an effective gene delivery method with which LCLs can be efficiently reprogrammed into iPSCs.
5.Prevalence Rates of Primary Headache Disorders and Evaluation and Treatment Patterns Among Korean Neurologists
Byung-Kun KIM ; Min Kyung CHU ; Soo Jin YU ; Grazia DELL’AGNELLO ; Hans-Peter HUNDEMER ; Tommaso PANNI ; Sara Prada ALONSO ; Sarah Louise ROCHE ; Jeong Hee HAN ; Soo-Jin CHO
Journal of Clinical Neurology 2022;18(5):571-580
Background:
and Purpose Several studies have found that the prevalence of migraine is higher among healthcare professionals than in the general population. Furthermore, several investigations have suggested that the personal experiences of neurologists with migraine can influence their perception and treatment of the disease. This study assessed these relationships in Korea.
Methods:
A survey was used to investigate the following characteristics among neurologists:1) the prevalence rates of migraine, primary stabbing headache, and cluster headache, and 2) their perceptions of migraine and the pain severity experienced by patients, diagnosing migraine, evaluation and treatment patterns, and satisfaction and difficulties with treatment.
Results:
The survey was completed by 442 actively practicing board-certified Korean neurologists. The self-reported lifetime prevalence rates of migraine, migraine with aura, primary stabbing headache, and cluster headache were 49.8%, 12.7%, 26.7%, and 1.4%, respectively. Few of the neurologists used a headache diary or validated scales with their patients, and approximately half were satisfied with the effectiveness of preventive medications. Significant differences were observed between neurologists who had and had not experienced migraine, regarding certain perceptions of migraine, but no differences were found between these groups in the evaluation and preventive treatment of migraine.
Conclusions
The high self-reported lifetime prevalence rates of migraine and other primary headache disorders among Korean neurologists may indicate that these rates are underreported in the general population, although potential population biases must be considered. From the perspective of neurologists, there is an unmet need for the proper application of headache diaries, validated scales, and effective preventive treatments for patients. While the past experiences of neurologists with migraine might not influence how they evaluate or apply preventive treatments to migraine, they may influence certain perceptions of the disease.
6.Organoid Studies in COVID-19 Research
Jihoon KIM ; Bon-Kyoung KOO ; Hans CLEVERS
International Journal of Stem Cells 2022;15(1):3-13
The current COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has completely changed human life for more than two years. Upon the emergence of this new lethal virus, multiple approaches were utilized to gain basic knowledge about its biology. Moreover, modern technologies, such as the organoid model system and next-generation sequencing, enabled us to rapidly establish strategies to tackle the disease, including vaccines and therapeutics. The recently developed organoid technology reflects human physiology more closely than other model systems. Coupled with its rapidness, high efficiency, and outstanding reliability, it has provided an opportunity to develop new drugs and understand the impact of the viral pathogen on the host. Recent findings using organoids have successfully revealed the cellular tropism of the virus in different organs and identified potential drug candidates that impact the disease. This review will summarize current achievements made with organoids in the fight against COVID-19.
7.Establishment of the Heart and Brain Team for Patent Foramen Ovale Closure in Stroke Patients: An Expert Opinion
Jong S. KIM ; Vincent THIJS ; Matias YUDI ; Kazunori TOYODA ; Masayuki SHIOZAWA ; Jin ZENING ; Brian CLAPP ; Bert ALBERS ; Hans-Christoph DIENER
Journal of Stroke 2022;24(3):345-351
The online 2021 Asian-Pacific Heart and Brain Summit was organized to present and discuss experiences within leading Asian-Pacific centers with regard to institutional heart and brain teams managing the diagnosis, treatment, and follow-up of cryptogenic stroke (CS) patients with patent foramen ovale (PFO). This manuscript presents a narrative review of presentations and discussions during the summit meeting. Percutaneous PFO closure is an established therapy for CS patients in whom PFO is considered to be causal. Guidelines and consensus statements emphasize the importance of multidisciplinary clinical decision-making regarding PFO closure with the involvement of several clinical specialties, including neurology, cardiology, and hematology. It is also recommended that the patient be closely involved in this process. The heart and brain team is a collaborative platform that facilitates such a multidisciplinary decision-making process and patient involvement. It also creates opportunities for education and evaluation of the healthcare provided to patients with CS. This review provides insights into the implementation, composition, organization, and operation of a heart and brain team. Methods and metrics are suggested to evaluate the team’s role. We suggest that an efficient heart and brain team can implement guideline-recommended multidisciplinary clinical decision-making with regard to PFO closure in CS patients and play an important role in the management of these patients.
8.A Review of Pre-Exposure Prophylaxis Adherenceamong Female Sex Workers
Ramy Abou GHAYDA ; Sung Hwi HONG ; Jae Won YANG ; Gwang Hun JEONG ; Keum Hwa LEE ; Andreas KRONBICHLER ; Marco SOLMI ; Brendon STUBBS ; Ai KOYANAGI ; Louis JACOB ; Hans OH ; Jong Yeob KIM ; Jae Il SHIN ; Lee SMITH
Yonsei Medical Journal 2020;61(5):349-358
Globally and in Africa specifically, female sex workers (FSWs) are at an extraordinarily high risk of contracting human immunodeficiencyvirus (HIV). Pre-exposure prophylaxis (PrEP) has emerged as an effective and ethical method with which to preventHIV infection among FSWs. PrEP efficacy is, however, closely linked to adherence, and adherence to PrEP among FSWs is a complexand interrelated process that has been shown to be of importance to public health policies and HIV control and interventionprograms. This comprehensive review categorizes barriers to and facilitators of adherence to HIV PrEP for FSWs, and describes fivestrategies for promoting PrEP adherence among FSWs. These strategies encompass 1) a long-term educational effort to decreasethe stigma associated with sex work and PrEP use, 2) education on how PrEP works, 3) lifestyle modification, 4) research on nextgenerationPrEP products to address the inconvenience of taking daily pills, and 5) integration of PrEP into existing services, suchas social services and routine primary care visits, to reduce the economic burden of seeking the medication. Our review is expectedto be useful for the design of future PrEP intervention programs. Multidisciplinary intervention should be considered to promotePrEP adherence among FSWs in order to help control the HIV epidemic.
9.Tissue integration of zirconia and titanium implants with and without buccal dehiscence defects
Hyun Chang LIM ; Ronald Ernst JUNG ; Christoph Hans Franz HÄMMERLE ; Myong Ji KIM ; Kyeong Won PAENG ; Ui Won JUNG ; Daniel Stefan THOMA
Journal of Periodontal & Implant Science 2018;48(3):182-192
PURPOSE: The purpose of the present study was to validate an experimental model for assessing tissue integration of titanium and zirconia implants with and without buccal dehiscence defects. METHODS: In 3 dogs, 5 implants were randomly placed on both sides of the mandibles: 1) Z1: a zirconia implant (modified surface) within the bony housing, 2) Z2: a zirconia implant (standard surface) within the bony housing, 3) T: a titanium implant within the bony housing, 4) Z1_D: a Z1 implant placed with a buccal bone dehiscence defect (3 mm), and 5) T_D: a titanium implant placed with a buccal bone dehiscence defect (3 mm). The healing times were 2 weeks (one side of the mandible) and 6 weeks (the opposite side). RESULTS: The dimensions of the peri-implant soft tissue varied depending on the implant and the healing time. The level of the mucosal margin was located more apically at 6 weeks than at 2 weeks in all groups, except group T. The presence of a buccal dehiscence defect did not result in a decrease in the overall soft tissue dimensions between 2 and 6 weeks (4.80±1.31 and 4.3 mm in group Z1_D, and 4.47±1.06 and 4.5±1.37 mm in group T_D, respectively). The bone-to-implant contact (BIC) values were highest in group Z1 at both time points (34.15%±21.23% at 2 weeks, 84.08%±1.33% at 6 weeks). The buccal dehiscence defects in groups Z1_D and T_D showed no further bone loss at 6 weeks compared to 2 weeks. CONCLUSIONS: The modified surface of Z1 demonstrated higher BIC values than the surface of Z2. There were minimal differences in the mucosal margin between 2 and 6 weeks in the presence of a dehiscence defect. The present model can serve as a useful tool for studying peri-implant dehiscence defects at the hard and soft tissue levels.
Animals
;
Dental Implants
;
Dogs
;
Housing
;
Mandible
;
Models, Theoretical
;
Mouth Mucosa
;
Osseointegration
;
Surface Properties
;
Titanium
10.Human papillomavirus 16/18 AS04-adjuvanted cervical cancer vaccine: immunogenicity and safety in 15-25 years old healthy Korean women.
Seung Cheol KIM ; Yong Sang SONG ; Young Tae KIM ; Young Tak KIM ; Ki Sung RYU ; Bhavyashree GUNAPALAIAH ; Dan BI ; Hans L BOCK ; Jong Sup PARK
Journal of Gynecologic Oncology 2011;22(2):67-75
OBJECTIVE: The study assessed the immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine in healthy Korean women aged 15-25 years. METHODS: Phase IIIB, double-blind, randomised (2:1), multi-centre trial was conducted in Korea from June 2007 to March 2008. The study enrolled 225 women in the HPV (N=149) and placebo (N=76) groups who received three doses of HPV-16/18 AS04-adjuvanted vaccine or placebo (aluminium hydroxide) administered intramuscularly at 0, 1, and 6 months and were followed until one month post-dose 3. Serum samples were collected pre-vaccination and one month post-dose 3. Safety and reactogenicity data were collected throughout. RESULTS: In this trial, 208 women completed the study (141 in HPV group; 67 in placebo group). At month 7, all initially seronegative women had seroconverted for HPV-16 and HPV-18 antibodies with anti-HPV-16 and anti-HPV-18 geometric mean titres of 9,351.4 El.U/mL (95% CI, 8,145.5 to 10,735.8) and 4204.1 El.U/mL (95% CI, 3,626.5 to 4,873.6), respectively. Initially seropositive women showed similar increase in geometric mean titre levels. Compliance to the three dose vaccination course was 95.3% in HPV and 89.5% in placebo group. Solicited local (pain) and general (fatigue, myalgia or headache) symptoms were commonly reported in both groups. Three serious adverse events were reported (two in HPV group; one in placebo group), all unrelated to vaccination by the investigator; all recovered. CONCLUSION: The HPV-16/18 AS04-adjuvanted vaccine was highly immunogenic with a clinically acceptable safety profile in Korean women. This study was in line with previous global studies in Europe, North America, and Brazil. (ClinicalTrials.gov number, NCT 00485732.)
Aged
;
Antibodies
;
Brazil
;
Compliance
;
Europe
;
Female
;
Human papillomavirus 16
;
Human papillomavirus 18
;
Humans
;
Korea
;
North America
;
Uterine Cervical Neoplasms
;
Vaccination

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