• Journal of Yeungnam Medical Science
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• 제36권2호
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• pp.148-151
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• 2019

The dose of CD34+ cells is known to influence the outcome of allogeneic peripheral blood stem cell (PBSC) and/or T-cell-depleted transplantation. A previous study proposed that $2{\times}10^6\;CD34+\;cells/kg$ is the ideal minimum dose for allogeneic transplantation, although lower doses did not preclude successful therapy. In the case we present here, CD34+ cells were collected from a matched sibling donor on the day of allogeneic hematopoietic stem cell transplantation; however, the number of cells was not sufficient for transplantation. Consequently, PBSCs were collected three additional times and were infused along with cord blood cells from the donor that were cryopreserved at birth. The cumulative dose of total nuclear cells and CD34+ cells was $15.9{\times}10^8\;cells/kg$ and $0.95{\times}10^6\;cells/kg$, respectively. White blood cells from this patient were engrafted on day 12. In summary, we report successful engraftment after infusion of multiple low doses of CD34+ cells in a patient with severe aplastic anemia.

• The Korean Journal of Physiology and Pharmacology
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• 제22권2호
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• pp.203-213
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• 2018

Tumor undergo uncontrolled, excessive proliferation leads to hypoxic microenvironment. To fulfill their demand for nutrient, and oxygen, tumor angiogenesis is required. Endothelial progenitor cells (EPCs) have been known to the main source of angiogenesis because of their potential to differentiation into endothelial cells. Therefore, understanding the mechanism of EPC-mediated angiogenesis in hypoxia is critical for development of cancer therapy. Recently, mitochondrial dynamics has emerged as a critical mechanism for cellular function and differentiation under hypoxic conditions. However, the role of mitochondrial dynamics in hypoxia-induced angiogenesis remains to be elucidated. In this study, we demonstrated that hypoxia-induced mitochondrial fission accelerates EPCs bioactivities. We first investigated the effect of hypoxia on EPC-mediated angiogenesis. Cell migration, invasion, and tube formation was significantly increased under hypoxic conditions; expression of EPC surface markers was unchanged. And mitochondrial fission was induced by hypoxia time-dependent manner. We found that hypoxia-induced mitochondrial fission was triggered by dynamin-related protein Drp1, specifically, phosphorylated DRP1 at Ser637, a suppression marker for mitochondrial fission, was impaired in hypoxia time-dependent manner. To confirm the role of DRP1 in EPC-mediated angiogenesis, we analyzed cell bioactivities using Mdivi-1, a selective DRP1 inhibitor, and DRP1 siRNA. DRP1 silencing or Mdivi-1 treatment dramatically reduced cell migration, invasion, and tube formation in EPCs, but the expression of EPC surface markers was unchanged. In conclusion, we uncovered a novel role of mitochondrial fission in hypoxia-induced angiogenesis. Therefore, we suggest that specific modulation of DRP1-mediated mitochondrial dynamics may be a potential therapeutic strategy in EPC-mediated tumor angiogenesis.

• BMB Reports
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• 제54권10호
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• pp.505-515
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• 2021

Human pluripotent stem cells (hPSCs) include human embryonic stem cells (hESCs) derived from blastocysts and human induced pluripotent stem cells (hiPSCs) generated from somatic cell reprogramming. Due to their self-renewal ability and pluripotent differentiation potential, hPSCs serve as an excellent experimental platform for human development, disease modeling, drug screening, and cell therapy. Traditionally, hPSCs were considered to form a homogenous population. However, recent advances in single cell technologies revealed a high degree of variability between individual cells within a hPSC population. Different types of heterogeneity can arise by genetic and epigenetic abnormalities associated with long-term in vitro culture and somatic cell reprogramming. These variations initially appear in a rare population of cells. However, some cancer-related variations can confer growth advantages to the affected cells and alter cellular phenotypes, which raises significant concerns in hPSC applications. In contrast, other types of heterogeneity are related to intrinsic features of hPSCs such as asynchronous cell cycle and spatial asymmetry in cell adhesion. A growing body of evidence suggests that hPSCs exploit the intrinsic heterogeneity to produce multiple lineages during differentiation. This idea offers a new concept of pluripotency with single cell heterogeneity as an integral element. Collectively, single cell heterogeneity is Janus-faced in hPSC function and application. Harmful heterogeneity has to be minimized by improving culture conditions and screening methods. However, other heterogeneity that is integral for pluripotency can be utilized to control hPSC proliferation and differentiation.

• 과학기술학연구
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• 제12권1호
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• pp.185-207
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• 2012

황우석 사태 이후 한국의 국가는 줄기세포 연구를 장려하고 시험관 아기 산업을 장려하겠다는 입장과 "글로벌 스탠다드"에 부합하는 윤리적 규제를 도입하겠다는, 많은 경우 서로 모순될 수밖에 없는 입장을 표명하여 왔다. 줄기세포 연구에 대한 윤리적 규제가 점점 강화되면서 인간배아세포 연구가 위축되면서, 연구 공동체와 바이오산업, 임상의사와 환자, 그리고 국가 자체를 위기로부터 구원해줄 대안으로 떠오른 것은 체세포 줄기세포였다. 그러나 한국 생명공학기술에 대한 연구들은 주로 배아줄기세포에 초점을 맞추고 있으며, 조혈줄기세포나 지방유래줄기세포와 같은 체세포 줄기세포에 대한 연구에는 상대적으로 관심이 적은 것으로 보인다. 배아줄기세포가 흔히 실험적이고 윤리적으로 논란거리로 여겨지는 반면에, 조혈모 혹은 간엽줄기세포와 체세포 줄기세포는 별다른 공적인 논의 없이 대중들의 일상 속으로 들어와 있다. 한국의 많은 일반인들은 조혈모 줄기세포 치료를 통해 백혈병으로부터 생명을 구한 환자들의 사례에 이미 익숙한가 하면, 다른 한편에서 지방유래줄기세포 치료를 선전하는 의사들의 수가 늘고 있고, 지방유래줄기세포의 개념을 활용하여 만든 화장품이 소비자들의 주목을 받고 있기도 한 현실이 이미 진행되고 있다. 이러한 맥락에서, 본 논문은 배아줄기세포나 국가 정책이나 연구 규제에만 집중되어 시장을 놓치고 있는 윤리적 논의는 한국에서 줄기세포 기술의 정치의 전모를 다루기에 한계가 크다는 사실을 주장하고자 한다.

• Journal of mucopolysaccharidosis and rare diseases
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• 제3권1호
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• pp.14-19
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• 2017

Lysosomal storage diseases (LSDs) are a group of rare inherited metabolic disorders caused by the deficiency of specific lysosomal enzymes and subsequent accumulation of substrates. Enzyme deficiency leads to progressive intra-lysosomal accumulation of the incompletely degraded substances, which cause dysfunction and destruction of the cell and eventually multiple organ damage. Patients have a broad spectrum of clinical phenotypes which are generally not specific for some LSDs, leading to missed or delayed diagnosis. Due to the availability of treatment including enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation for some LSDs, early diagnosis is important. ERT products have been approved with optimal outcomes for some LSDs in the recent decades, including Gaucher, Fabry, mucopolysaccharidosis (MPS) I, Pompe, MPS VI, MPS II, and MPS IVA diseases. ERT can stabilize the clinical condition, prevent disease progression, and improve the long-term outcome of these diseases, especially if started prior to irreversible organ damage. Based on the availability of therapy and suitable screening methods in the recent years, some LSDs, including Pompe, Fabry, Gaucher, MPS I, MPS II, and MPS VI diseases have been incorporated into nationwide newborn screening panels in Taiwan.

• Clinical and Experimental Reproductive Medicine
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• 제46권1호
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• pp.1-7
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• 2019

With the progress of regenerative medicine, mesenchymal stem cells (MSCs) have received attention as a way to restore ovarian function. It has been reported that MSCs derived from bone marrow, adipose, umbilical cord blood, menstrual blood, and amniotic fluid improved ovarian function. In light of previous studies and advances in this field, there are increased expectations regarding the utilization of MSCs to restore ovarian function. This review summarizes recent research into potential applications of MSCs in women with infertility or primary ovarian insufficiency, including cases where these conditions are induced by anticancer therapy.

• Clinical and Experimental Pediatrics
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• 제53권8호
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• pp.786-789
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• 2010

Induced pluripotent stem (iPS) cells are generated by epigenetic reprogramming of somatic cells through the exogenous expression of transcription factors. Recently, the generation of iPS cells from patients with a variety of genetic diseases was found to likely have a major impact on regenerative medicine, because these cells self-renew indefinitely in culture while retaining the capacity to differentiate into any cell type in the body, thereby enabling disease investigation and drug development. This review focuses on the current state of iPS cell technology and discusses the potential applications of these cells for disease modeling; drug discovery; and eventually, cell replacement therapy.

• BMB Reports
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• 제48권5호
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• pp.256-265
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• 2015

Cardiovascular and neurodegenerative diseases are major health threats in many developed countries. Recently, target tissues derived from human embryonic stem (hES) cells and induced pluripotent stem cells (iPSCs), such as cardiomyocytes (CMs) or neurons, have been actively mobilized for drug screening. Knowledge of drug toxicity and efficacy obtained using stem cell-derived tissues could parallel that obtained from human trials. Furthermore, iPSC disease models could be advantageous in the development of personalized medicine in various parts of disease sectors. To obtain the maximum benefit from iPSCs in disease modeling, researchers are now focusing on aging, maturation, and metabolism to recapitulate the pathological features seen in patients. Compared to pediatric disease modeling, adult-onset disease modeling with iPSCs requires proper maturation for full manifestation of pathological features. Herein, the success of iPSC technology, focusing on patient-specific drug treatment, maturation-based disease modeling, and alternative approaches to compensate for the current limitations of patient iPSC modeling, will be further discussed. [BMB Reports 2015; 48(5): 256-265]

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2004년도 춘계학술발표대회
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• pp.275-275
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• 2004

To evaluate the potential of the stem cell therapy as a method for prenatal management of spinal open neural tube defect (ONTD), the influence of embryonic stem cells injected into the amniotic cavity on the re-closure capacity of spinal ONTD was investgated. Spinal neural tube was incised open for a length of 6 somites using chick embryos of Hamburger and Hamilton stage 18 or 19. (omitted)

• 한국동물생명공학회지
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• 제39권1호
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• pp.58-61
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• 2024

Three different dogs who had immune-mediated hemolytic anemia (IMHA) were treated for more than two weeks with blood transfusion in an animal clinic. Despite this treatment and hospitalization, there was no clinical improvement in clinical signs as well as complete blood cell count (CBC) including hematocrit (HCT) and C-reactive protein (CRP). All cases were then injected two or three times with allogeneic stem cells through an intravenous route for treatment. Upon administrating stem cells to the IMHA dogs, clinical conditions and the indexes of HCT and CRP were clinically improved within or close to normal ranges.