• 제목/요약/키워드: Bone marrow stem cell

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돼지 골수 조혈 세포의 이종 마우스 동물 모델 생체 증식 및 분화 특성 (Effective Reconstitution of Porcine Hematopoietic Cells in Newborn NOD/SCID Mice Xenograft)

  • 이용수;이현주;김태식;김혜선;김유경;김재환;박진기;정학재;장원경;김동구
    • Reproductive and Developmental Biology
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    • 제32권1호
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    • pp.1-7
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    • 2008
  • 본 연구는 돼지 골수에서 존재하는 조혈 줄기 세포 및 전구 세포를 이용해 이종 동물 모델인 태아 마우스 복강 생체 이식을 통하여 돼지 조혈 세포의 이종 조혈 조직에서의 증식과 분화 특성을 규명하였다. 선천성 면역 부전 마우스인 NOD/SCID 마우스 태아 조혈 환경에 돼지 골수 유래 조혈 줄기 세포 및 전구 세포를 이식하고, 이식 후 5주령에 마우스 조혈기관에서의 돼지 조혈 세포의 증식과 분화 특성을 돼지 특이적 항체 면역 염색으로 유세포 분석을 실시한 결과, 마우스 조혈 조직인 골수, 흉선, 간장, 비장 및 림파절에서 돼지 조혈 세포의 분화 및 증식이 관찰되었다. 특히 돼지의 T 면역세포가 골수계 세포에 비해서 높은 chimerism이 관찰되어 태생 초기의 NOD/SCID 조혈 환경에 의한 특이적 T 면역세포의 증식에 적합한 조혈 환경을 제공하고 있다는 사실이 밝혀졌다. 본 마우스 신생 NOSD/SCID 복강 이식 동물 모델을 이용해 돼지 T 면역세포의 분화 발달 연구 및 이종 장기 이식 기전 연구에 좋은 모델로서 활용이 기대된다.

보조적 표준 항암 화학요법에 비한 자가조혈모세포 이식 유방암 환자 삶의 질 내용 비교 (Comparison of Trajectory of Quality of Life in Patients with High Risk Breast Cancer Undergoing Adjuvant Chemotherapy and Autogenous Bone Marrow Transplantation)

  • 이은옥
    • 종양간호연구
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    • 제1권1호
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    • pp.5-17
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    • 2001
  • It is known that aggressive treatment of chemotherapy, radiation and autogenous stem cell transplantation is effective for prevention of recurrence in the high-risk breast cancer patients. It was assumed that this procedure takes a longer time and decreases the quality of life more than the standard adjuvant chemotherapy. However, there are few studies comparing the quality of life of patients having bone marrow transplantation and adjuvant chemotherapy. Most of the studies were focused on the quality of life in one point of time, such as only during the early treatment stage, only overall quality of life rather than specific dimensions of the quality of life. The purposes of this study are 1) to identify the difference of the quality of life between two different treatment patterns, adjuvant chemotherapy and autogenous stem cell transplantation: 2) to identify the mostly affected dimension and the periods of time affected by the treatment patterns; and 3) to identify the trajectories of quality of life in each treatment pattern. This is a time series design that measures 4 different points of times. At the beginning of the study, 19 patients were placed in the chemotherapy group and 12 in the group of auto-peripheral blood stem cell transplantation. The inclusion criterion was the advanced disease stage of 3 or over with metastasis of more than 5 lymph nodes. The exclusion criteria were 1) anyone who has metastasis to other organ; 2) anyone who had psychological problems. Ferrell's Quality of Life Scale for Cancer Survivors 41 items on a 10 point scale was used. The QOL-CS includes 4 dimensions, which were labeled physical, psychological, social, and spiritual. The Cronbach‘s alpha of this scale was 0.89. Mann-Whitney U test and Friedman test were used to test each hypothesis. In comparison of the two groups, the quality of life of the bone marrow transplantation group dramatically increased at the 3rd and 6th month after transplantation, while the chemotherapy groups results stayed lower. The most affected dimension of the quality of life at the end of the treatment was the physical dimension. However, it and increased along with time, while the psychological dimension values remained low over the long-term period. Intensive nursing care is needed during the entire period of chemotherapy in all patients having chemotherapy, and is also required for right after cases of bone marrow transplantation.

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PROM1-mediated cell signal transduction in cancer stem cells and hepatocytes

  • Myeong-Suk Bahn;Young-Gyu Ko
    • BMB Reports
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    • 제56권2호
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    • pp.65-70
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    • 2023
  • Prominin-1 (PROM1), also called CD133, is a penta-span transmembrane protein that is localized in membrane protrusions, such as microvilli and filopodia. It is known to be expressed in cancer stem cells and various progenitor cells of bone marrow, liver, kidney, and intestine. Accumulating evidence has revealed that PROM1 has multiple functions in various organs, such as eye, tooth, peripheral nerve, and liver, associating with various molecular protein partners. PROM1 regulates PKA-induced gluconeogenesis, TGFβ-induced fibrosis, and IL-6-induced regeneration in the liver, associating with Radixin, SMAD7, and GP130, respectively. In addition, PROM1 is necessary to maintain cancer stem cell properties by activating PI3K and β-Catenin. PROM1-deficienct mice also show distinct phenotypes in eyes, brain, peripheral nerves, and tooth. Here, we discuss recent findings of PROM1-mediated signal transduction.

지방기질유래 줄기세포의 골 분화 시 성장인자의 효과 (THE EFFECT OF GROWTH FACTORS ON OSTEOGENIC DIFFERENTIATION OF ADIPOSE TISSUE-DERIVED STROMAL CELLS)

  • 김욱규;최연식;정진섭
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제32권4호
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    • pp.327-333
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    • 2006
  • Future cell-based therapies such as tissue engineering will benefit from a source of autogenous pluripotent stem cells. There are embryonic stem cells (ESC) and autologous adult stem cells, two general types of stem cells potentilally useful for these applications. But practical use of ESC is limited due to potential problems of cell regulation and ethical considerations. To get bone marrow stem cells is relatively burden to patients because of pain, anesthesia requirement. The ideal stem cells are required of such as the following advantages: easy to obtain, minimal patient discomfort and a capability of yielding enough cell numbers. Adipose autologus tissue taken from intraoral fatty pad or abdomen may represent such a source. Our study designed to demonstrate the ability of human adipose tissue-derived stromal cells (hATSC) from human abdominal adipose tissue diffentiating into osteocyte and adipocyte under culture in vitro conditions. As a result of experiment, we identified stromal cell derived adipose tissue has the multilineage potentiality under appropriate culture conditions. And the adipose stromal cells expressed several mesenchymal stem cell related antigen (CD29, CD44) reactions. Secondary, we compared the culture results of a group of hATSC stimulated with TGF-${\beta}$1, bFGF with a hATSC group without growth factors to confirm whether cytokines have a important role of the proliferation in osteogenic differentiation. The role of cytokines such as TGF-${\beta}$1, bFGF increased hATSC's osteogenic differentiation especially when TGF-${\beta}$1 and bFGF were used together. These results suggest that adipose stromal cells with growth factors could be efficiently available for cell-based bone regeneration.

Optimization of growth inducing factors for colony forming and attachment of bone marrow-derived mesenchymal stem cells regarding bioengineering application

  • Quan, Hongxuan;Kim, Seong-Kyun;Heo, Seong-Joo;Koak, Jai-Young;Lee, Joo-Hee
    • The Journal of Advanced Prosthodontics
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    • 제6권5호
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    • pp.379-386
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    • 2014
  • PURPOSE. These days, mesenchymal stem cells (MSCs) have received worldwide attention because of their potentiality in tissue engineering for implant dentistry. The purpose of this study was to evaluate various growth inducing factors in media for improvement of acquisition of bone marrow mesenchymal stem cells (BMMSCs) and colony forming unit-fibroblast (CFU-F). MATERIALS AND METHODS. The mouse BMMSCs were freshly obtained from female C3H mouse femur and tibia. The cells seeded at the density of $10^6$/dish in media supplemented with different density of fetal bovine serum (FBS), $1{\alpha}$, 25-dihydroxyvitamin (VD3) and recombinant human epidermal growth factor (rhEGF). After 14 days, CFU-F assay was conducted to analyze the cell attachment and proliferation, and moreover for VD3, the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay was additionally conducted. RESULTS. The cell proliferation was increased with the increase of FBS concentration (P<.05). The cell proliferation was highest at the density of 20 ng/mL rhEGF compared with 0 ng/mL and 200 ng/mL rhEGF (P<.05). For VD3, although the colony number was increased with the increase of its concentration, the difference was not statistically significant (P>.05). CONCLUTION. FBS played the main role in cell attachment and growth, and the growth factor like rhEGF played the additional effect. However, VD3 did not have much efficacy compare with the other two factors. Improvement of the conditions could be adopted to acquire more functional MSCs to apply into bony defect around implants easily.

Enhancement of In Vivo Bone Regeneration Efficacy of Human Mesenchymal Stem Cells

  • Kang, Sun-Woong;Lee, Jae-Sun;Park, Min Sun;Park, Jung-Ho;Kim, Byung-Soo
    • Journal of Microbiology and Biotechnology
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    • 제18권5호
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    • pp.975-982
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    • 2008
  • We investigated whether transplantation of osteogenically differentiated bone marrow-derived mesenchymal stem cells (BMMSCs) and the use of an hydroxyapatite (HAp) scaffold can enhance the in vivo bone formation efficacy of human BMMSCs. Three months after implantation to the subcutaneous dorsum of athymic mice, transplantation of osteogenically differentiated human BMMSCs increased the bone formation area and calcium deposition to 7.1- and 6.2-folds, respectively, of those of transplantation of undifferentiated BMMSCs. The use of the HAp scaffold increased the bone formation area and calcium deposition to 3.7- and 3.5-folds, respectively, of those of a polymer scaffold. Moreover, a combination of transplantation of osteogenically differentiated BMMSCs and HAp scaffold further increased the bone formation area and calcium deposition to 10.6- and 9.3-folds, respectively, of those of transplantation of undifferentiated BMMSCs seeded onto polymer scaffolds. The factorial experimental analysis showed that osteogenic differentiation of BMMSCs prior to transplantation has a stronger positive effect than the HAp scaffold on in vivo bone formation.

재생불량빈혈(Aplastic anemia) (Aplastic anemia)

  • 김학기
    • Clinical and Experimental Pediatrics
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    • 제50권6호
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    • pp.519-523
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    • 2007
  • Aplastic anemia is a rare disease, which is characterized by pancytopenia and hypocellular bone marrow without infiltration of abnormal cells or fibrosis. The incidence in Asia is higher than in the West and new cases are diagnosed at a rate of 5.1 per million pediatric populations per year in Korea. The pathophysiology is understood roughly by defective hematopoiesis, impaired bone marrow micro-environment and immune mechanism. Treatments are performed on basis of pathogenesis and selected depending on the severity. Immunosuppressive therapy with antilymphocyte or antithymocyte globulin and cyclosporine is effective in the majority of patients but has some problems including relapse or clonal evolution. Recently, there have been clinical trials of immunosuppression with hematopoietic growth factors or other drugs. Allogeneic hematopoietic stem cell transplantation (HSCT) is curative in children with severe aplastic anemia. The overall survival in HSCT from HLA-identical sibling is higher than alternative donor, including HLA matched unrelated donor or cord blood. We have to consider quality of life after HSCT because of high survival rate. However, chronic graft versus host disease and graft failure are important factors that affect the quality of life and overall survival. We need further investigation to make new regimens aimed at overcoming these risk factors and perform clinical trials.

Expression and Characterization of Purinergic Receptor, $P2Y_{10}$ in Hematopoietic Stem Cells

  • Lee Eun-Jong;Kim Dong-Ku
    • Reproductive and Developmental Biology
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    • 제29권2호
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    • pp.109-115
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    • 2005
  • Hematopoietic stem cells (HSC) are multipotent cells that reside in the bone marrow and replenish all adult hematopoietic lineages throughoutthe lifetime. In this study, we analyzed the expression of receptors of $P2Y_{10}$, purinergic receptor families in murine hematopoietic stem cells, hematopoietic progenitor cells. In addition, the biological activity of $P2Y_{10}$ was investigated with B lymphocyte cell line, Ba/F3 in effect to cell growth and cell cycle. From the analysis of expression in hematopoieticstem cell. and progenitor with RT-PCR, $P2Y_{10}$ was strongly expressed in murine hematopoieticstem cells (c-kit+ Sca-l+ Lin-) and progenitor cell population, such as c-kit- Sca-l+ Lin-, c-kit+ Sca-l- Lin- and c-kit- Sca-l- Lin-. To investigate the biological effects by $P2Y_{10}$, retroviral vector from subcloned murine $P2Y_{10}$ cDNA was used fur gene introduction into Ba/F3 cells, and stable transfectant cells were obtained by flow cytometry sorting. In cell proliferation assay, the proliferation ability of $P2Y_{10}$ receptor gene­transfected cells was strongly inhibited, and the cell cycle was arrested at G1 phase. These result suggest that the $P2Y_{10}$ may be involved the biological activity in hematopoietic stem cells and immature B lymphocytes.

분자 촉진제를 넘어, CD82: 전이억제자, 줄기세포 니쉬, 근육 재생 및 혈관신생에서의 역할 (Beyond the Molecular Facilitator, CD82: Roles in Metastasis Suppressor, Stem Cell Niche, Muscle Regeneration, and Angiogenesis)

  • 이현채;한정화;허진
    • 생명과학회지
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    • 제31권9호
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    • pp.856-861
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    • 2021
  • CD82/KAI1은 분자촉진제로서 암 전이억제자로 역할이 잘 알려져 있으나, 최근 줄기 전구 세포와 혈관 신생, 근육에서 다양한 역할들이 밝혀지고 있다. 이에 본 연구진은 최근에 보고된 CD82의 다양한 기능과 역할에 관하여 총설 하고자 한다. CD82는 4개의 막 통과 도메인을 가진 테트라스파닌의 한 종류로 암의 전이 과정에 관여하는 세포접착분자들과의 상호작용을 통하여 암세포의 이동 능력을 저해한다. 암 전이 억제자로의 기능 외에도 줄기세포 니쉬에서도 그 역할이 밝혀졌다. 골수에서 분화재생능력이 뛰어난 최상위 조혈모세포(LT-HSC)에서 CD82가 발현되며, DARC와의 상호결합으로 줄기세포의 휴면을 유도한다. 줄기세포의 휴면 조절 외에도, CD82는 Rac1 활성 조절을 통해 조혈모세포의 골수로의 귀환 및 생착에도 역할을 한다. 또한, CD82는 근육 줄기 세포의 분화능을 유지시키며, 혈관 내피세포에서 세포 접착 분자와 IL-6, VEGF와 같은 사이토카인의 발현을 저해하여 혈관 신생을 억제한다. CD82는 다양한 조직 및 줄기-전구 세포에서 계급을 구별할 수 있는 핵심 세포막 표면 단백질이며, 세포 자원의 증폭 및 검증에 있어 중요하다. 다양한 기관과 세포에서 CD82의 역할과 추가적인 연구들이 줄기세포치료의 임상적 적용에 있어 큰 도움이 되기를 기대한다.

인간 골수유래-중간엽 줄기세포(hBM-MSCs)에서 PDE4 억제조절을 통한 신경세포 분화 효율 개선 (Improvement of Neuronal Differentiation by PDE4 Inhibition in Human Bone Marrow-mesenchymal Stem Cells)

  • 정다희;조이슬;조광원
    • 생명과학회지
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    • 제26권12호
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    • pp.1355-1359
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    • 2016
  • 인간 중간엽 줄기세포(hMSCs)는 신경세포(neuron-like cells)를 포함한 다양한 세포로 분화할 수 있는 능력을 지닌 성체 줄기세포(adult stem cells)이다. 본 연구에서는 인간의 골수유래-중간엽 줄기세포(bone marrow-mesenchymal stem cells; hBM-MSCs)를 이용한 신경분화에서 신경세포 표지자(neuronal marker)인 NF-M, Tuj-1 뿐만 아니라 성상세포 표지자(glial marker)인 GFAP의 발현 역시 의미 있게 증가함을 real-time PCR, Western blot, and immunocytochemical staining법을 통하여 관찰하였다. 이를 개선하기 위하여, 신경분화에 중요한 신호전달자(signal intermediator)인 PDE4를 억제한 후 신경분화를 유도하였다. PDE4 억제자인 rolipram 혹은 resveratrol를 각각 처리하여 신경분화한 줄기세포(Roli- or RSV-dMSCs)에서 NF-M, Tuj-1의 발현이 증가하였고 반면, GFAP의 발현은 감소함을 real-time PCR, Western blot, and immunocytochemical staining법을 통하여 관찰하였다. 본 연구를 통하여, PDE4를 조절하며 줄기세포의 신경분화를 개선할 수 있음을 보였다.