• 한국한의학연구원논문집
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• 제9권2호
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• pp.107-119
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• 2003

In this study, Kami-honghwa-tang (KH-19) was designed and animal study was conducted to evaluate its efficacy on the reduction of the side effect of radiotherapy. Bone marrow toxicity is one of the major side effect of radiotherapy which cause the reduction of blood cells, and KH-19 was designed to protect and enforce blood. C57BL/6 mice were irradiated with 4 Gy of gamma ray, and divided into control group which was treated with water and KH-19 group which was treated with 1.5g/Kg of KH-19 up to 4 weeks. KH-19 group showed significantly increased white blood cells, lymphocytes and platelet count compared with control group (p<0.05). When bone marrows were examined, KH-19 group showed higher cell densities than control group (p=0.06). KH-19 may increase blood cell count after radiation by its protective effects on bone marrow.

• Journal of Ginseng Research
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• 제25권2호
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• pp.63-67
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• 2001

We previously reported that acidic polysaccharide from Panax ginseng induced the proliferation lymphocytes and the generation of activated killer cells. Here we found that polysaccharide (PG-75) precipitated with 75% EtOH from water extract of Panax ginseng also has both in vitron and in vivo hematopoietic activities. In vitro studied with bone marrow cells from BALB/c mouse revealed that PG-75 had direct effect on hematopoietic colony-forming cell(CFC) growth, increased granulocyte macrophage-colony forming cell numbers by 1.59 fold over than non-treated. the ability of PG-75 to modulate hematopoiesis in vivo was evaluated the bone marrow and spleen celluarity, granulocyte-macrophage progenitor cells. BALB/c female mice were administered G-75 intraperitoneally, PG-75 was found to significantly increase the number of BM cells, spleen cells, GM-CFU on 3 hours after injection. PG-75 was also able to induce significant augmentation of GM-CSF and IFN-${\gamma}$, production in sera. These studies illustrate than PG-75 has hematopoietic activities and that this agent may be useful in the prevention and/or treatment of radio- or chemotherapy-associated myelosuppression.

• 한국전기전자재료학회:학술대회논문집
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• 한국전기전자재료학회 2008년도 하계학술대회 논문집 Vol.9
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• pp.512-513
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• 2008

The study examined what effects 100kHz PWM LED light irradiation causes to bone marrow cells of SD-Rat when LED characterized cheap and safe is used onto the light therapy by replacing the low 1evel laser. We developed the equipment palpating cell proliferation using a high brightness LED. This equipment was fabricated using a micro-controller and a high brightness LED, and designed to enable us to control light irradiation time, intensity, frequency and so on. Especially, to control the light irradiation frequency, FPGA was used, and to control the change of output value, TLC5941 was used. Consequent1y, the current value could be controlled by the change of 1eve1 in Continue Wave(CW) and Pulse Width Modulation(PWM), and the output of a high brightness LED could be controlled stage by stage. MTT assay method was chosen to verify the cell increase of two groups and the effect of irradiation on cell proliferation was examined by measuring 590nm transmittance of ELISA reader. As a result, the cell increase of Rat bone marrow cells was verified in 100kHz PWM LED light irradiation group as compared to non-irradiation group.

• 대한의용생체공학회:의공학회지
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• 제29권2호
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• pp.159-163
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• 2008

The goal of this study is to investigate the effect and potential of three-dimensional Co-culture of BMSCs (bone marrow stromal Cells) and NP (nucleus pulposus) Cells on the differentiation of BMSCs into NP-like Cells. The NP Cells and BMSCs were isolated and cultured from New Zealand White rabbits. The isolated NP Cells and BMSCs were prepared in different alginate beads. Those two types of beads were separated by a track-etched membrane of $3\;{\mu}m$ pore in a 6-well culture plate. No growth factors were used. In addition to these, NP and BMSC were cultured in the beads independently for control. The number of Cells in Co-culturing system was half of those in two control groups. Proliferation and production of glycosaminoglycan (GAG) were evaluated along with histological observation. The GAG production rate(GAG contents/Cell) of Co-cultured BMSCs were much higher than that of BMSCs cultured alone. The total amounts of GAG produced by BMSCs in Co-culturing system were larger than those produced by BMSCs in control group and were comparable with those produced by NP alone even the number of each Cell was half of BMSCs in Co-culturing system. This study showed the potential of differentiation of BMSCs into NP-like Cells through three-dimensional Co-culture system even without any chemical agents.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제30권4호
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• pp.323-332
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• 2008

Aim of the study: Scaffolds are crucial to tissue engineering/regeneration. Biodegradable polymer/ceramic composite scaffolds can overcome the limitations of conventional ceramic bone substitutes such as brittleness and difficulty in shaping. In this study, poly(L-lactide)/hydroxyapatite(PLLA/HA) composite scaffolds were fabricated for in vivo bone tissue engineering. Material & methods: In this study, PLLA/HA composite microspheres were prepared by double emulsion-solvent evaporation method, and were evaluated in vivo bone tissue engineering. Bone marrow mesenchymal stem cell from rat iliac crest was differentiated to osteoblast by adding osteogenic medium, and was mixed with PLLA/HA composite scaffold in fibrin gel and was injected immediately into rat cranial bone critical size defect(CSD:8mm in diameter). At 1. 2, 4, 8 weeks after implantation, histological analysis by H-E staining, histomorphometric analysis and radiolographic analysis were done. Results: BMP-2 loaded PLLA/HA composite scaffolds in fibrin gel delivered with osteoblasts differentiated from bone marrow mesenchymal stem cells showed rapid and much more bone regeneration in rat cranial bone defects than control group. Conclusion: This results suggest the feasibility and usefulness of this type of scaffold in bone tissue engineering.

• Nuclear Medicine and Molecular Imaging
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• 제43권1호
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• pp.35-39
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• 2009

목적: F-18 FDG를 이용한 PET/CT에서 골수를 따라 미만성의 섭취증가는 드물게 보이는 소견으로 erythropoietin이나 G-CSF 같은 조혈 cytokines에 의한 섭취증가가 보고되고 있다. 하지만 이러한 기왕력이 없는 환자에서도 미만성 FDG 섭취를 보이는 경우들이 볼 수 있었고 따라서 본 연구에서는 PET/CT 검사에서 밝혀진 원인 없이 골수에 미만성의 섭취를 보이는 환자의 골수 생검과 일반 혈액검사 소견을 조사하였다. 대상 및 방법 PET/CT 검사를 시행한 환자들 중에서 골수에 미만성의 FDG 섭취증가를 보였던 환자 중 10일 이내에 골수 생검과 혈액검사를 모두 시행한 20명의 환자를 대상으로 하였다. 이 중 PET/CT시행전 G-CSF 또는 erythropoietin으로 치료한 기왕력이 있는 4명의 환자와 골수 생검에서 뚜렷한 병인을 보였던 있는 7명의 환자를 배제하였다. 일반 혈액 검사에서 백혈구, 혈색소, 혈소판 수치를 비교하였고 골수 생검의 비정상적인 소견과 세포 충실성을 알아보았다. 결과: 총 9명의 대상 환자(남:여=5:4, 나이 $49.0{\pm}21.9$세)에서 일반 혈액 검사 결과 혈색소 수치가 감소한 경우는 7예, 정상인 경우는 2예이었고 백혈구와 혈소판 수치는 감소와 증가, 정상의 환자가 각각 1예, 4예, 4예와 2예, 1예. 5예이었다. 골수 샘검에서는 3예에서 정상 소견을 보였고 그 외 과립구 증식이 2예, 호산구 증식, 반응성 림프구양 결절, 과세포성, 저세포성 골수 소견이 각각 1예씩이었다. 골수 생검에서 세포 충실성은 과세포성에서 증가, 저세포성 골수에서 감소를 보였고 나머지 경우 모두 정상 범위를 보였다. 결론: PET에서 미만성 골수 섭취증가를 보인 환자에서 골수 생검 및 혈액 검사 결과와 비교시 세포 충실성, 백혈구, 혈소판 수치보다는 혈색소의 감소와 연관성이 높았다. 따라서 혈색소 감소와 미만성 골수 섭취증가에 관련 기전에 대한 연구가 필요할 것으로 생각된다.

• Toxicological Research
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• 제18권4호
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• pp.369-374
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• 2002

The present study was performed to validate an automated image analysis system (Loats Automated Micronucleus Scoring System) for the mouse bone marrow micronucleus assay, comparing with conventional microscopic scoring. Two studies were conducted to provide slides for a comparison of micro-nucleated polychromatic erythrocytes (MNPCEs) values collected manually to those collected by the auto-mated system. Test article A was used as an example of a compound negative for the induction of micronuclei and test article B was wed as a micronucleus-inducing agent to elicit a positive response. Cyclophosphamide was included to provide an positive control in two studies. Bone marrow samples were collected 24 h after administration of test article A and B in male ICR mice. The cells were fixed with absolute methanol and stained with May-Grunwald and Giemsa. The number of MNPCEs was determined by the analysis of 1000 total PCEs per bone marrow sample. In addition to micronucleus scoring, an index of bone marrow toxicity based on PCE ratio (% of PCEs to total erythrocytes) was determined for each sample. The automated and manual scoring was similar when the MNPCEs incidence induced by each test article was less than 10. However manual scoring was able to effectively enumerate micronucleated PCEs in mouse bone marrow when MNPCEs incidence was more than 10, such as cyclophosphamide treatment. Conversely, PCE ratio was superior in computer-assisted image analysis. Taken together, it is suggested that improvement of the automated image analysis may be necessary to render the automatic scoring as sensitive as manual scoring for routine counting of micronuclei, especially because it is superior in objectivity and high throughput scoring.

• International Journal of Oral Biology
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• 제31권2호
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• pp.53-65
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• 2006

Calcium concentration in the bone resorption lacunae is high and is in the mM concentration range. Both osteoblast and osteoclast have calcium sensing receptor in the cell surface, suggesting the regulatory role of high extracellular calcium in bone metabolism. In vitro, high extracellular calcium stimulated osteoclastogenesis in coculture of mouse osteoblasts and bone marrow cells. Therefore we examined the genes that were commonly regulated by both high extracellular calcium and $1,25(OH)_2vitaminD_3(VD3)$ by using mouse oligo 11 K gene chip. In the presence of 10 mM $[Ca^{2+}]e$ or 10 nM VD3, mouse calvarial osteoblasts and bone marrow cells were co-cultured for 4 days when tartrate resistant acid phosphatase-positive multinucleated cells start to appear. Of 11,000 genes examined, the genes commonly regulated both by high extracellular calcium and by VD3 were as follows; 1) the expression of genes which were osteoclast differentiation markers or were associated with osteoclastogenesis were up-regulated both by high extracellular calcium and by VD3; trap, mmp9, car2, ctsk, ckb, atp6b2, tm7sf4, rab7, 2) several chemokine and chemokine receptor genes such as sdf1, scya2, scyb5, scya6, scya8, scya9, and ccr1 were up-regulated both by high extracellular calcium and by VD3, 3) the genes such as mmp1b, mmp3 and c3 which possibly stimulate bone resorption by osteoclast, were commonly up-regulated, 4) the gene such as c1q and msr2 which were related with macrophage function, were commonly down-regulated, 5) the genes which possibly stimulate osteoblast differentiation and/or mineralization of extracellular matrix, were commonly down-regulated; slc8a1, admr, plod2, lox, fosb, 6) the genes which possibly suppress osteoblast differentiation and/or mineralization of extracellular matrix, were commonly up-regulated; s100a4, npr3, mme, 7) the genes such as calponin 1 and tgfbi which possibly suppress osteoblast differentiation and/or mineralization of extracellular matrix, were up-regulated by high extracellular calcium but were down-regulated by VD3. These results suggest that in coculture condition, both high extracellular calcium and VD3 commonly induce osteoclastogenesis but suppress osteoblast differentiation/mineralization by regulating the expression of related genes.

• Biomolecules & Therapeutics
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• 제27권1호
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• pp.63-70
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• 2019

Myeloid-derived suppressor cells (MDSCs) that are able to suppress T cell function are a heterogeneous cell population frequently observed in cancer, infection, and autoimmune disease. Immune checkpoint molecules, such as programmed death 1 (PD-1) expressed on T cells and its ligand (PD-L1) expressed on tumor cells or antigen-presenting cells, have received extensive attention in the past decade due to the dramatic effects of their inhibitors in patients with various types of cancer. In the present study, we investigated the expression of PD-1 on MDSCs in bone marrow, spleen, and tumor tissue derived from breast tumor-bearing mice. Our studies demonstrate that PD-1 expression is markedly increased in tumor-infiltrating MDSCs compared to expression in bone marrow and spleens and that it can be induced by LPS that is able to mediate $NF-{\kappa}B$ signaling. Moreover, expression of PD-L1 and CD80 on $PD-1^+$ MDSCs was higher than on $PD-1^-$ MDSCs and proliferation of MDSCs in a tumor microenvironment was more strongly induced in $PD-1^+$ MDSCs than in $PD-1^-$ MDSCs. Although we could not characterize the inducer of PD-1 expression derived from cancer cells, our findings indicate that the study on the mechanism of PD-1 induction in MDSCs is important and necessary for the control of MDSC activity; our results suggest that $PD-1^+$ MDSCs in a tumor microenvironment may induce tumor development and relapse through the modulation of their proliferation and suppressive molecules.

• 대한정형외과학회지
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• 제54권6호
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• pp.490-497
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• 2019

최근 줄기세포에 대한 생물학적 지식의 발전으로 인해 이를 실제 환자의 치료에 적용시키기 위한 다양한 노력들이 이루어지고 있다. 중간엽 줄기세포는 골수 흡인물로부터 처음 발견되었으나 현재는 지방, 피부, 근육, 제대혈 등 다양한 조직으로부터 추출될 수 있는 다능성 기질세포로 이해되고 있다. 그동안 중간엽 줄기세포의 골형성능은 여러 실험 및 동물 연구를 통해 증명되었으며 골결손, 골괴사, 불유합 등의 어려운 임상 상황에서 일부 성공적인 골재생 결과들이 보고되고 있다. 하지만 아직까지 각 질환별 적응증이나 표준화된 적용법이 마련되어 있지 않으며 효능 및 안전성에 대한 객관적 증거가 부족한 상태이다. 중간엽 줄기세포를 이용한 골재생은 앞으로 더욱 확대될 가능성이 높으나 표준적인 치료로 인정받기 위해서는 아직 해결되어야 할 과제들 또한 남아 있다.