Kim, Jong-Myung;Yu, Ji-Min;Bae, Yong-Chan;Jung, Jin-Sup
Journal of Life Science
/
v.21
no.5
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pp.631-646
/
2011
Mesenchymal stem cells (MSC) are multipotent and can be isolated from diverse human tissues including bone marrow, fat, placenta, dental pulp, synovium, tonsil, and the thymus. They function as regulators of tissue homeostasis. Because of their various advantages such as plasticity, easy isolation and manipulation, chemotaxis to cancer, and immune regulatory function, MSCs have been considered to be a potent cell source for regenerative medicine, cancer treatment and other cell based therapy such as GVHD. However, relating to its supportive feature for surrounding cell and tissue, it has been frequently reported that MSCs accelerate tumor growth by modulating cancer microenvironment through promoting angiogenesis, secreting growth factors, and suppressing anti-tumorigenic immune reaction. Thus, clinical application of MSCs has been limited. To understand the underlying mechanism which modulates MSCs to function as tumor supportive cells, we co-cultured human adipose tissue derived mesenchymal stem cells (ASC) with cancer cell lines H460 and U87MG. Then, expression data of ASCs co-cultured with cancer cells and cultured alone were obtained via microarray. Comparative expression analysis was carried out using DAVID (Database for Annotation, Visualization and Integrated Discovery) and PANTHER (Protein ANalysis THrough Evolutionary Relationships) in divers aspects including biological process, molecular function, cellular component, protein class, disease, tissue expression, and signal pathway. We found that cancer cells alter the expression profile of MSCs to cancer associated fibroblast like cells by modulating its energy metabolism, stemness, cell structure components, and paracrine effect in a variety of levels. These findings will improve the clinical efficacy and safety of MSCs based cell therapy.
Song, Sun Ho;Han, Seung Kyu;Chun, Kyung Wook;Kim, Woo Kyung
Archives of Plastic Surgery
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v.36
no.6
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pp.679-684
/
2009
Purpose: Human lipoaspirate cells are relatively easy to obtain in large quantities without cell culture. The aim of this in vitro pilot study was to determine the effect of cell therapy using uncultured lipoaspirate cells on cell proliferation and collagen synthesis of diabetic fibroblasts, which are the major contributing factors in wound healing. Methods: In order to get diabetic fibroblasts, dermis tissues were obtained from foot skin of diabetic patients who underwent debridements or toe amputations(n = 4). In order to isolate lipoaspirate cells, the same diabetic patients' abdominal adipose tissues were obtained by liposuction. The diabetic fibroblasts were co - cultured with or without autogenous lipoaspirate cells using porous culture plate insert. Initial numbers of the lipoaspirate cells and diabetic fibroblasts seeded were 15,000 cells/well, respectively. For cell proliferation assay, two treatment groups were included. In group I, diabetic fibroblasts were cultured with the insert having no cells, which serves as a control. In group II, the lipoaspirate cells were added in the culture plate insert. For collagen synthesis assay, one additional group(group III), in which diabetic fibroblasts were not seeded in the well and only lipoaspirate cells inside the insert were incubated without diabetic fibroblasts, was included for a reference. Results: One hundred to one hundred sixty thousand lipoaspirate cells were isolated per ml of aspirated adipose tissue. After 3 - day incubation, the mean cell numbers in group I and II were 17,294/well and 22,163/well. The mean collagen level in group I, II, and III were 29, 41, and 2 ng/ml, respectively. These results imply that both cell proliferation and collagen synthesis in the lipoaspirate cell treatment group were 28 and 44 percents higher than in the control group, respectively(p < 0.05). Conclusion: Uncultured lipoaspirate cell autografts may stimulate the wound healing activity of diabetic fibroblasts.
This study evaluates the change of computer tomography (CT) number in the case of the metal artifact reduction (MAR) algorithm, using the phantom. The images were obtained from dual CT using a gammex 467 tissue characterization phantom, which is similar to human tissues. The test method was performed by dividing pre and post MAR algorithm and measured CT values of nonmagnetic materials within the phantom. In addition, the changes of CT values for each material were compared and analyzed after measuring CT values up to 140 keV, using the spectral HU curve followed by CT scan. As a result, in the cases of N rod (trabecular bone) and E rod (trabecular bone), the CT numbers decreased as keV increasing but were constant above 90 keV. In the cases of I rod (dense bone) and K rod (dense bone), the CT numbers also decreased as keV increased but were uniform above 90 keV. The CT numbers from 40 keV to 140 keV were consistent in the cases of J rod (liver), D rod (liver), L rod (muscle), and F rod (muscle). For A rod (adipose), G rod (adipose), B rod (breast) and O rod (breast), the CT numbers increased as keV increased but were constant after 90 keV. The CT numbers from 40 keV to 140 keV were consistent in the cases of C rod (lung (exhale)), P rod (lung (exhale)), M rod (lung (inhale)) and H rod (lung (exhale)). Conclusively, because dual CT exhibits no changes in image quality and is able to analyze nonmagnetic materials by measuring the CT values of various materials, it will be used in the future as a useful tool for the diagnosis of lesions.
To study the effect of dietary docosahexaenoic acid (DHA) enrichment on the expression of hepatic genes in pigs, weaned, crossbred pigs (30 d old) were fed diets supplemented with either 2% tallow or DHA oil for 18 d. Hepatic mRNA was extracted. Suppression subtractive hybridization was used to explore the hepatic genes that were specifically regulated by dietary DHA enrichment. After subtraction, we observed 288 cDNA fragments differentially expressed in livers from pigs fed either 2% DHA oil or 2% tallow for 18 d. After differential screening, 7 genes were found to be differentially expressed. Serum amyloid A protein 2 (SAA2) was further investigated because of its role in lipid metabolism. Northern analysis indicated that hepatic SAA2 was upregulated by dietary DHA enrichment (p<0.05). In a second experiment, feeding 10% DHA oil for 2d significantly increased the expression of SAA2 (compared to the 10% tallow group; p<0.05). The porcine SAA2 full length cDNA sequence was cloned and the sequence was compared to the human and mouse sequences. The homology of the SAA2 amino acid sequence between pig and human was 73% and between pig and mouse was 62%. There was a considerable difference in SAA2 sequences among these species. Of particular note was a deletion of 8 amino acids, in the pig compared to the human. This fragment is a specific characteristic for the SAA subtype that involved in acute inflammation reaction. Similar to human and mouse, porcine SAA2 was highly expressed in the liver of pigs. It was not detectable in the skeletal muscle, heart muscle, spleen, kidney, lung, and adipose tissue. These data suggest that SAA2 may be involved in mediation of the function of dietary DHA in the liver of the pig, however, the mechanism is not yet clear.
Park, Soyoung;Lim, Yeseo;Shin, Sunhye;Han, Sung Nim
Nutrition Research and Practice
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v.7
no.5
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pp.352-358
/
2013
Korean pine nut oil (PNO) has been reported to have favorable effects on lipid metabolism and appetite control. We investigated whether PNO consumption could influence weight gain, and whether the PNO-induced effect would result in an improvement of immune function in high-fat diet (HFD)-induced obese mice. C57BL/6 mice were fed control diets with 10% energy fat from either PNO or soybean oil (SBO), or HFDs with 45% energy fat from 10% PNO or SBO and 35% lard, 20% PNO or SBO and 25% lard, or 30% PNO or SBO and 15% lard for 12 weeks. The proliferative responses of splenocytes upon stimulation with concanavalin A (Con A) or lipopolysaccharide (LPS), Con A-stimulated production of interleukin (IL)-2 and interferon (IFN)-${\gamma}$, and LPS-stimulated production of IL-6, IL-$1{\beta}$, and prostaglandin $E_2$ ($PGE_2$) by splenocytes were determined. Consumption of HFDs containing PNO resulted in significantly less weight gain (17% less, P < 0.001), and lower weight gain was mainly due to less white adipose tissue (18% less, P = 0.001). The reduction in weight gain did not result in the overall enhancement in splenocyte proliferation. Overall, PNO consumption resulted in a higher production of IL-$1{\beta}$ (P = 0.04). Replacement of SBO with PNO had no effect on the production of IL-2, IFN-${\gamma}$, IL-6, or $PGE_2$ in mice fed with either the control diets or HFDs. In conclusion, consumption of PNO reduced weight gain in mice fed with HFD, but this effect did not result in the overall improvement in immune responses.
Lee, Jong-Ho;Kim, Oh-Yoen;Kim, Ji-Young;Park, Kyoung;Yangsoo Jang
Nutritional Sciences
/
v.5
no.1
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pp.13-19
/
2002
A mutation in the promoter region of uncoupling protein 3 (UCF3), specifically the -55C longrightarrow T transition, may influence an individual's energy metabolism and body weight. The objective of this study was to investigate the effect of a weight reduction program on endocrine functions and body fat distribution, related to UCP3 promoter genotype. Ninety overweight pre-menopausal female subjects participated in the weight reduction program at Yonsei University Hospital, and were placed on a calorie-restricted diet (300 kcal less than their daily requirements) for 12 weeks. After 12 weeks, all subjects on the program lost approximately 5% of their initial body weights and had lower Body Mass Index (BMI) values. Among the 90 women, 56 had a normal (without mutation) UCP3 genotype, while 34 women had mutations in the promoter region of UCP3. Despite similar weight reductions in both groups, a significantly higher decrease in abdominal adipose tissue was observed in the normal UCP3 genotype group, compared to the group with mutations. In particular, there was a significant reduction of fat at the lumbar 1 (Ll) level in the without-mutation group. Serum levels of total cholesterol, apolipoprotein Al were significantly decreased in the without-mutation group, by 4.4% and 5.7% respectively. Serum levels of hormones were not significantly changed in both groups artier the intervention. However, in the group without the mutations, the leptin level significantly reduced by 23.4% (p<0.001). Serum free fatty acid (FFA) concentration was significantly increased in the group with mutation following the weight reduction program. On the other hand, FFA responses were shown similar increases in both groups. In conclusion, although no difference was found in the magnitude of weight reduction in both groups, there were significant differences in body fat distribution and in endocrine function between the groups.
Neural tissue has limited intrinsic capacity of repair after injury, and the identification of alternate sources of neural stem cells has broad clinical potential. We isolated mesechymal-like stem cells from human adipose tissues (AT-MSCs), and studied on transdifferentiation-promoting conditions in neural cells. Dopaminergic and cholinergic neuron induction of AT-MSCs was also studied. Neural differentiation was induced by adding bFGF, EGF, dimethyl sulphoxide (DMSO) and butylated hydroxyanisole(BHA) in N2 Medium and N2 supplement. The immunoreactive cells for $\beta$-tubulin III, a neuron-specific marker, GFAP, an astrocyte marker, or Gal-C, an oligodendrocyte marker, were found. AT-MSCs treated with bFGF, SHH and FGF8 were differentiatied into dopaminergic neurons that were immunopositive for TH antibody. Differentiation of MSCs to cholinergic neurons was induced by combined treatment with basic fibroblast growth factor (bFGF), retinoic acid (RA) and sonic hedgehog (Shh). AT-MSCs treated with DMSO and BHA rapidly assumed the morphology of multipolar neurons. Both immunocytochemistry and RT-PCR analysis indicated that the expression of a number of neural markers including neuro D1, $\beta$-tubulin III, GFAP and nestinwas markedly elevated during this acute differentiation. While the stem cell markers such as SCF, C-kit, and Stat-3 were not expressed after preinduction medium culture, we confirmed the differentiation of dopaminergic and cholinergic neurons by TH/$\beta$-tubulin III or ChAT/ $\beta$-tubulin III positive cells. Conclusively, AT-MSCs can be differentiated into dopaminergic and cholinergic neuronsand these findings suggest that AT-MSCs are alternative cell source of treatment for neurodegenerative diseases.
Seongsu Kang;Seung-Hyun Jun;Jinyong Lee;Myoung Jin An;Nae Gyu Kang
Journal of the Society of Cosmetic Scientists of Korea
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v.49
no.4
/
pp.365-373
/
2023
Since the lips are a representative facial part that can express human attraction, aesthetic interest in them has always existed in human history. However, as lips age, they tend to form wrinkles, become thinner, and lose their volume. To counteract this phenomenon, medical procedures such as fillers or fat transplantation have been suggested. In this study, we verified that the one of main effective material complex of L G H&H L IPCERIN®, combination of cedrol, a sesquiterpene found in cedarwood, and three peptides (acetyl hexapeptide-8, acetyl tetrapeptide-9, and desamidocollagen) could ameliorate the photo-aging and reduce the wrinkles through in vitro experiments. The possibility of improving collagen and elastin expression in skin fibroblasts and reducing MMP expression under photoaging conditions was verified. In addition, it was confirmed that the amount of fat tissue in the lips can be increased by promoting adipose stem cell differentiation and increasing the amount of fat produced in the in vitro adipose stem cell differentiation experiment. Two weeks of human application tests confirmed that a combination of cedrol and peptides can improve the wrinkles, texture, elasticity, and volume of the lips. This study verified that the combination of cedrol and three peptides can be used as effective cosmetic materials to decrease the various signs of aging in the lips.
Insulin-responsive glucose transporter 4 (GLUT4) is a member of the glucose transporter family and mainly presents in skeletal muscle and adipose tissue. To clarify the molecular structure of porcine GLUT4, RACE was used to clone its cDNA. Several cDNA clones corresponding to different regions of GLUT4 were obtained by amplifying reverse-transcriptase products of total RNA extracted from Landrace porcine skeletal muscles. Nucleotide sequence analysis of the cDNA clones revealed that porcine GLUT4 cDNA was composed of 2,491 base pairs with a coding region of 509 amino acids. The deduced amino acid sequence was over 90% identical to human, rabbit and cattle GLUT4. The tissue distribution of GLUT4 was also examined by Real-time RT-PCR. The mRNA expression abundance of GLUT4 was heart>liver, skeletal muscle and brain>lung, kidney and intestine. The developmental expression of GLUT4 and insulin receptor (IR) was also examined by Real-time RT-PCR using total RNA extracted from longissimus dorsi (LM), semimembranosus (SM), and semitendinosus (SD) muscle of Landrace at the age of 1, 7, 30, 60 and 90 d. It was shown that there was significant difference in the mRNA expression level of GLUT4 in skeletal muscles of Landrace at different ages (p<0.05). The mRNA expression level of IR also showed significant difference at different ages (p<0.05). The developmental change in the mRNA expression abundance of GLUT4 was similar to that in IR, and both showed a higher level at birth and 30 d than at other ages. However, there was no significant tissue difference in the mRNA expression of GLUT4 or IR (p>0.05). These results showed that the nucleotide sequence of the cDNA clones was highly identical with human, rabbit and cattle GLUT4 and the developmental change of GLUT4 mRNA in skeletal muscles was similar to that of IR, suggesting that porcine GLUT4 might be an insulin-responsive glucose transporter. Moreover, the tissue distribution of GLUT4 mRNA showed that GLUT4 might be an important nutritional transporter in porcine skeletal muscles.
Kim, Young Suk;Park, Hee Jeong;Shin, Keun Koo;Lee, Sun Young;Bae, Yong Chan;Jung, Jin Sup
Journal of Life Science
/
v.27
no.7
/
pp.767-782
/
2017
MicroRNAs control the differentiation and proliferation of human adipose tissue-derived stromal cells (hADSCs). However, the role of miR-200a and miR210 on the osteogenic differentiaton of hADSCs has not been determined. hADSCs were isolated from human adipose tissues. Direct binding of mircoRNA to target mRNAs was determined by luciferase assay of the constructs containing putative microRNA binding sites within 3' untranslated region of target mRNAs. Overexpression of miR-200a increased the proliferation and osteogenic differentiation of hADSCs, while causing downregulation of the levels of ZEB2. Inhibition of miR-200a with antisense RNAs inhibited the proliferation and osteogenic differentiation of hADSCs. Overexpression of miR-210 was found to inhibit the proliferation of hADSCs but increase the osteogenic differentiation, while causing downregulation of the levels of IGFBP3. Inhibition of miR-210 with antisense RNAs increased the proliferation but inhibited the osteogenic differentiation of hADSCs. Analysis of the luciferase activity of the constructs containing the miR-200a target site within the ZEB2 3' region and the miR-210 target site within the IGFBP3 3' region revealed lower activity in the miR-200a- or miR-210-transfected hADSCs than in control miRNA-transfected hADSCs. Downregulation of ZEB2 or IGFBP3 in the hADSCs showed similar effects on both their proliferation and osteogenic differentiation with that of miR-200a and miR-210 overexpression, respectively. The results of the current study indicate that miR-200a and miR-210 regulate the osteogenic differentiation and proliferation of hADSCs through the direct targeting of IGFBP3 and ZEB2, respectively.
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