• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.4
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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.

• Archives of Craniofacial Surgery
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• v.21 no.4
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• pp.211-218
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• 2020

Autologous fat grafts are widely used in soft-tissue augmentation and reconstruction. To reduce the unpredictability of fat grafts and to improve their long-term survival, cell-assisted lipotransfer (CAL) was introduced. In this alternative method, autologous fat is mixed and grafted with stromal vascular fraction cells or adipose-derived stem/stromal cells (ASCs). In regenerative medicine, ASCs exhibit excellent therapeutic potential and are also simple to harvest. Although the efficacy of CAL has been demonstrated in experimental and clinical research, studies on its safety in terms of oncologic risk have reported inconclusive results. In order to establish CAL as a viable stem cell therapeutic approach, it will be necessary to demonstrate its oncologic safety in basic and clinical studies. Doing so could transform the paradigm of clinical strategy and practice for the treatment of a wide variety of diseases.

• Journal of Korean Neurosurgical Society
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• v.40 no.4
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• pp.267-272
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• 2006

Objective : There have been recent reports that mesenchymal stromal cells that are harvested from adipose tissue are able to differentiate into neurons. In the present study, we administered adipose tissue derived stem cells in rats with cerebral infarction in order to determine whether those stem cells could enhance the recovery of motor function. Methods : Cerebral infarction was induced by intraluminal occlusion of middle cerebral artery in rats. The adipose tissue-derived mesenchymal stem cells were harvested from inguinal fat pad and proliferated for 2 weeks in DMEM media. Approximately $1{\times}10^6$ cells were injected intravenously or into subdural space of the peri-lesional area. The rotor rod test was performed at preoperative state[before MCA occlusion], and 1, 2, 3, 4, 6, 8 and 10 weeks after the cell therapy. Results : The motor functions that were assessed by rotor rod test at 1 week of the cell therapy were nearly zero among the experimental groups. However, there was apparent motor function recovery after 2 weeks and 4 weeks of cell injection in intravenously treated rats and peri-lesionaly treated rats, respectively, while there was no significant improvement till 8 weeks in vehicle treated rats. Conclusion : These results demonstrate that the adipose derived stem cell treatment improves motor function recovery in rats with cerebral infarction.

• Tissue Engineering and Regenerative Medicine
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• v.15 no.6
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• pp.771-779
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• 2018

BACKGROUND: Mesenchymal stromal cells (MSCs) are multipotent stem cells that can differentiate into several cell types. In addition, many studies have shown that MSCs modulate the immune response. However, little information is currently available regarding the maintenance of immunomodulatory characteristics of MSCs through passages. Therefore, we investigated and compared cytokine and gene expression levels from adipose (AD) and bone marrow (BM)-derived MSCs relevant to immune modulation from early to late passages. METHODS: MSC immunophenotype, growth characteristics, cytokine expressions, and gene expressions were analyzed. RESULTS: AD-MSCs and BM-MSCs had similar cell morphologies and surface marker expressions from passage 4 to passage 10. Cytokines secreted by AD-MSCs and BM-MSCs were similar from early to late passages. AD-MSCs and BM-MSCs showed similar immunomodulatory properties in terms of cytokine secretion levels. However, the gene expressions of tumor necrosis factor-stimulated gene (TSG)-6 and human leukocyte antigen (HLA)-G were decreased and gene expressions of galectin-1 and -3 were increased in both AD- and BM-MSCs with repeated passages. CONCLUSION: Our study showed that the immunophenotype and expression of immunomodulation-related cytokines of AD-MSCs and BM-MSCs immunomodulation through the passages were not significantly different, even though the gene expressions of both MSCs were different.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.32 no.2
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• pp.97-106
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• 2010

Aim of the study: An alternative source of adult stem cells that could be obtained in large quantities, under local anesthesia, with minimal discomfort would be advantageous. Adipose tissue could be processed to obtain a fibroblast-like population of cells or adipose tissue-derived stromal cells (ATSCs). This study was performed to confirm the availability of ATSCs in bone tissue engineering. Materials amp; Methods: In this study, adipose tissue-derived mesenchymal stem cell was extracted from the liposuctioned abdominal fat of 24-old human and cultivated, and the stem cell surface markers of CD 105 and SCF-R were confirmed by immunofluorescent staining. The proliferation of bone marrow mesenchymal stem cell and ATSCs were compared, and evaluated the osteogenic differentiation of ATSCs in a specific osteogenic induction medium. Osteogenic differentiation was assessed by von Kossa and alkaline phosphatase staining. Expression of osteocyte specific BMP-2, ALP, Cbfa-1, Osteopontin and osteocalcin were confirmed by RT-PCR. With differentiation of ATSCs, calcium concentration was assayed, and osteocalcin was evaluated by ELISA (Enzyme-linked immunosorbant assay). The bone formation by 5-week implantation of HA/TCP block loaded with bone marrow mesenchymal stem cells and ATSCs in the subcutaneous pocket of nude mouse was evaluated by histologic analysis. Results: ATSCs incubated in the osteogenic medium were stained positively for von Kossa and alkaline phosphatase staining. Expression of osteocyte specific genes was also detected. ATSCs could be easily identified through fluorescence microscopy, and bone formation in vivo was confirmed by using ATSC-loaded HA/TCP scaffold. Conclusions: The present results show that ATSCs have an ability to differentiate into osteoblasts and formed bone in vitro and in vivo. So ATSCs may be an ideal source for further experiments on stem cell biology and bone tissue engineering.

• Biomolecules & Therapeutics
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• v.24 no.3
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• pp.260-267
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• 2016

Mesenchymal stem cells (MSCs) offer significant therapeutic promise for various regenerative therapies. However, MSC-based therapy for injury exhibits low efficacy due to the pathological environment in target tissues and the differences between in vitro and in vivo conditions. To address this issue, we developed adipose-derived MSC spheroids as a novel delivery method to preserve the stem cell microenvironment. MSC spheroids were generated by suspension culture for 3 days, and their sizes increased in a time-dependent manner. After re-attachment of MSC spheroids to the plastic dish, their adhesion capacity and morphology were not altered. MSC spheroids showed enhanced production of hypoxia-induced angiogenic cytokines such as vascular endothelial growth factor (VEGF), stromal cell derived factor (SDF), and hepatocyte growth factor (HGF). In addition, spheroid culture promoted the preservation of extracellular matrix (ECM) components, such as laminin and fibronectin, in a culture time- and spheroid size-dependent manner. Furthermore, phosphorylation of AKT, a cell survival signal, was significantly higher and the expression of pro-apoptotic molecules, poly (ADP ribose) polymerase-1 (PARP-1) and cleaved caspase-3, was markedly lower in the spheroids than in MSCs in monolayers. In the murine hindlimb ischemia model, transplanted MSC spheroids showed better proliferation than MSCs in monolayer. These findings suggest that MSC spheroids promote MSC bioactivities via secretion of angiogenic cytokines, preservation of ECM components, and regulation of apoptotic signals. Therefore, MSC spheroid-based cell therapy may serve as a simple and effective strategy for regenerative medicine.

• International Journal of Stem Cells
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• v.16 no.4
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• pp.425-437
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• 2023

Obesity, which continues to increase worldwide, was shown to irreversibly impair the differentiation potential and angiogenic properties of adipose tissue mesenchymal stromal cells (ADSCs). Because these cells are intended for regenerative medicine, especially for the treatment of inflammatory conditions, and the effects of obesity on the immunomodulatory properties of ADSCs are not yet clear, here we investigated how ADSCs isolated from former obese subjects (Ex-Ob) would influence macrophage differentiation and polarization, since these cells are the main instructors of inflammatory responses. Analysis of the subcutaneous adipose tissue (SAT) of overweight (OW) and Ex-Ob subjects showed the maintenance of approximately twice as many macrophages in Ex-Ob SAT, contained within the CD68⁺/FXIII-A^- inflammatory pool. Despite it, in vitro, coculture experiments revealed that Ex-Ob ADSCs instructed monocyte differentiation into a M2-like profile, and under inflammatory conditions induced by LPS treatment, inhibited HLA-DR upregulation by resting M0 macrophages, originated a similar percentage of TNF-α⁺ cells, and inhibited IL-10 secretion, similar to OW-ADSCs and BMSCs, which were used for comparison, as these are the main alternative cell types available for therapeutic purposes. Our results showed that Ex-Ob ADSCs mirrored OW-ADSCs in macrophage education, favoring the M2 immunophenotype and a mixed (M1/M2) secretory response. These results have translational potential, since they provide evidence that ADSCs from both Ex-Ob and OW subjects can be used in regenerative medicine in eligible therapies. Further in vivo studies will be fundamental to validate these observations.

• Archives of Plastic Surgery
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• v.39 no.5
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• pp.534-539
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• 2012

Background Autologous fat grafting evolved over the twentieth century to become a quick, safe, and reliable method for restoring volume. However, autologous fat grafts have some problems including uncertain viability of the grafted fat and a low rate of graft survival. To overcome the problems associated with autologous fat grafts, we used uncultured adipose tissue-derived stromal cell (stromal vascular fraction, SVF) assisted autologous fat grafting. Thus, the purpose of this study was to evaluate the effect of SVF in a clinical trial. Methods SVF cells were freshly isolated from half of the aspirated fat and were used in combination with the other half of the aspirated fat during the procedure. Between March 2007 and February 2008, a total of 9 SVF-assisted fat grafts were performed in 9 patients. The patients were followed for 12 weeks after treatment. Data collected at each follow-up visit included clinical examination of the graft site(s), photographs for historical comparison, and information from a patient questionnaire that measured the outcomes from the patient perspective. The photographs were evaluated by medical professionals. Results Scores of the left facial area grafted with adipose tissue mixed with SVF cells were significantly higher compared with those of the right facial area grafted with adipose tissue without SVF cells. There was no significant adverse effect. Conclusions The subjective patient satisfaction survey and surgeon survey showed that SVF-assisted fat grafting was a surgical procedure with superior results.

• Journal of Nutrition and Health
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• v.57 no.4
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• pp.376-388
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• 2024

Purpose: Adipocyte dysfunction has been reported in diabetes, and stimulating thermogenesis and suppressing senescence in adipocytes potentially alleviates metabolic dysregulation. This study aimed to investigate thermogenesis and cellular senescence in diabetic adipocytes under basal conditions and in response to stimuli. Methods: White and brown primary adipocytes derived from control (CON) and db/db (DB) mice were treated with β-agonists, such as norepinephrine (NE) and CL316,243, and 18-carbon fatty acids, including stearic acid, oleic acid (OLA), linoleic acid (LNA), and α-linolenic acid, and the expression of the genes related to thermogenesis and cellular senescence was measured. Results: Although no difference in the thermogenic and cellular senescence gene expression in white adipose tissue (WAT) was noted between the CON and DB mice, brown adipose tissue (BAT) from the DB mice exhibited lower uncoupling protein 1 (Ucp1) expression and higher cyclin-dependent kinase inhibitor (Cdkn)1a and Cdkn2a expression levels compared to that from the CON mice. Stromal vascular cells isolated from the BAT of the DB mice displayed higher peroxisome proliferator-activated receptor gamma (Pparg), CCAAT/enhancer-binding protein alpha (Cebpa), Cdkn1a, and Cdkn2a expression levels. White adipocytes from the DB mice exhibited lower Ucp1, peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (Pgc1a), and PR domain containing 16 (Prdm16) expression levels regardless of β-agonist treatment. NE upregulated Pgc1a in both white and brown adipocytes from the CON mice, but not in those from the DB mice. Although none of the fatty acids were observed to downregulate the cellular senescence genes in fully differentiated adipocytes, the OLA-treated brown adipocytes derived from DB mice exhibited lower Cdkn1a and Cdkn2b expression levels than the LNA-treated cells. Conclusion: These results indicate that the lower thermogenic capacity of diabetic adipocytes may be related to their cellular senescence, and different fatty acids potentially exert divergent effects on the expression of cellular senescence genes.

• Clinical and Experimental Reproductive Medicine
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• v.48 no.4
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• pp.322-336
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• 2021

Objective: Endometriosis is a chronic debilitating inflammatory condition characterized by the presence of endometrial tissues outside the uterine cavity. Pelvic soreness and infertility are the usual association. Due to the poor effectiveness of the hormone therapy and the high incidence of recurrence following surgical excision, there is no single effective option for management of endometriosis. Mesenchymal stem cells (MSCs) are multipotent stromal cells studied for their broad immunoregulatory and anti-inflammatory properties; however, their efficiency in endometriosis cases is still a controversial issue. Our study aim was to evaluate whether adipose tissue-derived MSCs (AD-MSCs) could help with endometriosis through their studied anti-inflammatory role. Methods: Female Wistar rats weighting 180 to 250 g were randomly divided into two groups: group 1, endometriosis group; established by transplanting autologous uterine tissue into rats' peritoneal cavities and group 2, stem cell treated group; treated with AD-MSCs on the 5th day after induction of endometriosis. The proliferative activity of the endometriosis lesions was evaluated through Ki67 staining. Quantitative estimation of interferon γ, tumor necrosis factor-α, interleukin (IL)-6, IL-1β, IL-10, and transforming growth factor β expression, as well as immunohistochemical detection of CD68 positive macrophages, were used to assess the inflammatory status. Results: The size and proliferative activity of endometriosis lesions were significantly reduced in the stem cell treated group. Stem cells efficiently mitigated endometriosis associated chronic inflammatory reactions estimated through reduction of CD68 positive macrophages and the expression of the proinflammatory cytokines. Conclusion: Stem cell therapy can be considered a novel remedy in endometriosis possibly through its anti-inflammatory and antiproliferative properties.