Conditioned medium from tonsil‑derived mesenchymal stem cells promotes adiponectin production

Kim,Yu‑Hee; Cho,Kyung‑Ah; Park,Minhwa; Webster,Julie   A.; Woo,So‑Youn; Ryu,Kyung‑Ha

doi:10.3892/mmr.2017.7335

Conditioned medium from tonsil‑derived mesenchymal stem cells promotes adiponectin production

Authors:
- Yu‑Hee Kim
- Kyung‑Ah Cho
- Minhwa Park
- Julie A. Webster
- So‑Youn Woo
- Kyung‑Ha Ryu
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Affiliations: Department of Microbiology, School of Medicine, Ewha Womans University, Seoul 07985, Republic of Korea, School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia, Department of Pediatrics, School of Medicine, Ewha Womans University, Seoul 07985, Republic of Korea
Published online on: August 23, 2017 https://doi.org/10.3892/mmr.2017.7335
Pages: 6170-6177

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Abstract

Mesenchymal stem cells (MSCs) are often considered to be a good source for the development of regenerative medicine. Previously, we reported that tonsil‑derived MSC conditioned medium (T‑MSC CM) produces visceral fat reducing effects. As reduced visceral adiposity is closely associated with an increase in circulating adiponectin, the present study investigated the effects of T‑MSC CM on adiponectin production. T‑MSC CM was collected from previously isolated and characterized T‑MSCs and injected into senescence‑accelerated mouse prone 6 mice, which exhibit characteristics of aging and obesity. The results demonstrated a reduction in mouse weight and epididymal adipose tissue (eAT) mass following injection of T‑MSC CM. Significant increases in adiponectin expression in the eAT, and total and high molecular weight (HMW) adiponectin in the circulation were observed in the T‑MSC CM‑injected mice compared with control mice using reverse transcription‑quantitative polymerase chain reaction, western blot analysis and ELISA. In 3T3‑L1 adipocytes, T‑MSC CM treatment increased adiponectin secretion and multimerization, as detected using western blotting under non‑reducing and non‑heat‑denaturing conditions. Furthermore, glucose oxidase was used to induce oxidative stress in 3T3‑L1 adipocytes and it was observed that T‑MSC CM reduced reactive oxygen species production and the expression of certain oxidative stress markers. In addition, the results also demonstrated that the production of HMW adiponectin was increased, which indicates that T‑MSC CM may enhance adiponectin multimerization via amelioration of oxidative stress. Further studies are required to elucidate anti‑oxidant molecules secreted from T‑MSCs, and these results highlight the potential therapeutic relevance of T‑MSC CM for the treatment of obesity or obesity‑associated diseases.

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1	Lavoie JR and Rosu-Myles M: Uncovering the secretes of mesenchymal stem cells. Biochimie. 95:2212–2221. 2013. View Article : Google Scholar : PubMed/NCBI
2	Konala VB, Mamidi MK, Bhonde R, Das AK, Pochampally R and Pal R: The current landscape of the mesenchymal stromal cell secretome: A new paradigm for cell-free regeneration. Cytotherapy. 18:13–24. 2016. View Article : Google Scholar : PubMed/NCBI
3	Li TS, Takahashi M, Ohshima M, Qin SL, Kubo M, Muramatsu K and Hamano K: Myocardial repair achieved by the intramyocardial implantation of adult cardiomyocytes in combination with bone marrow cells. Cell Transplant. 17:695–703. 2008. View Article : Google Scholar : PubMed/NCBI
4	Siegel G, Krause P, Wöhrle S, Nowak P, Ayturan M, Kluba T, Brehm BR, Neumeister B, Köhler D, Rosenberger P, et al: Bone marrow-derived human mesenchymal stem cells express cardiomyogenic proteins but do not exhibit functional cardiomyogenic differentiation potential. Stem Cells Dev. 21:2457–2470. 2012. View Article : Google Scholar : PubMed/NCBI
5	Bi B, Schmitt R, Israilova M, Nishio H and Cantley LG: Stromal cells protect against acute tubular injury via an endocrine effect. J Am Soc Nephrol. 18:2486–2496. 2007. View Article : Google Scholar : PubMed/NCBI
6	Cantinieaux D, Quertainmont R, Blacher S, Rossi L, Wanet T, Noël A, Brook G, Schoenen J and Franzen R: Conditioned medium from bone marrow-derived mesenchymal stem cells improves recovery after spinal cord injury in rats: An original strategy to avoid cell transplantation. PLoS One. 8:e695152013. View Article : Google Scholar : PubMed/NCBI
7	Janjanin S, Djouad F, Shanti RM, Baksh D, Gollapudi K, Prgomet D, Rackwitz L, Joshi AS and Tuan RS: Human palatine tonsil: A new potential tissue source of multipotent mesenchymal progenitor cells. Arthritis Res Ther. 10:R832008. View Article : Google Scholar : PubMed/NCBI
8	Ryu KH, Cho KA, Park HS, Kim JY, Woo SY, Jo I, Choi YH, Park YM, Jung SC, Chung SM, et al: Tonsil-derived mesenchymal stromal cells: Evaluation of biologic, immunologic and genetic factors for successful banking. Cytotherapy. 14:1193–1202. 2012. View Article : Google Scholar : PubMed/NCBI
9	Ryu KH, Kim SY, Kim YR, Woo SY, Sung SH, Kim HS, Jung SC, Jo I and Park JW: Tonsil-derived mesenchymal stem cells alleviate concanavalin A-induced acute liver injury. Exp Cell Res. 326:143–154. 2014. View Article : Google Scholar : PubMed/NCBI
10	Park M, Kim YH, Woo SY, Lee HJ, Yu Y, Kim HS, Park YS, Jo I, Park JW, Jung SC, et al: Tonsil-derived mesenchymal stem cells ameliorate CCl4-induced liver fibrosis in mice via autophagy activation. Sci Rep. 5:86162015. View Article : Google Scholar : PubMed/NCBI
11	Kim SY, Kim YR, Park WJ, Kim HS, Jung SC, Woo SY, Jo I, Ryu KH and Park JW: Characterisation of insulin-producing cells differentiated from tonsil derived mesenchymal stem cells. Differentiation. 90:27–39. 2015. View Article : Google Scholar : PubMed/NCBI
12	Park YS, Kim HS, Jin YM, Yu Y, Kim HY, Park HS, Jung SC, Han KH, Park YJ, Ryu KH and Jo I: Differentiated tonsil-derived mesenchymal stem cells embedded in Matrigel restore parathyroid cell functions in rats with parathyroidectomy. Biomaterials. 65:140–152. 2015. View Article : Google Scholar : PubMed/NCBI
13	Park S, Choi Y, Jung N, Yu Y, Ryu KH, Kim HS, Jo I, Choi BO and Jung SC: Myogenic differentiation potential of human tonsil-derived mesenchymal stem cells and their potential for use to promote skeletal muscle regeneration. Int J Mol Med. 37:1209–1220. 2016. View Article : Google Scholar : PubMed/NCBI
14	Kim YH, Park M, Cho KA, Kim BK, Ryu JH, Woo SY and Ryu KH: Tonsil-derived mesenchymal stem cells promote bone mineralization and reduce marrow and visceral adiposity in a mouse model of senile osteoporosis. Stem Cells Dev. 25:1161–1171. 2016. View Article : Google Scholar : PubMed/NCBI
15	Ryu JH, Park M, Kim BK, Ryu KH and Woo SY: Tonsil-derived mesenchymal stromal cells produce CXCR2-binding chemokines and acquire follicular dendritic cell-like phenotypes under TLR3 stimulation. Cytokine. 73:225–235. 2015. View Article : Google Scholar : PubMed/NCBI
16	Park M, Kim YH, Ryu JH, Woo SY and Ryu KH: Immune suppressive effects of tonsil-derived mesenchymal stem cells on mouse bone-marrow-derived dendritic cells. Stem Cells Int. 2015:1065402015. View Article : Google Scholar : PubMed/NCBI
17	Cho KA, Lee JK, Kim YH, Park M, Woo SY and Ryu KH: Mesenchymal stem cells ameliorate B-cell-mediated immune responses and increase IL-10-expressing regulatory B cells in an EBI3-dependent manner. Cell Mol Immunol. Jan 2–2017.(Epub ahead of print). View Article : Google Scholar :
18	Kim JY, Park M, Kim YH, Ryu KH, Lee KH, Cho KA and Woo SY: Tonsil-derived mesenchymal stem cells (T-MSCs) prevent Th17-mediated autoimmune response via regulation of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway. J Tissue Eng Regen Med. Jan 20–2017.(Epub ahead of print). View Article : Google Scholar
19	Whitehead JP, Richards AA, Hickman IJ, Macdonald GA and Prins JB: Adiponectin-a key adipokine in the metabolic syndrome. Diabetes Obes Metab. 8:264–280. 2006. View Article : Google Scholar : PubMed/NCBI
20	Liu M and Liu F: Regulation of adiponectin multimerization, signaling and function. Best Pract Res Clin Endocrinol Metab. 28:25–31. 2014. View Article : Google Scholar : PubMed/NCBI
21	Wang ZV and Scherer PE: Adiponectin, the past two decades. J Mol Cell Biol. 8:93–100. 2016. View Article : Google Scholar : PubMed/NCBI
22	Cnop M, Havel PJ, Utzschneider KM, Carr DB, Sinha MK, Boyko EJ, Retzlaff BM, Knopp RH, Brunzell JD and Kahn SE: Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: Evidence for independent roles of age and sex. Diabetologia. 46:459–469. 2003. View Article : Google Scholar : PubMed/NCBI
23	Furler SM, Gan SK, Poynten AM, Chisholm DJ, Campbell LV and Kriketos AD: Relationship of adiponectin with insulin sensitivity in humans, independent of lipid availability. Obesity (Silver Spring). 14:228–234. 2006. View Article : Google Scholar : PubMed/NCBI
24	Yu Y, Park YS, Kim HS, Kim HY, Jin YM, Jung SC, Ryu KH and Jo I: Characterization of long-term in vitro culture-related alterations of human tonsil-derived mesenchymal stem cells: Role for CCN1 in replicative senescence-associated increase in osteogenic differentiation. J Anat. 225:510–518. 2014. View Article : Google Scholar : PubMed/NCBI
25	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
26	Niimi K, Takahashi E and Itakura C: Adiposity-related biochemical phenotype in senescence-accelerated mouse prone 6 (SAMP6). Comp Med. 59:431–436. 2009.PubMed/NCBI
27	Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M and Shimomura I: Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 114:1752–1761. 2004. View Article : Google Scholar : PubMed/NCBI
28	Guo H, Ling W, Wang Q, Liu C, Hu Y and Xia M: Cyanidin 3-glucoside protects 3T3-L1 adipocytes against H2O2- or TNF-alpha-induced insulin resistance by inhibiting c-Jun NH2-terminal kinase activation. Biochem Pharmacol. 75:1393–1401. 2008. View Article : Google Scholar : PubMed/NCBI
29	Gustafson B, Hammarstedt A, Hedjazifar S and Smith U: Restricted adipogenesis in hypertrophic obesity: The role of WISP2, WNT, and BMP4. Diabetes. 62:2997–3004. 2013. View Article : Google Scholar : PubMed/NCBI
30	Choi SS, Kim ES, Jung JE, Marciano DP, Jo A, Koo JY, Choi SY, Yang YR, Jang HJ, Kim EK, et al: PPARγ antagonist Gleevec improves insulin sensitivity and promotes the browning of white adipose tissue. Diabetes. 65:829–839. 2016. View Article : Google Scholar : PubMed/NCBI
31	Matsubara M, Maruoka S and Katayose S: Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women. Eur J Endocrinol. 147:173–180. 2002. View Article : Google Scholar : PubMed/NCBI
32	Asayama K, Hayashibe H, Dobashi K, Uchida N, Nakane T, Kodera K, Shirahata A and Taniyama M: Decrease in serum adiponectin level due to obesity and visceral fat accumulation in children. Obes Res. 11:1072–1079. 2003. View Article : Google Scholar : PubMed/NCBI
33	Fujita K, Nishizawa H, Funahashi T, Shimomura I and Shimabukuro M: Systemic oxidative stress is associated with visceral fat accumulation and the metabolic syndrome. Circ J. 70:1437–1442. 2006. View Article : Google Scholar : PubMed/NCBI
34	Gradinaru D, Margina D, Borsa C, Ionescu C, Ilie M, Costache M, Dinischiotu A and Prada GI: Adiponectin: Possible link between metabolic stress and oxidative stress in the elderly. Aging Clin Exp Res. Sep 29–2016.(Epub ahead of print). PubMed/NCBI