Skip to main content
Top
Published in: BMC Complementary Medicine and Therapies 1/2017

Open Access 01-12-2017 | Research article

High–efficiency generation of induced pluripotent stem cells from human foreskin fibroblast cells using the Sagunja-tang herbal formula

Authors: Ki Mo Kim, Deok Rim Heo, Joo Young Lee, Chang-Seob Seo, Sun-Ku Chung

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

Login to get access

Abstract

Background

Sagunja-Tang (SGT-4) is a traditional herbal formula in Korean medicine that is used to treat anti-metabolic syndrome, and has antioxidant activity. In this study, we evaluated the effects of SGT-4 on the formation efficiency of induced pluripotent stem cells (iPSCs) from human foreskin fibroblasts (HFFs) by four reprogramming transcription factors: Oct4, Sox2, KIf4, and c-Myc (OSKM).

Methods

SGT-4 contained four different herbal medicines that are composed of Ginseng Radix, Glycyrrhizae Radix et Rhizoma, Atractylodis Rhizoma Alba, and Poria Sclerotium. The composition of SGT-4 was analyzed by high-performance liquid chromatography (HPLC). HFFs were transfected with episomal vectors contained by four OSKM. Western blotting, RT-PCR, immunofluroescence, and in vitro differentiation were used to assess the pluripotency of the iPSC cells.

Results

SGT-4 exhibited antioxidant activity against the generation of intracellular reactive oxygen species (ROS) as well as promoted the activation of superoxide dismutase 1 (SOD1), catalase, gluthathione peroxidase 1 (GPX1), and glutathione (GSH). Moreover, the ATP level was not significantly fluctuated depending on the concentration of SGT-4 in the hiPSCs.

Conclusion

Our results indicate that the SGT-4, herbal formula significantly increases the efficiency of human iPSC generation via the transcription factors (Oct4, Sox2, KIf4, and c-Myc).
Literature
1.
go back to reference Fung B, Ng JH, Heng JC, Ng HH. Molecules that promote or enhanced reprogramming of somatic cells to induced pluripotent stem cells. Cell. Stem Cell. 2009;4(4):301–12.CrossRef Fung B, Ng JH, Heng JC, Ng HH. Molecules that promote or enhanced reprogramming of somatic cells to induced pluripotent stem cells. Cell. Stem Cell. 2009;4(4):301–12.CrossRef
2.
go back to reference Huangfu D, Maehr R, Guo W, Eijkelenboom A, Snitow M, Chen AE, Melton DA. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol. 2008;26:795–7.CrossRefPubMed Huangfu D, Maehr R, Guo W, Eijkelenboom A, Snitow M, Chen AE, Melton DA. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol. 2008;26:795–7.CrossRefPubMed
4.
go back to reference Shi Y, Desponts C, Do JT, Hahm HS, Scholer HR, Ding S. Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and KIf4 with small molecule compounds. Cell. Stem Cell. 2008;6:568–74.CrossRef Shi Y, Desponts C, Do JT, Hahm HS, Scholer HR, Ding S. Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and KIf4 with small molecule compounds. Cell. Stem Cell. 2008;6:568–74.CrossRef
5.
go back to reference Shi Y, Do JT, Desponts C, Hahm HS, Scholer HR, Ding S. A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell. 2008;5:525–8.CrossRef Shi Y, Do JT, Desponts C, Hahm HS, Scholer HR, Ding S. A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell. 2008;5:525–8.CrossRef
6.
go back to reference Ware CB, Wang L, Mecham BH, Shen L, Nelson AM, Bar M, Lamba DA, Dauphin DS, Buckingham B, Askari B, Lim R, Tewari M, Gartler SM, Issa JP, Pavlidis P, Duan Z, Blau CA. Histone deacetylase inhibition elicits an evolutionarily conserved self-renewal program in embryonic stem cells. Cell. Stem Cell. 2009;3:359–69.CrossRef Ware CB, Wang L, Mecham BH, Shen L, Nelson AM, Bar M, Lamba DA, Dauphin DS, Buckingham B, Askari B, Lim R, Tewari M, Gartler SM, Issa JP, Pavlidis P, Duan Z, Blau CA. Histone deacetylase inhibition elicits an evolutionarily conserved self-renewal program in embryonic stem cells. Cell. Stem Cell. 2009;3:359–69.CrossRef
7.
go back to reference Newmark HL, Lupton JR, Young CW. Butyrate as a differentiating agent: pharmacokinetics, analogues and current status. Cancer Lett. 1994;1(78):1–5.CrossRef Newmark HL, Lupton JR, Young CW. Butyrate as a differentiating agent: pharmacokinetics, analogues and current status. Cancer Lett. 1994;1(78):1–5.CrossRef
8.
go back to reference Zhu S, Li W, Zhou H, Wei W, Ambasudhan R, Lin T, Kim J, Zhang K, Ding S. Reprogramming of human primary somatic cells by OCT4 and chemical compounds. Cell. Stem Cell. 2010;7(6):651–5.CrossRefPubMed Zhu S, Li W, Zhou H, Wei W, Ambasudhan R, Lin T, Kim J, Zhang K, Ding S. Reprogramming of human primary somatic cells by OCT4 and chemical compounds. Cell. Stem Cell. 2010;7(6):651–5.CrossRefPubMed
9.
go back to reference Chen CM, Lee CY, Lin PJ, Hsieh CL, Shih HC. Evaluation on the pharmacological effect of traditional Chinese medicine SiJunZiTang on stress-induced peptic ulcers. Evid Based Complement Altermat Med. 2013;2013:186076. Chen CM, Lee CY, Lin PJ, Hsieh CL, Shih HC. Evaluation on the pharmacological effect of traditional Chinese medicine SiJunZiTang on stress-induced peptic ulcers. Evid Based Complement Altermat Med. 2013;2013:186076.
10.
go back to reference Jung WY, Ryu BH, Kim JS, Yoon SH, Ryu KW. Effects of Sagunjatang and Sagunja-tang plus Mylabris phalerata in human stomach cancer cells. Korean J Intern Med. 2001;22:579–87. Jung WY, Ryu BH, Kim JS, Yoon SH, Ryu KW. Effects of Sagunjatang and Sagunja-tang plus Mylabris phalerata in human stomach cancer cells. Korean J Intern Med. 2001;22:579–87.
11.
go back to reference Kim SH, Oh S, Lee SE, Jo SK, Byun MW. Effects of Si-Wn-tang and Si-Jun-Zi-tang on survival of jejunal crypt cells and hematopoietic cells in irradiated mice. Food Sci Biotechnol. 1998;30:888–94. Kim SH, Oh S, Lee SE, Jo SK, Byun MW. Effects of Si-Wn-tang and Si-Jun-Zi-tang on survival of jejunal crypt cells and hematopoietic cells in irradiated mice. Food Sci Biotechnol. 1998;30:888–94.
12.
go back to reference Lee BR, Ann BC. The effects of Sagunjatang and Samunltang aqua-accpuncture on immune response. Korean oriental medicine. Society. 1997;18:357–74. Lee BR, Ann BC. The effects of Sagunjatang and Samunltang aqua-accpuncture on immune response. Korean oriental medicine. Society. 1997;18:357–74.
13.
go back to reference Esteban MA, Wang T, Qin B, Yang J, Qin D, Cai J, Li W, Weng Z, Chen J, Ni S, Chen K, Li Y, Liu X, Xu J, Zhang S, Li F, He W, Labuda K, Song Y, Peterbauer A, Wolbank S, Redl H, Zhong M, Cai D, Zeng L, Pei D, Vitamin C. Enhances the generation of mouse and human induced pluripotent stem cells. Cell Stem Cell. 2010;8:71–9.CrossRef Esteban MA, Wang T, Qin B, Yang J, Qin D, Cai J, Li W, Weng Z, Chen J, Ni S, Chen K, Li Y, Liu X, Xu J, Zhang S, Li F, He W, Labuda K, Song Y, Peterbauer A, Wolbank S, Redl H, Zhong M, Cai D, Zeng L, Pei D, Vitamin C. Enhances the generation of mouse and human induced pluripotent stem cells. Cell Stem Cell. 2010;8:71–9.CrossRef
14.
go back to reference Kim BH, Na KM, Oh I, Song IH, Lee YS, Shin J, Kim TY. Kurarinone regulates immune responses through regulation of the JAK/STAT and TCR-mediated signaling pathways. Biochem Pharmacol. 2013;85(8):1134–44.CrossRefPubMed Kim BH, Na KM, Oh I, Song IH, Lee YS, Shin J, Kim TY. Kurarinone regulates immune responses through regulation of the JAK/STAT and TCR-mediated signaling pathways. Biochem Pharmacol. 2013;85(8):1134–44.CrossRefPubMed
15.
go back to reference Yoo CH, Na HJ, Lee DS, Heo SC, An Y, Cha J, Choi C, Kim JH, Park JC, Cho YS. Endothelial progenitor cells from human dental pulp-derived iPS cells as a therapeutic target for ischemic vascular diseases. Biomaterials. 2013;34(33):8149–60.CrossRefPubMed Yoo CH, Na HJ, Lee DS, Heo SC, An Y, Cha J, Choi C, Kim JH, Park JC, Cho YS. Endothelial progenitor cells from human dental pulp-derived iPS cells as a therapeutic target for ischemic vascular diseases. Biomaterials. 2013;34(33):8149–60.CrossRefPubMed
16.
go back to reference Ye L, Gong J, Wang Y, Sun X. Pharmacological activities of Sijunzi decoction which are related to its antioxidant properties. Journal of Chemistry. 2014;2014:278318. Ye L, Gong J, Wang Y, Sun X. Pharmacological activities of Sijunzi decoction which are related to its antioxidant properties. Journal of Chemistry. 2014;2014:278318.
17.
go back to reference Ding J, Xu Y, Ma X, An J, Yang X, Liu Z, Lin N. Estrogenic effect of the extract of Renshen (radix ginseng) on reproductive tissues in immature mice. J Tradit Chin Med. 2015;35(4):460–7.CrossRefPubMed Ding J, Xu Y, Ma X, An J, Yang X, Liu Z, Lin N. Estrogenic effect of the extract of Renshen (radix ginseng) on reproductive tissues in immature mice. J Tradit Chin Med. 2015;35(4):460–7.CrossRefPubMed
18.
go back to reference Lee JC, Lee KY, Son YO, Choi KC, Kim J, Kim SH, Chung GH, Jang YS. Stimulating effects on mouse splenocytes of glycoproteins from the herbal medicine Atractylodes macrocephala Koidz. Phytomedicine. 2007;14(6):390–5.CrossRefPubMed Lee JC, Lee KY, Son YO, Choi KC, Kim J, Kim SH, Chung GH, Jang YS. Stimulating effects on mouse splenocytes of glycoproteins from the herbal medicine Atractylodes macrocephala Koidz. Phytomedicine. 2007;14(6):390–5.CrossRefPubMed
19.
go back to reference Chang MS, Choi MJ, Park SY, Park SK. Inhibitory effects of Hoelen extract on melanogenesis in B16/F1 melanoma cells. Phytother Res. 2010;24(9):1359–64.CrossRefPubMed Chang MS, Choi MJ, Park SY, Park SK. Inhibitory effects of Hoelen extract on melanogenesis in B16/F1 melanoma cells. Phytother Res. 2010;24(9):1359–64.CrossRefPubMed
20.
go back to reference Ruan Q, Qiao Y, Zhao Y, Xu Y, Wang M, Duan J, Wang D. Beneficial effects of Glycyrrhizae radix extract in preventing oxidative damage and extending the lifespan of Caenorhabditis Elegans. J Ethnopharmacol. 2016;117:101–10.CrossRef Ruan Q, Qiao Y, Zhao Y, Xu Y, Wang M, Duan J, Wang D. Beneficial effects of Glycyrrhizae radix extract in preventing oxidative damage and extending the lifespan of Caenorhabditis Elegans. J Ethnopharmacol. 2016;117:101–10.CrossRef
21.
go back to reference Liang W, Ge S, Yang L, Yang M, Ye Z, Yan M, Du J, Luo Z. Ginsenosides Rb1 and Rg1 promote proliferation and expression of neurotrophic factors in primary Schwann cell cultures. Brain Res. 2010;1357:19–25.CrossRefPubMed Liang W, Ge S, Yang L, Yang M, Ye Z, Yan M, Du J, Luo Z. Ginsenosides Rb1 and Rg1 promote proliferation and expression of neurotrophic factors in primary Schwann cell cultures. Brain Res. 2010;1357:19–25.CrossRefPubMed
22.
go back to reference Ji GQ, Chen RQ, Wang L. Anti-inflammatory activity of atractylenolide III through inhibition of nuclear factor-κB and mitogen-activated protein kinase pathways in mouse macrophages. Immunopharmacol Immunotoxicol. 2016;38(2):98–102.CrossRefPubMed Ji GQ, Chen RQ, Wang L. Anti-inflammatory activity of atractylenolide III through inhibition of nuclear factor-κB and mitogen-activated protein kinase pathways in mouse macrophages. Immunopharmacol Immunotoxicol. 2016;38(2):98–102.CrossRefPubMed
23.
go back to reference Kim YW, Zhao RJ, Park SJ, Lee JR, Cho IJ, Yang CH, Kim SG, Kim SC. Anti-inflammatory effects of liquiritigenin as a consequence of the inhibition of NF-kappaB-dependent iNOS and proinflammatory cytokines production. Br J Pharmacol. 2008;154(1):165–73.CrossRefPubMedPubMedCentral Kim YW, Zhao RJ, Park SJ, Lee JR, Cho IJ, Yang CH, Kim SG, Kim SC. Anti-inflammatory effects of liquiritigenin as a consequence of the inhibition of NF-kappaB-dependent iNOS and proinflammatory cytokines production. Br J Pharmacol. 2008;154(1):165–73.CrossRefPubMedPubMedCentral
24.
go back to reference Kiratipaiboon C, Tengamnuay P, Chanvorachote P. Glycyrrhizic acid attenuates stem cell-like phenotypes of human dermal papilla cells. Phytomedicine. 2015;22(14):1269–78.CrossRefPubMed Kiratipaiboon C, Tengamnuay P, Chanvorachote P. Glycyrrhizic acid attenuates stem cell-like phenotypes of human dermal papilla cells. Phytomedicine. 2015;22(14):1269–78.CrossRefPubMed
25.
go back to reference Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861–72.CrossRefPubMed Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861–72.CrossRefPubMed
26.
go back to reference Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–76.CrossRefPubMed Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–76.CrossRefPubMed
27.
go back to reference Li HY, Chien Y, Chen YJ, Chen SF, Chang YL, Chiang CH, Jeng SY, Chang CM, Wang ML, Chen LK, Hung SI, Huo TI, Lee SD, Chiou SH. Reprogramming induced pluripotent stem cells in the absence of c-Myc for differentiation into hepatocytes-like cells. Biomaterials. 2011;32(26):5994–6005.CrossRefPubMed Li HY, Chien Y, Chen YJ, Chen SF, Chang YL, Chiang CH, Jeng SY, Chang CM, Wang ML, Chen LK, Hung SI, Huo TI, Lee SD, Chiou SH. Reprogramming induced pluripotent stem cells in the absence of c-Myc for differentiation into hepatocytes-like cells. Biomaterials. 2011;32(26):5994–6005.CrossRefPubMed
28.
go back to reference Ito K, Hirao A, Arai F, Takubo K, Matsuoka S, Miyamoto K, Ohmura M, Naka K, Hosokawa K, Ikeda Y, Suda T. Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med. 2006;12(4):446–51.CrossRefPubMed Ito K, Hirao A, Arai F, Takubo K, Matsuoka S, Miyamoto K, Ohmura M, Naka K, Hosokawa K, Ikeda Y, Suda T. Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med. 2006;12(4):446–51.CrossRefPubMed
29.
go back to reference Saw CL, Yang AY, Cheng DC, Boyanapalli SS, ZY S, Khor TO, Gao S, Wang J, Jiang ZH, Kong AN. Pharmacodynamics of ginsenosides: antioxidant activities, activation of Nrf2, and potential synergistic effects of combinations. Chem Res Toxicol. 2012;25(8):1574–80.CrossRefPubMed Saw CL, Yang AY, Cheng DC, Boyanapalli SS, ZY S, Khor TO, Gao S, Wang J, Jiang ZH, Kong AN. Pharmacodynamics of ginsenosides: antioxidant activities, activation of Nrf2, and potential synergistic effects of combinations. Chem Res Toxicol. 2012;25(8):1574–80.CrossRefPubMed
30.
go back to reference Lee KJ, YC O, Cho WK, Ma JY. Antioxidant and anti-inflammatory activity determination of one hundred kinds of pure chemical compounds using offline and online screening HPLC assay. Evid Based Complement Alternat Med. 2015;2015:165457.PubMedPubMedCentral Lee KJ, YC O, Cho WK, Ma JY. Antioxidant and anti-inflammatory activity determination of one hundred kinds of pure chemical compounds using offline and online screening HPLC assay. Evid Based Complement Alternat Med. 2015;2015:165457.PubMedPubMedCentral
31.
go back to reference Choi EM, Suh KS, Lee YS. Liquiritigenin restores osteoblast damage through regulating oxidative stress and mitochondrial dysfunction. Phytother Res. 2014;28(6):880–6.CrossRefPubMed Choi EM, Suh KS, Lee YS. Liquiritigenin restores osteoblast damage through regulating oxidative stress and mitochondrial dysfunction. Phytother Res. 2014;28(6):880–6.CrossRefPubMed
32.
go back to reference Guan Y1, Li FF, Hong L, Yan XF, Tan GL, He JS, Dong XW, Bao MJ, Xie QM. Protective effects of liquiritin apioside on cigarette smoke-induced lung epithelial cell injury. Fundam Clin Phamacol. 2012;26(4):473–83.CrossRef Guan Y1, Li FF, Hong L, Yan XF, Tan GL, He JS, Dong XW, Bao MJ, Xie QM. Protective effects of liquiritin apioside on cigarette smoke-induced lung epithelial cell injury. Fundam Clin Phamacol. 2012;26(4):473–83.CrossRef
33.
go back to reference Sun YX1, Tang Y, AL W, Liu T, Dai XL, Zheng QS, Wang ZB. Neuroprotective effect of liquiritin against focal cerebral ischemia/reperfusion in mice via its antioxidant and antiapoptosis properties. J Asian Nat Prod Res. 2010;12(12):1051–60.CrossRefPubMed Sun YX1, Tang Y, AL W, Liu T, Dai XL, Zheng QS, Wang ZB. Neuroprotective effect of liquiritin against focal cerebral ischemia/reperfusion in mice via its antioxidant and antiapoptosis properties. J Asian Nat Prod Res. 2010;12(12):1051–60.CrossRefPubMed
34.
go back to reference Li XL, Zhou AG, Zhang L, Chen WJ. Antioxidant status and immune activity of glycyrrhizin in allergic rhinitis mice. Int J Mol Sci. 2011;12(2):905–16.CrossRefPubMedPubMedCentral Li XL, Zhou AG, Zhang L, Chen WJ. Antioxidant status and immune activity of glycyrrhizin in allergic rhinitis mice. Int J Mol Sci. 2011;12(2):905–16.CrossRefPubMedPubMedCentral
Metadata
Title
High–efficiency generation of induced pluripotent stem cells from human foreskin fibroblast cells using the Sagunja-tang herbal formula
Authors
Ki Mo Kim
Deok Rim Heo
Joo Young Lee
Chang-Seob Seo
Sun-Ku Chung
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-017-2043-2

Other articles of this Issue 1/2017

BMC Complementary Medicine and Therapies 1/2017 Go to the issue