Skip to main content
SpringerLink
Log in

Ion channels and transporters in adipose-derived stem cells

  • Review
  • Published:
Journal of Pharmaceutical Investigation Aims and scope Submit manuscript

Abstract

Adipose tissue-derived mesenchymal stem cells (ADSCs) can be expanded in vitro and differentiated into numerous specialized cell types because of their self-renewal and multipotential differentiation properties. Their main advantage over other tissue-derived mesenchymal stem cells is in being easily and repeatedly harvested using minimally invasive techniques with low morbidity. They have been used for tissue repair and regeneration and are currently recognized as attractive candidates for substituting tissue or organ transplantation. Ion channels and transporters are involved in various cell responses, which make them fascinating drug targets. This logic may also be applicable to ADSC and therefore, it is necessary to arrange ADSC’s ion channels and transporters information. Ion channels and transporters are involved in dynamic changes in survival, proliferation, and differentiation of ADSCs. Their protein expressions are heterogeneous among different types of stem cells. They are involved in regulating excitation genesis and impulse conduction in excitable cells and they play a role in cell proliferation, migration, and apoptosis in proliferative cells. This review aims to provide a brief overview of the expression of various ion channels and transporters in ADSCs and to discuss their functional roles in the proliferation and differentiation of ADSCs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Abbott BL (2006) ABCG2 (BCRP): a cytoprotectant in normal and malignant stem cells. Clin Adv Hematol Oncol 4(1):63–72

    PubMed  Google Scholar 

  • Abrahamse H, Hamblin MR (2017) Photomedicine and stem cells: the Janus face of photodynamic therapy (PDT) to kill cancer stem cells, and photobiomodulation (PBM) to stimulate normal stem cells, IOP Concise Physics, pp 135

  • Acosta E, Avila J, Mobasheri A, Martin-Vasallo P, Na+ (2011) K+-ATPase genes are down-regulated during adipose stem cell differentiation. Front Biosci (Elite Ed) 3:1229–1240

    Google Scholar 

  • Ang VT, Jenkins JS (1984) Neurohypophysial hormones in the adrenal medulla. J Clin Endocrinol Metab 58(4):688–691

    Article  CAS  PubMed  Google Scholar 

  • Beech DJ, Muraki K, Flemming R (2004) Non-selective cationic channels of smooth muscle and the mammalian homologues of Drosophila TRP. J Physiol 559(Pt 3):685–706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Benga G (2009) Water channel proteins (later called aquaporins) and relatives: past, present, and future. IUBMB Life 61(2):112–133

    Article  CAS  PubMed  Google Scholar 

  • Benham CD, Gunthorpe MJ, Davis JB (2003) TRPV channels as temperature sensors. Cell Calcium 33(5–6):479–487

    Article  CAS  PubMed  Google Scholar 

  • Bjorninen M, Siljander A, Pelto J, Hyttinen J, Kellomaki M, Miettinen S et al (2014) Comparison of chondroitin sulfate and hyaluronic acid doped conductive polypyrrole films for adipose stem cells. Ann Biomed Eng 42(9):1889–1900

    Article  PubMed  Google Scholar 

  • Brzoska M, Geiger H, Gauer S, Baer P (2005) Epithelial differentiation of human adipose tissue-derived adult stem cells. Biochem Biophys Res Commun 330(1):142–150

    Article  CAS  PubMed  Google Scholar 

  • Burke ZD, Thowfeequ S, Peran M, Tosh D (2007) Stem cells in the adult pancreas and liver. Biochem J 404(2):169–178

    Article  CAS  PubMed  Google Scholar 

  • Cao B, Huard J (2004) Muscle-derived stem cells. Cell Cycle 3(2):104–107

    Article  CAS  PubMed  Google Scholar 

  • Cao Y, Meng Y, Sun Z, Liao LM, Han Q, Li J et al (2005) Potential of human adipose tissue derived adult stem cells differentiate into endothelial cells. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 27(6):678–682

    CAS  PubMed  Google Scholar 

  • Chakraborthy A, Ramani P, Sherlin HJ, Premkumar P, Natesan A (2014) Antioxidant and pro-oxidant activity of vitamin C in oral environment. Indian J Dent Res 25(4):499–504

    Article  PubMed  Google Scholar 

  • Chaudhary PM, Roninson IB (1991) Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells. Cell 66(1):85–94

    Article  CAS  PubMed  Google Scholar 

  • Choi N, Shin S, Song SU, Sung JH. Minoxidil promotes hair growth through stimulation of growth factor release from adipose-derived stem cells. Int J Mol Sci 2018;19(3)

  • Dean M, Rzhetsky A, Allikmets R (2001) The human ATP-binding cassette (ABC) transporter superfamily. Genome Res 11(7):1156–1166

    Article  CAS  PubMed  Google Scholar 

  • Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315–317

    Article  CAS  PubMed  Google Scholar 

  • Forostyak O, Romanyuk N, Verkhratsky A, Sykova E, Dayanithi G (2013) Plasticity of calcium signaling cascades in human embryonic stem cell-derived neural precursors. Stem Cells Dev 22(10):1506–1521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gomes D, Agasse A, Thiebaud P, Delrot S, Geros H, Chaumont F (2009) Aquaporins are multifunctional water and solute transporters highly divergent in living organisms. Biochim Biophys Acta 1788(6):1213–1228

    Article  CAS  PubMed  Google Scholar 

  • Graziano ACE, Avola R, Pannuzzo G, Cardile V (2018) Aquaporin1 and 3 modification as a result of chondrogenic differentiation of human mesenchymal stem cell. J Cell Physiol 233(3):2279–2291

    Article  CAS  PubMed  Google Scholar 

  • Harrison FE, May JM (2009) Vitamin C function in the brain: vital role of the ascorbate transporter SVCT2. Free Radic Biol Med 46(6):719–730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu H, Li DL, Fan L, Ren J, Wang SP, Jia B et al (2010) Involvement of volume-sensitive Cl− channels in the proliferation of human subcutaneous pre-adipocytes. Clin Exp Pharmacol Physiol 37(1):29–34

    Article  PubMed  CAS  Google Scholar 

  • Hu J, Cheng D, Gao X, Bao J, Ma X, Wang H (2012) Vitamin C enhances the in vitro development of porcine pre-implantation embryos by reducing oxidative stress. Reprod Domest Anim 47(6):873–879

    Article  CAS  PubMed  Google Scholar 

  • Kaewsuwan S, Plubrukarn A, Utsintong M, Kim SH, Jeong JH, Cho JG et al (2016) Interruptin B induces brown adipocyte differentiation and glucose consumption in adipose-derived stem cells. Mol Med Rep 13(3):2078–2086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kew JNC (2010) Ion channels: from structure to function. Oxford University Press, Oxford

    Google Scholar 

  • Kim BS, Im YB, Jung SJ, Park CH, Kang SK (2012) Argonaute2 regulation for K+ channel-mediated human adipose tissue-derived stromal cells self-renewal and survival in nucleus. Stem Cells Dev 21(10):1736–1748

    Article  CAS  PubMed  Google Scholar 

  • Kim JH, Kim WK, Sung YK, Kwack MH, Song SY, Choi JS et al (2014) The molecular mechanism underlying the proliferating and preconditioning effect of vitamin C on adipose-derived stem cells. Stem Cells Dev 23(12):1364–1376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kotova PD, Sysoeva VY, Rogachevskaja OA, Bystrova MF, Kolesnikova AS, Tyurin-Kuzmin PA et al (2014) Functional expression of adrenoreceptors in mesenchymal stromal cells derived from the human adipose tissue. Biochim Biophys Acta 1843(9):1899–1908

    Article  CAS  PubMed  Google Scholar 

  • Lawrence JH, Tomaselli GF, Marban E (1993) Ion channels: structure and function. Heart Dis Stroke 2(1):75–80

    CAS  PubMed  Google Scholar 

  • Lin TM, Tsai JL, Lin SD, Lai CS, Chang CC (2005) Accelerated growth and prolonged lifespan of adipose tissue-derived human mesenchymal stem cells in a medium using reduced calcium and antioxidants. Stem Cells Dev 14(1):92–102

    Article  CAS  PubMed  Google Scholar 

  • Lindstad T, Qu S, Sikkeland J, Jin Y, Kristian A, Maelandsmo GM et al (2017) STAMP2 is required for human adipose-derived stem cell differentiation and adipocyte-facilitated prostate cancer growth in vivo. Oncotarget 8(54):91817–91827

    Article  PubMed  Google Scholar 

  • Littleton JT, Ganetzky B (2000) Ion channels and synaptic organization: analysis of the Drosophila genome. Neuron 26(1):35–43

    Article  CAS  PubMed  Google Scholar 

  • Locher KP (2009) Review. Structure and mechanism of ATP-binding cassette transporters. Philos Trans R Soc Lond B Biol Sci 364(1514):239–245

    Article  CAS  PubMed  Google Scholar 

  • Maeno S, Niki Y, Matsumoto H, Morioka H, Yatabe T, Funayama A et al (2005) The effect of calcium ion concentration on osteoblast viability, proliferation and differentiation in monolayer and 3D culture. Biomaterials 26(23):4847–4855

    Article  CAS  PubMed  Google Scholar 

  • Mellor LF, Mohiti-Asli M, Williams J, Kannan A, Dent MR, Guilak F et al (2015) Extracellular calcium modulates chondrogenic and osteogenic differentiation of human adipose-derived stem cells: a novel approach for osteochondral tissue engineering using a single stem cell source. Tissue Eng Part A 21(17–18):2323–2333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Noh S, Lee SR, Jeong YJ, Ko KS, Rhee BD, Kim N et al (2015) The direct modulatory activity of zinc toward ion channels. Integr Med Res 4(3):142–146

    Article  PubMed  PubMed Central  Google Scholar 

  • O’Conor CJ, Griffin TM, Liedtke W, Guilak F (2013) Increased susceptibility of Trpv4-deficient mice to obesity and obesity-induced osteoarthritis with very high-fat diet. Ann Rheum Dis 72(2):300–304

    Article  PubMed  CAS  Google Scholar 

  • Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee JH et al (2003) Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr 22(1):18–35

    Article  CAS  PubMed  Google Scholar 

  • Park HS, Kim JH, Sun BK, Song SU, Suh W, Sung JH (2016) Hypoxia induces glucose uptake and metabolism of adiposederived stem cells. Mol Med Rep 14(5):4706–4714

    Article  CAS  PubMed  Google Scholar 

  • Pelto J, Bjorninen M, Palli A, Talvitie E, Hyttinen J, Mannerstrom B et al (2013) Novel polypyrrole-coated polylactide scaffolds enhance adipose stem cell proliferation and early osteogenic differentiation. Tissue Eng Part A 19(7–8):882–892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Penkov DN, Akopyan Zh A, Kochegura TN, Egorov AD (2016) Transcriptional control of insulin-sensitive glucose carrier Glut4 expression in adipose tissue cells. Dokl Biochem Biophys 467(1):145–149

    Article  CAS  PubMed  Google Scholar 

  • Photomedicine and Stem Cells. 2017

  • Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284(5411):143–147

    Article  CAS  PubMed  Google Scholar 

  • Poleshko AG, Volotovski ID (2016) The role of ABCG2 protein in maintenance of viability and proliferative activity of bone marrow mesenchymal stem cells under hypoxic conditions. Biofizika 61(2):321–327

    CAS  PubMed  Google Scholar 

  • Prasad M, Zachar V, Fink T, Pennisi CP (2014) Moderate hypoxia influences potassium outward currents in adipose-derived stem cells. PLoS One 9(8):e104912

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Prevarskaya N, Zhang L, Barritt G (2007) TRP channels in cancer. Biochim Biophys Acta 1772(8):937–946

    Article  CAS  PubMed  Google Scholar 

  • Resende RR, da Costa JL, Kihara AH, Adhikari A, Lorencon E (2010) Intracellular Ca2+ regulation during neuronal differentiation of murine embryonal carcinoma and mesenchymal stem cells. Stem Cells Dev 19(3):379–394

    Article  CAS  PubMed  Google Scholar 

  • Rocchi E, Khodjakov A, Volk EL, Yang CH, Litman T, Bates SE et al (2000) The product of the ABC half-transporter gene ABCG2 (BCRP/MXR/ABCP) is expressed in the plasma membrane. Biochem Biophys Res Commun 271(1):42–46

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez LV, Alfonso Z, Zhang R, Leung J, Wu B, Ignarro LJ (2006) Clonogenic multipotent stem cells in human adipose tissue differentiate into functional smooth muscle cells. Proc Natl Acad Sci USA 103(32):12167–12172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scharenberg CW, Harkey MA, Torok-Storb B (2002) The ABCG2 transporter is an efficient Hoechst 33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors. Blood 99(2):507–512

    Article  CAS  PubMed  Google Scholar 

  • Sim SW, Park TS, Kim SJ, Park BC, Weinstein DA, Lee YM et al (2018) Aberrant proliferation and differentiation of glycogen storage disease type Ib mesenchymal stem cells. FEBS Lett 592(2):162–171

    Article  CAS  PubMed  Google Scholar 

  • Song YH, Gehmert S, Sadat S, Pinkernell K, Bai X, Matthias N et al (2007) VEGF is critical for spontaneous differentiation of stem cells into cardiomyocytes. Biochem Biophys Res Commun 354(4):999–1003

    Article  CAS  PubMed  Google Scholar 

  • Sun S, Liu Y, Lipsky S, Cho M (2007) Physical manipulation of calcium oscillations facilitates osteodifferentiation of human mesenchymal stem cells. FASEB J 21(7):1472–1480

    Article  CAS  PubMed  Google Scholar 

  • Toma JG, McKenzie IA, Bagli D, Miller FD (2005) Isolation and characterization of multipotent skin-derived precursors from human skin. Stem Cells 23(6):727–737

    Article  CAS  PubMed  Google Scholar 

  • Tran TD, Zolochevska O, Figueiredo ML, Wang H, Yang LJ, Gimble JM et al (2014) Histamine-induced Ca(2)(+) signalling is mediated by TRPM4 channels in human adipose-derived stem cells. Biochem J 463(1):123–134

    Article  CAS  PubMed  Google Scholar 

  • Tran TD, Yao S, Hsu WH, Gimble JM, Bunnell BA, Cheng H (2015) Arginine vasopressin inhibits adipogenesis in human adipose-derived stem cells. Mol Cell Endocrinol 406:1–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Uzman A (2001) Molecular cell biology (4th edition). Biochem Mol Biol Educ 29(3):126–128

    Article  Google Scholar 

  • van Dijk A, Naaijkens BA, Jurgens WJ, Oerlemans R, Scheffer GL, Kassies J et al (2012) The multidrug resistance protein breast cancer resistance protein (BCRP) protects adipose-derived stem cells against ischemic damage. Cell Biol Toxicol 28(5):303–315

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Huang YY, Wang Y, Lyu P, Hamblin MR (2016) Photobiomodulation (blue and green light) encourages osteoblastic-differentiation of human adipose-derived stem cells: role of intracellular calcium and light-gated ion channels. Sci Rep 6:33719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Huang YY, Wang Y, Lyu P, Hamblin MR (2017) Photobiomodulation of human adipose-derived stem cells using 810 nm and 980 nm lasers operates via different mechanisms of action. Biochim Biophys Acta 1861(2):441–449

    Article  CAS  Google Scholar 

  • Watson H (2015) Biological membranes. Essays Biochem 59:43–69

    Article  PubMed  PubMed Central  Google Scholar 

  • Wood IS, Trayhurn P (2003) Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br J Nutr 89(1):3–9

    Article  CAS  PubMed  Google Scholar 

  • Yeh WL, Tsai CF, Chen DR (2017) Peri-foci adipose-derived stem cells promote chemoresistance in breast cancer. Stem Cell Res Ther 8(1):177

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yibchok-anun S, Abu-Basha EA, Yao CY, Panichkriangkrai W, Hsu WH (2004) The role of arginine vasopressin in diabetes-associated increase in glucagon secretion. Regul Pept 122(3):157–162

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Li M, Kang ET, Neoh KG (2016a) Electrical stimulation of adipose-derived mesenchymal stem cells in conductive scaffolds and the roles of voltage-gated ion channels. Acta Biomater 32:46–56

    Article  CAS  PubMed  Google Scholar 

  • Zhang P, Li J, Qi Y, Zou Y, Liu L, Tang X et al (2016b) Vitamin C promotes the proliferation of human adipose-derived stem cells via p53-p21 pathway. Organogenesis 12(3):143–151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zippel N, Limbach CA, Ratajski N, Urban C, Luparello C, Pansky A et al (2012) Purinergic receptors influence the differentiation of human mesenchymal stem cells. Stem Cells Dev 21(6):884–900

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. STEMORE Co. Ltd., Incheon, South Korea

    Mei Zheng & Jong-Hyuk Sung

  2. College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahakro, Yeonsu-gu, Incheon, 406-840, South Korea

    Doo-Yeong Kim & Jong-Hyuk Sung

Authors
  1. Mei Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Doo-Yeong Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jong-Hyuk Sung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jong-Hyuk Sung.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Research involving human participants and/or animals

This article does not contain any studies with human and animal subjects performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zheng, M., Kim, DY. & Sung, JH. Ion channels and transporters in adipose-derived stem cells. J. Pharm. Investig. 49, 287–294 (2019). https://doi.org/10.1007/s40005-018-00413-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40005-018-00413-z

Keywords

Search

Navigation