Abstract
The attempt of adipocyte dedifferentiation is not for fat tissue repair or regeneration, since few would like too much fat tissue in their body. Attention has been long attracted by white adipose tissue because of its reversible and great capacity for expansion, which appears to be permanent throughout adult life. Adipose tissue enlargement is the result of adipocyte hypertrophy and the recruitment and differentiation of regenerative precursors that are situated in the stromal vascular fraction. The capillary network’s development, however, is also required to guarantee adipose tissue remodeling. Indeed, a decisive link exists between the capillary network and adipose cells. Endothelial cells and adipocytes own a common progenitor. Such adipose lineage cells take part in vascular-like structure and enhance the neovascularization reaction in ischemic tissue. Adipocytes are ideal cell type for mesoderm-derived tissue repair and regeneration. The dedifferentiated fat cells have the ability to redifferentiate into osteoblasts, chondrocytes, smooth muscle cells, and neurons. Besides, the dedifferentiated fat cells show the advantages of easy accessibility, which could be a wonderful substitute of mesenchymal stem cells. The author has summarized relevant knowledges of dedifferentiated fat cells’ gene expression, underlying signaling mechanism and multilineage differentiation potentials. The application of these potentials could shed light on osteogenesis, chondrogenesis, angiogenesis, and neurogenesis.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Hausman GJ, Dodson MV. Stromal vascular cells and adipogenesis: cells within adipose depots regulate adipogenesis. J Genomics. 2013;1:56–66.
Otto TC, Lane MD. Adipose development: from stem cell to adipocyte. Crit Rev Biochem Mol Biol. 2005;40(4):229–42.
Laflamme MA, Murry CE. Regenerating the heart. Nat Biotechnol. 2005;23(7):845–56.
Dodson MV, Fernyhough ME, Vierck JL, Hausman GJ. Adipocytes may not be a terminally differentiated cell type: implications for animal production. Anim Sci. 2005;80:239–40.
Dodson MV, Hausman GJ, Guan L, Du M, Jiang Z. Potential impact of mature adipocyte dedifferentiation in terms of cell numbers. Int J Stem Cells. 2011;4(1):76–8.
Fernyhough ME, Vierck JL, Dodson MV. Assessing a non-traditional view of adipogenesis: adipocyte dedifferentiation--mountains or molehills? Cells Tissues Organs. 2006;182(3–4):226–8.
Fernyhough ME, Hausman GJ, Guan LL, Okine E, Moore SS, Dodson MV. Mature adipocytes may be a source of stem cells for tissue engineering. Biochem Biophys Res Commun. 2008;368(3):455–7.
Sugihara H, Yonemitsu N, Miyabara S, Yun K. Primary cultures of unilocular fat cells: characteristics of growth in vitro and changes in differentiation properties. Differentiation. 1986;31(1):42–9.
Sugihara H, Yonemitsu N, Miyabara S, Toda S. Proliferation of unilocular fat cells in the primary culture. J Lipid Res. 1987;28(9):1038–45.
Vierck JL, McNamara JP, Dodson MV. Proliferation and differentiation of progeny of ovine unilocular fat cells (adipofibroblasts). In Vitro Cell Dev Biol Anim. 1996;32(9):564–72.
Himms-Hagen J, Melnyk A, Zingaretti MC, Ceresi E, Barbatelli G, Cinti S. Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes. Am J Physiol Cell Physiol. 2000;279(3):C670–81.
Matsumoto T, Kano K, Kondo D, Fukuda N, Iribe Y, Tanaka N, Matsubara Y, Sakuma T, Satomi A, Otaki M, Ryu J, Mugishima H. Mature adipocyte-derived dedifferentiated fat cells exhibit multilineage potential. J Cell Physiol. 2008;215(1):210–22.
Poloni A, Maurizi G, Leoni P, Serrani F, Mancini S, Frontini A, Zingaretti MC, Siquini W, Sarzani R, Cinti S. Human dedifferentiated adipocytes show similar properties to bone marrow-derived mesenchymal stem cells. Stem Cells. 2012;30(5):965–74.
Ohta Y, Takenaga M, Tokura Y, Hamaguchi A, Matsumoto T, Kano K, Mugishima H, Okano H, Igarashi R. Mature adipocyte-derived cells, dedifferentiated fat cells (DFAT), promoted functional recovery from spinal cord injury-induced motor dysfunction in rats. Cell Transplant. 2008;17(8):877–86.
Jumabay M, Abdmaulen R, Ly A, Cubberly MR, Shahmirian LJ, Heydarkhan-Hagvall S, Dumesic DA, Yao Y, Bostrom KI. Pluripotent stem cells derived from mouse and human white mature adipocytes. Stem Cells Transl Med. 2014;3(2):161–71.
Nobusue H, Endo T, Kano K. Establishment of a preadipocyte cell line derived from mature adipocytes of GFP transgenic mice and formation of adipose tissue. Cell Tissue Res. 2008;332(3):435–46.
Nobusue H, Kano K. Establishment and characteristics of porcine preadipocyte cell lines derived from mature adipocytes. J Cell Biochem. 2010;109(3):542–52.
Wei S, Du M, Jiang Z, Duarte MS, Fernyhough-Culver M, Albrecht E, Will K, Zan L, Hausman GJ, Elabd EM, Bergen WG, Basu U, Dodson MV. Bovine dedifferentiated adipose tissue (DFAT) cells: DFAT cell isolation. Adipocytes. 2013;2(3):148–59.
Wei S, Duarte MS, Du M, Paulino PVR, Jiang Z, Albrecht E, Fernyhough-Culver M, Zan L, Hausman GJ, Dodson MV. Bovine mature adipocytes readily return to a proliferative state. Tissue Cell. 2012;44(6):385–90.
Kono S, Kazama T, Kano K, Harada K, Uechi M, Matsumoto T. Phenotypic and functional properties of feline dedifferentiated fat cells and adipose-derived stem cells. Vet J. 2014;199(1):88–96.
Tholpady SS, Aojanepong C, Llull R, Jeong JH, Mason AC, Futrell JW, Ogle RC, Katz AJ. The cellular plasticity of human adipocytes. Ann Plast Surg. 2005;54(6):651–6.
Hildner F, Concaro S, Peterbauer A, Wolbank S, Danzer M, Lindahl A, Gatenholm P, Redl H, van Griensven M. Human adipose-derived stem cells contribute to chondrogenesis in coculture with human articular chondrocytes. Tissue Eng Part A. 2009;15(12):3961–9.
Kazama T, Fujie M, Endo T, Kano K. Mature adipocyte-derived dedifferentiated fat cells can transdifferentiate into skeletal myocytes in vitro. Biochem Biophys Res Commun. 2008;377(3):780–5.
Jumabay M, Matsumoto T, Yokoyama S, Kano K, Kusumi Y, Masuko T, Mitsumata M, Saito S, Hirayama A, Mugishima H, Fukuda N. Dedifferentiated fat cells convert to cardiomyocyte phenotype and repair infarcted cardiac tissue in rats. J Mol Cell Cardiol. 2009;47(5):565–75.
Jumabay M, Zhang R, Yao Y, Goldhaber JI, Bostrom KI. Spontaneously beating cardiomyocytes derived from white mature adipocytes. Cardiovasc Res. 2010;85(1):17–27.
Sakuma T, Matsumoto T, Kano K, Fukuda N, Obinata D, Yamaguchi K, Yoshida T, Takahashi S, Mugishima H. Mature, adipocyte derived, dedifferentiated fat cells can differentiate into smooth muscle-like cells and contribute to bladder tissue regeneration. J Urol. 2009;182(1):355–65.
Poloni A, Maurizi G, Anastasi S, Mondini E, Mattiucci D, Discepoli G, Tiberi F, Mancini S, Partelli S, Maurizi A, Cinti S, Olivieri A, Leoni P. Plasticity of human dedifferentiated adipocytes toward endothelial cells. Exp Hematol. 2015;43(2):137–46.
Jumabay M, Abdmaulen R, Urs S, Heydarkhan-Hagvall S, Chazenbalk GD, Jordan MC, Roos KP, Yao Y, Bostrom KI. Endothelial differentiation in multipotent cells derived from mouse and human white mature adipocytes. J Mol Cell Cardiol. 2012;53(6):790–800.
Shimizu Y, Sato S. In vitro study on regeneration of periodontal tissue microvasculature using human dedifferentiated fat cells. J Periodontol. 2015;86(1):129–36.
Song N, Kou L, Lu XW, Sugawara A, Shimizu Y, Wu MK, Du L, Wang H, Sato S, Shen JF. The perivascular phenotype and behaviors of dedifferentiated cells derived from human mature adipocytes. Biochem Biophys Res Commun. 2015;457(3):479–84.
Poloni A, Maurizi G, Foia F, Mondini E, Mattiucci D, Ambrogini P, Lattanzi D, Mancini S, Falconi M, Cinti S, Olivieri A, Leoni P. Glial-like differentiation potential of human mature adipocytes. J Mol Neurosci. 2015;55(1):91–8.
Oki Y, Watanabe S, Endo T, Kano K. Mature adipocyte-derived dedifferentiated fat cells can trans-differentiate into osteoblasts in vitro and in vivo only by all-trans retinoic acid. Cell Struct Funct. 2008;33(2):211–22.
Kikuta S, Tanaka N, Kazama T, Kazama M, Kano K, Ryu J, Tokuhashi Y, Matsumoto T. Osteogenic effects of dedifferentiated fat cell transplantation in rabbit models of bone defect and ovariectomy-induced osteoporosis. Tissue Eng Part A. 2013;19(15–16):1792–802.
Kishimoto N, Momota Y, Hashimoto Y, Ando K, Omasa T, Kotani J. Dedifferentiated fat cells differentiate into osteoblasts in titanium fiber mesh. Cytotechnology. 2013;65(1):15–22.
Shirakata Y, Nakamura T, Shinohara Y, Taniyama K, Sakoda K, Yoshimoto T, Noguchi K. An exploratory study on the efficacy of rat dedifferentiated fat cells (rDFATs) with a poly lactic-co-glycolic acid/hydroxylapatite (PLGA/HA) composite for bone formation in a rat calvarial defect model. J Mater Sci Mater Med. 2014;25(3):899–908.
Sugawara A, Sato S. Application of dedifferentiated fat cells for periodontal tissue regeneration. Hum Cell. 2014;27(1):12–21.
Obinata D, Matsumoto T, Ikado Y, Sakuma T, Kano K, Fukuda N, Yamaguchi K, Mugishima H, Takahashi S. Transplantation of mature adipocyte-derived dedifferentiated fat (DFAT) cells improves urethral sphincter contractility in a rat model. Int J Urol. 2011;18(12):827–34.
Soejima K, Kashimura T, Asami T, Kazama T, Matsumoto T, Nakazawa H. Effects of mature adipocyte-derived dedifferentiated fat (DFAT) cells on generation and vascularisation of dermis-like tissue after artificial dermis grafting. J Plast Surg Hand Surg. 2015;49(1):25–31.
Matsumine H, Takeuchi Y, Sasaki R, Kazama T, Kano K, Matsumoto T, Sakurai H, Miyata M, Yamato M. Adipocyte-derived and dedifferentiated fat cells promoting facial nerve regeneration in a rat model. Plast Reconstr Surg. 2014;134(4):686–97.
Yamada H, Ito D, Oki Y, Kitagawa M, Matsumoto T, Watari T, Kano K. Transplantation of mature adipocyte-derived dedifferentiated fat cells promotes locomotor functional recovery by remyelination and glial scar reduction after spinal cord injury in mice. Biochem Biophys Res Commun. 2014;454(2):341–6.
Fernyhough ME, Vierck JL, Hausman GJ, Mir PS, Okine EK, Dodson MV. Primary adipocyte culture: adipocyte purification methods may lead to a new understanding of adipose tissue growth and development. Cytotechnology. 2004;46(2–3):163–72.
Ono H, Oki Y, Bono H, Kano K. Gene expression profiling in multipotent DFAT cells derived from mature adipocytes. Biochem Biophys Res Commun. 2011;407(3):562–7.
Kou L, Lu XW, Wu MK, Wang H, Zhang YJ, Sato S, Shen JF. The phenotype and tissue-specific nature of multipotent cells derived from human mature adipocytes. Biochem Biophys Res Commun. 2014;444(4):543–8.
Gao Q, Zhao L, Song Z, Yang G. Expression pattern of embryonic stem cell markers in DFAT cells and ADSCs. Mol Biol Rep. 2012;39(5):5791–804.
Festy F, Hoareau L, Bes-Houtmann S, Pequin AM, Gonthier MP, Munstun A, Hoarau JJ, Cesari M, Roche R. Surface protein expression between human adipose tissue-derived stromal cells and mature adipocytes. Histochem Cell Biol. 2005;124(2):113–21.
Zhu JG, Xia L, Ji CB, Zhang CM, Zhu GZ, Shi CM, Chen L, Qin DN, Guo XR. Differential DNA methylation status between human preadipocytes and mature adipocytes. Cell Biochem Biophys. 2012;63(1):1–15.
Gustafson B, Smith U. Activation of canonical wingless-type MMTV integration site family (Wnt) signaling in mature adipocytes increases beta-catenin levels and leads to cell dedifferentiation and insulin resistance. J Biol Chem. 2010;285(18):14031–41.
Krishnan V, Bryant HU, Macdougald OA. Regulation of bone mass by Wnt signaling. J Clin Invest. 2006;116(5):1202–9.
Liu J, Wang H, Zuo Y, Farmer SR. Functional interaction between peroxisome proliferator-activated receptor gamma and beta-catenin. Mol Cell Biol. 2006;26(15):5827–37.
Song HY, Kim MR, Lee MJ, Jeon ES, Bae YC, Jung JS, Kim JH. Oncostatin M decreases adiponectin expression and induces dedifferentiation of adipocytes by JAK3- and MEK-dependent pathways. Int J Biochem Cell Biol. 2007;39(2):439–49.
Tanaka M, Miyajima A, Oncostatin M. A multifunctional cytokine. Rev Physiol Biochem Pharmacol. 2003;149:39–52.
Kubin T, Poling J, Kostin S, Gajawada P, Hein S, Rees W, Wietelmann A, Tanaka M, Lorchner H, Schimanski S, Szibor M, Warnecke H, Braun T. Oncostatin M is a major mediator of cardiomyocyte dedifferentiation and remodeling. Cell Stem Cell. 2011;9(5):420–32.
Yagi K, Kondo D, Okazaki Y, Kano K. A novel preadipocyte cell line established from mouse adult mature adipocytes. Biochem Biophys Res Commun. 2004;321(4):967–74.
Nakamura T, Shinohara Y, Momozaki S, Yoshimoto T, Noguchi K. Co-stimulation with bone morphogenetic protein-9 and FK506 induces remarkable osteoblastic differentiation in rat dedifferentiated fat cells. Biochem Biophys Res Commun. 2013;440(2):289–94.
Brunk BP, Goldhamer DJ, Emerson CP Jr. Regulated demethylation of the myoD distal enhancer during skeletal myogenesis. Dev Biol. 1996;177(2):490–503.
Wakitani S, Saito T, Caplan AI. Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine. Muscle Nerve. 1995;18(12):1417–26.
Yuasa S, Itabashi Y, Koshimizu U, Tanaka T, Sugimura K, Kinoshita M, Hattori F, Fukami S, Shimazaki T, Ogawa S, Okano H, Fukuda K. Transient inhibition of BMP signaling by Noggin induces cardiomyocyte differentiation of mouse embryonic stem cells. Nat Biotechnol. 2005;23(5):607–11.
Naito AT, Shiojima I, Akazawa H, Hidaka K, Morisaki T, Kikuchi A, Komuro I. Developmental stage-specific biphasic roles of Wnt/beta-catenin signaling in cardiomyogenesis and hematopoiesis. Proc Natl Acad Sci U S A. 2006;103(52):19812–7.
Planat-Benard V, Silvestre JS, Cousin B, Andre M, Nibbelink M, Tamarat R, Clergue M, Manneville C, Saillan-Barreau C, Duriez M, Tedgui A, Levy B, Penicaud L, Casteilla L. Plasticity of human adipose lineage cells toward endothelial cells: physiological and therapeutic perspectives. Circulation. 2004;109(5):656–63.
Yao Y, Jumabay M, Wang A, Bostrom KI. Matrix Gla protein deficiency causes arteriovenous malformations in mice. J Clin Invest. 2011;121(8):2993–3004.
Bergers G, Song S. The role of pericytes in blood-vessel formation and maintenance. Neuro-Oncology. 2005;7(4):452–64.
Franco M, Roswall P, Cortez E, Hanahan D, Pietras K. Pericytes promote endothelial cell survival through induction of autocrine VEGF-A signaling and Bcl-w expression. Blood. 2011;118(10):2906–17.
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143–7.
Chamberlain G, Fox J, Ashton B, Middleton J. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells. 2007;25(11):2739–49.
Katz AJ, Tholpady A, Tholpady SS, Shang H, Ogle RC. Cell surface and transcriptional characterization of human adipose-derived adherent stromal (hADAS) cells. Stem Cells. 2005;23(3):412–23.
Rigotti G, Marchi A, Sbarbati A. Adipose-derived mesenchymal stem cells: past, present, and future. Aesthet Plast Surg. 2009;33(3):271–3.
Mitchell JB, McIntosh K, Zvonic S, Garrett S, Floyd ZE, Kloster A, Di Halvorsen Y, Storms RW, Goh B, Kilroy G, Wu X, Gimble JM. Immunophenotype of human adipose-derived cells: temporal changes in stromal-associated and stem cell-associated markers. Stem Cells. 2006;24(2):376–85.
Crago AM, Singer S. Clinical and molecular approaches to well differentiated and dedifferentiated liposarcoma. Curr Opin Oncol. 2011;23(4):373–8.
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer-Verlag GmbH Germany
About this chapter
Cite this chapter
Fu, X., Zhao, A., Hu, T. (2018). Dedifferentiation and Adipose Tissue. In: Cellular Dedifferentiation and Regenerative Medicine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-56179-9_9
Download citation
DOI: https://doi.org/10.1007/978-3-662-56179-9_9
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-662-56177-5
Online ISBN: 978-3-662-56179-9
eBook Packages: MedicineMedicine (R0)