Characterization of human adipose tissue derived adult multipotent precursor cells

CHARACTERIZATION OF HUMAN ADIPOSE DERIVED ADULT MULTIPOTENT PRECURSOR CELLS LEONG TAI WEI DAVID NATIONAL UNIVERSITY OF SINGAPORE 2006 i CHARACTERIZATION OF HUMAN ADIPOSE DERIVED ADULT MULTIPOTENT PRECURSOR CELLS LEONG TAI WEI DAVID (Bachelor of Chemical Engineering, Hons) A THESIS SUBMITTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY DEPARTMENT OF BIOLOGICAL SCIENCES NATIONAL UNIVERSITY OF SINGAPORE 2006 ii PREFACE This thesis is submitted for the degree of Doctorate of Philosophy in the Department of Biological Sciences at the National University of Singapore No part of this thesis has been submitted for any other degree or equivalent to another university or institution All the work in this thesis is original unless references are made to other works Parts of this thesis had been published or presented in the following: International Refereed Journal Publications Cover pages of some of the following papers are found in the appendix Leong TW, Chew FT, Hutmacher DW Isolating bone marrow stem cells using sieve technology Stem Cells 2004; 22:1123-1125 *Ng KW, *Leong DT, Hutmacher DW The challenge to measure cell proliferation in three dimensions Tissue Engineering 2005; 11:182-191 Leong DT, Hutmacher DW, Chew FT, Lim TC Viability and adipogenic potential of human adipose tissue processed cell population obtained from pump-assisted and syringe-assisted liposuction Journal of Dermatological Science J Dermatol Sci 2005 37:169-176 Leong DT, Khor WM, Chew FT, Lim TC, Hutmacher DW Characterization of osteogenically induced adipose tissue derived precursor cells in 2-dimensional and 3-Dimensional environments Cells Tissues Organs 2006; 182(1):1-11 Leong DT, Abraham MC, Rath SN, Lim T-C, Chew FT and Hutmacher DW Investigating the effects of preinduction on human adipose derived precursor cells in an athymic rat model Differentiation In press iii Leong DT et al Absolute quantification of gene expression with real time PCR Biomaterials 2007; 28(2):203-210 *Gupta A, *Leong DT, Bai HF, SB Singh, Chew FT, Hutmacher DW The combined action of 1α, 25–dihydroxyvitamin D3, β–glycerophosphate and ascorbic acid is essential for the osteo – maturation of adipose derived stem cells Manuscript under preparation Leong DT, Hutmacher DW, Chew FT Genome wide gene expression revealed activating transcription factor (ATF5) to be responsible for maintaining stemness in adipose derived stem cells Manuscript under prep * contributed equally Book Chapters Hutmacher DW, Leong DT, Chen Fulin Polysaccharides in Tissue Engineering Applications, Handbook of Carbohydrate Engineering In press Intellectual Competition Finalist in Tan Kah Kee Young Inventors Awards 04 Making bone from fat International and Local Conferences Presentations and Awards Poster Presentation Preliminary studies on human adipose derived stem cells obtained from pump- assisted liposuction 4th Sino-Singapore Conference on Biotechnology, National University of Singapore, Singapore, November 11-13th, 2003 Leong TW, Chew FT, Hutmacher DW, Lim TC Oral Presentation Preliminary studies on human adipose derived stem cells obtained from pump- assisted liposuction 2nd prize for 8th Biological Sciences Graduate Congress, National University of Singapore, iv Singapore, December 3-5th, 2003 Leong TW, Chew FT, Hutmacher DW, Lim TC Oral Presentation Osteogenesis of human adipose derived stem cells The Asian Surgical Association - 14th Biennial Congress & Scientific Meeting, Kota Kinabalu, Malaysia December 4-6 2003 Leong TW, Chew FT, Hutmacher DW, Lim TC Poster Presentation: Viability of human adipose tissue stem cells from pump- vs syringe-assisted liposuction The Asian Surgical Association 14th Biennial Congress & Scientific Meeting, Kota Kinabalu, Malaysia December 4-6 2003 Leong TW, Chew FT, Hutmacher DW, Lim TC Poster Presentation The behavior of human adipose tissue derived precursor scaffolds cells Tissue seeded on Engineering polycaprolactone-tricalcium Society International, phosphate th Annual International Conference and Exposition, Orlando Florida, United States of America December 10-13, 2003 Leong TW, Khor WM, Chew FT, Hutmacher DW Poster Presentation Osteoprogenitor Cells induced from Adipose derived Mesenchymal Cells 8th National University of Singapore-National University Hospital Annual Meeting, October 7-8, 2004 Lim TC, Leong TW, Chew FT, Hutmacher DW Poster Presentation In vivo characterization of adipose derived osteoprogenitors within polycaprolactone-tricalcium phosphate scaffolds Regenerate 2005, June 1-3 2005, Atlanta Georgia Leong TW, Lim TC, Chew FT, Hutmacher DW v Acknowledgements “Therefore, since we are surrounded by such a great cloud of witnesses, let us throw off everything that hinders …, and let us run with perseverance the race marked out for us.” Hebrews Chapter 12, verse 1, The Holy Bible This thesis and its corresponding research work was a race, a race that would have been impossible for me to finish if not for the people that God had placed in my life I would like to thank them with my deepest gratitude Prof Chew Fook Tim, I will always remember how you believed in a stranger to the field of biology I hope that the many life lessons you have passed down to me had been and would continue to be useful to me Thank you for teaching me some skills that would ensure that I survived in this competitive arena Thank you for these many years of patience and huge funding for my experiments I hope that I would be as good as you, or even better, in research work, as you have once so expressed Thank you for making this experience fondly memorable Prof Dietmar Hutmacher, you are a well-spring of innovative ideas I hope that some of your creativity had rubbed off on me Thank you for looking out for me and nurturing me Thank you for your encouraging support to listen to my crazy ideas and actually funding some of them You have taught me so much over these four years I know that I will be able to give to my students in the future just as you have given to me Thank you Prof Lim Thiam Chye, many thanks for providing us with the adipose tissues Without which, it would be impossible for me to work Many thanks for giving your clinical inputs in my project To my good friends in TE laboratory, Kee Woei, Mohan, Suman and Amy Thanks for the many hours of tea sessions discussing our ideas and aspirations I will always treasure those times we had Kee Woei thank you for teaching me at the beginning of my thesis work It would not be as smooth if not for your help To my colleagues in TE laboratory, many thanks for your help over these four years Last but certainly not least, to the dearest people in my life, my wife, Shirley Ting – you are my light at the end of the long tunnel Thank you for your long-suffering patience I would never have made it without your constant encouragement Thank you love and my mom, Teo Siok Lew who never failed to support me in what I love to Thank you for teaching me perseverance in my growing up years Thank you mom Both of you share the degree with me Thank you for your support, sacrifice, patience and love during this period I love you This thesis is dedicated to the memory of my late father, Leong Fook Wing Above all, to God be the glory David Leong July 31, 2006 vi Table of Contents Page Preface iii Acknowledgements vi Table of Contents vii Summary x List of Tables xii List of Figures xiii Chapter – Introduction 1.1 Background 1.1.1 Clinical need requiring bone healing or regenerative intervention 1.1.2 The use of stem cells in regeneration of bone 1-1 1-1 1-2 Chapter – Literature Review 2.1 Description of the adipose tissue 2.2 Adipose tissue – a possible alternative to bone marrow as a source of adult mesenchymal stem cells 2.3 Adult mesenchymal stem cells or precursor cell populations 2-1 2-3 2-4 2.3.1 ADSC characteristics 2-5 2.3.2 Cell Surface Characterization 2-6 2.3.3 General information on ADSC 2-7 2.3.4 Specific differentiation capacity of ADSC 2-8 2.4 Scaffolds based bone engineering 2-12 2.5 Other potential applications in regenerative medicine 2-16 2.6 Gene delivery vehicles 2-17 vii Chapter – Research Program 3.1 Overview 3-1 3.2 Four study phases 3-2 3.2.1 Phase I: Procurement of adipose tissue and their viability (Chapter 5) 3.2.2 Phase II: Characterization of ADSC in culture plastic and polycaprolactone environments (Chapter and Chapter 7) 3.2.3 Phase III: Characterization of ADSC in in vivo environments (Chapter 8) 3.2.4 Phase IV: Genome-wide transcriptome analysis of ADSC under induction gave insights into differentiation behavior of ADSC (Chapter 9) 3-2 3-3 3-3 3-5 Chapter – General Materials and Methods Chapter – Viability and adipogenic potential of human adipose tissue derived stem cells isolated from tissue aspirated with a vacuum pump or syringe 5.1 Chapter Abstract 5-1 5.2 Introduction 5-2 5.3 Specific Materials And Methods 5-4 5.4 Results 5-6 5.5 Discussion 5-12 5.6 Conclusions 5-15 Chapter – The combined action of 1,25–dihydroxyvitamin D3, β– glycerophosphate and ascorbic acid was essential for the osteogenic induction of ADSC 6.1 Chapter Abstract 6-1 6.2 Introduction 6-3 6.3 Specific Materials And Methods 6-6 6.4 Results 6-7 6.5 Discussion 6-16 6.6 Conclusions 6-18 viii Chapter – Characterization of osteogenically induced adipose tissue derived precursor cells in 2D and 3D environments 7.1 Chapter Abstract 7-1 7.2 Introduction 7-2 7.3 Specific Materials And Methods 7-4 7.4 Results 7-8 7.5 Discussion 7-17 7.6 Conclusion 7-23 Chapter – Investigating the effects of preinduction on human adipose derived precursor cells in an athymic rat model 8.1 Chapter Abstract 8-1 8.2 Introduction 8-2 8.3 Specific Materials And Methods 8-5 8.4 Results 8-9 8.5 Discussion 8-21 8.6 Conclusion 8-24 Chapter – Genome wide analysis revealed ATF5 as potential transcription factor for downstream expression of a stemness gene in adipose derived stem cells 9.1 Chapter Abstract 9-1 9.2 Introduction 9-2 9.3 Specific Materials And Methods 9-7 9.4 Results And Discussion 9-13 9.5 Conclusion 9-29 Chapter 10 – Conclusions and Future Work 10.1 Summary Of Work 10-1 10.2 Further Work 10-5 Chapter 11 – References Chapter 12 – Appendix ix Summary of Thesis This thesis was motivated by the hypothesis that there is a subpopulation of cells in human adipose tissue which possesses multipotential differentiation properties for applications in regenerative medicine applications A sub-population of cells termed by Zuk et al (2002) as “adipose derived stem cells” (ADSC) adhered to tissue culture plastics and was able to proliferate well in standard tissue culture conditions Further characterizations were carried out on several fronts, from their responses to osteogenic induction on tissue culture conditions to 3-D environments in an athymic mouse model The characterization of ADSC for this thesis ended with the eludication of a potential stemness marker based on robust global gene expression array analysis from an in-house depository of donors’ adipose derived stem cells In this thesis, it was shown that ADSC isolated from adipose tissue aspirated with the vacuum pump were viable for subsequent cellular studies The osteogenic differentiation was chosen as a proof of principle of the multipotential properties of ADSC It was shown that 1,25–dihydroxyvitamin D3 worked synergistically with β-glycerophosphate and ascorbic acid to induce ADSC towards the osteogenic lineage ADSC were able to express bone matrix proteins and mineralization of its matrix under such conditions Progressing from culture plastics systems to 3dimensional studies using polycaprolactone-tricalcium phosphate scaffolds, ADSC were still able to express bone characteristics when induced Similar characteristics of ADSC were confirmed in an in vivo model x Chapter 12 References Hicok KC, Du Laney TV, Zhou YS, Halvorsen YD, Hitt DC, Cooper LF, Gimble JM Human adipose-derived adult stem cells produce osteoid in vivo Tissue Eng 2004; 10(3-4):371-380 Hong JH, Hwang ES, McManus MT, Amsterdam A, Tian Y, Kalmukova R, Mueller E, Benjamin T, Spiegelman BM, Sharp PA, Hopkins N, Yaffe MB TAZ, a transcriptional modulator of mesenchymal stem cell differentiation Science 2005; 309(5737):1074-1078 Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL, Neel M, Sussman M, Orchard P, Marx JC, Pyeritz RE, Brenner MK Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta Nat Med 1999; 5(3):309-313 Horwitz EM, Prockop DJ, Gordon PL, Koo WW, Fitzpatrick LA, Neel MD, McCarville ME, Orchard PJ, Pyeritz RE, Brenner MK Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta Blood 2001; 97(5):1227-1231 Horwitz EM, Gordon PL, Koo WK, Marx JC, Neel MD, McNall RY, Muul L, Hofmann T Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone Proc Natl Acad Sci U S A 2002; 99(13):8932-8937 Houghton A, Oyajobi BO, Foster GA, Russell RG, Stringer BM Immortalization of human marrow stromal cells by retroviral transduction with a temperature sensitive oncogene: identification of bipotential precursor cells capable of directed differentiation to either an osteoblast or adipocyte phenotype Bone 1998; 22(1):716 Housman TS, Lawrence N, Mellen BG, George MN, Filippo JS, Cerveny KA, DeMarco M, Feldman SR, Fleischer AB The safety of liposuction: results of a national survey Dermatol Surg 2002; 28(11):971-978 Huang JI, Beanes SR, Zhu M, Lorenz HP, Hedrick MH, Benhaim P Rat extramedullary adipose tissue as a source of osteochondrogenic progenitor cells Plast Reconstr Surg 2002; 109(3):1033-1041 Huang JI, Zuk PA, Jones NF, Zhu M, Lorenz HP, Hedrick MH, Benhaim P Chondrogenic potential of multipotential cells from human adipose tissue Plast Reconstr Surg 2004; 113(2):585-594 Huang YC, Kaigler D, Rice KG, Krebsbach PH, Mooney DJ Combined angiogenic and osteogenic factor delivery enhances bone marrow stromal celldriven bone regeneration J Bone Miner Res 2005; 20(5):848-857 Hung SC, Chen NJ, Hsieh SL, Li H, Ma HL, Lo WH Isolation and characterization of size-sieved stem cells from human bone marrow Stem Cells 2002; 20(3):249-258 12 – Chapter 12 References Hunter GK, Hauschka PV, Poole AR, Rosenberg LC, Goldberg HA Nucleation and inhibition of hydroxyapatite formation by mineralized tissue proteins Biochem J 1996; 317 ( Pt 1)(59-64 Huss R, Lange C, Weissinger EM, Kolb HJ, Thalmeier K Evidence of peripheral blood-derived, plastic-adherent CD34(-/low) hematopoietic stem cell clones with mesenchymal stem cell characteristics Stem Cells 2000; 18(4):252-260 Hutmacher DW Scaffolds in tissue engineering bone and cartilage Biomaterials 2000; 21(24):2529-2543 Hutmacher DW, Garcia AJ Scaffold-based bone engineering by using genetically modified cells Gene 2005; 347(1):1-10 Hutmacher DW, Rohner D, See P (2003) Craniofacial bone tissue engineering using medical imaging, computational modeling, rapid prototyping, bioresorbable scaffolds and bone marrow aspirates In: Polymer Based Systems in Tissue Engineering, Replacement and Regeneration Reis R, Cohn D, eds Dordrecht, The Netherlands: Kluwer Academic Publishers: 333-356 Hutmacher DW and Sugunan SLC (2005) Bone repair and adult stem cells In: Stem Cells From bench to bedside Bongso A and Lee EH, eds Singapore: World Scientific Publishing: 442-465 Irizarry RA, Bolstad BM, Collin F, Cope LM, Hobbs B, Speed TP Summaries of Affymetrix GeneChip probe level data Nucleic Acids Res 2003; 31(4):e15 Irwin S, Vandelft M, Pinchev D, Howell JL, Graczyk J, Orr HT, Truant R RNA association and nucleocytoplasmic shuttling by ataxin-1 J Cell Sci 2005; 118(Pt 1):233-242 Ishida Y, Tertinegg I, Heersche JN Progesterone and dexamethasone stimulate proliferation and differentiation of osteoprogenitors and progenitors for adipocytes and macrophages in cell populations derived from adult rat vertebrae J Bone Miner Res 1996; 11(7):921-930 Jaquiery C, Schaeren S, Farhadi J, Mainil-Varlet P, Kunz C, Zeilhofer HF, Heberer M, Martin I In vitro osteogenic differentiation and in vivo bone-forming capacity of human isogenic jaw periosteal cells and bone marrow stromal cells Ann Surg 2005; 242(6):859-867, discussion 867-858 Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM Pluripotency of mesenchymal stem cells derived from adult marrow Nature 2002; 418(6893):41-49 12 – Chapter 12 References Jikko A, Harris SE, Chen D, Mendrick DL, Damsky CH Collagen integrin receptors regulate early osteoblast differentiation induced by BMP-2 J Bone Miner Res 1999; 14(7):1075-1083 Justesen J, Pedersen SB, Stenderup K, Kassem M Subcutaneous adipocytes can differentiate into bone-forming cells in vitro and in vivo Tissue Eng 2004; 10(34):381-391 Kang SK, Jun ES, Bae YC, Jung JS Interactions between human adipose stromal cells and mouse neural stem cells in vitro Brain Res Dev Brain Res 2003; 145(1):141-149 Kang SK, Lee DH, Bae YC, Kim HK, Baik SY, Jung JS Improvement of neurological deficits by intracerebral transplantation of human adipose tissuederived stromal cells after cerebral ischemia in rats Exp Neurol 2003a; 183(2):355-366 Kang SK, Putnam L, Dufour J, Ylostalo J, Jung JS, Bunnell BA Expression of telomerase extends the lifespan and enhances osteogenic differentiation of adipose tissue-derived stromal cells Stem Cells 2004; 22(7):1356-1372 Kaplan FS, Hahn GV, Zasloff MA Heterotopic Ossification: Two Rare Forms and What They Can Teach Us J Am Acad Orthop Surg 1994; 2(5):288-296 Katz AJ, Llull R, Hedrick MH, Futrell JW Emerging approaches to the tissue engineering of fat Clin Plast Surg 1999; 26(4):587-603, viii Kehat I, Kenyagin-Karsenti D, Snir M, Segev H, Amit M, Gepstein A, Livne E, Binah O, Itskovitz-Eldor J, Gepstein L Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes J Clin Invest 2001; 108(3):407-414 Knabe C, Berger G, Gildenhaar R, Meyer J, Howlett CR, Markovic B, Zreiqat H Effect of rapidly resorbable calcium phosphates and a calcium phosphate bone cement on the expression of bone-related genes and proteins in vitro J Biomed Mater Res A 2004; 69(1):145-154 Krebsbach PH, Mankani MH, Satomura K, Kuznetsov SA, Robey PG Repair of craniotomy defects using bone marrow stromal cells Transplantation 1998; 66(10):1272-1278 Kronenwett R, Martin S, Haas R The role of cytokines and adhesion molecules for mobilization of peripheral blood stem cells Stem Cells 2000; 18(5):320-330 Kuboki Y, Jin Q, Takita H Geometry of carriers controlling phenotypic expression in BMP-induced osteogenesis and chondrogenesis J Bone Joint Surg Am 2001; 83-A Suppl 1(Pt 2):S105-115 Kucia M, Dawn B, Hunt G, Guo Y, Wysoczynski M, Majka M, Ratajczak J, Rezzoug F, Ildstad ST, Bolli R, Ratajczak MZ Cells expressing early cardiac 12 – 10 Chapter 12 References markers reside in the bone marrow and are mobilized into the peripheral blood after myocardial infarction Circ Res 2004; 95(12):1191-1199 Kuwana M, Okazaki Y, Kodama H, Izumi K, Yasuoka H, Ogawa Y, Kawakami Y, Ikeda Y Human circulating CD14+ monocytes as a source of progenitors that exhibit mesenchymal cell differentiation J Leukoc Biol 2003; 74(5):833-845 Lagasse E, Shizuru JA, Uchida N, Tsukamoto A, Weissman IL Toward regenerative medicine Immunity 2001 Apr;14(4):425-36 Lavon N, Yanuka O, Benvenisty N Differentiation and isolation of hepatic-like cells from human embryonic stem cells Differentiation 2004; 72(5):230-238 Lecka-Czernik B, Gubrij I, Moerman EJ, Kajkenova O, Lipschitz DA, Manolagas SC, Jilka RL Inhibition of Osf2/Cbfa1 expression and terminal osteoblast differentiation by PPARgamma2 J Cell Biochem 1999; 74(3):357-371 Lee HS, Huang GT, Chiang H, Chiou LL, Chen MH, Hsieh CH, Jiang CC Multipotential mesenchymal stem cells from femoral bone marrow near the site of osteonecrosis Stem Cells 2003; 21(2):190-199 Lee JA, Parrett BM, Conejero JA, Laser J, Chen J, Kogon AJ, Nanda D, Grant RT, Breitbart AS Biological alchemy: engineering bone and fat from fat-derived stem cells Ann Plast Surg 2003; 50(6):610-617 Lee RH, Kim B, Choi I, Kim H, Choi HS, Suh K, Bae YC, Jung JS Characterization and expression analysis of mesenchymal stem cells from human bone marrow and adipose tissue Cell Physiol Biochem 2004; 14(4-6):311-324 Lemoli RM, Gulati SC Effect of stem cell factor (c-kit ligand), granulocytemacrophage colony stimulating factor and interleukin on hematopoietic progenitors in human long-term bone marrow cultures Stem Cells 1993; 11(5):435-444 Lendeckel S, Jodicke A, Christophis P, Heidinger K, Wolff J, Fraser JK, Hedrick MH, Berthold L, Howaldt HP Autologous stem cells (adipose) and fibrin glue used to treat widespread traumatic calvarial defects: case report J Craniomaxillofac Surg 2004; 32(6):370-373 Leo BM, Li X, Balian G, Anderson DG In vivo bioluminescent imaging of virusmediated gene transfer and transduced cell transplantation in the intervertebral disc Spine 2004; 29(8):838-844 Leong DT, Gupta A, Bai HF, Wan Q, Yoong LF, Too HP, Chew FT, Hutmacher DW Absolute quantification of gene expression in biomaterials research using real time PCR Biomaterials 2007;28(2):203-210 Leong DT, Khor WM, Chew FT, Lim TC, Hutmacher DW Characterization of osteogenically induced adipose tissue-derived precursor cells in 2-dimensional and 3-dimensional environments Cells Tissues Organs 2006; 182(1):1-11 12 – 11 Chapter 12 References Leong TW, Chew FT, Hutmacher DW Isolating bone marrow stem cells using sieve technology Stem Cells 2004; 22(6):1123-1125 Li TS, Ito H, Hayashi M, Furutani A, Matsuzaki M, Hamano K Cellular expression of integrin-beta is of critical importance for inducing therapeutic angiogenesis by cell implantation Cardiovasc Res 2005; 65(1):64-72 Lis GJ, Rokita E, Podolec P, Pfitzner R, Dziatkowiak A, Cichocki T Mineralization and organic phase modifications as contributory factors of accelerated degeneration in homograft aortic valves J Heart Valve Dis 2003; 12(6):741-751 Mann V, Hobson EE, Li B, Stewart TL, Grant SF, Robins SP, Aspden RM, Ralston SH A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality J Clin Invest 2001; 107(7):899-907 Mark MP, Prince CW, Oosawa T, Gay S, Bronckers AL, Butler WT Immunohistochemical demonstration of a 44-KD phosphoprotein in developing rat bones J Histochem Cytochem 1987; 35(7):707-715 Mason JL, Angelastro JM, Ignatova TN, Kukekov VG, Lin G, Greene LA, Goldman JE ATF5 regulates the proliferation and differentiation of oligodendrocytes Mol Cell Neurosci 2005; 29(3):372-380 McKee MD, Nanci A Osteopontin at mineralized tissue interfaces in bone, teeth, and osseointegrated implants: ultrastructural distribution and implications for mineralized tissue formation, turnover, and repair Microsc Res Tech 1996a; 33(2):141-164 McKee MD, Nanci A Secretion of Osteopontin by macrophages and its accumulation at tissue surfaces during wound healing in mineralized tissues: a potential requirement for macrophage adhesion and phagocytosis Anat Rec 1996b; 245(2):394-409 Mie M, Ohgushi H, Yanagida Y, Haruyama T, Kobatake E, Aizawa M Osteogenesis coordinated in C3H10T1/2 cells by adipogenesis-dependent BMP-2 expression system Tissue Eng 2000; 6(1):9-18 Miranville A, Heeschen C, Sengenes C, Curat CA, Busse R, Bouloumie A Improvement of postnatal neovascularization by human adipose tissue-derived stem cells Circulation 2004; 110(3):349-355 Mizuno H, Zuk PA, Zhu M, Lorenz HP, Benhaim P, Hedrick MH Myogenic differentiation by human processed lipoaspirate cells Plast Reconstr Surg 2002; 109(1):199-209 Morizono K, De Ugarte DA, Zhu M, Zuk P, Elbarbary A, Ashjian P, Benhaim P, Chen IS, Hedrick MH Multilineage cells from adipose tissue as gene delivery vehicles Hum Gene Ther 2003; 14(1):59-66 12 – 12 Chapter 12 References Morrison SJ, Weissman IL The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype Immunity 1994; 1(8):661673 Muschler GF, Boehm C, Easley K Aspiration to obtain osteoblast progenitor cells from human bone marrow: the influence of aspiration volume J Bone Joint Surg Am 1997; 79(11):1699-1709 Muschler GF, Nitto H, Boehm CA, Easley KA Age- and gender-related changes in the cellularity of human bone marrow and the prevalence of osteoblastic progenitors J Orthop Res 2001; 19(1):117-125 Naslavsky N, Caplan S C-terminal EH-domain-containing proteins: consensus for a role in endocytic trafficking, EH? J Cell Sci 2005; 118(Pt 18):4093-4101 Negrin RS, Atkinson K, Leemhuis T, Hanania E, Juttner C, Tierney K, Hu WW, Johnston LJ, Shizurn JA, Stockerl-Goldstein KE, Blume KG, Weissman IL, Bower S, Baynes R, Dansey R, Karanes C, Peters W, Klein J Transplantation of highly purified CD34+Thy-1+ hematopoietic stem cells in patients with metastatic breast cancer Biol Blood Marrow Transplant 2000; 6(3):262-271 Neuber F, Fettransplantation Chir Kongr Verhandl Dsch Gesellsch Chir 22: 66, 1893 Neuss S, Becher E, Woltje M, Tietze L, Jahnen-Dechent W Functional expression of HGF and HGF receptor/c-met in adult human mesenchymal stem cells suggests a role in cell mobilization, tissue repair, and wound healing Stem Cells 2004; 22(3):405-414 Ng KW, Hutmacher DW, Schantz JT, Ng CS, Too HP, Lim TC, Phan TT, Teoh SH Evaluation of ultra-thin poly(epsilon-caprolactone) films for tissue-engineered skin Tissue Eng 2001; 7(4):441-455 Ng KW, Leong DT, Hutmacher DW The challenge to measure cell proliferation in two and three dimensions Tissue Eng 2005; 11(1-2):182-191 Nichols J, Zevnik B, Anastassiadis K, Niwa H, Klewe-Nebenius D, Chambers I, Scholer H, Smith A Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4 Cell 1998; 95(3):379-391 Niechajev I, Sevcuk O Long-term results of fat transplantation: clinical and histologic studies Plast Reconstr Surg 1994; 94(3):496-506 Nishimori M, Yamada Y, Hoshi K, Akiyama Y, Hoshi Y, Morishima Y, Tsuchida M, Fukuhara S, Kodera Y Health-related quality of life of unrelated bone marrow donors in Japan Blood 2002; 99(6):1995-2001 Nociari MM, Shalev A, Benias P, Russo C A novel one-step, highly sensitive fluorometric assay to evaluate cell-mediated cytotoxicity J Immunol Methods 1998; 213(2):157-167 12 – 13 Chapter 12 References Nuttall ME, Patton AJ, Olivera DL, Nadeau DP, Gowen M Human trabecular bone cells are able to express both osteoblastic and adipocytic phenotype: implications for osteopenic disorders J Bone Miner Res 1998; 13(3):371-382 Ogawa M, Nishikawa S, Yoshinaga K, Hayashi S, Kunisada T, Nakao J, Kina T, Sudo T, Kodama H, Nishikawa S Expression and function of c-Kit in fetal hemopoietic progenitor cells: transition from the early c-Kit-independent to the late c-Kit-dependent wave of hemopoiesis in the murine embryo Development 1993; 117(3):1089-1098 Ogawa R, Mizuno H, Watanabe A, Migita M, Shimada T, Hyakusoku H Osteogenic and chondrogenic differentiation by adipose-derived stem cells harvested from GFP transgenic mice Biochem Biophys Res Commun 2004; 313(4):871-877 Okamoto K, Okazawa H, Okuda A, Sakai M, Muramatsu M, Hamada H A novel octamer binding transcription factor is differentially expressed in mouse embryonic cells Cell 1990 Feb 9;60(3):461-72 Oreffo RO, Bord S, Triffitt JT Skeletal progenitor cells and ageing human populations Clin Sci (Lond) 1998; 94(5):549-555 Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P Bone marrow cells regenerate infarcted myocardium Nature 2001a; 410(6829):701-705 Owen M Marrow stromal stem cells J Cell Sci Suppl 1988; 10(63-76 Owen TA, Aronow M, Shalhoub V, Barone LM, Wilming L, Tassinari MS, Kennedy MB, Pockwinse S, Lian JB, Stein GS Progressive development of the rat osteoblast phenotype in vitro: reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix J Cell Physiol 1990; 143(3):420-430 Panagiotis M Classification of non-union Injury 2005; 36 Suppl 4(S30-37 Papayannopoulou T, Priestley GV, Nakamoto B Anti-VLA4/VCAM-1-induced mobilization requires cooperative signaling through the kit/mkit ligand pathway Blood 1998; 91(7):2231-2239 Park SR, Oreffo RO, Triffitt JT Interconversion potential of cloned human marrow adipocytes in vitro Bone 1999; 24(6):549-554 Pati D, Meistrich ML, Plon SE Human Cdc34 and Rad6B ubiquitin-conjugating enzymes target repressors of cyclic AMP-induced transcription for proteolysis Mol Cell Biol 1999; 19(7):5001-5013 Patrick CW, Jr., Chauvin PB, Hobley J, Reece GP Preadipocyte seeded PLGA scaffolds for adipose tissue engineering Tissue Eng 1999; 5(2):139-151 12 – 14 Chapter 12 References Patrick CW, Jr Tissue engineering strategies for adipose tissue repair Anat Rec 2001; 263(4):361-366 Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS, Goff JP Bone marrow as a potential source of hepatic oval cells Science 1999; 284(5417):1168-1170 Petite H, Viateau V, Bensaid W, Meunier A, de Pollak C, Bourguignon M, Oudina K, Sedel L, Guillemin G Tissue-engineered bone regeneration Nat Biotechnol 2000; 18(9):959-963 Phillips JE, Hutmacher DW, Guldberg RE, Garcia AJ Mineralization capacity of Runx2/Cbfa1-genetically engineered fibroblasts is scaffold dependent Biomaterials 2006 Jul 18; [Epub ahead of print] 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):143-147 Planat-Benard V, Menard C, Andre M, Puceat M, Perez A, Garcia-Verdugo JM, Penicaud L, Casteilla L Spontaneous cardiomyocyte differentiation from adipose tissue stroma cells Circ Res 2004a; 94(2):223-229 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 2004b; 109(5):656-663 Prince CW, Dickie D, Krumdieck CL Osteopontin, a substrate for transglutaminase and factor XIII activity Biochem Biophys Res Commun 1991; 177(3):1205-1210 Prockop DJ Marrow stromal cells as stem cells for nonhematopoietic tissues Science 1997; 276(5309):71-74 Puissant B, Barreau C, Bourin P, Clavel C, Corre J, Bousquet C, Taureau C, Cousin B, Abbal M, Laharrague P, Penicaud L, Casteilla L, Blancher A Immunomodulatory effect of human adipose tissue-derived adult stem cells: comparison with bone marrow mesenchymal stem cells Br J Haematol 2005; 129(1):118-129 Quarto R, Mastrogiacomo M, Cancedda R, Kutepov SM, Mukhachev V, Lavroukov A, Kon E, Marcacci M Repair of large bone defects with the use of autologous bone marrow stromal cells N Engl J Med 2001; 344(5):385-386 Radtke F, Clevers H Self-renewal and cancer of the gut: two sides of a coin Science 2005; 307(5717):1904-1909 12 – 15 Chapter 12 References Rafii S, Shapiro F, Rimarachin J, Nachman RL, Ferris B, Weksler B, Moore MA, Asch AS Isolation and characterization of human bone marrow microvascular endothelial cells: hematopoietic progenitor cell adhesion Blood 1994; 84(1):1019 Rai B, Teoh SH, Hutmacher DW, Cao T, Ho KH Novel PCL-based honeycomb scaffolds as drug delivery systems for rhBMP-2 Biomaterials 2005; 26(17):37393748 Rangappa S, Fen C, Lee EH, Bongso A, Sim EK Transformation of adult mesenchymal stem cells isolated from the fatty tissue into cardiomyocytes Ann Thorac Surg 2003; 75(3):775-779 Rauch F, Glorieux FH Osteogenesis imperfecta Lancet 2004; 363(9418):13771385 Rehman J, Traktuev D, Li J, Merfeld-Clauss S, Temm-Grove CJ, Bovenkerk JE, Pell CL, Johnstone BH, Considine RV, March KL Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells Circulation 2004; 109(10):1292-1298 Reyes M, Lund T, Lenvik T, Aguiar D, Koodie L, Verfaillie CM Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells Blood 2001; 98(9):2615-2625 Rieck B, Schlaak S Measurement in vivo of the survival rate in autologous adipocyte transplantation Plast Reconstr Surg 2003; 111(7):2315-2323 Roche P, Goldberg HA, Delmas PD, Malaval L Selective attachment of osteoprogenitors to laminin Bone 1999a; 24(4):329-336 Roche P, Rousselle P, Lissitzky JC, Delmas PD, Malaval L Isoform-specific attachment of osteoprogenitors to laminins: mapping to the short arms of laminin1 Exp Cell Res 1999b; 250(2):465-474 Rodan GA, Noda M Gene expression in osteoblastic cells Crit Rev Eukaryot Gene Expr 1991; 1(2):85-98 Rodriguez AM, Elabd C, Amri EZ, Ailhaud G, Dani C The human adipose tissue is a source of multipotent stem cells Biochimie 2005a; 87(1):125-128 Rodriguez AM, Pisani D, Dechesne CA, Turc-Carel C, Kurzenne JY, Wdziekonski B, Villageois A, Bagnis C, Breittmayer JP, Groux H, Ailhaud G, Dani C Transplantation of a multipotent cell population from human adipose tissue induces dystrophin expression in the immunocompetent mdx mouse J Exp Med 2005b; 201(9):1397-1405 Roebuck KA, Finnegan A Regulation of intercellular adhesion molecule-1 (CD54) gene expression J Leukoc Biol 1999; 66(6):876-888 12 – 16 Chapter 12 References Rotter N, Aigner J, Naumann A, Planck H, Hammer C, Burmester G, Sittinger M Cartilage reconstruction in head and neck surgery: comparison of resorbable polymer scaffolds for tissue engineering of human septal cartilage J Biomed Mater Res 1998; 42(3):347-356 Rupnick MA, Panigrahy D, Zhang CY, Dallabrida SM, Lowell BB, Langer R, Folkman MJ Adipose tissue mass can be regulated through the vasculature Proc Natl Acad Sci U S A 2002; 99(16):10730-10735 Safford KM, Hicok KC, Safford SD, Halvorsen YD, Wilkison WO, Gimble JM, Rice HE Neurogenic differentiation of murine and human adipose-derived stromal cells Biochem Biophys Res Commun 2002; 294(2):371-379 Safford KM, Safford SD, Gimble JM, Shetty AK, Rice HE Characterization of neuronal/glial differentiation of murine adipose-derived adult stromal cells Exp Neurol 2004; 187(2):319-328 Sahota O, Mundey MK, San P, Godber IM, Lawson N, Hosking DJ The relationship between vitamin D and parathyroid hormone: calcium homeostasis, bone turnover, and bone mineral density in postmenopausal women with established osteoporosis Bone 2004; 35(1):312-319 Sato N, Meijer L, Skaltsounis L, Greengard P, Brivanlou AH Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor Nat Med 2004; 10(1):55-63 Schantz JT, Hutmacher DW, Lam CX, Brinkmann M, Wong KM, Lim TC, Chou N, Guldberg RE, Teoh SH Repair of calvarial defects with customised tissueengineered bone grafts II Evaluation of cellular efficiency and efficacy in vivo Tissue Eng 2003; Suppl 1(S127-139 Schantz JT, Teoh SH, Lim TC, Endres M, Lam CX, Hutmacher DW Repair of calvarial defects with customized tissue-engineered bone grafts I Evaluation of osteogenesis in a three-dimensional culture system Tissue Eng 2003; Suppl 1(S113-126 Schecroun N, Delloye C In vitro growth and osteoblastic differentiation of human bone marrow stromal cells supported by autologous plasma Bone 2004; 35(2):517-524 Schmitt B, Ringe J, Haupl T, Notter M, Manz R, Burmester GR, Sittinger M, Kaps C BMP2 initiates chondrogenic lineage development of adult human mesenchymal stem cells in high-density culture Differentiation 2003; 71(910):567-577 Scholer HR, Balling R, Hatzopoulos AK, Suzuki N, Gruss P Octamer binding proteins confer transcriptional activity in early mouse embryogenesis EMBO J 1989; 8(9):2551-2557 12 – 17 Chapter 12 References Schuldiner M, Eiges R, Eden A, Yanuka O, Itskovitz-Eldor J, Goldstein RS, Benvenisty N Induced neuronal differentiation of human embryonic stem cells Brain Res 2001; 913(2):201-205 Segev H, Fishman B, Ziskind A, Shulman M, Itskovitz-Eldor J Differentiation of human embryonic stem cells into insulin-producing clusters Stem Cells 2004; 22(3):265-274 Sen A, Lea-Currie YR, Sujkowska D, Franklin DM, Wilkison WO, Halvorsen YD, Gimble JM Adipogenic potential of human adipose derived stromal cells from multiple donors is heterogeneous J Cell Biochem 2001; 81(2):312-319 Seo MJ, Suh SY, Bae YC, Jung JS Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo Biochem Biophys Res Commun 2005; 328(1):258-264 Shalhoub V, Aslam F, Breen E, van Wijnen A, Bortell R, Stein GS, Stein JL, Lian JB Multiple levels of steroid hormone-dependent control of osteocalcin during osteoblast differentiation: glucocorticoid regulation of basal and vitamin D stimulated gene expression J Cell Biochem 1998; 69(2):154-168 Shi YY, Nacamuli RP, Salim A, Longaker MT The osteogenic potential of adipose-derived mesenchymal cells is maintained with aging Plast Reconstr Surg 2005; 116(6):1686-1696 Shore EM, Ahn J, Jan de Beur S, Li M, Xu M, Gardner RJ, Zasloff MA, Whyte MP, Levine MA, Kaplan FS Paternally inherited inactivating mutations of the GNAS1 gene in progressive osseous heteroplasia N Engl J Med 2002; 346(2):99106 Shore EM, Xu M, Feldman GJ, Fenstermacher DA; Brown MA, Kaplan FS A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva Nat Genet 2006; 38(5):525-527 Silva WA, Jr., Covas DT, Panepucci RA, Proto-Siqueira R, Siufi JL, Zanette DL, Santos AR, Zago MA The profile of gene expression of human marrow mesenchymal stem cells Stem Cells 2003; 21(6):661-669 Simmons PJ, Masinovsky B, Longenecker BM, Berenson R, Torok-Storb B, Gallatin WM Vascular cell adhesion molecule-1 expressed by bone marrow stromal cells mediates the binding of hematopoietic progenitor cells Blood 1992; 80(2):388-395 Sodek J, Feng J, Yen EH, Melcher AH Effect of ascorbic acid on protein synthesis and collagen hydroxylation in continuous flow organ cultures of adult mouse periodontal tissues Calcif Tissue Int 1982; 34(4):408-415 Squillace RM, Chenault DM, Wang EH Inhibition of muscle differentiation by the novel muscleblind-related protein CHCR Dev Biol 2002; 250(1):218-230 12 – 18 Chapter 12 References Stein GS, Lian JB, van Wijnen AJ, Stein JL, Montecino M, Javed A, Zaidi SK, Young DW, Choi JY, Pockwinse SM Runx2 control of organization, assembly and activity of the regulatory machinery for skeletal gene expression Oncogene 2004; 23(24):4315-4329 Strem BM, Hedrick MH The growing importance of fat in regenerative medicine Trends Biotechnol 2005; 23(2):64-66 Strem BM, Hicok KC, Zhu M, Wulur I, Alfonso Z, Schreiber RE, Fraser JK, Hedrick MH Multipotential differentiation of adipose tissue-derived stem cells Keio J Med 2005a; 54(3):132-141 Strem BM, Zhu M, Alfonso Z, Daniels EJ, Schreiber R, Beygui R, MacLellan WR, Hedrick MH, Fraser JK Expression of cardiomyocytic markers on adipose tissuederived cells in a murine model of acute myocardial injury Cytotherapy 2005b; 7(3):282-291 Sudhoff T, Sohngen D Circulating endothelial adhesion molecules (sE-selectin, sVCAM-1 and sICAM-1) during rHuG-CSF-stimulated stem cell mobilization J Hematother Stem Cell Res 2002; 11(1):147-151 Sugunan S.L.C., Hutmacher D.W State of the Art and Future Directions of Scaffold Based Bone Engineering from a Materials Perspective Current Opinion in Solid State & Materials Science (in press 2006) Sun S, Guo Z, Xiao X, Liu B, Liu X, Tang PH, Mao N Isolation of mouse marrow mesenchymal progenitors by a novel and reliable method Stem Cells 2003; 21(5):527-535 Termine JD, Kleinman HK, Whitson SW, Conn KM, McGarvey ML, Martin GR Osteonectin, a bone-specific protein linking mineral to collagen Cell 1981; 26(1 Pt 1):99-105 Theise ND, Nimmakayalu M, Gardner R, Illei PB, Morgan G, Teperman L, Henegariu O, Krause DS Liver from bone marrow in humans Hepatology 2000; 32(1):11-16 Tholpady SS, Katz AJ, Ogle RC Mesenchymal stem cells from rat visceral fat exhibit multipotential differentiation in vitro Anat Rec A Discov Mol Cell Evol Biol 2003; 272(1):398-402 Thomas T, Gori F, Spelsberg TC, Khosla S, Riggs BL, Conover CA Response of bipotential human marrow stromal cells to insulin-like growth factors: effect on binding protein production, proliferation, and commitment to osteoblasts and adipocytes Endocrinology 1999; 140(11):5036-5044 Thompson DL, Lum KD, Nygaard SC, Kuestner RE, Kelly KA, Gimble JM, Moore EE The derivation and characterization of stromal cell lines from the bone marrow of p53-/- mice: new insights into osteoblast and adipocyte differentiation J Bone Miner Res 1998; 13(2):195-204 12 – 19 Chapter 12 References Tomita S, Li RK, Weisel RD, Mickle DA, Kim EJ, Sakai T, Jia ZQ Autologous transplantation of bone marrow cells improves damaged heart function Circulation 1999; 100(19 Suppl):II247-256 Trischmann TM, Schepers KG, Civin CI Measurement of CD34+ cells in bone marrow by flow cytometry J Hematother 1993; 2(3):305-313 Tse WT, Pendleton JD, Beyer WM, Egalka MC, Guinan EC Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation Transplantation 2003; 75(3):389-397 Tsukiyama-Kohara K, Vidal SM, Gingras AC, Glover TW, Hanash SM, Heng H, Sonenberg N Tissue distribution, genomic structure, and chromosome mapping of mouse and human eukaryotic initiation factor 4E-binding proteins and Genomics 1996; 38(3):353-363 Vodyanik MA, Bork JA, Thomson JA, Slukvin, II Human embryonic stem cellderived CD34+ cells: efficient production in the coculture with OP9 stromal cells and analysis of lymphohematopoietic potential Blood 2005; 105(2):617-626 von Heimburg D, Zachariah S, Heschel I, Kuhling H, Schoof H, Hafemann B, Pallua N Human preadipocytes seeded on freeze-dried collagen scaffolds investigated in vitro and in vivo Biomaterials 2001; 22(5):429-438 von Heimburg D, Zachariah S, Low A, Pallua N Influence of different biodegradable carriers on the in vivo behavior of human adipose precursor cells Plast Reconstr Surg 2001; 108(2):411-420 Wang L, Li L, Shojaei F, Levac K, Cerdan C, Menendez P, Martin T, Rouleau A, Bhatia M Endothelial and hematopoietic cell fate of human embryonic stem cells originates from primitive endothelium with hemangioblastic properties Immunity 2004; 21(1):31-41 Weidt C, Niggemann B, Hatzmann W, Zanker KS, Dittmar T Differential effects of culture conditions on the migration pattern of stromal cell-derived factorstimulated hematopoietic stem cells Stem Cells 2004; 22(6):890-896 Weissman IL Translating stem and progenitor cell biology to the clinic: barriers and opportunities Science 2000a; 287(5457):1442-1446 Weissman IL Stem cells: units of development, units of regeneration, and units in evolution Cell 2000b; 100(1):157-168 Weissman IL, Baltimore D Disappearing stem cells, disappearing science Science 2001; 292(5517):601 Wickham MQ, Erickson GR, Gimble JM, Vail TP, Guilak F Multipotent stromal cells derived from the infrapatellar fat pad of the knee Clin Orthop Relat Res 2003; 412):196-212 12 – 20 Chapter 12 References Williams JM, Adewunmi A, Schek RM, Flanagan CL, Krebsbach PH, Feinberg SE, Hollister SJ, Das S Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering Biomaterials 2005; 26(23):4817-4827 Winter A, Breit S, Parsch D, Benz K, Steck E, Hauner H, Weber RM, Ewerbeck V, Richter W Cartilage-like gene expression in differentiated human stem cell spheroids: a comparison of bone marrow-derived and adipose tissue-derived stromal cells Arthritis Rheum 2003; 48(2):418-429 Xu C, Police S, Rao N, Carpenter MK Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells Circ Res 2002; 91(6):501-508 Yang L, Zheng J, Liu X, Hui G, Fei J, Guo L Adipose tissue-derived stromal cells differentiate into neuron-like cells Sichuan Da Xue Xue Bao Yi Xue Ban 2003; 34(3):381-384 Yang X, Matsuda K, Bialek P, Jacquot S, Masuoka HC, Schinke T, Li L, Brancorsini S, Sassone-Corsi P, Townes TM, Hanauer A, Karsenty G ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology; implication for Coffin-Lowry Syndrome Cell 2004; 117(3):387-398 Young HE, Duplaa C, Romero-Ramos M, Chesselet MF, Vourc'h P, Yost MJ, Ericson K, Terracio L, Asahara T, Masuda H, Tamura-Ninomiya S, Detmer K, Bray RA, Steele TA, Hixson D, el-Kalay M, Tobin BW, Russ RD, Horst MN, Floyd JA, Henson NL, Hawkins KC, Groom J, Parikh A, Blake L, Bland LJ, Thompson AJ, Kirincich A, Moreau C, Hudson J, Bowyer FP, 3rd, Lin TJ, Black AC, Jr Adult reserve stem cells and their potential for tissue engineering Cell Biochem Biophys 2004; 40(1):1-80 Younger EM, Chapman MW Morbidity at bone graft donor sites J Orthop Trauma 1989; 3(3):192-195 Zhan X, Dravid G, Ye Z, Hammond H, Shamblott M, Gearhart J, Cheng L Functional antigen-presenting leucocytes derived from human embryonic stem cells in vitro Lancet 2004; 364(9429):163-171 Zhao LR, Duan WM, Reyes M, Keene CD, Verfaillie CM, Low WC Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats Exp Neurol 2002; 174(1):11-20 Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH Multilineage cells from human adipose tissue: implications for cellbased therapies Tissue Eng 2001; 7(2):211-228 Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH Human adipose tissue is a source of multipotent stem cells Mol Biol Cell 2002; 13(12):4279-4295 12 – 21 Chapter 12 References Zur Nieden NI, Kempka G, Ahr HJ In vitro differentiation of embryonic stem cells into mineralized osteoblasts Differentiation 2003; 71(1):18-27 12 – 22 .. .CHARACTERIZATION OF HUMAN ADIPOSE DERIVED ADULT MULTIPOTENT PRECURSOR CELLS LEONG TAI WEI DAVID (Bachelor of Chemical Engineering, Hons) A THESIS SUBMITTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY... of stem cells in regeneration of bone 1-1 1-1 1-2 Chapter – Literature Review 2.1 Description of the adipose tissue 2.2 Adipose tissue – a possible alternative to bone marrow as a source of adult. .. Reliable procurement of autologous ADSC • Characterization of cells in in vitro culture plastic environment • Characterization of cells in in vitro 3-D environment • Characterization of cells in in vivo