Adipose-Derived Stem Cells: Characterization and Current Application in Orthopaedic Tissue Repair

Orthopaedic tissues, such as bone, cartilage, intervertebral disc and tendon, contain cells that are difficult to culture and stimulate in vitro for repair of damaged tissue. Stem cells have the ability to self-renew and differentiate into many tissue types. Recent progress in stem cell research has led to an enthusiastic effort to utilize stem cells for orthopaedic tissue regeneration. Due to ease of harvest and abundance, adipose-derived mesenchymal cells (ASC) are an attractive, readily available adult stem cell that has become increasingly popular for use in many stem cell applications. Recent progress has been made in characterizing ASC and looking mechanistically at gene expression and cellular pathways involved in differentiation. This review focuses on (i) the characterization of ASC through expression of appropriate surface markers; (ii) modulation of in vitro differentiation of ASC through different scaffolds, growth factors, and media; and (iii) the use of ASC in orthopaedic tissue repair. Strategies for repair involve the use of differentiated or undifferentiated, fresh or passaged ASC, in conjunction with appropriate choice of media, growth factors and scaffolds. Recent in vivo studies utilizing ASC are discussed giving results on defect repair and potential for clinical orthopaedic tissue regeneration.

[1]  K. Burg,et al.  Cellular ingrowth and thickness changes in poly-L-lactide and polyglycolide matrices implanted subcutaneously in the rat. , 1998, Journal of biomedical materials research.

[2]  R. Ritchie,et al.  Analysis of the material properties of early chondrogenic differentiated adipose-derived stromal cells (ASC) using an in vitro three-dimensional micromass culture system. , 2007, Biochemical and biophysical research communications.

[3]  Byung-Ho Choi,et al.  Injectable bone using chitosan-alginate gel/mesenchymal stem cells/BMP-2 composites. , 2005, Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery.

[4]  James D. Kang,et al.  Feasibility of a stem cell therapy for intervertebral disc degeneration. , 2008, The spine journal : official journal of the North American Spine Society.

[5]  I. Koshima,et al.  Rapid expansion of human adipose-derived stromal cells preserving multipotency. , 2007, Cytotherapy.

[6]  D. Prockop,et al.  Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. , 2006, Cytotherapy.

[7]  Sunil S Tholpady,et al.  Cell Surface and Transcriptional Characterization of Human Adipose‐Derived Adherent Stromal (hADAS) Cells , 2005, Stem cells.

[8]  Min Zhu,et al.  Human adipose tissue is a source of multipotent stem cells. , 2002, Molecular biology of the cell.

[9]  G. Boland,et al.  Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells , 2004, Journal of cellular biochemistry.

[10]  S. Levenberg,et al.  Engineering three-dimensional tissue structures using stem cells. , 2006, Methods in enzymology.

[11]  Miya Ishihara,et al.  Osteogenic Potential of Human Adipose Tissue-Derived Stromal Cells as an Alternative Stem Cell Source , 2004, Cells Tissues Organs.

[12]  F. Guilak,et al.  Potent induction of chondrocytic differentiation of human adipose-derived adult stem cells by bone morphogenetic protein 6. , 2006, Arthritis and rheumatism.

[13]  P. A. Revell,et al.  Tissue engineered intervertebral disc repair in the pig using injectable polymers , 2007, Journal of materials science. Materials in medicine.

[14]  H. Lorenz,et al.  Multilineage cells from human adipose tissue: implications for cell-based therapies. , 2001, Tissue engineering.

[15]  W. Wilkison,et al.  Extracellular matrix mineralization and osteoblast gene expression by human adipose tissue-derived stromal cells. , 2001, Tissue engineering.

[16]  G. Evans,et al.  In vivo osteogenic potential of human adipose-derived stem cells/poly lactide-co-glycolic acid constructs for bone regeneration in a rat critical-sized calvarial defect model. , 2007, Tissue engineering.

[17]  G. Schuurhuis,et al.  Phenotypical and functional characterization of freshly isolated adipose tissue-derived stem cells. , 2007, Stem cells and development.

[18]  N Schütze,et al.  Anterior cruciate ligament constructs fabricated from human mesenchymal stem cells in a collagen type I hydrogel. , 2005, Cytotherapy.

[19]  Farshid Guilak,et al.  Chondrogenic differentiation of adipose-derived adult stem cells in agarose, alginate, and gelatin scaffolds. , 2004, Biomaterials.

[20]  M. Gonthier,et al.  Surface protein expression between human adipose tissue-derived stromal cells and mature adipocytes , 2005, Histochemistry and Cell Biology.

[21]  J. Gimble,et al.  Surface protein characterization of human adipose tissue‐derived stromal cells , 2001, Journal of cellular physiology.

[22]  Miya Ishihara,et al.  Bone formation using human adipose tissue-derived stromal cells and a biodegradable scaffold. , 2006, Journal of biomedical materials research. Part B, Applied biomaterials.

[23]  L. Pénicaud,et al.  Immunomodulatory effect of human adipose tissue‐derived adult stem cells: comparison with bone marrow mesenchymal stem cells , 2005, British journal of haematology.

[24]  Sanjin Zvonic,et al.  Immunophenotype of Human Adipose‐Derived Cells: Temporal Changes in Stromal‐Associated and Stem Cell–Associated Markers , 2006, Stem cells.

[25]  G. Finkenzeller,et al.  Differential expression pattern of extracellular matrix molecules during chondrogenesis of mesenchymal stem cells from bone marrow and adipose tissue. , 2006, Tissue engineering.

[26]  P. Clegg,et al.  Stem cells in veterinary medicine--attempts at regenerating equine tendon after injury. , 2007, Trends in biotechnology.

[27]  Mahidhar M. Durbhakula,et al.  Chondrogenic potential of progenitor cells derived from human bone marrow and adipose tissue: A patient‐matched comparison , 2005, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[28]  Marc Hedrick,et al.  Healing of critically sized femoral defects, using genetically modified mesenchymal stem cells from human adipose tissue. , 2005, Tissue engineering.

[29]  R. Yañez,et al.  Adipose Tissue‐Derived Mesenchymal Stem Cells Have In Vivo Immunosuppressive Properties Applicable for the Control of the Graft‐Versus‐Host Disease , 2006, Stem cells.

[30]  飛田 護邦.  Periodontal tissue regeneration with adipose-derived stem cells , 2010 .

[31]  Jeffrey C. Wang,et al.  Stem cells from human fat as cellular delivery vehicles in an athymic rat posterolateral spine fusion model. , 2008, The Journal of bone and joint surgery. American volume.

[32]  W. Richter,et al.  Reduced chondrogenic potential of adipose tissue derived stromal cells correlates with an altered TGFβ receptor and BMP profile and is overcome by BMP‐6 , 2007, Journal of cellular physiology.

[33]  C. Dani,et al.  Human adipose tissue-derived multipotent stem cells differentiate in vitro and in vivo into osteocyte-like cells. , 2007, Biochemical and biophysical research communications.

[34]  W. Ansorge,et al.  Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. , 2005, Experimental hematology.

[35]  V. Goldberg,et al.  FGF‐2 enhances the mitotic and chondrogenic potentials of human adult bone marrow‐derived mesenchymal stem cells , 2005, Journal of cellular physiology.

[36]  J. Rubin,et al.  A Novel Perfluoroelastomer Seeded with Adipose-Derived Stem Cells for Soft-Tissue Repair , 2006, Plastic and reconstructive surgery.

[37]  J. Dragoo,et al.  Healing full-thickness cartilage defects using adipose-derived stem cells. , 2007, Tissue engineering.

[38]  Farshid Guilak,et al.  Chondrogenic potential of adipose tissue-derived stromal cells in vitro and in vivo. , 2002, Biochemical and biophysical research communications.

[39]  A. Katz,et al.  Mesenchymal stem cells from rat visceral fat exhibit multipotential differentiation in vitro. , 2003, The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology.

[40]  Christopher H Contag,et al.  Adipose-derived adult stromal cells heal critical-size mouse calvarial defects , 2004, Nature Biotechnology.

[41]  B. Lim,et al.  Identification of Common Pathways Mediating Differentiation of Bone Marrow‐ and Adipose Tissue‐Derived Human Mesenchymal Stem Cells into Three Mesenchymal Lineages , 2007, Stem cells.

[42]  Shyni Varghese,et al.  Chondroitin sulfate based niches for chondrogenic differentiation of mesenchymal stem cells. , 2008, Matrix biology : journal of the International Society for Matrix Biology.

[43]  Boon Chin Heng,et al.  Directing Stem Cell Differentiation into the Chondrogenic Lineage In Vitro , 2004, Stem cells.

[44]  R. Bank,et al.  Differentiation of adipose stem cells by nucleus pulposus cells: configuration effect. , 2007, Biochemical and biophysical research communications.

[45]  M. Longaker,et al.  Mitogenic and chondrogenic effects of fibroblast growth factor-2 in adipose-derived mesenchymal cells. , 2006, Biochemical and biophysical research communications.

[46]  P. Arner,et al.  Functional studies of mesenchymal stem cells derived from adult human adipose tissue. , 2005, Experimental cell research.

[47]  G. Vassaux,et al.  Proliferation and differentiation of rat adipose precursor cells in chemically defined medium: Differential action of anti‐adipogenic agents , 1994, Journal of cellular physiology.

[48]  R. Bank,et al.  Influence of collagen type II and nucleus pulposus cells on aggregation and differentiation of adipose tissue-derived stem cells , 2008, Journal of cellular and molecular medicine.

[49]  S. Miller.  Collagenous Microbeads as a Scaffold for Tissue Engineering with Adipose-Derived Stem Cells , 2009 .

[50]  T. Tsuchiya,et al.  FGF-2 increases osteogenic and chondrogenic differentiation potentials of human mesenchymal stem cells by inactivation of TGF-β signaling , 2007, Cytotechnology.

[51]  Gil Navon,et al.  Neotendon formation induced by manipulation of the Smad8 signalling pathway in mesenchymal stem cells. , 2006, The Journal of clinical investigation.

[52]  M. Salto‐Tellez,et al.  Derivation of Clinically Compliant MSCs from CD105+, CD24− Differentiated Human ESCs , 2007, Stem cells.

[53]  Lindolfo da Silva Meirelles,et al.  Mesenchymal stem cells reside in virtually all post-natal organs and tissues , 2006, Journal of Cell Science.

[54]  Wei Tang,et al.  Molecular and cellular characterization during chondrogenic differentiation of adipose tissue-derived stromal cells in vitro and cartilage formation in vivo , 2008, Cell Research.

[55]  F J van Milligen,et al.  Adipose tissue-derived mesenchymal stem cell yield and growth characteristics are affected by the tissue-harvesting procedure. , 2006, Cytotherapy.

[56]  M. Haniffa,et al.  Adult Human Fibroblasts Are Potent Immunoregulatory Cells and Functionally Equivalent to Mesenchymal Stem Cells1 , 2007, The Journal of Immunology.

[57]  R. Tuan,et al.  Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation , 2007, Arthritis research & therapy.

[58]  J. Klein-Nulend,et al.  Stem cells from adipose tissue allow challenging new concepts for regenerative medicine. , 2007, Tissue engineering.

[59]  J. Rubin,et al.  The Osteogenic Potential of Adipose-Derived Stem Cells for the Repair of Rabbit Calvarial Defects , 2006, Annals of plastic surgery.

[60]  Y. Wei,et al.  Regulation of adipose-derived adult stem cells differentiating into chondrocytes with the use of rhBMP-2. , 2006, Cytotherapy.

[61]  F. Guilak,et al.  Adipose-derived adult stem cells: isolation, characterization, and differentiation potential. , 2003, Cytotherapy.

[62]  A. Kundu,et al.  Adhesion of mesenchymal stem cells to polymer scaffolds occurs via distinct ECM ligands and controls their osteogenic differentiation. , 2006, Journal of biomedical materials research. Part A.

[63]  I. Sekiya,et al.  Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue, and muscle , 2007, Cell and Tissue Research.

[64]  J. Lou,et al.  Bone regeneration by implantation of adipose-derived stromal cells expressing BMP-2. , 2007, Biochemical and biophysical research communications.

[65]  C. Lengner,et al.  Networks and hubs for the transcriptional control of osteoblastogenesis , 2006, Reviews in Endocrine and Metabolic Disorders.

[66]  M. Hedrick,et al.  Multipotential differentiation of adipose tissue-derived stem cells. , 2005, The Keio journal of medicine.

[67]  J. Klein-Nulend,et al.  Osteogenesis versus chondrogenesis by BMP-2 and BMP-7 in adipose stem cells. , 2006, Biochemical and biophysical research communications.

[68]  J. Gimble,et al.  Human adipose-derived adult stem cells produce osteoid in vivo. , 2004, Tissue engineering.

[69]  H. Lorenz,et al.  Rat extramedullary adipose tissue as a source of osteochondrogenic progenitor cells. , 2002, Plastic and reconstructive surgery.

[70]  J. Hui,et al.  The potential of stem cells in orthopaedic surgery. , 2006, The Journal of bone and joint surgery. British volume.

[71]  Chang-long Yu,et al.  ACL reconstruction in a rabbit model using irradiated Achilles allograft seeded with mesenchymal stem cells or PDGF-B gene-transfected mesenchymal stem cells , 2007, Knee Surgery, Sports Traumatology, Arthroscopy.

[72]  Joji Mochida,et al.  Differentiation of Mesenchymal Stem Cells Transplanted to a Rabbit Degenerative Disc Model: Potential and Limitations for Stem Cell Therapy in Disc Regeneration , 2005, Spine.

[73]  M. Pittenger,et al.  Multilineage potential of adult human mesenchymal stem cells. , 1999, Science.