REGENERATIVE MEDICINE Concise Review: Adipose-Derived Stem Cells as a Novel Tool for Future Regenerative Medicine

The potential use of stem cell‐based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift that may provide alternative therapeutic solutions for a number of diseases. The use of either embryonic stem cells (ESCs) or induced pluripotent stem cells in clinical situations is limited due to cell regulations and to technical and ethical considerations involved in the genetic manipulation of human ESCs, even though these cells are, theoretically, highly beneficial. Mesenchymal stem cells seem to be an ideal population of stem cells for practical regenerative medicine, because they are not subjected to the same restrictions. In particular, large number of adipose‐derived stem cells (ASCs) can be easily harvested from adipose tissue. Furthermore, recent basic research and preclinical studies have revealed that the use of ASCs in regenerative medicine is not limited to mesodermal tissue but extends to both ectodermal and endodermal tissues and organs, although ASCs originate from mesodermal lineages. Based on this background knowledge, the primary purpose of this concise review is to summarize and describe the underlying biology of ASCs and their proliferation and differentiation capacities, together with current preclinical and clinical data from a variety of medical fields regarding the use of ASCs in regenerative medicine. In addition, future directions for ASCs in terms of cell‐based therapies and regenerative medicine are discussed. STEM CELLS 2012;30:804–810

[1]  J. Rubin,et al.  Regional Anatomic and Age Effects on Cell Function of Human Adipose-Derived Stem Cells , 2008, Annals of plastic surgery.

[2]  H. Mizuno,et al.  Tendon regeneration and repair with adipose derived stem cells. , 2010, Current stem cell research & therapy.

[3]  Albert D. Donnenberg,et al.  Stromal vascular progenitors in adult human adipose tissue , 2009, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[4]  R. Hammer,et al.  White Fat Progenitor Cells Reside in the Adipose Vasculature , 2008, Science.

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

[6]  Hakan Orbay,et al.  Adipose-derived stem cells: current findings and future perspectives. , 2011, Discovery medicine.

[7]  S. Phadnis,et al.  Generation of Pancreatic Hormone‐Expressing Islet‐Like Cell Aggregates from Murine Adipose Tissue‐Derived Stem Cells , 2009, Stem cells.

[8]  K. Harii,et al.  Cell-Assisted Lipotransfer for Cosmetic Breast Augmentation: Supportive Use of Adipose-Derived Stem/Stromal Cells , 2007, Aesthetic Plastic Surgery.

[9]  J. Cigudosa,et al.  Spontaneous human adult stem cell transformation. , 2005, Cancer research.

[10]  Xiying Wu,et al.  Culture effects of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) on cryopreserved human adipose‐derived stromal/stem cell proliferation and adipogenesis , 2009, Journal of tissue engineering and regenerative medicine.

[11]  K. Yoshimura,et al.  Adipose-derived stem/progenitor cells: roles in adipose tissue remodeling and potential use for soft tissue augmentation. , 2009, Regenerative medicine.

[12]  Farshid Guilak,et al.  Isolation of adipose-derived stem cells and their induction to a chondrogenic phenotype , 2010, Nature Protocols.

[13]  J. Krieger,et al.  TRANSPLANTATION AND CELLULAR ENGINEERING: Adipose tissue mesenchymal stem cell expansion in animal serum‐free medium supplemented with autologous human platelet lysate , 2009, Transfusion.

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

[15]  L. Pénicaud,et al.  Spontaneous Cardiomyocyte Differentiation From Adipose Tissue Stroma Cells , 2004, Circulation research.

[16]  F. Guilak,et al.  Concise Review: Adipose‐Derived Stromal Vascular Fraction Cells and Stem Cells: Let's Not Get Lost in Translation , 2011, Stem cells.

[17]  C. Dani,et al.  Autocrine Fibroblast Growth Factor 2 Signaling Is Critical for Self‐Renewal of Human Multipotent Adipose‐Derived Stem Cells , 2006, Stem cells.

[18]  Daniel A. De Ugarte,et al.  In Vivo Distribution of Human Adipose‐Derived Mesenchymal Stem Cells in Novel Xenotransplantation Models , 2007, Stem cells.

[19]  M. Marazzi,et al.  Purification and Characterization of Adipose-Derived Stem Cells from Patients with Lipoaspirate Transplant , 2010, Cell transplantation.

[20]  Keith L. March,et al.  Secretion of Angiogenic and Antiapoptotic Factors by Human Adipose Stromal Cells , 2004, Circulation.

[21]  Min Du,et al.  Skeletal Muscle Stem Cells from Animals I. Basic Cell Biology , 2010, International journal of biological sciences.

[22]  K. Timper,et al.  Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells. , 2006, Biochemical and biophysical research communications.

[23]  N. Bresolin,et al.  Human skin‐derived stem cells migrate throughout forebrain and differentiate into astrocytes after injection into adult mouse brain , 2004, Journal of neuroscience research.

[24]  J. Ringe,et al.  Specific plasma membrane protein phenotype of culture-amplified and native human bone marrow mesenchymal stem cells. , 2008, Blood.

[25]  Natalia de Isla,et al.  Long term culture of mesenchymal stem cells in hypoxia promotes a genetic program maintaining their undifferentiated and multipotent status , 2011, BMC Cell Biology.

[26]  M. Desai,et al.  Obesity is associated with macrophage accumulation in adipose tissue. , 2003, The Journal of clinical investigation.

[27]  S. Kang,et al.  Autologous adipose tissue-derived stromal cells for treatment of spinal cord injury. , 2006, Stem cells and development.

[28]  P. Sharpe,et al.  Perivascular cells as mesenchymal stem cells , 2010, Expert opinion on biological therapy.

[29]  M. Hedrick,et al.  Myogenic Differentiation by Human Processed Lipoaspirate Cells , 2002, Plastic and reconstructive surgery.

[30]  J. Jonas,et al.  Retinal pigment epithelial phenotype induced in human adipose tissue-derived mesenchymal stromal cells. , 2009, Cytotherapy.

[31]  A. Jödicke,et al.  Autologous stem cells (adipose) and fibrin glue used to treat widespread traumatic calvarial defects: case report. , 2004, Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery.

[32]  H. Mizuno,et al.  Periodontal disease and periodontal tissue regeneration. , 2010, Current stem cell research & therapy.

[33]  F. Guilak,et al.  Clinical and preclinical translation of cell-based therapies using adipose tissue-derived cells , 2010, Stem Cell Research & Therapy.

[34]  R. Tuan,et al.  Comparison of Proliferative and Multilineage Differentiation Potential of Human Mesenchymal Stem Cells Derived from Umbilical Cord and Bone Marrow , 2007, Stem cells.

[35]  R. Izadpanah,et al.  Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue , 2006, Journal of cellular biochemistry.

[36]  S. Yamashita,et al.  MESENCHYMAL STEM CELL THERAPY FOR CUTANEOUS RADIATION SYNDROME , 2010, Health physics.

[37]  J. Rubin,et al.  Cardiomyogenic differentiation potential of human adipose precursor cells. , 2009, International journal of cardiology.

[38]  J. Gimble,et al.  Cytokine profile of human adipose‐derived stem cells: Expression of angiogenic, hematopoietic, and pro‐inflammatory factors , 2007, Journal of cellular physiology.

[39]  P. Zuk.  The Adipose-derived Stem Cell: Looking Back and Looking Ahead , 2010, Molecular biology of the cell.

[40]  J. Rubin,et al.  Adipose tissue regeneration. , 2010, Current stem cell research & therapy.

[41]  Rocky S Tuan,et al.  Origin and characterization of multipotential mesenchymal stem cells derived from adult human trabecular bone. , 2005, Stem cells and development.

[42]  L. Tartaglia,et al.  Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. , 2003, The Journal of clinical investigation.

[43]  J. Gimble,et al.  Adipose-derived stem cells for regenerative medicine. , 2007, Circulation research.

[44]  J. Roh,et al.  Systemic transplantation of human adipose stem cells attenuated cerebral inflammation and degeneration in a hemorrhagic stroke model , 2007, Brain Research.

[45]  K. Kusumoto,et al.  Proliferation-Promoting Effect of Platelet-Rich Plasma on Human Adipose–Derived Stem Cells and Human Dermal Fibroblasts , 2008, Plastic and reconstructive surgery.

[46]  G. Rho,et al.  Characterization and comparison of telomere length, telomerase and reverse transcriptase activity and gene expression in human mesenchymal stem cells and cancer cells of various origins , 2011, Cell and Tissue Research.

[47]  Manuel A. González,et al.  Treatment of experimental arthritis by inducing immune tolerance with human adipose-derived mesenchymal stem cells. , 2009, Arthritis and rheumatism.

[48]  Hyunjin Cho,et al.  Role of CD9 in proliferation and proangiogenic action of human adipose-derived mesenchymal stem cells , 2007, Pflügers Archiv - European Journal of Physiology.

[49]  H. Roh,et al.  Immunomodulatory effects of adipose-derived stem cells in airway allergic diseases. , 2010, Current stem cell research & therapy.

[50]  T. Iwama,et al.  Comparison of mesenchymal stem cells from adipose tissue and bone marrow for ischemic stroke therapy. , 2011, Cytotherapy.

[51]  R. Deans,et al.  Mesenchymal stem cells: biology and potential clinical uses. , 2000, Experimental hematology.

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

[53]  I. B. Borel Rinkes,et al.  Mesenchymal Stem Cell Therapy for Protection and Repair of Injured Vital Organs , 2008 .

[54]  P. Gentile,et al.  Concise Review: Adipose‐Derived Stromal Vascular Fraction Cells and Platelet‐Rich Plasma: Basic and Clinical Implications for Tissue Engineering Therapies in Regenerative Surgery , 2012, Stem cells translational medicine.

[55]  J. Dragoo,et al.  Tissue-engineered cartilage and bone using stem cells from human infrapatellar fat pads. , 2003, The Journal of bone and joint surgery. British volume.

[56]  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.

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

[58]  Patricia Zuk,et al.  Epithelial differentiation of adipose‐derived stem cells for laryngeal tissue engineering , 2010, The Laryngoscope.

[59]  R. Zhao,et al.  Favorable response to human adipose tissue-derived mesenchymal stem cells in steroid-refractory acute graft-versus-host disease. , 2007, Transplantation proceedings.

[60]  Stan Gronthos,et al.  Investigation of multipotent postnatal stem cells from human periodontal ligament , 2004, The Lancet.

[61]  S. Yamanaka,et al.  Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors , 2006, Cell.

[62]  N. Benvenisty,et al.  The tumorigenicity of human embryonic and induced pluripotent stem cells , 2011, Nature Reviews Cancer.

[63]  H. Mizuno.  Adipose-derived stem and stromal cells for cell-based therapy: current status of preclinical studies and clinical trials. , 2010, Current opinion in molecular therapeutics.

[64]  J. Hengstler,et al.  Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo , 2008, Gut.

[65]  K. Harii,et al.  Cell‐Assisted Lipotransfer for Facial Lipoatrophy: Efficacy of Clinical Use of Adipose‐Derived Stem Cells , 2008, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[66]  Shingo Nakamura,et al.  Accelerated Wound Healing in Healing-Impaired db/db Mice by Autologous Adipose Tissue-Derived Stromal Cells Combined With Atelocollagen Matrix , 2009, Annals of plastic surgery.

[67]  Jae Hyun Kim,et al.  Role of c‐Jun N‐terminal kinase in the PDGF‐induced proliferation and migration of human adipose tissue‐derived mesenchymal stem cells , 2005, Journal of cellular biochemistry.

[68]  Farshid Guilak,et al.  Three-dimensional culture systems to induce chondrogenesis of adipose-derived stem cells. , 2011, Methods in molecular biology.

[69]  N Lenoir,et al.  Europe confronts the embryonic stem cell research challenge. , 2000, Science.

[70]  F. Luyten,et al.  Multipotent mesenchymal stem cells from adult human synovial membrane. , 2001, Arthritis and rheumatism.

[71]  Won-Serk Kim,et al.  Protective role of adipose-derived stem cells and their soluble factors in photoaging , 2009, Archives of Dermatological Research.

[72]  A. Bailey,et al.  Characterization of adipose-derived stem cells: an update. , 2009, Current stem cell research & therapy.

[73]  B. Spiegelman,et al.  PRDM16 controls a brown fat/skeletal muscle switch , 2008, Nature.

[74]  D. García-Olmo,et al.  Expanded Adipose-Derived Stem Cells for the Treatment of Complex Perianal Fistula: a Phase II Clinical Trial , 2009, Diseases of the colon and rectum.

[75]  P. Collas,et al.  Isolation of stromal stem cells from human adipose tissue. , 2006, Methods in molecular biology.

[76]  Yong-Soo Choi,et al.  Multipotency and growth characteristic of periosteum-derived progenitor cells for chondrogenic, osteogenic, and adipogenic differentiation , 2008, Biotechnology Letters.

[77]  R. Martin,et al.  Tumor necrosis factor-alpha stimulates cell proliferation in adipose tissue-derived stromal-vascular cell culture: promotion of adipose tissue expansion by paracrine growth factors. , 2000, Obesity research.

[78]  Min Zhu,et al.  Comparison of Multi-Lineage Cells from Human Adipose Tissue and Bone Marrow , 2003, Cells Tissues Organs.

[79]  Masakazu Ishikawa,et al.  Acceleration of Skeletal Muscle Regeneration in a Rat Skeletal Muscle Injury Model by Local Injection of Human Peripheral Blood‐Derived CD133‐Positive Cells , 2009, Stem cells.

[80]  C. Dani,et al.  Adipocyte differentiation of multipotent cells established from human adipose tissue. , 2004, Biochemical and biophysical research communications.

[81]  S. Zarkesh-Esfahani,et al.  Phenotypic Characterizations and Comparison of Adult Dental Stem Cells with Adipose-Derived Stem Cells , 2010, International journal of preventive medicine.

[82]  S. Gauer,et al.  Epithelial differentiation of human adipose tissue-derived adult stem cells. , 2005, Biochemical and biophysical research communications.

[83]  J. Gimble,et al.  Characterization of neuronal/glial differentiation of murine adipose-derived adult stromal cells , 2004, Experimental Neurology.

[84]  T. Ochiya,et al.  Rapid hepatic fate specification of adipose‐derived stem cells and their therapeutic potential for liver failure , 2009, Journal of gastroenterology and hepatology.

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

[86]  A. Cometa,et al.  Human bone marrow-derived mesenchymal stem cells do not undergo transformation after long-term in vitro culture and do not exhibit telomere maintenance mechanisms , 2010 .

[87]  D. García-Olmo,et al.  Treatment of enterocutaneous fistula in Crohn’s Disease with adipose-derived stem cells: a comparison of protocols with and without cell expansion , 2008, International Journal of Colorectal Disease.

[88]  K. Yoshimura,et al.  Functional Implications of Cd34 Expression in Human Adipose–derived Stem/progenitor Cells , 2022 .

[89]  J. H. Kim,et al.  Oncostatin M induces proliferation of human adipose tissue-derived mesenchymal stem cells. , 2005, The international journal of biochemistry & cell biology.

[90]  J. Daly.  Accelerated Wound Healing in Healing-Impaired db/db Mice by Autologous Adipose Tissue-Derived Stromal Cells Combined With Atelocollagen Matrix , 2010 .

[91]  Stan Gronthos,et al.  SHED: Stem cells from human exfoliated deciduous teeth , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[92]  J. Cigudosa,et al.  Pitfalls in spontaneous in vitro transformation of human mesenchymal stem cells. , 2010, Experimental cell research.

[93]  R. Bjerkvig,et al.  Spontaneous malignant transformation of human mesenchymal stem cells reflects cross-contamination: putting the research field on track - letter. , 2010, Cancer research.

[94]  K. Marra,et al.  Adipose-derived stem cells for soft tissue reconstruction. , 2009, Regenerative medicine.

[95]  C. S. Freitas,et al.  Multiple sources of non-embryonic multipotent stem cells: processed lipoaspirates and dermis as promising alternatives to bone-marrow-derived cell therapies , 2006, Cell and Tissue Research.

[96]  J. Rubin,et al.  Adipose-Derived Stem Cells for Wound Healing Applications , 2011, Annals of plastic surgery.

[97]  Yao‐Hua Song,et al.  Thrombin Peptide (TP508) Promotes Adipose Tissue-Derived Stem Cell Proliferation via PI3 Kinase/Akt Pathway , 2008, Journal of Vascular Research.

[98]  Paul Emery,et al.  Optimization of a flow cytometry‐based protocol for detection and phenotypic characterization of multipotent mesenchymal stromal cells from human bone marrow , 2006, Cytometry. Part B, Clinical cytometry.

[99]  W. Arap,et al.  A Population of Multipotent CD34-Positive Adipose Stromal Cells Share Pericyte and Mesenchymal Surface Markers, Reside in a Periendothelial Location, and Stabilize Endothelial Networks , 2008, Circulation research.

[100]  G. Sukhikh,et al.  Comparison of Mesenchymal Stem Cells Obtained from Different Human Tissues , 2005, Bulletin of Experimental Biology and Medicine.

[101]  L. Pénicaud,et al.  From heterogeneity to plasticity in adipose tissues: site-specific differences. , 2006, Experimental cell research.

[102]  J. Gimble,et al.  Adipose tissue derived stem cells secretome: soluble factors and their roles in regenerative medicine. , 2010, Current Stem Cell Research & Therapy.

[103]  Kotaro Yoshimura,et al.  Characterization of freshly isolated and cultured cells derived from the fatty and fluid portions of liposuction aspirates , 2006, Journal of cellular physiology.

[104]  R. Suuronen,et al.  Novel maxillary reconstruction with ectopic bone formation by GMP adipose stem cells. , 2009, International journal of oral and maxillofacial surgery.

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

[106]  G. Baroni,et al.  Clinical Treatment of Radiotherapy Tissue Damage by Lipoaspirate Transplant: A Healing Process Mediated by Adipose-Derived Adult Stem Cells , 2007, Plastic and reconstructive surgery.

[107]  I. Pitanguy,et al.  Tissue engineering with adipose-derived stem cells (ADSCs): current and future applications. , 2010, Journal of plastic, reconstructive & aesthetic surgery : JPRAS.