Human mesenchymal stem cells: From immunophenotyping by flow cytometry to clinical applications

Modern medicine will unequivocally include regenerative medicine as a major breakthrough in the re‐establishment of damaged or lost tissues due to degenerative diseases or injury. In this scenario, millions of patients worldwide can have their quality of life improved by stem cell implantation coupled with endogenous secretion or administration of survival and differentiation promoting factors. Large efforts, relying mostly on flow cytometry and imaging techniques, have been put into cell isolation, immunophenotyping, and studies of differentiation properties of stem cells of diverse origins. Mesenchymal stem cells (MSCs) are particularly relevant for therapy due to their simplicity of isolation. A minimal phenotypic pattern for the identification of MSCs cells requires them to be immunopositive for CD73, CD90, and CD105 expression, while being negative for CD34, CD45, and HLA‐DR and other surface markers. MSCs identified by their cell surface marker expression pattern can be readily purified from patient's bone marrow and adipose tissues. Following expansion and/or predifferentiation into a desired tissue type, stem cells can be reimplanted for tissue repair in the same patient, virtually eliminating rejection problems. Transplantation of MSCs is subject of almost 200 clinical trials to cure and treat a very broad range of conditions, including bone, heart, and neurodegenerative diseases. Immediate or medium term improvements of clinical symptoms have been reported as results of many clinical studies. © 2012 International Society for Advancement of Cytometry

[1]  K. Houkin,et al.  Comparative analysis of remyelinating potential of focal and intravenous administration of autologous bone marrow cells into the rat demyelinated spinal cord , 2003, Glia.

[2]  N. Câmara,et al.  Mesenchymal Stem Cell Therapy Modulates the Inflammatory Response in Experimental Traumatic Brain Injury , 2011, Neurology research international.

[3]  A. Benabid,et al.  Functional Neuronal Differentiation of Bone Marrow‐Derived Mesenchymal Stem Cells , 2006, Stem cells.

[4]  R. Brenner,et al.  Identification, quantification and isolation of mesenchymal progenitor cells from osteoarthritic synovium by fluorescence automated cell sorting. , 2003, Osteoarthritis and cartilage.

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

[6]  C. Cobbs,et al.  Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates. , 2003, Blood.

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

[8]  T. Jensen,et al.  Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells , 2002, Nature Biotechnology.

[9]  L. Mazzini,et al.  Stem cell therapy in amyotrophic lateral sclerosis: a methodological approach in humans , 2003, Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases.

[10]  J. Krieger,et al.  Rat Adipose Tissue-Derived Stem Cells Transplantation Attenuates Cardiac Dysfunction Post Infarction and Biopolymers Enhance Cell Retention , 2010, PloS one.

[11]  K. Matsumoto,et al.  Myocardial protection from ischemia/reperfusion injury by endogenous and exogenous HGF. , 2000, The Journal of clinical investigation.

[12]  Mingyao Liu,et al.  Autologous mesenchymal stem cell transplantation induce VEGF and neovascularization in ischemic myocardium , 2004, Regulatory Peptides.

[13]  Q. Han,et al.  Human adipose tissue-derived stem cells differentiate into endothelial cells in vitro and improve postnatal neovascularization in vivo. , 2005, Biochemical and biophysical research communications.

[14]  L. del Vecchio,et al.  Comparative characteristics of mesenchymal stem cells from human bone marrow and placenta: CD10, CD49d, and CD56 make a difference. , 2008, Stem Cells and Development.

[15]  J. Ingwall,et al.  Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts , 2003, Nature Medicine.

[16]  C. Lois,et al.  Mesenchymal Stem Cells Instruct Oligodendrogenic Fate Decision on Adult Neural Stem Cells , 2006, Stem cells.

[17]  P. Dash,et al.  Intravenous mesenchymal stem cell therapy for traumatic brain injury. , 2009, Journal of neurosurgery.

[18]  E. Benveniste,et al.  Cytokine actions in the central nervous system. , 1998, Cytokine & growth factor reviews.

[19]  L. Stone,et al.  Bone marrow stromal cells as replacement cells for Parkinson's disease: generation of an anatomical but not functional neuronal phenotype. , 2011, Translational research : the journal of laboratory and clinical medicine.

[20]  Yen Chang,et al.  Direct intramyocardial injection of mesenchymal stem cell sheet fragments improves cardiac functions after infarction. , 2008, Cardiovascular research.

[21]  Charles P. Lin,et al.  Endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone maintenance and regeneration. , 2012, Cell stem cell.

[22]  R Cancedda,et al.  Repair of large bone defects with the use of autologous bone marrow stromal cells. , 2001, The New England journal of medicine.

[23]  B. Min,et al.  Differentiation, engraftment and functional effects of pre-treated mesenchymal stem cells in a rat myocardial infarct model , 2005, Acta cardiologica.

[24]  Hidezo Mori,et al.  Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction , 2006, Nature Medicine.

[25]  Jeff W M Bulte,et al.  Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. , 2010, Archives of neurology.

[26]  J. Uney,et al.  Enhanced green fluorescent protein-expressing human mesenchymal stem cells retain neural marker expression , 2008, Journal of Neuroimmunology.

[27]  C. Ide,et al.  Bone marrow stromal cells infused into the cerebrospinal fluid promote functional recovery of the injured rat spinal cord with reduced cavity formation , 2004, Experimental Neurology.

[28]  J. Neuwirth,et al.  Autologous bone marrow transplantation in patients with subacute and chronic spinal cord injury. , 2006, Cell transplantation.

[29]  S. Miller,et al.  Human bone marrow‐derived mesenchymal stem cells induce Th2‐polarized immune response and promote endogenous repair in animal models of multiple sclerosis , 2009, Glia.

[30]  A. Manira,et al.  Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[31]  A. Caplan,et al.  Human Mesenchymal Stem Cells Signals Regulate Neural Stem Cell Fate , 2007, Neurochemical Research.

[32]  E. Alsberg,et al.  Imaging stem cell differentiation for cell-based tissue repair. , 2012, Methods in enzymology.

[33]  A. Grimaldi,et al.  Growth and endothelial differentiation of adipose stem cells on polycaprolactone. , 2012, Journal of biomedical materials research. Part A.

[34]  J. Pak Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: a case series , 2011, Journal of medical case reports.

[35]  P. Pinton,et al.  Hyaluronan and Fibrin Biomaterial as Scaffolds for Neuronal Differentiation of Adult Stem Cells Derived from Adipose Tissue and Skin , 2011, International journal of molecular sciences.

[36]  J. Kocsis,et al.  Remyelination of the Rat Spinal Cord by Transplantation of Identified Bone Marrow Stromal Cells , 2002, The Journal of Neuroscience.

[37]  H. Ulrich,et al.  Phenotypes of stem cells from diverse origin , 2010, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[38]  J. Kantelip,et al.  Mesenchymal Progenitor Cells Differentiate into an Endothelial Phenotype, Enhance Vascular Density, and Improve Heart Function in a Rat Cellular Cardiomyoplasty Model , 2003, Circulation.

[39]  M. Fehlings,et al.  Current status of experimental cell replacement approaches to spinal cord injury. , 2008, Neurosurgical focus.

[40]  B. Gersh,et al.  Cardiac cell repair therapy: a clinical perspective. , 2009, Mayo Clinic proceedings.

[41]  M. Zurita,et al.  Functional recovery in chronic paraplegia after bone marrow stromal cells transplantation , 2004, Neuroreport.

[42]  Mandi J. Lopez,et al.  Mesenchymal stromal cells: past, present, and future. , 2011, Veterinary surgery : VS.

[43]  F. Prósper,et al.  Adipose-derived cardiomyogenic cells: in vitro expansion and functional improvement in a mouse model of myocardial infarction. , 2009, Cardiovascular research.

[44]  Xue-lian Zhang,et al.  e0086 Sinoaortic denervation disrupted the circadian rhythm of the oscillation of molecular clock and activity of RAS in cardiovascular , 2010, Heart.

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

[46]  Antonio Uccelli,et al.  Mesenchymal stem cells effectively modulate pathogenic immune response in experimental autoimmune encephalomyelitis , 2007, Annals of neurology.

[47]  F. Fernández‐Avilés,et al.  Review Article Phases I–iii Clinical Trials Using Adult Stem Cells 1. Concept and Types of Randomized Clinical Trials 2. Clinical Research in Stem Cell Therapy: Same Methodology with a New Objective , 2022 .

[48]  Masayuki Yamato,et al.  Cell sheet-based myocardial tissue engineering: new hope for damaged heart rescue. , 2009, Current pharmaceutical design.

[49]  N. Scolding New cells from old , 2001, The Lancet.

[50]  I. Fischer,et al.  In vitro differentiation of human marrow stromal cells into early progenitors of neural cells by conditions that increase intracellular cyclic AMP. , 2001, Biochemical and biophysical research communications.

[51]  M. Chopp,et al.  Therapeutic Benefit of Intravenous Administration of Bone Marrow Stromal Cells After Cerebral Ischemia in Rats , 2001, Stroke.

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

[53]  M. Chopp,et al.  Human marrow stromal cell therapy for stroke in rat: Neurotrophins and functional recovery , 2002, Neurology.

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

[55]  S. Kyurkchiev,et al.  Characterization of mesenchymal stem cells isolated from the human umbilical cord , 2008, Cell biology international.

[56]  M. Goldring,et al.  Cartilage homeostasis in health and rheumatic diseases , 2009, Arthritis research & therapy.

[57]  Yong Sun,et al.  The antiapoptotic effect of mesenchymal stem cell transplantation on ischemic myocardium is enhanced by anoxic preconditioning. , 2009, The Canadian journal of cardiology.

[58]  H. Ulrich,et al.  Neural differentiation of rat aorta pericyte cells , 2012, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[59]  M. L. Bringas-Vega,et al.  Autologous bone marrow stem cell neurotransplantation in stroke patients. An open study. , 2009, Restorative neurology and neuroscience.

[60]  E. Sim,et al.  Transformation of adult mesenchymal stem cells isolated from the fatty tissue into cardiomyocytes. , 2003, The Annals of thoracic surgery.

[61]  R. Storb,et al.  Allogeneic hematopoietic cell transplantation: the state of the art , 2010, Expert review of hematology.

[62]  B. Wang,et al.  Changing potency by spontaneous fusion , 2022 .

[63]  J. Parisi,et al.  Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination , 2000, Annals of neurology.

[64]  V. Silani,et al.  Noninvasive near-infrared live imaging of human adult mesenchymal stem cells transplanted in a rodent model of Parkinson’s disease , 2012, International journal of nanomedicine.

[65]  Y. Torrente,et al.  Mesenchymal Stem Cell Transplantation for Neurodegenerative Diseases , 2008, Cell transplantation.

[66]  L. Muul,et al.  Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[67]  Samuel Bernard,et al.  Evidence for Cardiomyocyte Renewal in Humans , 2008, Science.

[68]  R. Poulsom,et al.  Bone marrow derivation of pericryptal myofibroblasts in the mouse and human small intestine and colon , 2002, Gut.

[69]  A. Donnenberg,et al.  Mesenchymal markers on human adipose stem/progenitor cells , 2013, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[70]  Xiran Zhang,et al.  Mesenchymal Stern Cells from Adult Human Bone Marrow Differentiate into a Cardiomyocyte Phenotype In Vitro , 2004, Experimental biology and medicine.

[71]  D. Prockop,et al.  Multipotential marrow stromal cells transduced to produce L-DOPA: engraftment in a rat model of Parkinson disease. , 1999, Human gene therapy.

[72]  J. Gimble,et al.  Phases I–III Clinical Trials Using Adult Stem Cells , 2010, Stem Cells International.

[73]  F Beaujean,et al.  Percutaneous autologous bone-marrow grafting for nonunions. Influence of the number and concentration of progenitor cells. , 2005, The Journal of bone and joint surgery. American volume.

[74]  R. Zhao,et al.  Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. , 2008, Cell Stem Cell.

[75]  S. Badylak,et al.  A perivascular origin for mesenchymal stem cells in multiple human organs. , 2008, Cell stem cell.

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

[77]  R. Cahill,et al.  Infantile hypophosphatasia: transplantation therapy trial using bone fragments and cultured osteoblasts. , 2007, The Journal of clinical endocrinology and metabolism.

[78]  G. Lin,et al.  Defining adipose tissue-derived stem cells in tissue and in culture. , 2010, Histology and histopathology.

[79]  T. Pursche,et al.  The Cell Surface Proteome of Human Mesenchymal Stromal Cells , 2011, PloS one.

[80]  H. Ulrich,et al.  Novel perspectives of neural stem cell differentiation: From neurotransmitters to therapeutics , 2009, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[81]  M. Kaplitt,et al.  Future and current surgical therapies in Parkinson's disease , 2003, Current opinion in neurology.

[82]  A. Folsom,et al.  Heart failure incidence and survival (from the Atherosclerosis Risk in Communities study). , 2008, The American journal of cardiology.

[83]  A. Uccelli,et al.  Mesenchymal stem cells in health and disease , 2008, Nature Reviews Immunology.

[84]  M. Chopp,et al.  Human bone marrow stromal cell treatment improves neurological functional recovery in EAE mice , 2005, Experimental Neurology.

[85]  R. Pochampally,et al.  Angiogenic Effects of Human Multipotent Stromal Cell Conditioned Medium Activate the PI3K‐Akt Pathway in Hypoxic Endothelial Cells to Inhibit Apoptosis, Increase Survival, and Stimulate Angiogenesis , 2007, Stem cells.

[86]  Jeffrey Robbins,et al.  Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury , 2007, Nature Medicine.

[87]  Paul Emery,et al.  Isolation and characterization of bone marrow multipotential mesenchymal progenitor cells. , 2002, Arthritis and rheumatism.

[88]  S. Ogawa,et al.  Cardiomyocytes can be generated from marrow stromal cells in vitro. , 1999, The Journal of clinical investigation.

[89]  C. Carlo-Stella,et al.  Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. , 2002, Blood.

[90]  Dai Fukumura,et al.  Bone marrow-derived mesenchymal stem cells facilitate engineering of long-lasting functional vasculature. , 2008, Blood.

[91]  A. Schäffler,et al.  Concise Review: Adipose Tissue‐Derived Stromal Cells—Basic and Clinical Implications for Novel Cell‐Based Therapies , 2007, Stem cells.

[92]  M. Westgren,et al.  Ten years follow up after prenatal transplantation of fetal mesenchymal stem cell in a patient with severe osteogenesis imperfecta , 2013 .

[93]  J. Kocsis,et al.  Transplantation of an acutely isolated bone marrow fraction repairs demyelinated adult rat spinal cord axons , 2001, Glia.

[94]  A. Björklund,et al.  Transplantation in the rat model of Parkinson's disease: ectopic versus homotopic graft placement. , 2000, Progress in brain research.

[95]  W. Janssen,et al.  Adult Bone Marrow Stromal Cells Differentiate into Neural Cells in Vitro , 2000, Experimental Neurology.

[96]  G. Prestwich,et al.  Recruitment of endogenous stem cells for tissue repair. , 2008, Macromolecular bioscience.

[97]  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.

[98]  M. Jansson,et al.  Fetal Mesenchymal Stem-Cell Engraftment in Bone after In Utero Transplantation in a Patient with Severe Osteogenesis Imperfecta , 2005, Transplantation.

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

[100]  D. Youn,et al.  Bone Marrow‐Derived Mesenchymal Stem Cells Promote Neuronal Networks with Functional Synaptic Transmission After Transplantation into Mice with Neurodegeneration , 2007, Stem cells.

[101]  J. Frisén,et al.  Differentiation potential of adult stem cells. , 2001, Current opinion in genetics & development.

[102]  Darwin J. Prockop,et al.  Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta , 1999, Nature Medicine.

[103]  K Walsh,et al.  Cardiomyocyte grafting for cardiac repair: graft cell death and anti-death strategies. , 2001, Journal of molecular and cellular cardiology.

[104]  I. Black,et al.  Adult rat and human bone marrow stromal cells differentiate into neurons , 2000, Journal of neuroscience research.

[105]  M. Eisenberg,et al.  Coronary artery disease in the developing world. , 2004, American heart journal.

[106]  M. Chopp,et al.  Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats , 2001, Journal of the Neurological Sciences.

[107]  R Busse,et al.  Improvement of Postnatal Neovascularization by Human Adipose Tissue–Derived Stem Cells , 2004, Circulation.

[108]  D J Prockop,et al.  Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[109]  W. Koo,et al.  Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta. , 2001, Blood.

[110]  Oh Young Bang,et al.  Autologous mesenchymal stem cell transplantation in stroke patients , 2005, Annals of neurology.

[111]  J. Kocsis,et al.  Remyelination of the spinal cord following intravenous delivery of bone marrow cells , 2002, Glia.

[112]  Miles C. Miller,et al.  Encapsulated native and glucagon-like peptide-1 transfected human mesenchymal stem cells in a transgenic mouse model of Alzheimer's disease , 2011, Neuroscience Letters.

[113]  Paul D. Kessler,et al.  Human Mesenchymal Stem Cells Differentiate to a Cardiomyocyte Phenotype in the Adult Murine Heart , 2002, Circulation.

[114]  S. Sell Adult stem cell plasticity , 2007, Stem Cell Reviews.

[115]  Larry Kedes,et al.  Washout of transplanted cells from the heart: a potential new hurdle for cell transplantation therapy. , 2005, Cardiovascular research.

[116]  Yongchang Chen,et al.  Human mesenchymal stem cells isolated from the umbilical cord , 2008, Cell biology international.

[117]  M. Chopp,et al.  Intracerebral transplantation of bone marrow stromal cells in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease , 2001, Neuroscience Letters.

[118]  P. Doevendans,et al.  Human relevance of pre-clinical studies in stem cell therapy: systematic review and meta-analysis of large animal models of ischaemic heart disease. , 2011, Cardiovascular research.

[119]  V. Tunaitis,et al.  Proteomic analysis of stromal cells derived from the dental pulp of human exfoliated deciduous teeth. , 2010, Stem cells and development.

[120]  J. Kurtzberg,et al.  Marrow Cell Transplantation for Infantile Hypophosphatasia , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[121]  K. Satomura,et al.  Circulating Skeletal Stem Cells , 2001, The Journal of cell biology.

[122]  Eric O. Aboagye,et al.  An In Vivo Multimodal Imaging Study Using MRI and PET of Stem Cell Transplantation after Myocardial Infarction in Rats , 2008, Molecular Imaging and Biology.

[123]  D. Bodine,et al.  Bone marrow stem cells regenerate infarcted myocardium , 2003, Pediatric transplantation.

[124]  N. Theodore,et al.  Stem cell biology and its therapeutic applications in the setting of spinal cord injury , 2008 .

[125]  B. Fleischmann,et al.  Bone marrow–derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation , 2004, Nature Medicine.

[126]  J. K. Bubien,et al.  Differentiation of adult bone marrow stem cells into neuroprogenitor cells in vitro , 2002, Neuroreport.

[127]  Maurilio Marcacci,et al.  Stem cells associated with macroporous bioceramics for long bone repair: 6- to 7-year outcome of a pilot clinical study. , 2007, Tissue engineering.

[128]  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.

[129]  M. Al-mallah,et al.  Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. , 2007, Archives of internal medicine.

[130]  R. Luo,et al.  Optimal temporal delivery of bone marrow mesenchymal stem cells in rats with myocardial infarction. , 2007, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[131]  K. Meldrum,et al.  Human progenitor cells from bone marrow or adipose tissue produce VEGF, HGF, and IGF-I in response to TNF by a p38 MAPK-dependent mechanism. , 2006, American journal of physiology. Regulatory, integrative and comparative physiology.

[132]  M Chopp,et al.  Spinal cord injury in rat: treatment with bone marrow stromal cell transplantation , 2000, Neuroreport.

[133]  H. Hartung,et al.  New concepts in the immunopathogenesis of multiple sclerosis , 2002, Nature Reviews Neuroscience.

[134]  Shinil K. Shah,et al.  Direct intrathecal implantation of mesenchymal stromal cells leads to enhanced neuroprotection via an NFkappaB-mediated increase in interleukin-6 production. , 2010, Stem cells and development.

[135]  R. Ribeiro‐dos‐Santos,et al.  [Early results of bone marrow cell transplantation to the myocardium of patients with heart failure due to Chagas disease]. , 2006, Arquivos brasileiros de cardiologia.

[136]  D. Prockop Adult stem cells gradually come of age , 2002, Nature Biotechnology.

[137]  J. Lévesque,et al.  Molecular trafficking mechanisms of multipotent mesenchymal stem cells derived from human bone marrow and placenta. , 2008, Stem cells and development.

[138]  S. Cepok,et al.  Pathogenesis of multiple sclerosis: an update on immunology , 2002, Current opinion in neurology.

[139]  G. Mancardi,et al.  Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. , 2005, Blood.

[140]  T. Taketani,et al.  New bone formation by allogeneic mesenchymal stem cell transplantation in a patient with perinatal hypophosphatasia. , 2009, The Journal of pediatrics.