Myocardial Ischemic Subject’s Thymus Fat: A Novel Source of Multipotent Stromal Cells

Objective Adipose Tissue Stromal Cells (ASCs) have important clinical applications in the regenerative medicine, cell replacement and gene therapies. Subcutaneous Adipose Tissue (SAT) is the most common source of these cells. The adult human thymus degenerates into adipose tissue (TAT). However, it has never been studied before as a source of stem cells. Material and Methods We performed a comparative characterization of TAT-ASCs and SAT-ASCs from myocardial ischemic subjects (n = 32) according to the age of the subjects. Results TAT-ASCs and SAT-ASCs showed similar features regarding their adherence, morphology and in their capacity to form CFU-F. Moreover, they have the capacity to differentiate into osteocyte and adipocyte lineages; and they present a surface marker profile corresponding with stem cells derived from AT; CD73+CD90+CD105+CD14-CD19-CD45-HLA-DR. Interestingly, and in opposition to SAT-ASCs, TAT-ASCs have CD14+CD34+CD133+CD45- cells. Moreover, TAT-ASCs from elderly subjects showed higher adipogenic and osteogenic capacities compared to middle aged subjects, indicating that, rather than impairing; aging seems to increase adipogenic and osteogenic capacities of TAT-ASCs. Conclusions This study describes the human TAT as a source of mesenchymal stem cells, which may have an enormous potential for regenerative medicine.

[1]  C. Barbas,et al.  Altered Metabolic and Stemness Capacity of Adipose Tissue-Derived Stem Cells from Obese Mouse and Human , 2015, PloS one.

[2]  Olivia S. Beane,et al.  Impact of Aging on the Regenerative Properties of Bone Marrow-, Muscle-, and Adipose-Derived Mesenchymal Stem/Stromal Cells , 2014, PloS one.

[3]  Claire Yu,et al.  Comparison of Human Adipose‐Derived Stem Cells Isolated from Subcutaneous, Omental, and Intrathoracic Adipose Tissue Depots for Regenerative Applications , 2014, Stem cells translational medicine.

[4]  D. Harris,et al.  Donor age negatively impacts adipose tissue-derived mesenchymal stem cell expansion and differentiation , 2014, Journal of Translational Medicine.

[5]  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.

[6]  C. Rosen,et al.  New insights into osteoporosis: the bone–fat connection , 2012, Journal of internal medicine.

[7]  G. Vilahur,et al.  The subcutaneous adipose tissue reservoir of functionally active stem cells is reduced in obese patients , 2012, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[8]  T. Hardingham,et al.  Fat pad‐derived mesenchymal stem cells as a potential source for cell‐based adipose tissue repair strategies , 2012, Cell proliferation.

[9]  H. Atta,et al.  Therapeutic applications of mesenchymal stroma cells in pediatric diseases: Current aspects and future perspectives , 2011, Medical science monitor : international medical journal of experimental and clinical research.

[10]  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.

[11]  R. de Caterina,et al.  Age‐dependent impairment of number and angiogenic potential of adipose tissue‐derived progenitor cells , 2011, European journal of clinical investigation.

[12]  L. Lau,et al.  The Matricellular Protein CCN1/CYR61 Induces Fibroblast Senescence and Restricts Fibrosis in Cutaneous Wound Healing , 2010, Nature Cell Biology.

[13]  K. M. Lin,et al.  Mechanical strain modulates age-related changes in the proliferation and differentiation of mouse adipose-derived stromal cells , 2010, BMC Cell Biology.

[14]  H. Jabbour,et al.  F-Prostaglandin receptor regulates endothelial cell function via fibroblast growth factor-2 , 2010, BMC Cell Biology.

[15]  F. Tinahones,et al.  VEGF Gene Expression in Adult Human Thymus Fat: A Correlative Study with Hypoxic Induced Factor and Cyclooxigenase-2 , 2009, PloS one.

[16]  M. Furue,et al.  Characterization and comparison of adipose tissue‐derived cells from human subcutaneous and omental adipose tissues , 2009, Cell biochemistry and function.

[17]  M. V. van Luyn,et al.  CD34+ cells augment endothelial cell differentiation of CD14+ endothelial progenitor cells in vitro , 2009, Journal of cellular and molecular medicine.

[18]  M. Hedrick,et al.  The effect of age on osteogenic, adipogenic and proliferative potential of female adipose‐derived stem cells , 2009, Journal of tissue engineering and regenerative medicine.

[19]  Zhao-Jun Liu,et al.  Trafficking and differentiation of mesenchymal stem cells , 2009, Journal of cellular biochemistry.

[20]  T. Hardingham,et al.  The epitope characterisation and the osteogenic differentiation potential of human fat pad-derived stem cells is maintained with ageing in later life. , 2009, Injury.

[21]  J. Bertho,et al.  Characterization and histological localization of multipotent mesenchymal stromal cells in the human postnatal thymus. , 2008, Stem cells and development.

[22]  D. Hutmacher,et al.  Autocrine Fibroblast Growth Factor 2 Increases the Multipotentiality of Human Adipose‐Derived Mesenchymal Stem Cells , 2008, Stem cells.

[23]  M. Yoder,et al.  Lung microvascular endothelium is enriched with progenitor cells that exhibit vasculogenic capacity. , 2008, American journal of physiology. Lung cellular and molecular physiology.

[24]  James L. Kirkland,et al.  Aging in adipocytes: Potential impact of inherent, depot-specific mechanisms , 2007, Experimental Gerontology.

[25]  M. Harmsen,et al.  Efficient differentiation of CD14+ monocytic cells into endothelial cells on degradable biomaterials. , 2007, Biomaterials.

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

[27]  A. Sbarbati,et al.  Induction of neural-like differentiation in human mesenchymal stem cells derived from bone marrow, fat, spleen and thymus. , 2007, Bone.

[28]  R. A. Forse,et al.  Fat Depot–Specific Characteristics Are Retained in Strains Derived From Single Human Preadipocytes , 2006, Diabetes.

[29]  M. Harmsen,et al.  Circulating CD34+ progenitor cells modulate host angiogenesis and inflammation in vivo. , 2006, Journal of molecular and cellular cardiology.

[30]  Hermann Eichler,et al.  Comparative Analysis of Mesenchymal Stem Cells from Bone Marrow, Umbilical Cord Blood, or Adipose Tissue , 2006, Stem cells.

[31]  M. Hedrick,et al.  Fat tissue: an underappreciated source of stem cells for biotechnology. , 2006, Trends in biotechnology.

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

[33]  M. Longaker,et al.  The Osteogenic Potential of Adipose-Derived Mesenchymal Cells Is Maintained with Aging , 2005, Plastic and reconstructive surgery.

[34]  A. Carrière,et al.  Plasticity of adipose tissue: a promising therapeutic avenue in the treatment of cardiovascular and blood diseases? , 2005, Archives des maladies du coeur et des vaisseaux.

[35]  Yihai Cao Emerging mechanisms of tumour lymphangiogenesis and lymphatic metastasis , 2005, Nature Reviews Cancer.

[36]  Y. Sonoda,et al.  Identification and Hematopoietic Potential of CD45− Clonal Cells with Very Immature Phenotype (CD45−CD34−CD38−Lin−) in Patients with Myelodysplastic Syndromes , 2005, Stem cells.

[37]  Nan Ma,et al.  Human cord blood cells induce angiogenesis following myocardial infarction in NOD/scid-mice. , 2005, Cardiovascular research.

[38]  T. Schmid,et al.  CD133 positive endothelial progenitor cells contribute to the tumour vasculature in non-small cell lung cancer , 2004, Journal of Clinical Pathology.

[39]  Hyun-Jae Kang,et al.  Characterization of Two Types of Endothelial Progenitor Cells and Their Different Contributions to Neovasculogenesis , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[40]  L. Hale,et al.  Histologic and molecular assessment of human thymus. , 2004, Annals of diagnostic pathology.

[41]  Christian Clausen,et al.  Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. , 2003, Bone.

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

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

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

[45]  F. C. Lucibello,et al.  Endothelial-like cells derived from human CD14 positive monocytes. , 2000, Differentiation; research in biological diversity.

[46]  M. Greaves,et al.  Expression of the CD34 gene in vascular endothelial cells. , 1990, Blood.

[47]  Maria C. Mitterberger,et al.  Adipogenic differentiation is impaired in replicative senescent human subcutaneous adipose-derived stromal/progenitor cells. , 2014, The journals of gerontology. Series A, Biological sciences and medical sciences.

[48]  Gang Liu,et al.  The comparison of multilineage differentiation of bone marrow and adipose-derived mesenchymal stem cells. , 2012, Clinical laboratory.

[49]  N. Gerry,et al.  Identification of depot-specific human fat cell progenitors through distinct expression profiles and developmental gene patterns. , 2007, American journal of physiology. Endocrinology and metabolism.

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

[51]  Mary L Bouxsein,et al.  Mechanisms of Disease: is osteoporosis the obesity of bone? , 2006, Nature Clinical Practice Rheumatology.

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