LNGFR(+)THY-1(+)VCAM-1(hi+) cells reveal functionally distinct subpopulations in mesenchymal stem cells.
Human mesenchymal stem cells (hMSCs), which conventionally are isolated based on their adherence to plastic, are heterogeneous and have poor growth and differentiation, limiting our ability to investigate their intrinsic characteristics. We report an improved prospective clonal isolation technique and reveal that the combination of three cell-surface markers (LNGFR, THY-1, and VCAM-1) allows for the selection of highly enriched clonogenic cells (one out of three isolated cells). Clonal characterization of LNGFR(+)THY-1(+) cells demonstrated cellular heterogeneity among the clones. Rapidly expanding clones (RECs) exhibited robust multilineage differentiation and self-renewal potency, whereas the other clones tended to acquire cellular senescence via P16INK4a and exhibited frequent genomic errors. Furthermore, RECs exhibited unique expression of VCAM-1 and higher cellular motility compared with the other clones. The combination marker LNGFR(+)THY-1(+)VCAM-1(hi+) (LTV) can be used selectively to isolate the most potent and genetically stable MSCs.
Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan ; Department of Biochemistry and Biophysics, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan.
Yo
Y
Mabuchi
Satoru
S
Morikawa
Seiko
S
Harada
Kunimichi
K
Niibe
Sadafumi
S
Suzuki
Francois
F
Renault-Mihara
Diarmaid D
DD
Houlihan
Chihiro
C
Akazawa
Hideyuki
H
Okano
Yumi
Y
Matsuzaki
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D005269:Femur / Q000166:cytology; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D018800:Thy-1 Antigens / Q000235:genetics / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
D019941:Cyclin-Dependent Kinase Inhibitor p16; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; D018800:Thy-1 Antigens; D019010:Vascular Cell Adhesion Molecule-1