TY - JOUR
T1 - LNGFR+THY-1+VCAM-1hi+ cells reveal functionally distinct subpopulations in mesenchymal stem cells
AU - Mabuchi, Yo
AU - Morikawa, Satoru
AU - Harada, Seiko
AU - Niibe, Kunimichi
AU - Suzuki, Sadafumi
AU - Renault-Mihara, Francois
AU - Houlihan, Diarmaid D.
AU - Akazawa, Chihiro
AU - Okano, Hideyuki
AU - Matsuzaki, Yumi
PY - 2013
Y1 - 2013
N2 - 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-1hi+ (LTV) can be used selectively to isolate the most potent and genetically stable MSCs.
AB - 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-1hi+ (LTV) can be used selectively to isolate the most potent and genetically stable MSCs.
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U2 - 10.1016/j.stemcr.2013.06.001
DO - 10.1016/j.stemcr.2013.06.001
M3 - Article
C2 - 24052950
AN - SCOPUS:84881338267
SN - 2213-6711
VL - 1
SP - 152
EP - 165
JO - Stem Cell Reports
JF - Stem Cell Reports
IS - 2
ER -