Novel markers for the prospective isolation of human MSC.
The isolation of mesenchymal stem cells (MSC) from primary tissue is hampered by the limited selectivity of available markers. So far, CD271 is one of the most specific markers for bone marrow (BM)-derived MSC. In search of additional markers, monoclonal antibodies (mAbs) with specificity for immature cells were screened by flow cytometry for their specific reactivity with the rare CD271(+) population. The recognized CD271(+) populations were fractionated by fluorescence-activated cell sorting and the clonogenic capacity of the sorted cells was analyzed for their ability to give rise to CFU-F. The results showed that only the CD271(bright) but not the CD271(dim) population contained CFU-F. Two-color flow cytometry analysis revealed that only the CD271(bright) population was positive for the established MSC markers CD10, CD13, CD73, and CD105. In addition, a variety of mAbs specific for novel and partially unknown antigens selectively recognized the CD271(bright) population but no other BM cells. The new MSC-specific molecules included the platelet-derived growth factor receptor-beta (CD140b), HER-2/erbB2 (CD340), frizzled-9 (CD349), the recently described W8B2 antigen, as well as cell-surface antigens defined by the antibodies W1C3, W3D5, W4A5, W5C4, W5C5, W7C6, 9A3, 58B1, F9-3C2F1, and HEK-3D6. In conclusion, the described markers are suitable for the prospective isolation of highly purified BM-MSC. These MSC may be used as an improved starting population for transplantation in diseases like osteogenesis imperfecta, cartilage repair, and myocardial infarction.
Bühring
Hans-Jörg
HJ
Department of Internal Medicine II, University Clinic, Medical Research Center, Otfried-Müller-Str. 27, 72076 Tübingen, Germany. hans-joerg.buehring@uni-tuebingen.de
Battula
Venkata Lokesh
VL
Treml
Sabrina
S
Schewe
Bernhard
B
Kanz
Lothar
L
Vogel
Wichard
W
D015720:5'-Nucleotidase / Q000096:biosynthesis; D000068816:Adapalene; D015703:Antigens, CD / Q000096:biosynthesis; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D018826:CD13 Antigens / Q000096:biosynthesis; D018929:Cell Culture Techniques / Q000379:methods*; D002469:Cell Separation / Q000379:methods*; D017690:Cell Transplantation; D000071063:Endoglin; D005434:Flow Cytometry; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009281:Naphthalenes / Q000737:chemistry; D015260:Neprilysin / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D009281:Naphthalenes; D011956:Receptors, Cell Surface; D000068816:Adapalene; D015720:5'-Nucleotidase; D018826:CD13 Antigens; D015260:Neprilysin