Identification of human placenta-derived mesenchymal stem cells involved in re-endothelialization.
Human placenta is an attractive source of mesenchymal stem cells (MSC) for regenerative medicine. The cell surface markers expressed on MSC have been proposed as useful tools for the isolation of MSC from other cell populations. However, the correlation between the expression of MSC markers and the ability to support tissue regeneration in vivo has not been well examined. Here, we established several MSC lines from human placenta and examined the expression of their cell surface markers and their ability to differentiate toward mesenchymal cell lineages. We found that the expression of CD349/frizzled-9, a receptor for Wnt ligands, was positive in placenta-derived MSC. So, we isolated CD349-negative and -positive fractions from an MSC line and examined how successfully cell engraftment repaired fractured bone and recovered blood flow in ischemic regions using mouse models. CD349-negative and -positive cells displayed a similar expression pattern of cell surface markers and facilitated the repair of fractured bone in transplantation experiments in mice. Interestingly, CD349-negative, but not CD349-positive cells, showed significant effects on recovering blood flow following vascular occlusion. We found that induction of PDGFβ and bFGF mRNAs by hypoxia was greater in CD349-negative cells than in CD349-positive cells while the expression of VEGF was not significantly different in CD349-negative and CD349-positive cells. These findings suggest the possibility that CD349 could be utilized as a specialized marker for MSC isolation for re-endothelialization.
Tran
Tu Cam
TC
Department of Regenerative Medicine and Stem Cell Biology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennodai, Tsukuba, Japan.
Kimura
Kenichi
K
Nagano
Masumi
M
Yamashita
Toshiharu
T
Ohneda
Kinuko
K
Sugimori
Haruhiko
H
Sato
Fujio
F
Sakakibara
Yuzuru
Y
Hamada
Hiromi
H
Yoshikawa
Hiroyuki
H
Hoang
Son Nghia
SN
Ohneda
Osamu
O
D000818:Animals; D001861:Bone Regeneration / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D050723:Fractures, Bone / Q000628:therapy; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
C549560:FZD9 protein, human; D051157:Frizzled Receptors; D008565:Membrane Proteins; D020574:Proto-Oncogene Proteins c-sis; D043562:Receptors, G-Protein-Coupled; D042461:Vascular Endothelial Growth Factor A