Endothelial progenitor cells contribute to accelerated liver regeneration.
Two classes of circulating endothelial cells (CECs) have been identified and are distinguished by the expression of the stem cell markers CD117 or CD133 together with endothelial-specific antigens. Stem cell marker-positive CECs originate from bone marrow and have been designated as circulating endothelial progenitors (CEPs). We have demonstrated that exogenous vascular endothelial growth factor (VEGF) effectively mobilizes CEP cells. Furthermore, it has been demonstrated that VEGF regulates liver regeneration after partial hepatectomy. Although local endothelial cells can regulate tissue mass during liver regeneration, the contribution of CEPs to this process is unknown. We discovered loss of CD117 and CD133 from murine CEP cells and that both markers underestimated the number of bone marrow-derived CEP cells. We therefore used wild type and green fluorescent protein (GFP)-bone marrow transplanted into wild-type mice and performed 70% hepatectomies. Furthermore, we found that treatment with exogenous VEGF accelerated liver regeneration after 70% hepatectomy, whereas immunohistochemical analysis showed a 7-fold increase in the incorporation of CEP cells into liver vasculature. These results suggest that CEP cells play a role in regulating liver regeneration and that VEGF treatment can mobilize CEP cells to accelerate this process.
Beaudry
Paul
P
Vascular Biology Program, Department of Surgery, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Hida
Yasuhiro
Y
Udagawa
Taturo
T
Alwayn
Ian P
IP
Greene
Arin K
AK
Arsenault
Danielle
D
Folkman
Judah
J
Heymach
John V
JV
Ryeom
Sandra
S
Puder
Mark
M
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D016026:Bone Marrow Transplantation; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism; D006498:Hepatectomy; D007124:Immunoenzyme Techniques; D008099:Liver / Q000166:cytology*; D008115:Liver Regeneration / Q000502:physiology*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology; D010455:Peptides / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D018709:Statistics, Nonparametric; D042442:Vascular Endothelial Growth Factors / Q000097:blood / Q000494:pharmacology
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D010455:Peptides; C000606024:Prom1 protein, mouse; D042442:Vascular Endothelial Growth Factors; D019009:Proto-Oncogene Proteins c-kit