Overexpression of stromal cell-derived factor-1 enhances endothelium-supported transmigration, maintenance, and proliferation of hematopoietic progenitor cells.
To clarify the direct effects of aberrant overexpression of stromal cell-derived factor-1 (SDF-1) by the human endothelium on circulating progenitor cells, we overexpressed the SDF-1 gene in human umbilical vein endothelial cells using an adenoviral vector (HUVEC/AdeSDF-1) and examined the endothelium-supported trafficking and growth of hematopoietic progenitor cells (HPCs) in mobilized peripheral blood (mPB). In culture, the HUVEC/AdeSDF-1 monolayers induced the migration of mPB CD34(+) cells underneath the endothelium within a few hours, whereas HUVEC monolayers that expressed the LacZ gene (HUVEC/AdeLacZ) did not have this effect. In the Transwell system, the HUVEC/AdeSDF-1 cells supported a higher level of spontaneous transmigration of mPB CD34(+) cells than did the HUVEC/AdeLacZ cells. The co-culturing of mPB CD34(+) cells with HUVEC/ AdeSDF-1 cells led to a greater expansion of CD45(+) cells and colony-forming cells and reduced cellular apoptosis. Furthermore, the co-culturing of mPB CD34(+) cells with HUVEC/AdeSDF-1 cells led to the formation of numerous cobblestone-like areas, whereas co-cultures of mPB CD34(+) cells and HUVEC/AdeLacZ supported only a few cobblestone-like areas. These results indicate that SDF- 1 produced by endothelial cells plays an important role not only in the transmigration but also in the growth of HPCs that are in contact with endothelial cells. Our findings suggest that the enhanced expression and production of SDF-1 in the endothelium are essential steps for stem cell or progenitor cell recruitment to specific tissues and for the maintenance of these cells in situ.
Hwang
Jin-Hee
JH
Division of Hematology/Oncology, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejon, Korea.
Kim
Seong-Woo
SW
Park
Sang-Eun
SE
Yun
Hwan-Jung
HJ
Lee
Younghee
Y
Kim
Samyong
S
Jo
Deog-Yeon
DY
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018952:Antigens, CD34 / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics / Q000502:physiology*; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000235:genetics; D006133:Growth Substances / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D037342:Pertussis Toxin / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000276:immunology; D017154:Stromal Cells / Q000166:cytology; D014162:Transfection
D000906:Antibodies; D018952:Antigens, CD34; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D006133:Growth Substances; D019718:Receptors, CXCR4; D037342:Pertussis Toxin; D017493:Leukocyte Common Antigens