Increased engraftment of hepatic progenitors after activation of the hepatocyte growth factor signaling pathway by protein transduction.
Cell transplantation has become a major focus in biomedical research. However, efficient engraftment in solid tissues remains a challenge. Hepatocyte growth factor (HGF) signaling increases survival, proliferation, migration, and invasion of many cell types through Met, its cell surface receptor. Therefore, activation of this signaling pathway may improve the ability of many cells to be transplanted. We constructed a constitutively activated form of Met (Tpr-Met) fused to the protein transduction domain of HIV-TAT to activate the HGF/Met pathway for a few hours following cell injection. Matrix-assisted refolding was used to renature TAT-Tpr-Met protein, which was efficiently delivered into cells and recapitulated several biological functions of Met in vitro. Furthermore, treatment of hepatic progenitors with this molecule for one hour before transplantation significantly improved engraftment efficiency (31% untreated cells, 58% treated cells). These findings suggest that the transient transfer of Tpr-Met may provide a new approach to increase the proportion of successfully engrafted cells.
Kellermann
Guillaume
G
INSERM U804 and University Paris-Sud, 94276 Kremlin-Bicêtre, France. guillaume.kellermann@inserm.fr
Boudechiche
Lyes
L
Weber
Anne
A
Hadchouel
Michelle
M
D000818:Animals; D002460:Cell Line; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D022781:Hepatocytes / Q000502:physiology*; D051379:Mice; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000502:physiology*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism
D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D017228:Hepatocyte Growth Factor