HGF, SDF-1, and MMP-9 are involved in stress-induced human CD34+ stem cell recruitment to the liver
J. Clin. Invest. Orit Kollet, et al. 112:160 doi:10.1172/JCI17902 [
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Figure 1SDF-1/CXCR4 interactions mediate homing and engraftment of irradiated NOD/SCID mouse liver by human CD34
+ cells. (
a) Homing of human CB or MPB enriched CD34
+ cells to the murine BM, spleen (Spl), and liver is inhibited by neutralizing CXCR4. Data present inhibition as percentage of control.
P ≤ 0.008, comparing anti-CXCR4–treated samples with their control counterparts. (
b) A representative homing experiment shows human CD34
+/CD38
–/low homing cells (gated) in the liver of mice transplanted with nontreated cells (top), or CXCR4-neutralized cells (middle). A noninjected (Non-inj) mouse served as a negative control (bottom). Numbers indicate human homing cells/1.5 × 10
6 acquired cells. (
c) Four-hour homing of CXCR4-neutralized or nontreated CD34
+ cells to the liver of nonirradiated mice. Human SDF-1 was injected into the liver parenchyma as indicated. Cells were collected from the injected lobe to determine the homing of human CD34
+ cells. (
d) Human cell engraftment of the liver by CB nonstimulated CD34
+ cells or CD34
+ cells that migrated toward SDF-1, determined by Southern blot specific for human DNA. A representative blot is shown (*mouse transplanted with CD34
+ cells migrating toward SDF-1). (
e) Data as presented in
d, summarizing three independent experiments (
n = 37 mice). (
f) SDF-1 levels in liver extracts of mice with no irradiation (ctrl), 24 hours and 48 hours after irradiation, determined by ELISA. Data summarize three experiments.