Stromal progenitor cells promote leukocyte migration through production of stromal-derived growth factor 1alpha: a potential mechanism for stromal progenitor cell-mediated enhancement of cellular recruitment to wounds.
OBJECTIVE
Stromal progenitor cells (SPC) enhance tissue repair in a variety of injury models. However, the mechanisms by which SPCs facilitate tissue repair remain poorly understood. We hypothesized that SPC-enhanced tissue repair is, in part, because of SPC-mediated recruitment of circulating cells to areas of tissue injury. To test this, we examined the migration of leukocytes in response to SPC in vitro.


METHODS
Leukocyte migration was assessed in response to SPC, SPC + transforming growth factor (TGF)-beta1, or SPC + AMD3100 using a Transwell assay system (Corning, distributed by Fisher Scientific, Pittsburgh, PA). Supernatants were collected from lower chambers and analyzed for leukocyte content, leukocyte viability, and stromal-derived growth factor (SDF)-1alpha concentration.


RESULTS
Stromal progenitor cells increased leukocyte migration compared to media alone (450 +/- 70 vs 112 +/- 17 cells/microL; P < .05). SPC treatment with TGF-beta1 resulted in a 36% increase in leukocyte migration and correlated with an increase in SDF-1alpha production. Treatment with AMD3100 resulted in inhibition of leukocyte migration.


CONCLUSIONS
Stromal progenitor cells promote leukocyte migration, and this appears to be mediated through SDF-1alpha production. The SPC production of SDF-1alpha may be modulated by other cytokines present in the microenvironment during wound healing. Together, these observations provide a potential mechanism by which SPC may augment healing through enhanced recruitment of inflammatory cells and tissue progenitor cells to areas of tissue injury.
The Center for Fetal Research at The Children's Hospital of Philadelphia, The University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Andrea T
AT
Badillo
Liping
L
Zhang
Kenneth W
KW
Liechty
D000818:Animals; D001596:Benzylamines; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D000080027:Cyclams; D005260:Female; D006571:Heterocyclic Compounds / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007962:Leukocytes / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D011336:Probability; D012680:Sensitivity and Specificity; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D015854:Up-Regulation; D014945:Wound Healing / Q000502:physiology*
D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D047908:Intracellular Signaling Peptides and Proteins; D053773:Transforming Growth Factor beta1; C088327:plerixafor