Background: Developmentally early cells, including hematopoietic stem progenitor cells (HSPCs), as well as very small embryonic-like stem cells (VSELs), are mobilized into peripheral blood (PB) in response to tissue and organ injury (e.g., heart infarct or stroke).
Objective: We seek to determine whether these cells are also mobilized into PB in patients with skin burn injuries.
Methods: Forty-four (44) patients (33-57 years of age) with total body surface burn area of 30-60%, as well as 23 healthy control subjects, were recruited and PB samples were harvested during the first 24 hours, day +2, and day +5 after burn injury and compared to normal controls. The circulating human CD34(+)CD133(+) cells enriched for HSPCs, as well as small CXCR4(+)CD34(+)CD133(+) subsets of Lin(-)CD45(-) cells that correspond to the population of VSELs, were counted by FACS and evaluated by direct immunofluorescence staining for pluripotency markers (Oct-4, Nanog, and SSEA-4). In parallel, we also measured by ELISA the serum concentration of factors that regulate stem cell trafficking, such as SDF-1, VEGF, and HGF.
Results: Our data indicate that skin burn injury mobilizes cells expressing stem cell-associated markers, such as CD133, CD34, and CXCR4, into PB. More importantly, we found an increase in the number of circulating primitive, small Oct-4(+)Nanog(+)SSEA-4(+)CXCR4(+)lin(-)CD45(-) VSELs. All these changes were accompanied by increased serum concentrations of SDF-1 and VEGF.
Limitations: Further studies are needed to fully assess the role of mobilized stem cells in the healing process to see if they can contribute to skin regeneration.
Conclusion: Skin burn injury triggers the mobilization of HSPCs and CXCR4(+) VSELs, while the significance and precise role of mobilized VSELs in skin repair requires further study.