Laboratory of Cell &Tissue Engineering, Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387, Cracow, Poland.
Stem Cell Rev Rep. 2012 Mar;8(1):184-94. doi: 10.1007/s12015-011-9272-4.
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).
We seek to determine whether these cells are also mobilized into PB in patients with skin burn injuries.
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.
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.
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.
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.
发育早期细胞,包括造血干细胞祖细胞(HSPCs)和非常小的胚胎样干细胞(VSELs),在组织和器官损伤(如心肌梗死或中风)时会动员到外周血(PB)中。
我们旨在确定这些细胞是否也会在皮肤烧伤患者的 PB 中动员。
招募了 44 名(33-57 岁)全身烧伤面积为 30-60%的患者以及 23 名健康对照者,在烧伤后第 1 天、第 2 天和第 5 天采集 PB 样本,并与正常对照者进行比较。通过流式细胞术计数循环中富含 HSPC 的人 CD34(+)CD133(+)细胞,以及对应于 VSEL 群体的 Lin(-)CD45(-)小 CXCR4(+)CD34(+)CD133(+)细胞亚群,并通过直接免疫荧光染色评估多能性标记物(Oct-4、Nanog 和 SSEA-4)。同时,我们还通过 ELISA 测量了调节干细胞迁移的因子(如 SDF-1、VEGF 和 HGF)的血清浓度。
我们的数据表明,皮肤烧伤动员表达干细胞相关标记物(如 CD133、CD34 和 CXCR4)的细胞进入 PB。更重要的是,我们发现循环中原始的、小的 Oct-4(+)Nanog(+)SSEA-4(+)CXCR4(+)lin(-)CD45(-)VSEL 数量增加。所有这些变化都伴随着 SDF-1 和 VEGF 血清浓度的增加。
需要进一步研究以充分评估动员的干细胞在愈合过程中的作用,以确定它们是否有助于皮肤再生。
皮肤烧伤会引发 HSPC 和 CXCR4(+)VSEL 的动员,而动员的 VSEL 在皮肤修复中的意义和确切作用需要进一步研究。