Fetal progenitor cells naturally transferred through pregnancy participate in inflammation and angiogenesis during wound healing

Fetal progenitor cells naturally transferred through pregnancy participate in inflammation and angiogenesis during wound healing
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DOI:
10.1096/fj.11-180695
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发表时间:
2012-01-01
期刊:
影响因子:
4.8
通讯作者:
Aractingi, Selim
Aractingi, Selim
中科院分区:
生物学2区
文献类型:
--
作者:
Nassar, Dany;Droitcourt, Catherine;Aractingi, Selim

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胎儿微嵌合细胞在妊娠期间转移到母体循环中的表型和命运尚未得到很好的描述。由于来自远端部位的祖细胞在伤口愈合过程中调动,我们分析了胎儿祖细胞在母体伤口中的招募和可塑性。在具有荧光GFP(+)胎儿的分娩或怀孕野生型雌性正常和博莱霉素诱导的纤维化皮肤上产生伤口。通过PCR、免疫组织化学和流式细胞术对皮肤和血液标本进行分析。对照组为无伤口的分娩和怀孕雌鼠和有伤口的处女雌鼠。只要未愈合,在分娩小鼠的所有皮肤标本中都检测到胎儿细胞。在伤口愈合的早期阶段,胎儿细胞主要表达白细胞标记物,而在后期阶段内皮标记物占主导地位。胎儿来源的血管连接到母体循环也被发现,证明胎儿内皮祖细胞的转移。在怀孕期间,损伤调动了胎儿的CD34(+) ckit(-)细胞进入血液。该人群中大多数是CD11b(-)VEGFR2(-)。另一部分是CD11b(+),部分表达VEGFR2。含有vegfa的Matrigel塞部分模拟了这种胎儿祖细胞的招募和进入血液的动员。综上所述,在受伤反应中动员的胎儿细胞主要是祖细胞,并参与血管生成和炎症。-Nassar, D., Droitcourt, C., Mathieu-d'Argent, E., Kim, M. J., Khosrotehrani, K., Aractingi, S.通过妊娠自然转移的胎儿祖细胞参与伤口愈合过程中的炎症和血管生成。中华医学杂志,26,149-157(2012)。www.fasebj.org
The phenotype and fate of fetal microchimeric cells transfered into the maternal circulation during pregnancy are not well described. Since progenitors from distal sites mobilize during wound healing, we analyzed the recruitment and plasticity of fetal progenitors into maternal wounds. Wounds were generated on normal and bleomycin-induced fibrotic skin of parous or pregnant wild-type females with fluorescent GFP(+) fetuses. Analyses were performed on skin and blood specimens through PCR, immunohistochemistry, and flow cytometry. Controls consisted of parous and pregnant females without wounds and virgin females with wounds. Fetal cells were detected in all skin specimens of parous mice as long as healing was not achieved. During early stages of wound healing, fetal cells expressed mainly leukocyte markers, while in later phases endothelial markers prevailed. Fetally derived vessels connected to maternal circulation were also found, demonstrating the transfer of fetal endothelial progenitor cells. Wounding mobilized fetal CD34(+) ckit(-) cells into the blood during pregnancy. Most of this population was CD11b(-)VEGFR2(-). Another part was CD11b(+) with a fraction expressing VEGFR2. VEGFa-spiked Matrigel plugs partially mimicked this fetal progenitor recruitment and mobilization into the blood. In summary, fetal cells that mobilize in response to wounding are mainly progenitor cells and participate in angiogenesis and inflammation.-Nassar, D., Droitcourt, C., Mathieu-d'Argent, E., Kim, M. J., Khosrotehrani, K., Aractingi, S. Fetal progenitor cells naturally transferred through pregnancy participate in inflammation and angiogenesis during wound healing. FASEB J. 26, 149-157 (2012). www.fasebj.org