Shieh Hester F, Ahmed Azra, Tracy Sarah A, Zurakowski David, Fauza Dario O
Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA.
Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA.
J Pediatr Surg. 2017 Oct 12. doi: 10.1016/j.jpedsurg.2017.10.033.
Donor cell engraftment patterns following transamniotic stem cell therapy (TRASCET) with amniotic fluid mesenchymal stem cells (afMSCs) are incompatible with solely direct amniotic seeding. We sought to determine whether fetal bone marrow is a component of such engraftment and to examine the chronology of afMSC placental trafficking.
Two groups of Sprague-Dawley rat fetuses received volume-matched intraamniotic injections on gestational day 17 (E17; term E22): either afMSCs labeled with a luciferase reporter gene or luciferase protein alone. Placental samples were procured at daily time points thereafter until term. Fetal bone marrow was obtained at term only owing to size constraints. Specimens were screened for luminescence via microplate luminometry.
Donor afMSCs were identified in the bone marrow and placenta of fetuses receiving labeled afMSCs, but not in those receiving luciferase alone (P<0.001). Luminescence was significantly higher in placentas at E18 compared to E19 (P<0.001), E20 (P=0.007), and E21 (P=0.004), with no difference with E22/term (P=0.97).
Donor mesenchymal stem cells home to the fetal bone marrow after intraamniotic injection. The chronology of placental trafficking is suggestive of controlled cell routing rather than plain cell clearance. Fetal bone marrow engraftment of donor cells significantly expands potential applications of transamniotic stem cell therapy.
经羊膜干细胞疗法（TRASCET）使用羊水间充质干细胞（afMSCs）后的供体细胞植入模式与单纯直接羊膜接种不相容。我们试图确定胎儿骨髓是否是这种植入的一个组成部分，并研究afMSCs胎盘转运的时间顺序。
两组Sprague-Dawley大鼠胎儿在妊娠第17天（E17；足月为E22）接受体积匹配的羊膜内注射：要么是用荧光素酶报告基因标记的afMSCs，要么是单独的荧光素酶蛋白。此后每天采集胎盘样本直至足月。由于大小限制，仅在足月时获取胎儿骨髓。通过微孔板发光法对样本进行发光筛选。
在接受标记的afMSCs的胎儿的骨髓和胎盘中鉴定出供体afMSCs，但在接受单独荧光素酶的胎儿中未鉴定出（P<0.001）。与E19（P<0.001）、E20（P=0.007）和E21（P=0.004）相比，E18时胎盘的发光显著更高，与E22/足月时无差异（P=0.97）。
羊膜内注射后，供体间充质干细胞归巢至胎儿骨髓。胎盘转运的时间顺序提示细胞路由受到控制，而非单纯的细胞清除。供体细胞在胎儿骨髓中的植入显著扩展了经羊膜干细胞疗法的潜在应用。
