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. 2020 Jun;55(6):1113-1116. doi: 10.1016/j.jpedsurg.2020.02.041. Epub 2020 Feb 26.
We sought to examine donor mesenchymal stem cell (MSC) fate after birth following transamniotic stem cell therapy (TRASCET) in a healthy model.
Lewis rat fetuses (n = 91) were divided into two groups based on the content of volume-matched intraamniotic injections performed on gestational day 17 (term = 21-22 days): either a suspension of amniotic fluid-derived MSCs (afMSCs) labeled with luciferase (n = 38) or acellular luciferase only (n = 53). Infused afMSCs consisted of syngeneic Lewis rat cells phenotyped by flow cytometry. Samples from 14 anatomical sites (heart, lung, brain, liver, spleen, pancreas, bowel, kidney, thyroid, skin, skeletal muscle, thymus, peripheral blood and bone marrow) from survivors were screened for luciferase activity 16 days after birth. Statistical analysis was by logistic regression and the Wald test (p < 0.05).
Overall survival was 32% (29/91). When controlled by the acellular luciferase injections, donor afMSCs were not identified at any anatomical site in any neonate as measured by relative light units (all p > 0.05). Donor afMSC viability was confirmed in term placentas.
Donor mesenchymal stem cells are not detectable in the neonate after intraamniotic injection in a normal syngeneic rodent model. This finding suggests that clinical trials of transamniotic stem cell therapy may be amenable to regulatory approval.
N/A (animal and laboratory study).
我们旨在研究在健康模型中通过经羊膜腔干细胞治疗（TRASCET）进行胎牛来源间充质干细胞（MSC）移植后出生后的供体 MSC 命运。
根据在妊娠第 17 天（足月= 21-22 天）进行的等容羊膜内注射内容物，将 Lewis 胎鼠（n=91）分为两组：羊膜液衍生 MSC（afMSC）与荧光素酶标记物的混悬液组（n=38）或无细胞荧光素酶仅组（n=53）。注入的 afMSC 由流式细胞术表型鉴定的同种 Lewis 胎鼠细胞组成。对出生后 16 天的幸存者的 14 个解剖部位（心脏、肺、脑、肝、脾、胰腺、肠、肾、甲状腺、皮肤、骨骼肌、胸腺、外周血和骨髓）的样本进行荧光素酶活性筛选。统计分析采用逻辑回归和 Wald 检验（p<0.05）。
总体存活率为 32%（29/91）。当通过无细胞荧光素酶注射进行控制时，通过相对光单位测量，在任何新生儿的任何解剖部位均未发现供体 afMSC（所有 p>0.05）。在足月胎盘中证实了供体 afMSC 的活力。
在正常同基因啮齿动物模型中，经羊膜腔注射后，在新生儿中无法检测到供体间充质干细胞。这一发现表明，经羊膜腔干细胞治疗的临床试验可能符合监管部门的批准。
N/A（动物和实验室研究）。
