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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Human umbilical cord blood cells transfected with VEGF and L_1CAM do not differentiate into neurons but transform into vascular endothelial cells and secrete neuro-trophic factors to support neuro-genesis-a novel approach in stem cell therapy.
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Human umbilical cord blood cells transfected with VEGF and L_1CAM do not differentiate into neurons but transform into vascular endothelial cells and secrete neuro-trophic factors to support neuro-genesis-a novel approach in stem cell therapy.

机译：用VEGF和L_1CAM转染的人脐带血细胞不分化为神经元，而是转化为血管内皮细胞并分泌神经营养因子来支持神经发生，这是干细胞治疗中的一种新方法。

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摘要

Genetically modified mono-nuclear cell fraction from human umbilical cord blood (HUCB) expressing human vascular endothelial growth factor (VEGF) and mouse neural L(1) cell adhesion molecule (L(1)CAM) were used for gene-stem cell therapy of transgenic (G)93(A) mice adopted as an animal amyotrophic lateral sclerosis (ALS) model. We generated non-viral plasmid constructs, expressing human VEGF(165) (pcDNA-VEGF) and mouse neural L(1) cell adhesion molecule (pcDNA-mL(1)CAM). Mono-nuclear fraction of HUCB cells were transiently transfected by electro-poration with a mixture of expression plasmids (pcDNA-VEGF+pcDNA-mL(1)CAM). Sixteen transgenic female and male mice were randomly assigned to three groups: (1) transplantation of genetically modified HUCB cells expressing L(1) and VEGF (n=6), (2) transplantation of un-transfected HUCB cells (n=5), and (3) control group (n=5). In first two experimental groups 1x10(6) cells were injected retro-orbitally in pre-symptomatic 22-25-week-old (G)93(A) mice. Our resultsdemonstrate that HUCB cells successfully grafted into nervous tissue of ALS mice and survived for over 3 months. Therefore, genetically modified HUCB cells migrate in the spinal cord parenchyma, proliferate, but instead of transforming into nerve cells, they differentiate into endothelial cells forming new blood vessels. We propose that: (A) expression of mouse neural L(1)CAM is responsible for increased homing and subsequent proliferation of transplanted cells at the site of neuro-degeneration, (B) expression of human VEGF directs HUCB cell differentiation into endothelial cells, and (C) neuro-protective effect may stem from the delivery of various neuro-trophic factors from newly formed blood vessels.
机译：表达人血管内皮生长因子（VEGF）的人脐带血（HUCB）的转基因单核细胞级分和小鼠神经L（1）细胞粘附分子（L（1）CAM）被用于基因干细胞疗法转基因（G）93（A）小鼠被用作动物肌萎缩性侧索硬化（ALS）模型。我们生成了非病毒质粒构建体，表达人VEGF（165）（pcDNA-VEGF）和小鼠神经L（1）细胞粘附分子（pcDNA-mL（1）CAM）。 HUCB细胞的单核级分通过表达质粒（pcDNA-VEGF + pcDNA-mL（1）CAM）的混合物进行电穿孔而瞬时转染。将16只转基因雌性和雄性小鼠随机分为三组：（1）表达L（1）和VEGF的转基因HUCB细胞移植（n = 6），（2）未转染的HUCB细胞移植（n = 5） ，和（3）对照组（n = 5）。在前两个实验组中，将有症状的22-25周龄（G）93（A）小鼠眶后注射1x10（6）细胞。我们的结果表明，HUCB细胞成功移植到ALS小鼠的神经组织中，并存活了3个月以上。因此，转基因的HUCB细胞在脊髓实质内迁移并增殖，但没有转化为神经细胞，而是分化为形成新血管的内皮细胞。我们建议：（A）小鼠神经L（1）CAM的表达负责归巢和随后的神经变性部位移植细胞的增殖，（B）人VEGF的表达指导HUCB细胞分化为内皮细胞， （C）神经保护作用可能源于从新生血管中输送的各种神经营养因子。

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