Nishikawa Eri, Matsumoto Taro, Isige Mika, Tsuji Takashi, Mugisima Hideo, Takahashi Syouri
Department of Pediatrics, Nihon University School of Medicine, 30-1 Ooyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan.
Department of Functional Morphology, Division of Cell Regeneration and Transplantation, Nihon University School of Medicine, 30-1 Ooyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan.
Regen Ther. 2016 Mar 2;4:48-61. doi: 10.1016/j.reth.2015.12.002. eCollection 2016 Jun.
Cord blood is utilized as a useful source of cells for hematopoietic stem cell transplantation, but this can be problematic because there is a high rate of graft failure compared to when other graft sources are used. A previous study successfully avoided graft failure by simultaneously grafting cord blood and bone marrow mesenchymal stem cells (MSCs) that are considered to function in the hematopoietic stem cell niche of the bone marrow.Organs of the fetal life support system such as the placenta and umbilical cord, which are discarded after delivery, contain an abundance of MSCs as well as cells that function in the hematopoietic stem cell niche. By identifying and collecting such cells and subsequently co-transplanting them with cord blood, an improvement in graft survival can be anticipated.
Three types of stem cells, amnion epithelial stem cells (AM-Epi), amnion mesenchymal stem cells (AM-Mes), and Wharton's jelly (WJ)-MSCs, all of which can be isolated and cultured from the placenta amnion or umbilical cord WJ, were investigated for the expression of hematopoietic stem cell niche markers and for their capabilities to maintain hematopoietic stem cells when co-cultured with cord blood hematopoietic stem cells.
All types of isolated cells showed profiles that met the MSC minimal criteria according to surface marker analysis. In addition, all cell types expressed the hematopoietic stem cell niche marker stromal cell-derived factor-1 (SDF-1) (in order: AM-Epi > WJ-MSCs ≫ AM-Mes), although the expression declined with further passaging.After 5 days of co-culturing with cord blood CD34+ cells, the percentages of CD34+, CD45- cells were: AM-Epi 37.8%, AM-Mes 38.8%, WJ-MSCs 27.3%, and fibroblasts 27.4%; and the number of CFU-GM colonies were: AM-Epi 255.5 ± 21.6, AM-Mes 246.3 ± 28.5, WJ-MSCs 118.3 ± 11.8, fibroblasts 147.8 ± 19.0, and NC 121.3 ± 6.5. Statistical analyses demonstrated that AM-Epi and AM-Mes produced significantly greater numbers of CFU-GM compared to WJ-MSC, fibroblasts, or NC (p < 0.05).
These findings indicated that cells derived from the fetal life support system such as AM-Epi and AM-Mes can be anticipated as potential cell sources for clinical application in cell therapies for the purpose of enhancing graft survival during hematopoietic stem cell transplantation.
脐带血被用作造血干细胞移植的有用细胞来源，但这可能存在问题，因为与使用其他移植来源相比，移植失败率很高。先前的一项研究通过同时移植脐带血和骨髓间充质干细胞（MSC）成功避免了移植失败，骨髓间充质干细胞被认为在骨髓造血干细胞龛中发挥作用。胎儿生命支持系统的器官，如胎盘和脐带，在分娩后被丢弃，其中含有大量的间充质干细胞以及在造血干细胞龛中发挥作用的细胞。通过识别和收集这些细胞，随后将它们与脐带血共同移植，可以预期移植存活率会提高。
研究了三种干细胞，即羊膜上皮干细胞（AM-Epi）、羊膜间充质干细胞（AM-Mes）和华通氏胶（WJ）-间充质干细胞，所有这些干细胞都可以从胎盘羊膜或脐带华通氏胶中分离和培养，检测它们造血干细胞龛标志物的表达以及与脐带血造血干细胞共培养时维持造血干细胞的能力。
根据表面标志物分析，所有类型的分离细胞均显示出符合间充质干细胞最低标准的特征。此外，所有细胞类型均表达造血干细胞龛标志物基质细胞衍生因子-1（SDF-1）（顺序为：AM-Epi > WJ-间充质干细胞≫ AM-Mes），尽管随着传代次数增加表达下降。与脐带血CD34+细胞共培养5天后，CD34+、CD45-细胞的百分比分别为：AM-Epi 37.8%、AM-Mes 38.8%、WJ-间充质干细胞27.3%、成纤维细胞27.4%；CFU-GM集落数分别为：AM-Epi 255.5±21.6、AM-Mes 246.3±28.5、WJ-间充质干细胞118.3±11.8、成纤维细胞147.8±19.0、阴性对照121.3±6.5。统计分析表明，与WJ-间充质干细胞、成纤维细胞或阴性对照相比，AM-Epi和AM-Mes产生的CFU-GM数量显著更多（p < 0.05）。
这些发现表明，来自胎儿生命支持系统的细胞，如AM-Epi和AM-Mes，有望作为临床应用的潜在细胞来源，用于细胞治疗，以提高造血干细胞移植期间的移植存活率。
