Differentiation of encapsulated embryonic stem cells after transplantation
Differentiation of encapsulated embryonic stem cells after transplantation
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DOI：
10.1097/01.tp.0000239518.23354.64
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发表时间：
2006-11-15
期刊：
影响因子：
6.2
通讯作者：
Tuch, Bernard E.
中科院分区：
文献类型：
--
作者：
Dean, Sophia K.;Yulyana, Yulyana;Tuch, Bernard E.
背景。当胚胎干细胞（ESC）移植到具有不同主要组织相容性抗原的受体中时，可能会产生排斥反应，特别是当细胞分化和这些抗原的表达增加时。防止排斥反应的一种方法是将发育中的ESC放入微胶囊中。目前尚不清楚胶囊化对ESC的分化能力有什么影响。将人ESC （hESC； hES03系）和小鼠ESC （mESC； R1系）包封在2.2%海藻酸钡中，分别移植到SCID和BALB/c小鼠腹腔内。在SCID小鼠4周和BALB/c小鼠3个月后提取胶囊，对细胞形态、活力和基因特性进行评估。囊化分别阻止hESC和mESC形成畸胎瘤长达4周和3个月。mESC而非hESC在胶囊内形成聚集体，保持无纤维化。部分（但不是全部）移植的包被hESC向所有三种谱系分化，但更倾向于向内胚层谱系分化，如α胎蛋白表达增加所示。这与包被和未包被hESC体外培养两周时的结果相似。与hESC相比，移植包被的mESC主要向外胚层分化，巢蛋白和胶质纤维酸性蛋白的表达增加。在体外，包被和未包被的mESC也开始分化，但没有任何特定的谱系。被封装的ESC确实会分化，尽管在移植和培养中都有多种途径，就像未封装的ESC从饲养层移除时一样。
Background. Embryonic stem cells (ESC) when transplanted into recipients with different major histocompatibility antigens may be rejected, especially as cells differentiate and expression of these antigens increases. One method to prevent rejection is to place the developing ESC in microcapsules. It is currently unknown what effect encapsulation has on the ability of ESC to differentiate.Methods. Human ESC (hESC; hES03 line) and mouse ESC (mESC; R1 line) were encapsulated in 2.2% barium alginate and transplanted intraperitoneally in SCID and BALB/c mice respectively. Cell morphology, viability, and gene characterization were assessed after retrieving the capsules up to four weeks from SCID mice and three months from BALB/c mice.Results. Encapsulation prevented hESC and mESC from forming teratomas up to four weeks and three months, respectively. mESC but not hESC formed aggregates within the capsules, which remained free of fibrosis. Some but not all the transplanted encapsulated hESC differentiated towards all three lineages, but more so towards an endodermal lineage as shown by increased expression of alpha fetoprotein. This was similar to what occurred when encapsulated and non-encapsulated hESC were cultured in vitro for two weeks. In contrast to the hESC, transplanted encapsulated mESC differentiated mostly towards an ectodermal lineage as shown by increased expression of nestin and glial fibrillary acidic protein. In vitro, encapsulated and nonencapsulated mESC also began to differentiate, but not down any specific lineage.Conclusions. Encapsulated ESC do differentiate, although along multiple pathways, both when transplanted and maintained in culture, just as nonencapsulated ESC do when removed from their feeder layer.