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移植后封装胚胎干细胞的分化

Differentiation of encapsulated embryonic stem cells after transplantation.

作者信息

Dean Sophia K, Yulyana Yulyana, Williams Georgia, Sidhu Kuldip S, Tuch Bernard E

机构信息

Diabetes Transplant Unit, Prince of Wales Hospital, and The University of New South Wales, Sydney, Australia.

出版信息

Transplantation. 2006 Nov 15;82(9):1175-84. doi: 10.1097/01.tp.0000239518.23354.64.

DOI:10.1097/01.tp.0000239518.23354.64
PMID:17102769
Abstract

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.

摘要

背景

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体内时可能会被排斥,尤其是当细胞分化且这些抗原的表达增加时。一种防止排斥的方法是将发育中的ESC置于微胶囊中。目前尚不清楚包封对ESC分化能力有何影响。

方法

将人ESC(hESC;hES03系)和小鼠ESC(mESC;R1系)封装在2.2%的海藻酸钡中,分别腹腔移植到SCID小鼠和BALB/c小鼠体内。从SCID小鼠体内取出胶囊长达四周,从BALB/c小鼠体内取出胶囊长达三个月后,评估细胞形态、活力和基因特征。

结果

包封分别在长达四周和三个月的时间内防止hESC和mESC形成畸胎瘤。mESC而非hESC在胶囊内形成聚集体,且这些聚集体未出现纤维化。部分但并非所有移植的包封hESC向所有三个谱系分化,但如甲胎蛋白表达增加所示,更多地向内胚层谱系分化。这与包封和未包封的hESC在体外培养两周时的情况相似。与hESC不同,移植的包封mESC大多向外胚层谱系分化,如巢蛋白和胶质纤维酸性蛋白表达增加所示。在体外,包封和未包封的mESC也开始分化,但未分化为任何特定谱系。

结论

包封的ESC确实会分化,尽管在移植和培养过程中会沿着多种途径分化,就像未包封的ESC从饲养层移除后一样。

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