Human amniotic epithelial cells can differentiate into granulosa cells and restore folliculogenesis in a mouse model of chemotherapy-induced premature ovarian failureReport as inadecuate

Human amniotic epithelial cells can differentiate into granulosa cells and restore folliculogenesis in a mouse model of chemotherapy-induced premature ovarian failure - Download this document for free, or read online. Document in PDF available to download.

Stem Cell Research and Therapy

, 4:124

First Online: 14 October 2013Received: 02 July 2013Revised: 19 September 2013Accepted: 09 October 2013


IntroductionOvarian dysfunction frequently occurs in female cancer patients after chemotherapy, but human amniotic epithelial cells hAECs that can differentiate into cell types that arise from all three germ layers may offer promise for restoration of such dysfunction. Previous studies confirmed that hAECs could differentiate into cells that express germ cell-specific markers, but at this time hAECs have not been shown to restore ovarian function.

MethodsTo model premature ovarian failure, hAECs infected with lenti-virus carrying green fluorescent protein were injected into the tail vein of mice sterilized with cyclophosphamide and busulphan. hAECs migrated to the mouse ovaries and overall ovarian function was measured using immunohistochemical techniques.

ResultsSeven days to two months after hAECs transplantation, ovarian cells were morphologically restored in sterilized mice. Hemotoxylin and eosin staining revealed that restored ovarian cells developed follicles at all stages. No follicles were observed in control mice at the same time period. Immunostaining with anti-human antigen antibodies and pre-transplantation labeling with green fluorescent protein GFP revealed that the grafted hAECs survived and migrated to mouse ovary, differentiating into granulosa cells. Furthermore, the ovarian function marker, anti-Müllerian hormone, was evident in treated mouse ovaries after hAEC transplantation.

ConclusionsIntravenously injected hAECs reached the ovaries of chemotherapy-treated mice and restored folliculogenesis, data which suggest promise for hAECs for promoting reproductive health and improving the quality of life for female cancer survivors.

AbbreviationsAMHAnti-Müllerian hormone

BLIMP1B-lymphocyte-induced maturation protein

BMBone marrow

c-MOSOocyte maturation factor mos


DAZLDeleted in azoospermia-like

DMSODimethyl sulfoxide

EGFPGreen fluorescent protein

FSHRFollicular stimulating hormone receptor

GFPGreen fluorescent protein

GnRHGonadotropin-releasing hormone

HandEHemotoxylin and eosin

hAECsHuman amniotic epithelial cells

MSCsMesenchymal stem cells

PBSPhosphate-buffered saline

PGCsPrimordial germ cells

SCIDSevere combined immunodeficiency

SCP1 and SCP3Syntaptonemal complex protein 1 and 3

STELLADevelopmental pluripotency-associated protein 3, stella-related protein

STRA8Stimulated by retinoic acid gene 8

VASAProbable ATP-dependent RNA helicase DDX4, vasa homolog.

Electronic supplementary materialThe online version of this article doi:10.1186-scrt335 contains supplementary material, which is available to authorized users.

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Author: Fangyuan Wang - Li Wang - Xiaofen Yao - Dongmei Lai - Lihe Guo


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