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Microparticle‐Mediated Delivery of BMP4 for Generation of Meiosis‐Competent Germ Cells from Embryonic Stem Cells
Author(s) -
Esfandiari Fereshteh,
Ashtiani Mohammad Kazemi,
SharifiTabar Mehdi,
Saber Maryam,
Daemi Hamed,
Ghanian Mohammad Hossein,
Shahverdi Abdolhossein,
Baharvand Hossein
Publication year - 2017
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201600284
Subject(s) - bone morphogenetic protein 4 , embryonic stem cell , meiosis , microbiology and biotechnology , stem cell , chemistry , downregulation and upregulation , biology , biochemistry , gene
Producing meiosis‐competent germ cells (GCs) from embryonic stem cells (ESCs) is essential for developing advanced therapies for infertility. Here, a novel approach is presented for generation of GCs from ESCs. In this regard, microparticles (MPs) have been developed from alginate sulfate loaded with bone morphogenetic protein 4 (BMP4). The results here show that BMP4 release from alginate sulfate MPs is significantly retarded by the sulfated groups compared to neat alginate. Then, BMP4‐laden MPs are incorporated within the aggregates during differentiation of GCs from ESCs. It is observed that BMP4‐laden MPs increase GC differentiation from ESCs at least twofold compared to the conventional soluble delivery method. Interestingly, following meiosis induction, Dazl , an intrinsic factor that enables GCs to enter meiosis, and two essential meiosis genes ( Stra8 and Smc1b ) are upregulated significantly in MP‐induced aggregates compared to aggregates, which are formed by the conventional method. Together, these data show that controlled delivery of BMP4 during ESC differentiation into GC establish meiosis‐competent GCs which can serve as an attractive GC source for reproductive medicine.