title: Microparticle-Mediated Delivery of BMP4 for Generation of Meiosis-Competent Germ Cells from Embryonic Stem Cells.
abstract: 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.
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, 1665659911, Iran.|Department of Developmental Biology, University of Science and Culture, Tehran, 1461968151, Iran.
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Esfandiari
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, 1665659911, Iran.
authors.forename: Mohammad Kazemi
authors.initials: MK
authors.lastname: Ashtiani
authors.affiliation: Department of Molecular Systems Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, 1665659911, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Sharifi-Tabar
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, 1665659911, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Saber
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, 1665659911, Iran.
authors.forename: Hamed
authors.initials: H
authors.lastname: Daemi
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, 1665659911, Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Ghanian
authors.affiliation: Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, 1665659911, Iran.
authors.forename: Abdolhossein
authors.initials: A
authors.lastname: Shahverdi
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, 1665659911, Iran.|Department of Developmental Biology, University of Science and Culture, Tehran, 1461968151, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Baharvand
mesh_terms: D000464:Alginates / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000008:administration & dosage / Q000737:chemistry*; D002454:Cell Differentiation / Q000187:drug effects*; D055252:Cell-Derived Microparticles / Q000737:chemistry; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects*; D005854:Germ Cells / Q000187:drug effects / Q000254:growth & development; D020723:Glucuronic Acid / Q000008:administration & dosage / Q000737:chemistry; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000737:chemistry; D008540:Meiosis / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice
chemical_list: D000464:Alginates; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D006603:Hexuronic Acids; D020723:Glucuronic Acid
keywords: germ cells; growth factor delivery; infertility; meiosis; microparticles