Differentiation Potential of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells and Paracrine Signaling Interaction Contribute to Improve the In Vitro Maturation of Mouse Cumulus Oocyte Complexes

Martin Maldonado,Tianhua Huang,Jianying Chen,Ying Zhong

doi:10.1155/2018/7609284

Martin Maldonado, Tianhua Huang + Show 2 more

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https://doi.org/10.1155/2018/7609284

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Abstract

In vitro maturation (IVM) in cumulus oocyte complexes (COCs) can be improved by the presence of human Wharton's jelly-derived MSCs (hWJ-MSCs), under specific culture conditions. COCs were cultured in twelve different culture systems, composed of four stock media, stock media conditioned with hWJ-MSCs, and stock media in which the oocytes were indirectly cocultured with the hWJ-MSCs. The rates of maturation to meiosis II were compared among the groups. G2-PLUS and coculture with DMEM-F12 were the most efficient systems for the maturation of COCs. The fertilization rate and rate of development to the blastocyst stage were compared between these two groups. Moreover, hWJ-MSC-conditioned media showed no benefits for the COC-IVM. The analysis of OCT4 expression of hWJ-MSCs in G1-PLUS, TYH, and G2-PLUS showed a downregulation of OCT4 by 25.9, 24.7, and 6.6%, respectively, compared to that in hWJ-MSCs cultured in DMEM-F12. Finally, we have demonstrated that two prerequisites appeared to be necessary for the hWJ-MSCs to improve the IVM of COCs: hWJ-MSCs' differentiation potential and the presence of coordinated paracrine interaction between the stem cells and COCs. Under the appropriate conditions, the paracrine factors produced in the coculture system with DMEM-F12 may help to develop synthetic media for successful in vitro culture of COCs.

Highlights

In vitro maturation (IVM) in cumulus oocyte complexes (COCs) can be improved by the presence of human Wharton’s jelly-derived MSCs, under specific culture conditions.Mesenchymal stem cells (MSCs) are attractive candidates for cell-based therapeutic strategies, primarily due to their intrinsic ability to self-renew and undergo multipotential differentiation and because they are amenable to genetic manipulation [1,2,3].In a coculture, MSCs provide a target cell source with multipotent differentiation capacity but can act as assisting cells to promote tissue homeostasis, metabolism, growth, and repair [4]
Since cytokines and growth factors are known to stimulate meiotic progress and the processes associated with IVM, the aim of the present study was to determine whether IVM in cumulus oocyte complexes (COCs) could be improved by the presence of hWJ-MSCs through nonspecific release of cytokines and soluble factors using conditioned medium or by paracrine signaling from hWJ-MSCs using indirect coculture conditions
Among the 12 culture systems analyzed in this work, G2PLUS and coculture-DMEM-F12 were the most effective media conditions for IVM

Summary

Introduction

MSCs provide a target cell source with multipotent differentiation capacity but can act as assisting cells to promote tissue homeostasis, metabolism, growth, and repair [4]. Their incorporation into coculture systems seems to be important for creating complex tissues or organs by cell-to-cell contact or/and through the delivery of soluble factors to the target cells. HWJ-MSCs reprogram resident cells to favor tissue regeneration, attenuate wound inflammation, and inhibit fibrosis [6, 7] They interact with host cells and influence the stem cell niche through differentiation and/ or paracrine signaling mechanisms [6, 8, 9].

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