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Three-dimensional microenvironmental priming of human mesenchymal stem cells in hydrogels facilitates efficient and rapid retroviral gene transduction via accelerated cell cycle synchronization

Authors
Lee Y.Arai Y.Ahn J.Kim D.Oh S.Kang D.Hyungsuk LeeMoon J.J.Choi B.Lee S.-H.
Issue Date
Jun-2019
Publisher
NATURE PUBLISHING GROUP
Keywords
stem cells
Citation
NPG ASIA MATERIALS, v.11, no.1, pp.27-1 - 27-11
Journal Title
NPG ASIA MATERIALS
Volume
11
Number
1
Start Page
27-1
End Page
27-11
URI
https://yscholarhub.yonsei.ac.kr/handle/2021.sw.yonsei/5264
DOI
10.1038/s41427-019-0127-9
ISSN
1884-4049
Abstract
There are numerous approaches to improve the low transduction efficiency of retroviral vectors in two-dimensional (2D) cell culture substrates. However, the effect of a three-dimensional (3D) microenvironment, which better mimics in vivo conditions, is unknown. Cytocompatible hyaluronic acid (HA) hydrogels are a good candidate to study this issue. Here, photocrosslinkable HA hydrogels with an elastic modulus of 1.0?2.7 kPa were successfully prepared by varying the degree of methacrylation in the HA backbone. Culturing human adipose-derived stem cells (hASCs) in a 3D microenvironment significantly reduces the amount of time required for retroviral gene transduction compared with the conventional 2D method and maintains a high transduction efficiency. This acceleration of retroviral gene transduction correlates with the rate of cell-cycle synchronization. hASCs cultured in a 3D microenvironment have a shorter G1 phase and total cell-cycle length than hASCs cultured using the conventional 2D method. This cell-cycle regulation is dependent on expression of cyclin D1. In summary, prior culturing of hASCs in a 3D microenvironment accelerates retroviral gene transduction by regulating cyclin D1 expression and accelerating cell-cycle synchronization. We conclude that priming via culturing in a 3D microenvironment facilitates efficient and rapid retroviral gene transduction of hASCs without inducing apoptosis.
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