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.
We construct a consistent truncation of six-dimensional matter coupled F(4) gauged supergravity on a cornucopia of two-dimensional surfaces including a spindle, disc, domain wall and other novel backgrounds to four-dimensional minimal gauged supergravity. Using our consistent truncation we uplift known AdS2× Σ1 solutions giving rise to four-dimensional orbifold solutions, AdS2× Σ1 ⋉ Σ2. We further uplift our solutions to massive type IIA supergravity by constructing the full uplift formulae for six-dimensional U(1)2-gauged supergravity including all fields and arbitrary Romans mass and gauge coupling. The solutions we construct are naturally interpreted as the near-horizon geometries of asymptotically AdS6 black holes with a four-dimensional orbifold horizon. Alternatively, one may view them as the holographic duals of superconformal quantum mechanical theories constructed by compactifying five-dimensional USp(2N) theory living on a stack of D4-D8 branes on the four-dimensional orbifolds. As a first step to identifying these quantum mechanical theories we compute the Bekenstein-Hawking entropy holographically.
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