Prolonged Three-Dimensional Co-Delivery of Yamanaka Factors for Cell Reprogramming.

Reprogramming somatic cells into a pluripotent state has been widely investigated in two-dimensional (2D) systems but not described in the more biologically faithful three-dimensional (3D) scaffolds. Here, we devise a 3D porous tissue engineering scaffold that could achieve successful and efficient induction of pluripotency. To construct this 3D scaffold, nonviral hybrid nanoparticles were fabricated beforehand by employing calcium phosphate and cationized Pleurotus eryngii polysaccharide to codeliver plasmids OCT4, SOX2, KLF4 ,and C-MYC (pOSKM). These hybrid nanoparticles were then loaded into a 3D porous collagen scaffold to obtain the so-called pOSKM-activated 3D scaffold. This 3D scaffold could reprogram human umbilical cord mesenchymal stem cells (HUMSCs) into a pluripotent state, generating 3D cell spheres which showed positive expression of pluripotency markers in the 3D scaffolds and tightly packed colonies when transferred to 2D feeder layers. Besides sharing similar morphology, epigenetic modifi...