Abstract

BackgroundA number of studies generated induced neural progenitor cells (iNPCs) from human fibroblasts by viral delivering defined transcription factors. However, the potential risks associated with gene delivery systems have limited their clinical use. We propose it would be safer to induce neural progenitor-like cells from human adult fibroblasts via a direct non-genetic alternative approach.Methodology/Principal FindingsHere, we have reported that seven rounds of TAT-SOX2 protein transduction in a defined chemical cocktail under a 3D sphere culture gradually morphed fibroblasts into neuroepithelial-like colonies. We were able to expand these cells for up to 20 passages. These cells could give rise to cells that expressed neurons and glia cell markers both in vitro and in vivo.Conclusions/SignificanceThese results show that our approach is beneficial for the genetic material-free generation of iNPCs from human fibroblasts where small chemical molecules can provide a valuable, viable strategy to boost and improve induction in a 3D sphere culture.

Highlights

  • The unique capability of neural progenitor cells (NPCs) to induce regeneration in several animal models of neurological disorders [1] make them the best potential cell source for regenerative medicine

  • We demonstrated that TAT could efficiently translocate EGFP into the fibroblasts within 4–8 h posttransduction

  • These results demonstrated that TAT was capable of delivering EGFP as an active protein into human fibroblasts under 3D sphere culture conditions

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Summary

Introduction

The unique capability of neural progenitor cells (NPCs) to induce regeneration in several animal models of neurological disorders [1] make them the best potential cell source for regenerative medicine. Human NPCs can be generated from pluripotent stem cells (PSCs), the remainder of even a few undifferentiated PSCs in the resultant cell mixture can cause tumor formation after transplantation [3,4]. To address this problem, tremendous efforts have been undertaken to convert one cell type directly into induced neural progenitor cells (iNPCs) from accessible cell types such as skin fibroblasts by forced expression of defined transcription factors [5,6,7,8,9]. We propose it would be safer to induce neural progenitor-like cells from human adult fibroblasts via a direct non-genetic alternative approach

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