Bioengineering tools to elucidate and control the fate of transplanted stem cells

Abstract

For the last decade, stem cell therapies have demonstrated enormous potential for solving some of the most tragic illnesses, diseases and tissue defects worldwide. Currently, more than 1300 clinical trials use stem cell therapy to solve a spectrum of cardiovascular, neurodegenerative and autoimmune diseases (http://www.clinicaltrials.gov, Jan 2014, search term: stem cell therapy; only currently recruiting and completed studies are included in the search). However, the efficacy of stem cell transplantation in patients has not been well established, and recent clinical trials have produced mixed results. We attribute this lack of efficacy in part to an incomplete understanding of the fate of stem cells following transplantation and the lack of control over cell fate, especially cell-homing and therapeutic functions. In the present review, we present two of our recently developed technologies that aim to address the above-mentioned bottlenecks in stem cell therapy specifically in the areas of MSCs (mesenchymal stem cells): (i) aptamer-based cell-surface sensors to study cellular microenvironments, and (ii) mRNA engineering technology to enhance the homing and immunomodulatory efficacy of transplanted stem cells. The first engineering strategy aims to elucidate the basic cellular signalling that occurs in the microenvironment of transplanted stem cells in real time. The second technique involves a simple mRNA transfection that improves the homing and anti-inflammatory capability of MSCs. Although we have specifically applied these engineering techniques to MSCs, these strategies can be incorporated for almost any cell type to determine and control the fate of transplanted stem cells.