Delivery of Differentiation Factors by Mesoporous Silica Particles Assists Advanced Differentiation of Transplanted Murine Embryonic Stem Cells

Author:

Garcia-Bennett Alfonso E.12,Kozhevnikova Mariya3,König Niclas3,Zhou Chunfang2,Leao Richardson3,Knöpfel Thomas4,Pankratova Stanislava5,Trolle Carl3,Berezin Vladimir5,Bock Elisabeth5,Aldskogius Håkan3,Kozlova Elena N.3

Affiliation:

1. Nanotechnology and Functional Materials, Department of Engineering Sciences, Ångstrom Laboratory, Uppsala University, Uppsala, Sweden

2. Nanologica AB, Stockholm, Sweden

3. Department of Neuroscience, Uppsala University Biomedical Center, Uppsala, Sweden

4. RIKEN Brain Science Institute, Saitama, Japan

5. Protein Laboratory, Department of Neuroscience and Pharmacology, Panum Institute, Copenhagen University, Copenhagen, Denmark

Abstract

Abstract Stem cell transplantation holds great hope for the replacement of damaged cells in the nervous system. However, poor long-term survival after transplantation and insufficiently robust differentiation of stem cells into specialized cell types in vivo remain major obstacles for clinical application. Here, we report the development of a novel technological approach for the local delivery of exogenous trophic factor mimetics to transplanted cells using specifically designed silica nanoporous particles. We demonstrated that delivering Cintrofin and Gliafin, established peptide mimetics of the ciliary neurotrophic factor and glial cell line-derived neurotrophic factor, respectively, with these particles enabled not only robust functional differentiation of motor neurons from transplanted embryonic stem cells but also their long-term survival in vivo. We propose that the delivery of growth factors by mesoporous nanoparticles is a potentially versatile and widely applicable strategy for efficient differentiation and functional integration of stem cell derivatives upon transplantation.

Funder

Swedish Research Council

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,General Medicine

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