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Stem cell transplantation therapy has emerged as a potentially promising way forward in the treatment of neurodegenerative disorders. However, the field is fraught with practical difficulties, including the tendency of stem cells not to survive in the long-term after transplantation and the difficulty in inducing robust differentiation of stem cells in vivo. A recent paper in Stem Cells Translational Medicine may point the way to overcoming some of these obstacles. In this paper, research groups from Uppsala University, Sweden, the RIKEN Brain Science Institute, Japan and Copenhagen University, Denmark describe the use of specifically designed silica nanoporous particles to deliver trophic factor mimetics to transplanted embryonic stem cells in animal models. This induced both a robust functional differentiation of motor neurons from transplanted embryonic stem cells and enhanced their long-term survival.

Nanoparticles are an area of intense research interest in the field of gene delivery in many areas beyond neurodegeneration, for example in cancer and in acute liver failure (ALF). Studies on Chinese experimental mini-swine suffering from ALF, for example, showed that administration of IL-1Ra chitosan nanoparticles in conjunction with mesenchymal stem cell transplant resulted in synergistic effects on inflammation suppression and elevation of growth factors. Meanwhile, bone marrow hematopoietic stem cell-based gene therapy is being viewed as a potential way to overcome the difficulty in delivering trophic factors across the blood-brain barrier in Parkinson's disease and other neurodegenerative disorders. For example studies in mice showed that when bone marrow cells were transduced ex vivo with lentivirus expressing the neurturin (NTN) gene and then transplanted into mice, the mice were protected from the neurodegenerative effects of subsequent neurotoxin administration. Thus current research is considering both delivery of trophic factors to transplanted stem cells via nanoparticles and the use of transplanted stem cells as delivery systems for trophic factors in different models.

In the recent Stem Cells Translational Medicine paper, the authors used their mesoporous nanoparticles to deliver Cintrofin, a peptide mimetic of ciliary neurotrophic factor and Gliafin, a peptide mimetic of glial cell line-derived neurotrophic factor to transplanted embryonic stem cells in mice with positive effects for stem cell differentiation. This opens the way for improvements in stem cell therapy implementation in neurodegenerative diseases. However, further animal studies and future human clinical trials will determine how widely applicable this new delivery technology will prove to be. News reports suggest that the researchers are in negotiations to have their innovative approach commercialised.

Sources

BIJU, K.C. et al., 2013. Bone marrow-derived microglia-based neurturin delivery protects against dopaminergic neurodegeneration in a mouse model of Parkinson's disease. Neuroscience letters, 535, pp. 24-29

GARCIA-BENNETT, A. et al., 2013. Delivery of Differentiation Factors by Mesoporous Silica Particles Assists Advanced Differentiation of Transplanted Murine Embryonic Stem Cells. Stem Cells Translational Medicine, 2013

XIAO, J. et al., 2013. Administration of IL-1Ra chitosan nanoparticles enhances the therapeutic efficacy of mesenchymal stem cell transplantation in acute liver failure. Archives of Medical Research, 44(5), pp. 370-379

Stockholm University. "New take on efficient delivery in regenerative medicine." ScienceDaily, 22 Oct. 2013. [Accessed 23 Oct. 2013].