In an in vivo study the transplantation of hPSC SCP

In an in vivo study, the transplantation of hPSC-SCP-SCs into a sciatic nerve-injured mouse promoted nerve fiber regeneration, and the transplanted cells integrated into renewed influenza m2 protein (Figures 5 and S6). However, without SC transplantation, demyelinated axons and nerve defects were not restored (Figure S6C). These observations suggest that our myelin-generating hPSC-SCP-SCs contribute to the therapeutic effect of peripheral nerve regeneration through the release of neurotrophic factors that promote axonal growth. This report provides the evidence that hPSC-derived SCs, obtained via an intermediate step, SCPs, can give rise to myelinating SCs both in vitro as well as in vivo. Although the myelination capacity of hPSC-SCP-SCs appears to be low, and still needs to be improved, the self-renewing hPSC-SCPs promise a valuable resource to produce functional hSCs that can myelinate neurons both in vitro and in vivo. Because SCs have the ability to myelinate CNS axons, transplantation of SCs has the potential to promote the regeneration of spinal nerves (Bachelin et al., 2005; Biernaskie et al., 2007; Kocsis and Waxman, 2007; Papastefanaki et al., 2007; Pearse et al., 2007). Thus, it is highly probable that our SCPs are applicable to cell therapy for repair in both the PNS and CNS, which we will investigate in future studies. When using the sciatic nerve-injured mouse model system, there are limits to analyzing the potential contributions of exogenous and endogenous SCs to restore remyelination and nerve defects in detail. Further evaluation of the functionality and myelination capacity hPSC-SCP-SCs in a demyelination animal model such as shiverer mice (McKenzie et al., 2006) would be valuable to understand the mechanisms of demyelination and remyelination and to develop therapeutics to promote nerve regeneration. Our work provides an efficient protocol for generating functional, clinical-grade SCs from patient- or disease-specific hPSCs via SCPs, which can easily be expanded and stored within a short period of time (Figure 6). Currently, hiPSCs generated from patient-derived cells have become an ideal source for combined cell and gene therapy, which is at the forefront of developing treatments for human disease. Thus, the application of patient- and disease-specific hPSCs from patients with SC-related genetic diseases and their derivatives, SCPs and SCs, into rapidly evolving stem cell and gene therapy approaches is highly desirable and offers hope for the development of future treatments.
Experimental Procedures
Author Contributions
Acknowledgments We heartily thank Professor Hwan Tae Park of Dong-A University for advice and suggestions during this work. This work was supported by the National Research Foundation of Korea (NRF; 2012M3A9C7050224) and by the National Research Council of Science & Technology (NST) Grant from the Korean government (MSIP) (No. CRC-15-02-KRIBB).
Introduction Microglia are brain-resident macrophages, with important homeostatic functions that provide a supportive environment to neurons. This includes pruning incompetent synapses during development, and clearance of dead cells, misfolded proteins, and other cellular debris (Ransohoff, 2016). However, they can become activated by inflammatory stimuli, producing a battery of cytokines, including the potentially damaging tumor necrosis factor α (TNFα). If not satisfactorily resolved, this response can lead to a chronically damaging cycle of activation and neuronal destruction. Numerous genes associated with Alzheimer\'s disease (AD), Parkinson\'s disease (PD), motor neuron disease/amyotrophic lateral sclerosis (MND/ALS), and frontotemporal dementia (FTD) are expressed in microglia, including TREM2, CD33, LRRK2, and C9orf72 (O\'Rourke et al., 2016; Russo et al., 2014; Villegas-Llerena et al., 2016), prompting a growing interest in microglia biology and their relevance to neurodegenerative disease.