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B-0429 - Directing neuronal differentiation of stem cells with a small interfering RNA-complexed MRI-visible cationic polymersome to counteract inhibitory microenvironment in stroke

L. Lu, J. Shen, X. Duan, F. Zhang, W. Young, H. Chen; Guangzhou/CN Type: Scientific Paper
Area of Interests: Neuroradiology brain, Vascular, Molecular imaging
Imaging Technique: MR
Procedures: Molecular imaging, Thrombolysis
Special Focuses: Acute, Ischemia / Infarction, Cerebral palsy
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Purpose:  A major challenge to effective treatment after stroke is the restoration of neuronal function. Although exogenous neural stem cell (NSC) could differentiate into neurons to replace damaged cells, poor control over cell differentiation limits therapeutic prospects. Myelin associated i[...]

Methods and materials: A type of MRI-visible cationic polymersome (SPION-CP), based on diblock copolymers of poly(etherimide) and poly(D, L-lactide) (PEI-PDLLA) was synthesized, in which superparamagnetic iron oxide nanoparticles (SPIONs) was loaded. The siRNA condensation ability and the other characteristics of the[...]

Results:   siRNA was fully neutralized at the N/P ratio of about 8  in agarose gel (Fig. 2A). TEM revealed that the SPIONs were loaded in the core of polymersomes (Fig. 2b) and siRNA were binding well the membrane of polymersomes after complexing with siRNA. The r2 relaxitivitySPION-loaded ploymers[...]

Conclusion:   In summary, MRI-visible cationic polymersome was used for the first time to mediate efficient intracellular siRNA delivery into NSCs for the purpose of directing neuronal differentiation. Epigenetic downregulation of NgR gene counteracted the extrinsic inhibitory microenvironment in stroke, r[...]

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References: [1] Schwab ME. Functions of Nogo proteins and their receptors in the nervous system. Nat Rev Neurosci 2010;11(12):799-811. [2]  Fournier AE, GrandPre T, Strittmatter SM. Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature 2001;409(6818):341-6. [3]  Dom[...]

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