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Tissue Eng Part A. 2016 Jun;22(11-12):850-61. doi: 10.1089/ten.TEA.2016.0008.

Semaphorin 3C Released from a Biocompatible Hydrogel Guides and Promotes Axonal Growth of Rodent and Human Dopaminergic Neurons.

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1 Instituto de Fisiología Celular-Neurociencias, Universidad Nacional Autónoma de México , México, D.F., México .
2 Laboratorio de Reprogramación Celular IFC/UNAM en el Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez," México, D.F., México .
3 GENYO: Centre for Genomics and Oncological Research Pfizer-University of Granada-Junta de Andalucía , PTS Granada, Spain .
4 Unidad Periférica de Neurociencias Facultad de Medicina-UNAM en el Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez," México, D.F., México .


Cell therapy in experimental models of Parkinson's disease replaces the lost dopamine neurons (DAN), but we still need improved methods to guide dopaminergic axons (DAx) of grafted neurons to make proper connections. The protein Semaphorin 3C (Sema3C) attracts DAN axons and enhances their growth. In this work, we show that the hydrogel PuraMatrix, a self-assembling peptide-based matrix, incorporates Sema3C and releases it steadily during 4 weeks. We also tested if hydrogel-delivered Sema3C attracts DAx using a system of rat midbrain explants embedded in collagen gels. We show that Sema3C released by this hydrogel attracts DAx, in a similar way to pretectum, which is known to attract growing DAN axons. We assessed the effect of Sema3C on the growth of DAx using microfluidic devices. DAN from rat midbrain or those differentiated from human embryonic stem cells showed enhanced axonal extension when exposed to hydrogel-released Sema3C, similar to soluble Sema3C. Notably, DAN of human origin express the cognate Sema3C receptors, Neuropilin1 and Neuropilin2. These results show that PuraMatrix is able to incorporate and release Sema3C, and such delivery guides and promotes the axonal growth of DAN. This biocompatible hydrogel might be useful as a Sema3C carrier for in vivo studies in parkinsonian animal models.

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