Pharmacologically active microcarriers delivering BDNF within a hydrogel: Novel strategy for human bone marrow-derived stem cells neural/neuronal differentiation guidance and therapeutic secretome enhancement.

作者: Saikrishna Kandalam , Laurence Sindji , Gaëtan J-R Delcroix , Fabien Violet , Xavier Garric

DOI: 10.1016/J.ACTBIO.2016.11.030

关键词:

摘要: Stem cells combined with biodegradable injectable scaffolds releasing growth factors hold great promises in regenerative medicine, particularly the treatment of neurological disorders. We here integrated human marrow-isolated adult multilineage-inducible (MIAMI) stem and pharmacologically active microcarriers (PAMs) into an non-toxic silanized-hydroxypropyl methylcellulose (Si-HPMC) hydrogel. The goal is to obtain cell factor delivery device. It should direct survival and/or neuronal differentiation grafted cells, safely transplant them central nervous system, enhance their tissue repair properties. A model protein was used optimize nanoprecipitation conditions neuroprotective brain-derived neurotrophic (BDNF). BDNF nanoprecipitate encapsulated fibronectin-coated (FN) PAMs vitro release profile evaluated. showed a prolonged, bi-phasic, bioactive BDNF, without burst effect. demonstrated that Si-HPMC hydrogel increased expression neural/neuronal markers MIAMI after 1 week. Moreover, 3D environment (PAMs or hydrogel) secretion (b-NGF, SCF, HGF, LIF, PlGF-1, SDF-1α, VEGF-A & D) chemokines (MIP-1α β, RANTES, IL-8). These results show delivering represent useful novel local tool context not only provides but also bone marrow-derived benefit from by displaying neural commitment improved neuroprotective/reparative secretome. preliminary evidence promising pro-angiogenic, axonal growth-promoting device for system.

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