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Open AccessArticle

A Combinatorial Cell and Drug Delivery Strategy for Huntington’s Disease Using Pharmacologically Active Microcarriers and RNAi Neuronally-Committed Mesenchymal Stromal Cells

1
CRCINA, UMR 1232, INSERM, Université de Nantes, Université d’Angers, F-49933 Angers, France
2
Geriatric Research, Education, and Clinical Center, and Research Service, Bruce W. Carter Department of Veterans Affairs Medical Center, Miami, FL 33125, USA
3
College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL 33125, USA
*
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(10), 526; https://doi.org/10.3390/pharmaceutics11100526
Received: 18 June 2019 / Revised: 15 September 2019 / Accepted: 2 October 2019 / Published: 12 October 2019
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
For Huntington’s disease (HD) cell-based therapy, the transplanted cells are required to be committed to a neuronal cell lineage, survive and maintain this phenotype to ensure their safe transplantation in the brain. We first investigated the role of RE-1 silencing transcription factor (REST) inhibition using siRNA in the GABAergic differentiation of marrow-isolated adult multilineage inducible (MIAMI) cells, a subpopulation of MSCs. We further combined these cells to laminin-coated poly(lactic-co-glycolic acid) PLGA pharmacologically active microcarriers (PAMs) delivering BDNF in a controlled fashion to stimulate the survival and maintain the differentiation of the cells. The PAMs/cells complexes were then transplanted in an ex vivo model of HD. Using Sonic Hedgehog (SHH) and siREST, we obtained GABAergic progenitors/neuronal-like cells, which were able to secrete HGF, SDF1 VEGFa and BDNF, of importance for HD. GABA-like progenitors adhered to PAMs increased their mRNA expression of NGF/VEGFa as well as their secretion of PIGF-1, which can enhance reparative angiogenesis. In our ex vivo model of HD, they were successfully transplanted while attached to PAMs and were able to survive and maintain this GABAergic neuronal phenotype. Together, our results may pave the way for future research that could improve the success of cell-based therapy for HDs. View Full-Text
Keywords: tissue engineering; Huntington’s disease; siRNA; nanoparticles; microcarriers; mesenchymal stromal cells tissue engineering; Huntington’s disease; siRNA; nanoparticles; microcarriers; mesenchymal stromal cells
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MDPI and ACS Style

André, E.M.; Delcroix, G.J.; Kandalam, S.; Sindji, L.; Montero-Menei, C.N. A Combinatorial Cell and Drug Delivery Strategy for Huntington’s Disease Using Pharmacologically Active Microcarriers and RNAi Neuronally-Committed Mesenchymal Stromal Cells. Pharmaceutics 2019, 11, 526.

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