Abstract

Bone marrow mesenchymal stem cells undergo differentiation to different lineages with different efficiencies when induced by different factors. We added a bFGF-chitosan controlled release system (bFGF-CCRS) as an inducer into conditioned medium to facilitate the oriented differentiation of BMSCs into neural lineage cells (eventually mature neurons); furthermore, we synchronized BMSCs to the G0/G1 phase via serum starvation to observe the effect of the inducer on the differentiation direction and efficiency. The nonsynchronized group, chitosan alone (not loaded with bFGF) group, soluble bFGF group, and conditioned medium group served as controls, and we observed the dynamic process of differentiation of BMSCs into neural lineage cells at different time points after the beginning of coculture. We analyzed the binding patterns of bFGF and chitosan and assayed the expression differences of key factors (FGFR1, ERK, and c-fos) and molecular switches (BTG2) that regulate the transformation from cell proliferation to differentiation. We also investigated the potential molecular mechanism of BMSC differentiation into neural lineage cells at a high percentage when induced by bFGF-CCRS.

Highlights

  • Many neurodegenerative diseases have been shown to be associated with the degeneration of specific types of neurons accompanied by functional loss

  • Compared with the soluble bFGF and chitosan alone groups, the results suggest that, in the bFGF-chitosan controlled release scaffold group, the position of the absorption peak that corresponded to the stretching vibration of double-bond C=O changed as follows: the stretching vibration peak of C=O split into two peaks, with peak values of 1643 and 1666 cm−1 (Figures 1(a) and 1(b)), indicating that both bFGF and chitosan may have formed hydrogen bonds between C=O groups

  • To further investigate the thermal stability of the bFGFchitosan controlled release scaffold, we analyzed the TGA curves of these three materials and obtained the DTG curves. These curves suggest that as the temperature increased from room temperature to 800∘C, bFGF experienced one weight loss, which peaked at a decomposition temperature of 285∘C

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Summary

Introduction

Many neurodegenerative diseases have been shown to be associated with the degeneration of specific types of neurons accompanied by functional loss. Bone marrow mesenchymal stem cells (BMSCs) originating from bone marrow are regarded as the best candidates for cell replacement. They have advantages including ease of isolation, strong proliferation capacity, and immunological naivety, and there are no ethical issues concerning their use 6. BMSCs can differentiate into other cell types, including osteoblasts, adipose cells, and chondrocytes [3]. According to some in vitro experimental results, when BMSCs were induced to differentiate into neurons, they generated glial cells [4, 5]. When BMSCs were exposed to an environment harboring FGF2, FGF-8, brain-derived neurotrophic factors (BDNF), or some special substrates, respectively, they could be induced

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