Abstract

Astaxanthin is a highly potent antioxidant which can be extracted from Haematococcus pluvialis when cultivated and induced at high stress conditions. Due to astaxanthin’s hydrophobicity, methoxypolyethylene glycol-polycaprolactone (mPEG-PCL) copolymer was synthesized to form polymeric micelles for the encapsulation of astaxanthin. Astaxanthin-loaded polymeric micelles were then used to examine the effects on the proliferation and differentiation of human mesenchymal stem cells (MSCs). Dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FT-IR) confirmed astaxanthin was encapsulated into mPEG-PCL micelles. Astaxanthin loading and encapsulation efficiency, determined by UV/Vis spectroscopy, were 3.27% and 96.67%, respectively. After 48 h, a total of 87.31% of astaxanthin was released from the polymeric micelles. The drug release profile was better fit by the Michaelis-Menten type model than the power law model. The MSC culture results showed that culture medium supplemented with 0.5 μg/mL astaxanthin-encapsulated polymeric micelles led to a 26.3% increase in MSC proliferation over an 8-day culture period. MSC differentiation results showed that 20 ng/mL astaxanthin-encapsulated polymeric micelles enhanced adipogenesis, chondrogenesis, and osteogenesis of MSCs by 52%, 106%, and 182%, respectively.

Highlights

  • Mesenchymal stem cell (MSC) has been widely used in tissue engineering and regenerative medicine due to its unique properties of self-renewal and multipotency [1]

  • Our results showed that culture medium supplemented with 0.5 μg/mL astaxanthin-encapsulated polymeric micelles led to a notable increase in MSC proliferation over an 8-day culture period

  • Astaxanthin was extracted from H. pluvialis by mechanical disruption in dimethyl sulfoxide (DMSO)

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Summary

Introduction

Mesenchymal stem cell (MSC) has been widely used in tissue engineering and regenerative medicine due to its unique properties of self-renewal and multipotency [1]. Increased reactive oxygen species (ROS) levels have been shown to reduce the self-renewal ability and proliferation of MSCs [3]. Antioxidants are known to enhance in vitro proliferation of adipose-derived MSCs by regulation of cyclin-dependent kinase (CDK) and CDK inhibitor levels [4]. Proliferation of human and mouse bone marrow-derived MSCs have been improved by supplementing culture medium with antioxidants such as ascorbic acid 2-phosphate, phenyl-α-tert-butylnitrone and N-acetyl-L-cysteine [5, 6]. Supplementation of ascorbic acid 2-phosphate enhanced adipogenesis and osteogenesis of bone marrow-derived MSCs [6]

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