Abstract

Adipose-derived mesenchymal stem cells (ASCs) are well known for their secretory potential, which confers them useful properties in cell therapy. Nevertheless, this therapeutic potential is reduced after transplantation due to their short survival in the human body and their migration property. This study proposes a method to protect cells during and after injection by encapsulation in microparticles of calcium alginate. Besides, the consequences of encapsulation on ASC proliferation, pluripotential, and secretome were studied. Spherical particles with a mean diameter of 500 µm could be obtained in a reproducible manner with a viability of 70% after 16 days in vitro. Moreover, encapsulation did not alter the proliferative properties of ASCs upon return to culture nor their differentiation potential in adipocytes, chondrocytes, and osteocytes. Concerning their secretome, encapsulated ASCs consistently produced greater amounts of interleukin-6 (IL-6), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) compared to monolayer cultures. Encapsulation therefore appears to enrich the secretome with transforming growth factor β1 (TGF-β1) and macrophage inflammatory protein-1β (MIP-1β) not detectable in monolayer cultures. Alginate microparticles seem sufficiently porous to allow diffusion of the cytokines of interest. With all these cytokines playing an important role in wound healing, it appears relevant to investigate the impact of using encapsulated ASCs on the wound healing process.

Highlights

  • Several diseases, such as osteo-articular disorders, diabetes, cancers, cardiovascular diseases, and skin disorders, could be treated using adipose-derived mesenchymal stem cells (ASCs), and these cells have been used in many studies [1,2,3,4,5,6]

  • The morphology and diameter of microparticles were compared on D0 and D16 after encapsulation for three donors at passage 3 (P3), and one donor at P3 and passages and 4 (P4) (Figure 1)

  • During the 16 days of culture, no cell was observed growing outside the microparticles, but after 16 days, the apparent fragility correlated with cellular escape, and few cells were found in culture flasks beyond this period

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Summary

Introduction

Several diseases, such as osteo-articular disorders, diabetes, cancers, cardiovascular diseases, and skin disorders, could be treated using adipose-derived mesenchymal stem cells (ASCs), and these cells have been used in many studies [1,2,3,4,5,6]. They represent an alternative to bone marrow-derived stem cells in cell therapy applications. The strategy with the most potential appeared to us to be microencapsulation of ASCs in biomaterials as it is compatible with long-duration cellular survival [26,27]. This improved survival would allow the use of ASCs in humans for a wound healing purpose [28]

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