Mesenchymal stem cell spheroids: potential cell materials for cell therapy

Abstract

Mesenchymal stromal/stem cells (MSCs) have been applied in clinical trials with an increasing number in recent years. MSCs showed their great potentials in regenerative medicine for their extensive sources, multilineage differentiation potential, low immunogenicity and self-renewal ability. However, the clinical application of MSCs still confronts many challenges including the requirement of large quantity of cells, low survival ability in vivo and the loss of main original characteristics due to two-dimensional (2D) culture although it is beneficial to cells fast expansion. Three-dimensional (3D) culture artificially creates an environment that permits cells to grow or interact with their surroundings in all three dimensions. Therefore, 3D culture was widely regarded as a more preferable and closer physiological microenvironment for cells growth. Recently, many different 3D spheroid culture methods have been developed to optimize MSCs biological characteristics to meet the demand of regenerative medicine. In this review, we comprehensively discussed the merits and demerits of different spheroid formation methods, expounded the mechanisms of spheroid formation and its microenvironment, and illustrated their optimized biological functions and the pre-clinical applications in various tissue injury and regeneration. In the end, we prospected the trends of this research field and proposed the key problems needed to be solved in the future.

Keywords

• Mesenchymal stromal/stem cells
• Three-dimensional culture
• Spheroids
• Stem cell optimization
• Regenerative medicine