Abstract

Intrinsic cellular properties of several types of cells are dramatically altered as the culture condition shifts from two-dimensional (2D) to three-dimensional (3D) environment. Currently, several lines of evidence have demonstrated the therapeutic potential of mesenchymal stem cells (MSCs) in regenerative medicine. MSCs not only replenish the lost cells, they also promote the regeneration of impaired tissues by modulating the immune responses. Following the development of 3D cell culture, the enhanced therapeutic efficacy of spheroid-forming MSCs have been identified in several animal disease models by promoting differentiation or trophic factor secretion, as compared to planar-cultured MSCs. Due to the complicated and multifunctional applications in the medical field, MSCs are recently named as medicinal signaling cells. In this review, we summarize the predominant differences of cell–environment interactions for the MSC spheroids formed by chitosan-based substrates and other scaffold-free approaches. Furthermore, several important physical and chemical factors affecting cell behaviors in the cell spheroids are discussed. Currently, the understanding of MSCs spheroid interactions is continuously expanding. Overall, this article aims to review the broad advantages and perspectives of MSC spheroids in regenerative medicine and in future healthcare.

Highlights

  • The definition of 3D cell culture systems is that cells are cultured on/in the 3D

  • With the continuing development of 3D cell culture, it is generally agreed that the cell physiology and cell behavior are dramatically distinct for cells cultured within a 2D or 3D environment [1,2,3]

  • The up-regulated expression levels of N-cadherin and/or E-cadherin were observed in mesenchymal stem cells (MSCs) spheroids formed by different scaffold-free 3D culture systems including hanging drop method and CS substrates, comparing to those cultured on tissue culture polystyrene (TCPS) [71,73], indicating the involvement of cadherin-mediated signaling in the formation of MSC spheroids

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Summary

Their Perspectives in Future Healthcare

Center of Tissue Engineering and 3D Printing, National Taiwan University, Taipei 10617, Taiwan Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan 35053, Taiwan Received: 29 November 2018; Accepted: 2 February 2019; Published: 13 February 2019

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Thiswork work supported the Program for Regenerative

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