Biotechnology and Bioprocess Engineering 2019; 24(5): 734-744  
Exosome-mediated Bidirectional Signaling between Mesenchymal Stem Cells and Chondrocytes for Enhanced Chondrogenesis
Young Guk Kim1,†, Uiseon Park1,†, Beom Jun Park1, and Kyobum Kim2,*
1Division of Bioengineering, Incheon National University, Incheon 22012, Korea
2Department of Chemical & Biochemical Engineeing, Dongguk University, Seoul 04620, Korea
Correspondence to: Kyobum Kim
Department of Chemical & Biochemical Engineeing, Dongguk University, Seoul 04620, Korea
Tel: +82-2-2260-8597
Email: kyobum.kim@dongguk.edu

Equal contribution.
Received: August 20, 2019; Revised: August 24, 2019; Accepted: August 24, 2019; Published online: October 31, 2019.
© The Korean Society for Biotechnology and Bioengineering. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Exosomes of human mesenchymal stem cells (hMSC) are known to effectively increase the proliferation rate of chondrocytes and stimulate cartilage extracellular matrix. However, the therapeutic efficacy of the other signaling direction (i.e., the effect of chondrocyte-derived exosomes on hMSC) has not been extensively investigated. Therefore, the present study was designed to investigate exosome-mediated in vitro bidirectional signalings between progenitor hMSC and mature chondrocytes in cartilage tissues with various culture medial formulations. The exosomes isolated from bovine chondrocytes (BC) and hMSC (50 µg/ mL of exosomes per 3000 cells) were treated to hMSC and BC, respectively. Both cells were cultured in media formulations with 10% FBS, 10% exosome free-FBS, and 0.5% FBS. A variety of cellular responses by exosome treatments including proliferation, chondrogenic differentiation, cartilage extracellular matrix (ECM) deposition were evaluated using WST-1 assay, RT-PCR, and alcian blue staining for glycosaminoglycan (GAG) content. The results demonstrated that bidirectional exosome treatments increased proliferation of both BC and hMSC, and similar bidirectional influences including chondrogenic differentiation, glycosaminoglycan (GAG) ECM deposition were also up-regulated in both cell populations. Moreover, exosome-mediated in vitro activation between two cell populations could be regulated by media formulations. Therefore, exosomes could play important signaling roles in communication between two major cell populations in cartilage tissues.
Keywords: exosome, bidirectional signaling, mesenchymal stem cell, chondrocyte, cartilage regeneration


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