Extended Abstract (for invited Faculty only) Biomaterials and Scaffolds

14.0.4 - Significance of Living Mesenchymal Stromal Cells within Natural Bio-Scaffold in Osteochondral Repair (Pre-Recorded)

Presentation Topic
Biomaterials and Scaffolds
Date
14.04.2022
Lecture Time
09:15 - 09:30
Room
Potsdam 1
Session Type
Plenary Session
Speaker
  • N. Nakamura (Osaka, JP)
Authors
  • N. Nakamura (Osaka, JP)

Abstract

Introduction

Biomaterials are often used to support the 3D environment of the implanted tissue as well as to reinforce adhesion to the osteochondral lesion base and surrounding tissue. However, there have been few studies to clearly elucidate the significance of the presence of mesenchymal stromal cells (MSCs) within the implanted biomaterials. In discussing whether cell-based or cell-free strategy to be used, it is important to address to bio- and mechanical function of the tested materials, however we have not had appropriate experimental model to test the significance of living MSCs within the biomaterials in the repair and remodeling of osteochondral lesions.

Content

Here we introduce a model of osteochondral repair using iPS cell-derived cartilaginous spheroids and synovial MSCs-derived tissue engineered construct whose matrix are natural matrix produced by the MSCs. Human iPSC-derived cartilaginous particles (iPSC-CP) developed via sequencial in vitro differentiation are a spherical body of hyaline cartilage-like tissue (1), which could be implanted to the osteochondral defect to repair and regenerate the lesion. However, due to its relatively low adhesive properties, the spheroid was wrapped by MSC-based tissue-engineered constructs (TEC) (2) to secure adhesion to the lesion base and surrounding osteochondral tissue. As the control, Freeze-dried TEC was used to wrap the spheroid. Regardless of freeze-dried preparation, wrapped spheroids attained secure defect filling with good integration to adjacent tissue in a rat osteochondral injury model over a 24-week post-implantation period. Conversely, the outcome of spheroid implantation was totally different between the TEC and Freeze-dried TEC group. The presence of living MSCs in the hybrid implants (TEC group) contributed to accomplish biphasic osteochondral repair. Defects reconstituted with a freeze-dried TEC initially maintained the original matrix of the spheroid but hereafter did not support osteochondral repair. Thus, it has been revealed that living MSCs have crucial function to induce proper biphasic osteochondral repair potentially by facilitating the communication with recipient cells.

Although this study use only one specific type of cell (synovial mesenchymal stromal cells) and matrix developed by the synovial MSCs, the present study suggests the presence of MSCs within natural matrix significantly determine the out come of tissue repair and remodelling. The use of iPC-derived chondral pheroid-based osteochondral repair model could be a good model to test the significant relation between pupulating MSCs and biomaterials. Further studies are required to test the phenomenon observed in the present study is applicable to other cells and biomaterials.

References

1. Generation of scaffoldless hyaline cartilaginous tissue from human iPSCs. Yamashita A, Morioka M, Yahara Y, Okada M, Kobayashi T, Kuriyama S, Matsuda S, Tsumaki N. Stem Cell Reports. 2015 Mar 10;4(3):404-18.

2. Cartilage repair using an in vitro generated scaffold-free tissue-engineered construct derived from porcine synovial mesenchymal stem cells. Ando W, Tateishi K, Hart DA, Katakai D, Tanaka Y, Nakata K, Hashimoto J, Fujie H, Shino K, Yoshikawa H, Nakamura N. Biomaterials. 2007 Dec;28(36):5462-70.

Acknowledgments

This study was supported by the grant for Research Center Network for Realization of Regenerative Medicine, Japan Agency for Medical Research and Development.

I appreciate Dr. N. Tsumaki for providing iPS cell-derived spheroids and for valuabke discussions.

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