G. Im (Goyang, KR)

Dongguk University Research Institute for Integrative Regenerative Biomedical Engineering

Presenter Of 1 Presentation

Extended Abstract (for invited Faculty only) Stem Cells

14.0.1 - Cell Survival & Engraftment in Cytotherapy for Osteoarthritis

Presentation Topic
Stem Cells
Date
14.04.2022
Lecture Time
08:30 - 08:45
Room
Potsdam 1
Session Type
Plenary Session

Abstract

Introduction

The original hypothesis and expectation when the cell therapy for cartilage regeneration first started was that the implanted cells would survive, engraft to chondral defects, and differentiated to articular chondrocyte that would subsequently produce extracellular matrix (ECM). The cell therapy would thus achieve structural modification of damaged joint by regeneration of AC, which might also eventually supplant conventional treatments for OA. Therefore, early experimental studies for MSC-based cartilage regeneration focused on the chondrogenic induction from MSCs. Numerous studies were performed to induce chondrogenesis from MSC by the appropriate combination of growth factors or transforming cells by transfer of chondrogenic genes. Other studies also investigated the application of biomechanical stimuli to enhance chondrogenic differentiation from MSCs.10-11 As one distinctive shortcoming of MSCs as chondrogenic cell source was early induction of hypertrophic markers such as type X collagen, great efforts were made to devise ways to suppress hypertrophy in MSC chondrogenesis.

Content

The tracking of administered cell is essential for understanding the mode of action in a stem cell therapy. Whilst engraftment and chondrogenic differentiation was purposed in the beginning, on the other hand, it became apparent that IA-administered cells survive only transiently and undergo rapid cell death as also reported from stem cell implantation in other tissues such as myocardium. Most IA-administered stem cells undergo rapid cell death, surviving from 3 days to several weeks depending on the mode of administration and the IA environment. Paracrine factors that are released before undergoing apoptosis possess predominantly immunosuppressive and anti-inflammatory actions rather than chondrogenic effects. Rapid death of implanted cells is not limited to MSCs. Chondrocytes also undergo rapid clearance when injected into joints within 2 weeks. Interestingly, stem cells survived longer when focally implanted rather than injected. Rapid death of administered cells in vivo makes the efforts for the chondrogenic differentiation or hypertrophy inhibition in vitro quite meaningless. Instead, the focus of research then can move to prolongation of survival of implanted cells that could exert prolonged paracrine effects and/or engraftment with chondrogenic differentiation. For example, adipose stem cells (ASCs) in spheroid form survive longer post-IA injection than do ASCs that are injected in a free single cell suspension. These findings suggest that a sort of communication/interaction between cells can promote IA cell survival. Also, our preliminary experiments demonstrated that when ASCs were immobilized on the focal chondral defect using a strong bioadhesive (mussel adhesive protein) showed longer-term survival than those fixed using weak adhesive such as fibrin glue. These results indicate that stem cells can survive longer when forced to stay at the site of implantation. While it is not yet proven that these preliminary findings of prolonged cell survival may be translated into tangible difference in clinical application, the concept deserves further inquiry and investigation.

References

1. Ko JY, Park JW, Kim J, Im GI. Characterization of adipose-derived stromal/stem cell spheroids versus single-cell suspension in cell survival and arrest of osteoarthritis progression. J Biomed Mater Res A. 2021 Jun;109(6):869-87

2. Im GI. Current status of regenerative medicine in osteoarthritis. Bone Joint Res. 2021 Feb;10(2):134-136

3. Im GI, Kim TK. Regenerative Therapy for Osteoarthritis: A Perspective.Int J Stem Cells. 2020 Jul 30;13(2):177-181

Acknowledgments

This research was supported by a grant of the National Research Foundation of
Korea (NRF-2020R1A2C2008266).

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