Overcoming Current Dilemma in Cartilage Regeneration: Will Direct Conversion Provide a Breakthrough?

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Online ISSN 2212-5469

REVIEW ARTICLE

Overcoming Current Dilemma in Cartilage Regeneration: Will Direct Conversion Provide a Breakthrough? Gun-il Im1



Tae-Kyung Kim1

Received: 18 August 2020 / Revised: 5 September 2020 / Accepted: 16 September 2020 Ó The Korean Tissue Engineering and Regenerative Medicine Society 2020

Abstract Direct reprogramming/direct conversion/transdifferentiation is a process that induces conversion between completely different matured (differentiated) cells in higher organisms. Unlike the process of reprogramming of differentiated cells into induced pluripotent stem cells (iPSCs) and re-differentiation into the desired cell types, differentiated cells undergo the conversion into another type of differentiated cells without going through the iPSCs state. Osteoarthritis (OA) is the most common type of arthritis that causes a significant deterioration in patients’ quality of life. The high prevalence of OA as well as the current lack of disease-modifying drugs has led to a rise in regenerative strategy for OA treatment. Regenerative therapy in OA started with the concept of engraftment of the administered cells within the cartilage lesion and differentiation to chondrocytes after the engraftment. However, recent studies show that cells, particularly when injected in suspension, rapidly undergo apoptosis after exerting a transient paracrine effect. In this perspective review, the general overview and current status of direct conversion are introduced along with the conceptual strategy and future directions for possible application of regenerative therapy using stem cells in OA. In vivo direct conversion may open a new stage of regenerative medicine for OA treatment. Recent advances in in vivo gene transfer and smart biomaterials can bring the concept into reality in near future. Direct conversion can be a new type of treatment technology that has the potential to overcome the limitations of current cell therapy. Keywords Direct conversion  Osteoarthritis  Regenerative medicine  Chondrogenesis

1 Overview of direct conversion Direct reprogramming/direct conversion/trans-differentiation is a process that induces conversion between completely different matured (differentiated) cells in higher organisms. Unlike the process of reprogramming of differentiated cells into induced pluripotent stem cells (iPSCs) and re-differentiation into the desired cell types, in this process, the differentiated cells undergo the conversion into

& Gun-il Im [email protected] 1

Integrative Research Institute for Regenerative Biomedical Engineering, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10326, Republic of Korea

another type of differentiated cells without going through the iPSCs state. Reprogramming refers to deletion of the original cell’s traits and development of new characteristics [1]. This concept was first established by Gurdon’s somatic cell nuclear transfer (SCNT) [2]. One major difference between direct converted cells and iPSCs is the presence of epigenetic memory from c