Application of Induced Pluripotent Stem Cells for Disease Modeling and 3D Model Construction: Focus on Osteoarthritis.

Joel Jihwan Hwang,Ji Hyeon Ju,Yoojun Nam,Jinhyeok Choi,Yeri Alice Rim

doi:10.3390/cells10113032

Joel Jihwan Hwang, Ji Hyeon Ju + Show 3 more

Open Access

https://doi.org/10.3390/cells10113032

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Abstract

Since their discovery in 2006, induced pluripotent stem cells (iPSCs) have shown promising potential, specifically because of their accessibility and plasticity. Hence, the clinical applicability of iPSCs was investigated in various fields of research. However, only a few iPSC studies pertaining to osteoarthritis (OA) have been performed so far, despite the high prevalence rate of degenerative joint disease. In this review, we discuss some of the most recent applications of iPSCs in disease modeling and the construction of 3D models in various fields, specifically focusing on osteoarthritis and OA-related conditions. Notably, we comprehensively reviewed the successful results of iPSC-derived disease models in recapitulating OA phenotypes for both OA and early-onset OA to encompass their broad etiology. Moreover, the latest publications with protocols that have used iPSCs to construct 3D models in recapitulating various conditions, particularly the OA environment, were further discussed. With the overall optimistic results seen in both fields, iPSCs are expected to be more widely used for OA disease modeling and 3D model construction, which could further expand OA drug screening, risk assessment, and therapeutic capabilities.

Highlights

Pluripotent stem cells (PSCs) have promising potential in regenerative medicine because of their ability to undergo unlimited self-renewal and differentiate into any adult cell type (Figure 1) [1,2]
The induced PSCs (iPSCs)-derived cartilage model was treated with IL-1α in a serum-free chondrogenic medium for 3 days
IPSC-derived models could be used for drug screening and closely examine pathology

Summary

Introduction

Pluripotent stem cells (PSCs) have promising potential in regenerative medicine because of their ability to undergo unlimited self-renewal and differentiate into any adult cell type (Figure 1) [1,2]. 2. Induced Pluripotent Stem Cells (iPSCs) and Their Advantages the delivery of four transcription factors: OCT3/4, Sox, KLF4, and c-MYC. Inas2006, iPSCs were(Figure first generated from murine embryonic and adultfactors fibroblasts via known Together, these four transcription via the delivery of four transcription factors: OCT3/4, Sox, KLF4, and c-MYC. Theyfactors, are grammed the somatic cellsfactors to re-acquire [13].KLF4, Using same known as OSKM Together, these four transcription factors reproiPSC generation was successfully replicated in adult human fibroblasts a year later [14]. Patient-specific urine, blood, andiPSCs skin surpass the limitations presented by animal models (interspecies differences, i.e., iPSCs etiology) are the common samples to collect cells.construction, patient-specific. The most common somatic cells used to generate iPSCs are obtained from blood, skin, and urine (Figure 2) [7,15]. Regulations and guidelines for iPSC studies must be developed to closely monitor clinical trials involving iPSCs [32]

Osteoarthritis

Generating iPSCs from Patients with OA

Results

Study Results

Conclusions