Chondrogenic Differentiation from Induced Pluripotent Stem Cells Using Non-Viral Minicircle Vectors.

Yeri Alice Rim,Kijun Lee,Jennifer Lee,Narae Park,Ji Hyeon Ju,Yoojun Nam,Hyerin Jung

doi:10.3390/cells9030582

Yeri Alice Rim, Kijun Lee + Show 5 more

Open Access

https://doi.org/10.3390/cells9030582

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Journal: Cells	Publication Date: Mar 1, 2020
Citations: 24	License type: CC BY 4.0

Affiliation: Catholic University of Korea, Seoul St. Mary's Hospital

Abstract

Human degenerative cartilage has low regenerative potential. Chondrocyte transplantation offers a promising strategy for cartilage treatment and regeneration. Currently, chondrogenesis using human pluripotent stem cells (hiPSCs) is accomplished using human recombinant growth factors. Here, we differentiate hiPSCs into chondrogenic pellets using minicircle vectors. Minicircles are a non-viral gene delivery system that can produce growth factors without integration into the host genome. We generated minicircle vectors containing bone morphogenetic protein 2 (BMP2) and transforming growth factor beta 3 (TGFβ3) and delivered them to mesenchymal stem cell-like, hiPSC-derived outgrowth (OG) cells. Cell pellets generated using minicircle-transfected OG cells successfully differentiated into the chondrogenic lineage. The implanted minicircle-based chondrogenic pellets recovered the osteochondral defects in rat models. This work is a proof-of-concept study that describes the potential application of minicircle vectors in cartilage regeneration using hiPSCs.

Highlights

The poor recovery of damaged cartilage has prompted researchers to develop a defined regeneration strategy [1]
The parental plasmid was purchased from SBI
The cells transfected with the mock vector had the highest transfection efficacy

Summary

Introduction

The poor recovery of damaged cartilage has prompted researchers to develop a defined regeneration strategy [1]. It has been reported that the chondrogenic potential of adult stem cells depends on the pathological status of the donor. Because of these reasons, studies on regeneration using pluripotent stem cells have robustly been carried out over the past decade. Human induced pluripotent stem cells (hiPSCs) have shown boundless possibilities in tissue regeneration. To this end, hiPSCs expand significantly and maintain their pluripotency for several passages [4]. The use of hiPSCs in cell-based therapy is promising for damaged tissues with low regenerative abilities

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