Generation of human induced pluripotent stem cells from osteoarthritis patient–derived synovial cells
Min-Jeong Kim
Korea Research Institute of Bioscience and Biotechnology and University of Science and Technology, Daejeon, Republic of Korea
Search for more papers by this authorMyung Jin Son
Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
Search for more papers by this authorMi-Young Son
Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
Search for more papers by this authorBinna Seol
Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
Search for more papers by this authorJanghwan Kim
Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
Search for more papers by this authorJongjin Park
Korea Research Institute of Bioscience and Biotechnology and University of Science and Technology, Daejeon, Republic of Korea
Search for more papers by this authorJung Hwa Kim
Asan Medical Center and University of Ulsan College of Medicine, Seoul, Republic of Korea
Search for more papers by this authorYong-Hoon Kim
Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
Search for more papers by this authorSu A Park
Korea Institute of Machinery and Materials, Daejeon, Republic of Korea
Search for more papers by this authorChul-Ho Lee
Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
Search for more papers by this authorKang-Sik Lee
Asan Medical Center and University of Ulsan College of Medicine, Seoul, Republic of Korea
Search for more papers by this authorYong-Mahn Han
Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
Search for more papers by this authorJae-Suk Chang
Asan Medical Center and University of Ulsan College of Medicine, Seoul, Republic of Korea
Search for more papers by this authorCorresponding Author
Yee Sook Cho
Korea Research Institute of Bioscience and Biotechnology and University of Science and Technology, Daejeon, Republic of Korea
Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of KoreaSearch for more papers by this authorMin-Jeong Kim
Korea Research Institute of Bioscience and Biotechnology and University of Science and Technology, Daejeon, Republic of Korea
Search for more papers by this authorMyung Jin Son
Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
Search for more papers by this authorMi-Young Son
Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
Search for more papers by this authorBinna Seol
Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
Search for more papers by this authorJanghwan Kim
Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
Search for more papers by this authorJongjin Park
Korea Research Institute of Bioscience and Biotechnology and University of Science and Technology, Daejeon, Republic of Korea
Search for more papers by this authorJung Hwa Kim
Asan Medical Center and University of Ulsan College of Medicine, Seoul, Republic of Korea
Search for more papers by this authorYong-Hoon Kim
Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
Search for more papers by this authorSu A Park
Korea Institute of Machinery and Materials, Daejeon, Republic of Korea
Search for more papers by this authorChul-Ho Lee
Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
Search for more papers by this authorKang-Sik Lee
Asan Medical Center and University of Ulsan College of Medicine, Seoul, Republic of Korea
Search for more papers by this authorYong-Mahn Han
Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
Search for more papers by this authorJae-Suk Chang
Asan Medical Center and University of Ulsan College of Medicine, Seoul, Republic of Korea
Search for more papers by this authorCorresponding Author
Yee Sook Cho
Korea Research Institute of Bioscience and Biotechnology and University of Science and Technology, Daejeon, Republic of Korea
Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of KoreaSearch for more papers by this authorAbstract
Objective
This study was undertaken to generate and characterize human induced pluripotent stem cells (PSCs) from patients with osteoarthritis (OA) and to examine whether these cells can be developed into disease-relevant cell types for use in disease modeling and drug discovery.
Methods
Human synovial cells isolated from two 71-year-old women with advanced OA were characterized and reprogrammed into induced PSCs by ectopic expression of 4 transcription factors (Oct-4, SOX2, Klf4, and c-Myc). The pluripotency status of each induced PSC line was validated by comparison with human embryonic stem cells (ESCs).
Results
We found that OA patient–derived human synovial cells had human mesenchymal stem cell (MSC)–like characteristics, as indicated by the expression of specific markers, including CD14−, CD19−, CD34−, CD45−, CD44+, CD51+, CD90+, CD105+, and CD147+. Microarray analysis of human MSCs and human synovial cells further determined their unique and overlapping gene expression patterns. The pluripotency of established human induced PSCs was confirmed by their human ESC–like morphology, expression of pluripotency markers, gene expression profiles, epigenetic status, normal karyotype, and in vitro and in vivo differentiation potential. The potential of human induced PSCs to differentiate into distinct mesenchymal cell lineages, such as osteoblasts, adipocytes, and chondrocytes, was further confirmed by positive expression of markers for respective cell types and positive staining with alizarin red S (osteoblasts), oil red O (adipocytes), or Alcian blue (chondrocytes). Functional chondrocyte differentiation of induced PSCs in pellet culture and 3-dimensional polycaprolactone scaffold culture was assessed by chondrocyte self-assembly and histology.
Conclusion
Our findings indicate that patient-derived synovial cells are an attractive source of MSCs as well as induced PSCs and have the potential to advance cartilage tissue engineering and cell-based models of cartilage defects.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
| Filename | Description |
|---|---|
| ART_30488_sm_SuppInfo.doc53 KB | Supplementary Data |
| ART_30488_sm_SuppFigs.doc34.2 MB | Supplementary Figures |
| ART_30488_sm_SuppTab1.doc69 KB | Supplementary Table 1. |
| ART_30488_sm_SuppTab2.doc51.5 KB | Supplementary Table 2. |
| ART_30488_sm_SuppTab3.doc235.5 KB | Supplementary Table 3. |
| ART_30488_sm_SuppTab4.doc89 KB | Supplementary Table 4. |
| ART_30488_sm_SuppTab5.doc41.5 KB | Supplementary Table 5. |
| ART_30488_sm_SuppTab6.doc134.5 KB | Supplementary Table 6. |
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