한빛사 논문
Ji-Young Yoon a,b,d, Nandin Mandakhbayar a,b,c, Jeongeun Hyun a,b,c,d, Dong Suk Yoon a,e, Kapil D. Patel a,b, Keunsoo Kang f, Hosup Shim a,b, Hae-Hyoung Lee a,b,c,g,h, Jung-Hwan Lee a,b,c,d,g,h,i,*, Kam W. Leong b,j,k, Hae-Won Kim a,b,c,d,g,h,i,*
a Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea b Department of Nanobiomedical Science and BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea c Cell & Matter Institute, Dankook University, Cheonan, 31116, Republic of Korea d Department of Regenerative Dental Medicine, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea e Department of Orthopedic Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea f Department of Microbiology, College of Science & Technology, Dankook University, Cheonan, 31116, South Korea g Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea h UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, Republic of Korea i Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan, 31116, Republic of Korea j Department of Biomedical Engineering, Columbia University, New York, NY, 10027, USA k Department of Systems Biology, Columbia University, New York, NY, 10027, USA
* Corresponding author.
Abstract
Cell reprogramming can satisfy the demands of obtaining specific cell types for applications such as tissue regeneration and disease modeling. Here we report the reprogramming of human fibroblasts to produce chemically-induced osteogenic cells (ciOG), and explore the potential uses of ciOG in bone repair and disease treatment. A chemical cocktail of RepSox, forskolin, and phenamil was used for osteogenic induction of fibroblasts by activation of RUNX2 expression. Following a maturation, the cells differentiated toward an osteoblast phenotype that produced mineralized nodules. Bulk and single-cell RNA sequencing identified a distinct ciOG population. ciOG formed mineralized tissue in an ectopic site of immunodeficiency mice, unlike the original fibroblasts. Osteogenic reprogramming was modulated under engineered culture substrates. When generated on a nanofiber substrate ciOG accelerated bone matrix formation in a calvarial defect, indicating that the engineered biomaterial promotes the osteogenic capacity of ciOG in vivo. Furthermore, the ciOG platform recapitulated the genetic bone diseases Proteus syndrome and osteogenesis imperfecta, allowing candidate drug testing. The reprogramming of human fibroblasts into osteogenic cells with a chemical cocktail thus provides a source of specialized cells for use in bone tissue engineering and disease modeling.
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