title: Efficient Generation of Chemically Induced Mesenchymal Stem Cells from Human Dermal Fibroblasts.
abstract: Human mesenchymal stromal/stem cells (MSCs) are multipotent and currently undergoing hundreds of clinical trials for disease treatments. To date, no studies have generated induced MSCs from skin fibroblasts with chemicals or growth factors. Here, we established the first chemical method to convert primary human dermal fibroblasts into multipotent, induced MSC-like cells (iMSCs). The conversion method uses a defined cocktail of small molecules and growth factors, and it can achieve efficient conversion with an average rate of 38% in 6 days. The iMSCs have much higher clonogenicity than fibroblasts, and they can be maintained and expanded in regular MSC medium for at least 8 passages and further differentiated into osteoblasts, adipocytes, and chondrocytes. Moreover, the iMSCs can suppress LPS-mediated acute lung injury as effectively as bone marrow-derived mesenchymal stem cells. This finding may greatly benefit stem cell biology, cell therapy, and regenerative medicine.
authors.affiliation: Genome and Systems Biology Degree Program, College of Life Science, National Taiwan University, Taipei, Taiwan.|Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Pei-Lun
authors.initials: PL
authors.lastname: Lai
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan.
authors.forename: Hsuan
authors.initials: H
authors.lastname: Lin
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.|Institute of Molecular and Cellular Biology and Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Shang-Fu
authors.initials: SF
authors.lastname: Chen
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Shang-Chih
authors.initials: SC
authors.lastname: Yang
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Kuo-Hsuan
authors.initials: KH
authors.lastname: Hung
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Ching-Fang
authors.initials: CF
authors.lastname: Chang
authors.affiliation: Genome and Systems Biology Degree Program, College of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Hsiang-Yi
authors.initials: HY
authors.lastname: Chang
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan.
authors.forename: Frank Leigh
authors.initials: FL
authors.lastname: Lu
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Yi-Hsuan
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Yu-Chuan
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Genome and Systems Biology Degree Program, College of Life Science, National Taiwan University, Taipei, Taiwan.|Institute of Molecular and Cellular Biology and Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan.|Graduate Institute of Electronics Engineering, College of Electrical Engineering and Computer Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Hsiao-Chun
authors.initials: HC
authors.lastname: Huang
authors.affiliation: Genome and Systems Biology Degree Program, College of Life Science, National Taiwan University, Taipei, Taiwan.|Genomics Research Center, Academia Sinica, Taipei, Taiwan.|National RNAi Platform/National Core Facility Program for Biotechnology, Taipei, Taiwan.|Department of Life Science, Tzu Chi University, Hualien, Taiwan.
authors.forename: Jean
authors.initials: J
authors.lastname: Lu
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D012867:Skin / Q000166:cytology / Q000187:drug effects; D054852:Small Molecule Libraries / Q000494:pharmacology
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D054852:Small Molecule Libraries