Efficient Generation of Chemically Induced Mesenchymal Stem Cells from Human Dermal Fibroblasts

• Published in: Scientific reports Vol. 7; no. 1; p. 44534
• Main Authors: Lai, Pei-Lun, Lin, Hsuan, Chen, Shang-Fu, Yang, Shang-Chih, Hung, Kuo-Hsuan, Chang, Ching-Fang, Chang, Hsiang-Yi, Lu, Frank Leigh, Lee, Yi-Hsuan, Liu, Yu-Chuan, Huang, Hsiao-Chun, Lu, Jean
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.03.2017; Nature Publishing Group
• Subjects: 631/532/2063; 631/92/613; 64/60; 82/51; Adipocytes; Bone marrow; Chondrocytes; Clinical trials; Fibroblasts; Growth factors; Humanities and Social Sciences; Lipopolysaccharides; Lungs; Medical treatment; Mesenchymal stem cells; Mesenchyme; multidisciplinary; Osteoblasts; Regenerative medicine; Science; Skin & tissue grafts; Stem cells
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep44534

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.