RT Journal Article SR Electronic T1 Pharmaceutical efficacy of human epiphyseal chondrocytes with differential replication numbers for cellular therapy products JF bioRxiv FD Cold Spring Harbor Laboratory SP 085688 DO 10.1101/085688 A1 Michiyo Nasu A1 Shinichiro Takayama A1 Akihiro Umezawa YR 2016 UL http://biorxiv.org/content/early/2016/11/04/085688.abstract AB The cell-based therapy for cartilage or bone requires a large number of cells serial passages of chondrocytes are, therefore, needed. However, fates of expanded chondrocytes from extra fingers remains unclarified. The chondrocytes from human epiphyses morphologically changed from small polygonal cells, to bipolar elongated spindle cells and to large polygonal cells with degeneration at early passages. Gene of type II collagen was expressed in the cells only at a primary culture (Passage 0) and Passage 1 (P1) cells. The nodules by implantation of P0 to P8 cells were composed of cartilage and perichondrium. The cartilage consisted of chondrocytes with round nuclei and type II collagen-positive matrix, and the perichondrium consisted of spindle cells with type I collage-positive matrix. The cartilage and perichondrium developed to bone with marrow cavity through enchondral ossification. Chondrogenesis and osteogenesis by epiphyseal chondrocytes depended on replication number in culture. It is noteworthy to take population doubling level in correlation with pharmaceutical efficacy into consideration when we use chondrocytes for cell-based therapies.