Pharmaceutical efficacy of human epiphyseal chondrocytes with differential replication numbers for cellular therapy products

Abstract

1The cell-based therapy for cartilage or bone requires a large number of cells serial 2 passages of chondrocytes are, therefore, needed. However, fates of expanded 3 chondrocytes from extra fingers remains unclarified. The chondrocytes from human 4 epiphyses morphologically changed from small polygonal cells, to bipolar elongated 5 spindle cells and to large polygonal cells with degeneration at early passages. Gene of 6 type II collagen was expressed in the cells only at a primary culture (Passage 0) and 7 Passage 1 (P1) cells. The nodules by implantation of P0 to P8 cells were composed of 8 cartilage and perichondrium. The cartilage consisted of chondrocytes with round nuclei 9 and type II collagen-positive matrix, and the perichondrium consisted of spindle cells 10 with type I collage-positive matrix. The cartilage and perichondrium developed to bone 11 with marrow cavity through enchondral ossification. Chondrogenesis and osteogenesis 12 by epiphyseal chondrocytes depended on replication number in culture. It is noteworthy 13 to take population doubling level in correlation with pharmaceutical efficacy into 14 consideration when we use chondrocytes for cell-based therapies. 15 16 17