Growth and differentiation of fetal rat limb buds transplanted in athymic (nude) mice

Limb buds of day 14 rat fetuses were cut into pieces and transplanted into the subcutaneous tissue of athymic (nude) mice. In day 14 fetal limbs, mesenchymal cells have begun to condense to form cartilaginous anlage, but no cartilage has been formed. Within 7 days after grafting, masses of hyaline cartilage developed. Numerous osteoblasts appeared, and new bone formation began by 14 days. By 20 days, osteoclasts appeared, and the formation of bone trabeculae and marrow cavities progressed. The cytological characteristics of chondrocytes, osteoblasts and osteoclasts were essentially the same as those seen in vivo. Many grafts developed into long bones, having the diaphysis and epiphysis. The mode of chondrogenesis and osteogenesis in the grafts was histologically similar to the corresponding process in vivo, although the differentiation was slower in the grafted limbs. Since the grafted limb buds showed remarkable growth and tissue differentiation for at least several weeks, this heterotransplantation system would be of potential use for the study of bone formation and resorption as well as for developmental toxicological studies.