Abstract
Cell condensation and mechanical stimuli play roles in osteogenesis and chondrogenesis; thus, they are promising for facilitating self-organizing bone/cartilage tissue formation in vitro from induced pluripotent stem cells (iPSCs). Here, single mouse iPSCs were first seeded in micro-space culture plates to form 3-dimensional spheres. At day 12, iPSC spheres were subjected to shaking culture and maintained in osteogenic induction medium for 31 days (Os induction). In another condition, the osteogenic induction medium was replaced by chondrogenic induction medium at day 22 and maintained for a further 21 days (Os-Chon induction). Os induction produced robust mineralization and some cartilage-like tissue, which promoted expression of osteogenic and chondrogenic marker genes. In contrast, Os-Chon induction resulted in partial mineralization and a large area of cartilage tissue, with greatly increased expression of chondrogenic marker genes along with osterix and collagen 1a1. Os-Chon induction enhanced mesodermal lineage commitment with brachyury expression followed by high expression of lateral plate and paraxial mesoderm marker genes. These results suggest that combined use of micro-space culture and mechanical stimuli facilitates hybrid bone/cartilage tissue formation from iPSCs, and that the bone/cartilage tissue ratio in iPSC constructs could be manipulated through the induction protocol.
Highlights
The treatment of articular cartilage and osteochondral defects remains challenging, but cell-based tissue engineering is expected to enable the regeneration of osteochondral tissue [1]
Freeman and McNamara [6] reported that chondrocytes produce extracellular matrix (ECM) to maintain the space and load bearing for bone formation
retinoic acid (RA)-treated embryoid bodies (EB) formed from mouse embryonic stem cells (ESCs) produce pre-somatic mesoderm and neural crest cells, both of which provide immature mesenchymal cells that can differentiate into osteoblasts and chondrocytes [23]
Summary
The treatment of articular cartilage and osteochondral defects remains challenging, but cell-based tissue engineering is expected to enable the regeneration of osteochondral tissue [1]. Generation of osteochondral tissue is important for bone tissue engineering. Bone has innate potential for regeneration after injury, excessive bone defects exceed the capacity for natural bone healing, resulting in impairment of bone formation [2]. Critical-size bone defects require additional intervention, especially tissue-engineered grafts, to facilitate the healing process. Most severe bone injuries heal by remodeling of hypertrophic cartilaginous anlage, known as endochondral ossification. Endochondral ossification can promote angiogenesis and bone tissue formation. Endochondral ossification-based strategies are promising to provide sufficient bone regeneration in large defects
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