Published online Feb 26, 2020. doi: 10.4252/wjsc.v12.i2.110
Peer-review started: May 20, 2019
First decision: August 23,2019
Revised: October 19, 2019
Accepted: January 14, 2020
Article in press: January 14, 2020
Published online: February 26, 2020
Scaffold-free techniques in the developmental tissue engineering area are designed to mimic in vivo embryonic processes with the aim of biofabricating, in vitro, tissues with more authentic properties. Cell clusters called spheroids are the basis for scaffold-free tissue engineering. In this review, we explore the use of spheroids from adult mesenchymal stem/stromal cells as a model in the developmental engineering area in order to mimic the developmental stages of cartilage and bone tissues. Spheroids from adult mesenchymal stromal/stem cells lineages recapitulate crucial events in bone and cartilage formation during embryogenesis, and are capable of spontaneously fusing to other spheroids, making them ideal building blocks for bone and cartilage tissue engineering. Here, we discuss data from ours and other labs on the use of adipose stromal/stem cell spheroids in chondrogenesis and osteogenesis in vitro. Overall, recent studies support the notion that spheroids are ideal "building blocks" for tissue engineering by “bottom-up” approaches, which are based on tissue assembly by advanced techniques such as three-dimensional bioprinting. Further studies on the cellular and molecular mechanisms that orchestrate spheroid fusion are now crucial to support continued development of bottom-up tissue engineering approaches such as three-dimensional bioprinting.
Core tip: Classic approaches to tissue engineering rely on scaffold-based strategies, which have limited ability to recapitulate organogenesis in vitro and are not capable of generating hierarchical engineered tissues. Scaffold-free strategies, in particular those using spheroids, are appealing, mainly due to the capacity of spheroids to recapitulate three main embryonic processes: (1) Cell-to-cell and cell-to-extracellular matrix interactions; (2) Cell differentiation; and (3) Fusion. The use of spheroids to recapitulate embryonic tissue formation in vitro represents a potent strategy in developmental tissue engineering. In particular, the fusion capacity of spheroids allows their use as building-blocks in bottom-up tissue engineering through three-dimensional bioprinting techniques.