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World J Stem Cells. Feb 26, 2020; 12(2): 110-122
Published online Feb 26, 2020. doi: 10.4252/wjsc.v12.i2.110
Cartilage and bone tissue engineering using adipose stromal/stem cells spheroids as building blocks
Gabriela S Kronemberger, Renata Akemi Morais Matsui, Guilherme de Almeida Santos de Castro e Miranda, José Mauro Granjeiro, Leandra Santos Baptista
Gabriela S Kronemberger, Renata Akemi Morais Matsui, Guilherme de Almeida Santos de Castro e Miranda, José Mauro Granjeiro, Leandra Santos Baptista, Laboratory of Tissue Bioengineering, Directory of Metrology Applied to Life Sciences, National Institute of Metrology, Quality and Technology (INMETRO), Duque de Caxias, RJ 25250-020, Brazil
Gabriela S Kronemberger, Leandra Santos Baptista, Post-graduate Program in Translational Biomedicine (Biotrans), Unigranrio, Campus I, Duque de Caxias, RJ 25250-020, Brazil
Renata Akemi Morais Matsui, José Mauro Granjeiro, Leandra Santos Baptista, Post-graduate Program in Biotechnology, National Institute of Metrology, Quality and Technology (INMETRO), Duque de Caxias, RJ 25250-020, Brazil
Guilherme de Almeida Santos de Castro e Miranda, Federal University of Rio de Janeiro (UFRJ), Campus Duque de Caxias, Duque de Caxias, RJ 25250-020, Brazil
José Mauro Granjeiro, Laboratory of Clinical Research in Odontology, Fluminense Federal University (UFF), Niterói 25255-030 Brazil
Leandra Santos Baptista, Multidisciplinary Center for Biological Research (Numpex-Bio), Federal University of Rio de Janeiro (UFRJ) Campus Duque de Caxias, Duque de Caxias, RJ 25245-390, Brazil
Author contributions: Kronemberger GS drafted the article, contributed to the conception and design of the manuscript and wrote the article. Matsui RAM drafted and wrote the article. Miranda GASC drafted and wrote the article. Granjeiro JM contributed to the writing of the manuscript, made critical revisions related to relevant intellectual content of the manuscript and approved the final version of the article. Baptista LS drafted the article, contributed to the conception and design of the manuscript, contributed to the writing of the manuscript, made critical revisions related to relevant intellectual content of the manuscript and approved the final version of the article.
Supported by the Coordination for the Improvement of Higher Education Personnel (CAPES), No. 88882.366181/2019-01; the Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ), No. E-26/202.682/2018; National Council for Scientific and Technological Development (CNPq), No. 467513/2014-7.
Conflict-of-interest statement: The authors declare no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Leandra Santos Baptista, PhD, Associate Professor, Laboratory of Tissue Bioengineering, Directory of Metrology Applied to Life Sciences, National Institute of Metrology, Quality and Technology (INMETRO), Duque de Caxias, RJ 25250-020, Brazil. leandrabaptista@xerem.ufrj.br
Received: May 18, 2019
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
Abstract

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.

Keywords: Adipose stromal/stem cells, Spheroids, Building-blocks, Bottom-up, Developmental tissue engineering, Cartilage and bone

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.