Open AccessProbing Multicellular Tissue Fusion of Cocultured Spheroids—A 3D‐Bioassembly Model
Author(s) -
Lindberg Gabriella C. J.,
Cui Xiaolin,
Durham Mitchell,
Veenendaal Laura,
Schon Benjamin S.,
Hooper Gary J.,
Lim Khoon S.,
Woodfield Tim B. F.
Publication year - 2021
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202103320
Subject(s) - spheroid , multicellular organism , microbiology and biotechnology , mesenchymal stem cell , stromal cell , cartilage , cell fusion , fusion , cell , extracellular matrix , chemistry , tissue engineering , biology , in vitro , anatomy , cancer research , biochemistry , linguistics , philosophy , genetics
While decades of research have enriched the knowledge of how to grow cells into mature tissues, little is yet known about the next phase: fusing of these engineered tissues into larger functional structures. The specific effect of multicellular interfaces on tissue fusion remains largely unexplored. Here, a facile 3D‐bioassembly platform is introduced to primarily study fusion of cartilage–cartilage interfaces using spheroids formed from human mesenchymal stromal cells (hMSCs) and articular chondrocytes (hACs). 3D‐bioassembly of two adjacent hMSCs spheroids displays coordinated migration and noteworthy matrix deposition while the interface between two hAC tissues lacks both cells and type‐II collagen. Cocultures contribute to increased phenotypic stability in the fusion region while close initial contact between hMSCs and hACs (mixed) yields superior hyaline differentiation over more distant, indirect cocultures. This reduced ability of potent hMSCs to fuse with mature hAC tissue further underlines the major clinical challenge that is integration. Together, this data offer the first proof of an in vitro 3D‐model to reliably study lateral fusion mechanisms between multicellular spheroids and mature cartilage tissues. Ultimately, this high‐throughput 3D‐bioassembly model provides a bridge between understanding cellular differentiation and tissue fusion and offers the potential to probe fundamental biological mechanisms that underpin organogenesis.