Long-term in vivo survival of 3D-bioprinted human lipoaspirate-derived adipose tissue: proteomic signature and cellular content

Karin Säljö; Peter Apelgren; Linnea Stridh Orrhult; Susann Li; Matteo Amoroso; Paul Gatenholm; Lars Kölby

doi:10.1080/21623945.2021.2014179

Long-term in vivo survival of 3D-bioprinted human lipoaspirate-derived adipose tissue: proteomic signature and cellular content

Adipocyte. 2022 Dec;11(1):34-46. doi: 10.1080/21623945.2021.2014179.

Authors

Karin Säljö^{1

2}, Peter Apelgren^{1

2}, Linnea Stridh Orrhult³, Susann Li⁴, Matteo Amoroso^{1

2}, Paul Gatenholm³, Lars Kölby^{1

2}

Affiliations

¹ Department of Plastic Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
² Department of Plastic Surgery, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
³ 3D Bioprinting Centre, Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Gothenburg, Sweden.
⁴ Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska University Hospital, Göteborg, Sweden.

Abstract

Three-dimensional (3D)-bioprinted lipoaspirate-derived adipose tissue (LAT) is a potential alternative to lipo-injection for correcting soft-tissue defects. This study investigated the long-term in vivo survival of 3D-bioprinted LAT and its proteomic signature and cellular composition. We performed proteomic and multicolour flow cytometric analyses on the lipoaspirate and 3D-bioprinted LAT constructs were transplanted into nude mice, followed by explantation after up to 150 days. LAT contained adipose-tissue-derived stem cells (ASCs), pericytes, endothelial progenitor cells (EPCs) and endothelial cells. Proteomic analysis identified 6,067 proteins, including pericyte markers, adipokines, ASC secretome proteins, proangiogenic proteins and proteins involved in adipocyte differentiation and developmental morphogenic signalling, as well as proteins not previously described in human subcutaneous fat. 3D-bioprinted LAT survived for 150 days in vivo with preservation of the construct shape and size. Furthermore, we identified human blood vessels after 30 and 150 days in vivo, indicating angiogenesis from capillaries. These results showed that LAT has a favourable proteomic signature, contains ASCs, EPCs and blood vessels that survive 3D bioprinting and can potentially facilitate angiogenesis and successful autologous fat grafting in soft-tissue reconstruction.

Keywords: 3D bioprinting; Lipoaspirate-derived adipose tissue; adipose-derived stem cells/ASCs; endothelial progenitor cells/EPCs; flow cytometry; proteomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue / metabolism
Animals
Endothelial Progenitor Cells*
Humans
Mice
Mice, Nude
Proteomics*
Secretome

Grants and funding

This work was supported by the grants from the Swedish State under the agreement between the government and the county councils [the ALF-agreement (ALFGBG-716621)]. The Knut and Alice Wallenberg Foundation is kindly acknowledged for financial support of this research in the framework of the Wallenberg Wood Science Center (WWSC). Furthermore, this study has been supported by grants from the Göteborg Medical Society, the Mary von Sydow Foundation, the Magnus Bergvalls Foundation, the Sigurd and Elsa Goljes Foundation, Ann-Mari and Per Ahlqvist Foundation, and the Anna-Lisa and Bror Björnssons Foundation.