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EDITED AND REVIEWED BY
Ranieri Cancedda,
Independent researcher, Genova, Italy

*CORRESPONDENCE
Arnaud Scherberich,
✉ arnaud.scherberich@usb.ch

RECEIVED 12 May 2023

ACCEPTED 16 May 2023

PUBLISHED 23 May 2023

CITATION

Noël D and Scherberich A (2023),
Editorial: Biology and clinical applications
of adipose-derived cells for
skeletal regeneration.

Front. Bioeng. Biotechnol. 11:1221444.
doi: 10.3389/fbioe.2023.1221444

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Editorial: Biology and clinical
applications of adipose-derived
cells for skeletal regeneration

Danièle Noël¹ and Arnaud Scherberich²,³*

¹IRMB, University of Montpellier, INSERM, Montpellier, France, ²Bone Regeneration, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland, ³Department of Biomedical Engineering, University of Basel, Basel, Switzerland

KEYWORDS

adipose derived mesenchymal cells, endochondral ossification, cell characterization, extracellular vesicles, osteogenic differentiation, stromal vascular tissue, chondrogenic differentiation

Editorial on the Research Topic

Biology and clinical applications of adipose-derived cells for skeletal regeneration

Adipose-derived cells is a very generic term to refer to the various cell types, which can be
obtained from a biopsy of human adipose tissue. Starting from a liposuction sample or a solid
resection of adipose, it most commonly involves a step of cell isolation based on either enzymatic
digestion or mechanical disruption, and sometimes even a combination thereof (Tiryaki et al.,
2022). The enzymatic digestion of adipose tissue leads, after centrifugation to discard floating
adipocytes, to a pellet of cells called the Stromal Vascular Fraction (SVF). SVF is a complex
mixture of vascular endothelial progenitors and mesenchymal stromal progenitor cells,
hematopoietic cells of various nature, preadipocytes, fibroblasts, smooth muscle cells and
others yet to be fully characterized (Ramakrishnan and Boyd, 2018). Upon seeding of SVF
cells onto tissue culture plastic and subsequent culture as monolayer, mesenchymal stromal cells
present in SVF, referred to as adipose-derived mesenchymal stromal cells (ASC) attach and
proliferate very similarly to bone marrow mesenchymal stromal cells (MSC), leading to a very
strong enrichment in ASC already after the very first step of expansion (i.e., before passaging cells
for the first time) (Müller et al., 2009). After this initial stage of expansion, ASC, characterized as
CD73+, CD90+, CD44+, CD34+ cells, account for >70–80% of the expanded cells, reaching >95%
at the end of the passage 1 (Bony et al., 2016). The remaining cells are mostly composed of
vascular endothelial cells, important for some of their functional properties (Guerrero et al.,
2022).

The mechanical dissociation of adipose results in a suspension of small pieces of body fat tissue, containing SVF cells and extracellular matrix (ECM), with or without maintenance of viable adipocytes. It is then called either Coleman Fat, microfat or nanofat (Ding et al., 2022). The term nanofat is however inappropriate since the resulting tissue is far from nanometric dimension by nature. A recent discussion at the 7th International Congress on Adipose Stem cell Treatments (AIRMESS/iCAST 2022) held at the Nescens Clinic in Génoliers, Switzerland, on 3 December 2022, suggested to define such fractionated adipose as Stromal Vascular Tissue (SVT) (https://sscf.ch/icast/icast2022/). Whatever the denomination and way of generating it, such SVT has been shown to be very helpful for various clinical applications (Ding et al., 2022). A better characterization of SVT is however of importance to account for and predict its quality and regenerative potential. In
the present Research Topic, Claudia Cicione and colleagues compared different techniques to generate SVT and showed that this might have a very important effect on the stemness properties of ASC and the clinical potential of SVT.

It is important to note, in the context of the present Research Topic, that ASC, unlike bone marrow-derived MSC, are non-skeletal MSC by nature. There is however a plethora of evidence and reports since almost 2 decades showing that adipose-derived cells can be switched to genuine skeletal cells and be used for skeletal regeneration. SVF cells and monolayer-expanded ASC can become chondrogenic or osteogenic cells when combined with scaffolding materials, as reviewed in this Research Topic by Gohar Rahman and colleagues. A practical example of that is the fact that ASC-derived extracellular vesicles (EV) can induce osteogenic differentiation of ASC in graphene porous titanium alloy scaffolds, as shown by Xu Sun and colleagues. Another example is the following: Chen Cheng and colleagues show that ASC grown directly inside SVT in vitro and differentiated into hypertrophic chondrocytes are able to generate bone by endochondral ossification and repair a mandibular defect in rat. There is no doubt that bone regeneration with adipose-derived cells, thanks to a minimally invasive sourcing and a relevant abundance, will continue to raise interest and progress in the future.

## References

Bony, C., Cren, M., Domergue, S., Toupet, K., Jorgensen, C., and Noël, D. (2016). Adipose mesenchymal Stem cells isolated after manual or water-jet-assisted liposuction display similar properties. *Front. Immunol.* 6, 655. doi:10.3389/fimmu.2015.00655

Ding, F., Ma, Z., Liu, F., Lu, L., Sun, D., Gao, H., et al. (2022). Comparison of the rheological properties and structure of fat derivatives generated via different mechanical processing techniques: Coleman fat, nanofat, and stromal vascular fraction-gel. *Facial Plast. Surg. Aesthet. Med.* 24 (5), 391–396. doi:10.1089/fpsam.2021.0019

Guerrero, J., Dasen, B., Frismantiene, A., Pigeot, S., Ismail, T., Schaefer, D. J., et al. (2022). T-Cadherin expressing cells in the stromal vascular fraction of human adipose tissue: Role in osteogenesis and angiogenesis. *Stem Cells Transl. Med.* 11 (2), 213–229. doi:10.1093/stcltm/szab021

## Author contributions

All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.

## Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

## Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Müller, A. M., Davenport, M., Verrier, S., Droeser, R., Alini, M., Bocelli-Tyndall, C., et al. (2009). Platelet lysate as a serum substitute for 2D static and 3D perfusion culture of stromal vascular fraction cells from human adipose tissue. *Tissue Eng. Part A* 15 (4), 869–875. doi:10.1089/ten.tea.2008.0498

Ramakrishnan, V. M., and Boyd, N. L. (2018). The adipose stromal vascular fraction as a complex cellular source for tissue engineering applications. *Tissue Eng. Part B Rev.* 24 (4), 289–299. doi:10.1089/ten.TEB.2017.0061

Tiryaki, T., Cohen, S. R., Canikyan Turkay, S., Kocak, P., Sterodimas, A., Schlaudraff, K. U., et al. (2022). Hybrid stromal vascular fraction (Hybrid-SVF): A new paradigm in mechanical regenerative cell processing. *Plast. Reconstr. Surg. Glob. Open* 10 (12), e4702. doi:10.1097/GOX.0000000000004702