Safety Concern between Autologous Fat Graft, Mesenchymal Stem Cell and Osteosarcoma Recurrence
Open accessAbstract
BACKGROUND: Osteosarcoma is the most common malignant primary bone tumour in young adult treated by neo adjuvant chemotherapy, surgical tumor removal and adjuvant multidrug chemotherapy. For correction of soft tissue defect consecutive to surgery and/or tumor treatment, autologous fat graft has been proposed in plastic and reconstructive surgery. PRINCIPAL FINDINGS: We report here a case of a late local recurrence of osteosarcoma which occurred 13 years after the initial pathology and 18 months after a lipofilling procedure. Because such recurrence was highly unexpected, we investigated the possible relationship of tumor growth with fat injections and with mesenchymal stem/stromal cell like cells which are largely found in fatty tissue. Results obtained in osteosarcoma pre-clinical models show that fat grafts or progenitor cells promoted tumor growth. SIGNIFICANCE: These observations and results raise the question of whether autologous fat grafting is a safe reconstructive procedure in a known post neoplasic context.
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Successive pre-clinical models showed that mesenchymal stromal cells/stromal cells included in the fatty tissue interact with osteosarcoma cells and induce their proliferation.
“Successive pre-clinical models showed that MSCs/stromal cells included in the fatty tissue interact with osteosarcoma cells and induce their proliferation [101].”
From Mesenchymal stromal cells for bone sarcoma treatment: Roadmap to clinical practice (2019) · cites this paper as [101]
The Results report that injected fat contained MSC-like cells and that MSCs increased osteosarcoma-cell proliferation in co-culture. But the paper describes the role of MSC-like cells in the fat graft as a hypothesis; it does not show that those fat-derived cells themselves caused the increased proliferation. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredHuman adipose-tissue stromal cells included in fat grafts increased migration and metastases of breast tumour and osteosarcoma animal models.
“However, as referred to earlier, there were safety concerns about human adipose-tissue stromal cells (ASC) included in fat grafts that increased migration and metastases of breast tumour and osteosarcoma animal models [74], [101].”
From Mesenchymal stromal cells for bone sarcoma treatment: Roadmap to clinical practice (2019) · cites this paper as [101]
The Results report that injected human fat increased osteosarcoma growth in mice, and the Discussion identifies MSC-like cells in the fat grafts. The Discussion also reports breast-cancer-cell migration and osteosarcoma pulmonary metastasis findings, but the latter involved bone-marrow-derived MSCs, not adipose stromal cells in fat grafts. This paper does not establish that fat-graft ASCs increased metastases in either animal model. (LLM, conf=0.88)
Experimental — accuracy not yet measuredHuman ADSC included in fat grafts were found to increase migration and metastases in a breast tumour and osteosarcoma models.
“There were some safety concerns about human ADSC included in fat grafts, however, that were found to increase migration and metastases in a breast tumour and osteosarcoma models [74], [101].”
From Mesenchymal stromal cells for bone sarcoma treatment: Roadmap to clinical practice (2019) · cites this paper as [101]
The Results (no page provided) show that a human fat graft increased osteosarcoma growth and that the graft contained MSC-like cells, but they do not show that those cells increased migration or metastasis. The Discussion (no page provided) reports breast-cancer-cell migration and osteosarcoma pulmonary metastasis from other studies; the latter involved bone-marrow-derived MSCs, not ADSCs in fat grafts. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAutologous fat grafts used in reconstructive surgery have been related to late local recurrence, 13 years following the onset of osteosarcoma in a female human patient.
“Autologous fat grafts used in reconstructive surgery have also been related to late local recurrence, 13 years following the onset of osteosarcoma in a female human patient.”
From Mesenchymal stromal cells for bone sarcoma treatment: Roadmap to clinical practice (2019) · cites this paper as [101]
Mesenchymal stem cells have been implicated in osteosarcoma metastasis and therapeutic resistance.
“Mesenchymal stem cells (MSCs) have been implicated in osteosarcoma metastasis and therapeutic resistance 57,58,59 .”
From Osteosarcoma (2022) · cites this paper as [58]
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References 59 · Cited by 120
- Authors
- Perrot, P., Rousseau, J., Bouffaut, A.-L., Rédini, F., Cassagnau, E., Deschaseaux, F., Heymann, M.-F., Heymann, D., Duteille, F., Trichet, V., & Gouin, F.
- Affiliations
- Inserm (FR)
- Centre Hospitalier Universitaire de Nantes (FR)
- Établissement Français du Sang (FR)
- Corresponding author
- Gouin, François
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-06-08
- Volume
- 5
- Issue
- 6
- Pages
- e10999
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2882323
- OpenAlex
- W2100224830
- Cited by
- 120
- References
- 59
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 7 · 2021: 10 · 2020: 10 · 2019: 4 · 2018: 6 · 2017: 13 · 2016: 10 · 2015: 14 · 2014: 13 · 2013: 7 · 2012: 9
- FWCI
- 6.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- HAL (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ligue Contre le Cancer
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Rheumatology › Bone Tumor Diagnosis and Treatments
- Keywords
- osteosarcoma, autologous fat grafting, mesenchymal stem cells, tumor recurrence, fat grafting, soft tissue reconstruction, tumor growth promotion
- MeSH terms
- Adipose Tissue, Animals, Child, Combined Modality Therapy, Female, Humans, Mice, Inbred C3H, Recurrence, Osteosarcoma, Cell Line, Tumor, Mice, Mesenchymal Stem Cells
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