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Interaction of adipose-derived stem cells with active and dormant breast cancer cells
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.ORCID iD: 0000-0003-2596-5936
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2023 (English)In: Journal of Plastic, Reconstructive & Aesthetic Surgery, ISSN 1748-6815, E-ISSN 1878-0539, Vol. 83, p. 69-76Article in journal (Refereed) Published
Abstract [en]

Background: Although autologous fat grafting is considered a successful method for the management of contour deformities, the fat graft could potentially induce cancer reappearance by fueling dormant breast cancer cells. Our aim was to characterize the role of adipose-derived stem cells on active and dormant breast cancer cell growth.

Methods: Cobalt chloride was used to induce dormancy in MCF-7 cancer cells. Proliferation of active and dormant cancer cells was determined in the presence of adipose-derived stem cells. A proteome array was used to detect cancer-related protein expression in the cell-conditioned medium. The migration of cancer cells was measured in response to conditioned medium from the adipose-derived stem cells.

Results: The adipose-derived stem cells showed variable effects on active MCF-7 cells growth and inhibited MCF-7 proliferation after the withdrawal of cobalt chloride. Of the 84 different proteins measured in the conditioned medium, only tenascin-C was differentially expressed in the co-cultures. MCF-7 cells alone did not express tenascin-C, whereas co-cultures between MCF-7 and adipose-derived stem cells expressed more tenascin-C versus adipose-derived stem cells alone. The conditioned medium from co-cultures significantly increased the migration of the cancer cells.

Conclusions: Adipose-derived stem cells themselves neither increased the growth or migration of cancer cells, suggesting that autologous fat grafting may be oncologically safe if reconstruction is postponed until there is no evidence of active disease. However, interactions between adipose-derived stem cells and MCF-7 cancer cells could potentially lead to the production of factors, which further promote cancer cell migration.

Place, publisher, year, edition, pages
Elsevier, 2023. Vol. 83, p. 69-76
Keywords [en]
Adipose-derived stem cells (ASCs), Autologous fat grafting (AFG), Dormant breast cancer cells, Tenascin-C
National Category
Cell and Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:umu:diva-209546DOI: 10.1016/j.bjps.2023.05.006ISI: 001020879400001PubMedID: 37270997Scopus ID: 2-s2.0-85160658685OAI: oai:DiVA.org:umu-209546DiVA, id: diva2:1766534
Conference
Scandinavian Association of Plastic Surgeons Congress, Reykjavik, Iceland, June 13–15, 2022
Funder
Umeå UniversityRegion VästerbottenAvailable from: 2023-06-13 Created: 2023-06-13 Last updated: 2024-01-26Bibliographically approved
In thesis
1. Optimizing stem cells for reconstructive surgery
Open this publication in new window or tab >>Optimizing stem cells for reconstructive surgery
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Optimering av stamceller för rekonstruktiv kirurgi
Abstract [en]

Fat grafting has become an established method in plastic surgery for treating soft tissue defects. The results for survival of the fat being transplanted is unpredictable and supplementation of the graft with the Stromal Vascular Fraction (SVF) or cultures Adipose tissue-derived stem cells (ASCs) can enhance graft viability. The ASCs are a heterogenous group of cells with various cell membrane markers, and differing growth promoting and differentiation characteristics of the stem cells derived from the fat. It is of high importance when expanding cells prior to the transplantation of the cells into patients, that the culture conditions are well defined and ideally are xenofree, avoiding use of animal-derived products. Furthermore, the procedures must be safe and not increase risk for recurrence of cancer after reconstructive surgeries. This thesis explores the phenotypic properties of a selected population of ASCs, with a view to determining their suitability for transplantation into fat grafts. ASCs were isolated from SVF of human abdominal fat and CD146+ cells were selected using immunomagnetic beads. The proliferation, angiogenic and adipogenic properties were significantly higher in the CD146+ cells. Stem cells were also isolated from lipoaspirate obtained using two different liposuction methods. Waterjet lipoaspirates yielded the greatest number of CD146+ cells with high adipogenic potential and angiogenic activity. The cells could also be successfully isolated using a closed processing system. Cells were expanded in either foetal bovine serum, platelet lysate or a chemically defined xenofree (XV) medium. Cultures in XV medium proliferated the fastest, expressed the highest number of CD146+ cells, and showed the best adipogenic and angiogenic properties. To test possible ASCs interactions with cancer cells, co-cultures with MCF-7 breast cancer cells were established. Conditioned medium from co-cultures significantly increased the migration of the cancer cells but not their proliferation, and there was increased expression of Tenascin-C in these cultures. The research in this thesis work has shown more optimal ways to isolate and expand ASCs, potentially offering new therapeutic reconstructive treatment options for a variety of medical conditions.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2024. p. 64
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2281
Keywords
Adipose tissue-derived stem cells, liposuction, oncological safety, xenofree growth medium
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Human Anatomy
Identifiers
urn:nbn:se:umu:diva-220039 (URN)9789180702638 (ISBN)9789180702621 (ISBN)
Public defence
2024-02-23, Sal N410, Naturvetarhuset, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2024-02-02 Created: 2024-01-26 Last updated: 2024-01-29Bibliographically approved

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Nyström, MariaLauvrud, Anne-TheresePérez-Díaz, SergioKingham, Paul J.Wiberg, Rebecca

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Journal of Plastic, Reconstructive & Aesthetic Surgery
Cell and Molecular BiologyMedical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

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