Stem cells from adipose tissue and breast cancer: hype, risks and hope

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Abstract

Several recent papers have generated new hope about the use of white adipose tissue (WAT)-derived progenitor cells for soft tissue reconstruction in a variety of diseases including breast cancer (BC), a procedure that is increasingly used worldwide. We revised the available literature about WAT cells and BC. In the BC field, we believe that the hype for the exciting results in terms of WAT progenitor cell engraftment and tissue augmentation should be tempered when considering the recent and abundant preclinical studies, indicating that WAT progenitors may promote BC growth and metastasis. White adipose tissue progenitors can contribute to tumour vessels, pericytes and adipocytes, and were found to stimulate local and metastatic BC progression in several murine models. Moreover, there are clinical retrospective data showing a significant increase in the local recurrence frequency in patients with intraepithelial neoplasia who received a lipofilling procedure for breast reconstruction compared with controls. Retrospective and prospective clinical trials are warranted to investigate in depth the safety of this procedure in BC. Preclinical models should be used to find mechanisms able to inhibit the tumour-promoting activity of WAT progenitors while sparing their tissue reconstruction potential.

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Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival: a randomised placebo-controlled trial.

Arthur M Talman, Stig-Frederik Kølle, S. Oliveri … (2013)

Autologous fat grafting is increasingly used in reconstructive surgery. However, resorption rates ranging from 25% to 80% have been reported. Therefore, methods to increase graft viability are needed. Here, we report the results of a triple-blind, placebo-controlled trial to compare the survival of fat grafts enriched with autologous adipose-derived stem cells (ASCs) versus non-enriched fat grafts. Healthy participants underwent two liposuctions taken 14 days apart: one for ASC isolation and ex-vivo expansion, and another for the preparation of fat grafts. Two purified fat grafts (30 mL each) taken from the second liposuction were prepared for each participant. One graft was enriched with ASCs (20 × 10(6) cells per mL fat), and another graft without ASC enrichment served as a control. The fat grafts were injected subcutaneously as a bolus to the posterior part of the right and left upper arm according to the randomisation sequence. The volumes of injected fat grafts were measured by MRI immediately after injection and after 121 days before surgical removal. The primary goal was to compare the residual graft volumes of ASC-enriched grafts with those of control grafts. This study is registered at www.clinicaltrialsregister.eu, number 2010-023006-12. 13 participants were enrolled, three of whom were excluded. Compared with the control grafts, the ASC-enriched fat grafts had significantly higher residual volumes: 23·00 (95% CI 20·57-25·43) cm(3) versus 4·66 (3·16-6·16) cm(3) for the controls, corresponding to 80·9% (76·6-85·2) versus 16·3% (11·1-21·4) of the initial volumes, respectively (p<0·0001). The difference between the groups was 18·34 (95% CI 15·70-20·98) cm(3), equivalent to 64·6% (57·1-72·1; p<0·0001). No serious adverse events were noted. The procedure of ASC-enriched fat grafting had excellent feasibility and safety. These promising results add significantly to the prospect of stem cell use in clinical settings, and indicate that ASC graft enrichment could render lipofilling a reliable alternative to major tissue augmentation, such as breast surgery, with allogeneic material or major flap surgery. Danish Cancer Society, Centre of Head and Orthopaedics Rigshospitalet, and Moalem Weitemeyer Bendtsen. Copyright © 2013 Elsevier Ltd. All rights reserved.

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Risk of tumorigenicity in mesenchymal stromal cell-based therapies--bridging scientific observations and regulatory viewpoints.

Arnaud Foussat, Sophie Lucas, Egbert Flory … (2013)

In the past decade, the therapeutic value of mesenchymal stromal cells (MSCs) has been studied in various indications, thereby taking advantage of their immunosuppressive properties. Easy procurement from bone marrow, adipose tissue or other sources and conventional in vitro expansion culture have made their clinical use attractive. Bridging the gap between current scientific knowledge and regulatory prospects on the transformation potential and possible tumorigenicity of MSCs, the Cell Products Working Party and the Committee for Advanced Therapies organized a meeting with leading European experts in the field of MSCs. This meeting elucidated the risk of potential tumorigenicity related to MSC-based therapies from two angles: the scientific perspective and the regulatory point of view. The conclusions of this meeting, including the current regulatory thinking on quality, nonclinical and clinical aspects for MSCs, are presented in this review, leading to a clearer way forward for the development of such products. Copyright © 2013 International Society for Cellular Therapy. All rights reserved.

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Origins of the Tumor Microenvironment: Quantitative Assessment of Adipose-Derived and Bone Marrow–Derived Stroma

Shannon Kidd, Erika Spaeth, Keri B. Watson … (2012)

To meet the requirements for rapid tumor growth, a complex array of non-neoplastic cells are recruited to the tumor microenvironment. These cells facilitate tumor development by providing matrices, cytokines, growth factors, as well as vascular networks for nutrient and waste exchange, however their precise origins remain unclear. Through multicolored tissue transplant procedures; we have quantitatively determined the contribution of bone marrow-derived and adipose-derived cells to stromal populations within syngeneic ovarian and breast murine tumors. Our results indicate that subpopulations of tumor-associated fibroblasts (TAFs) are recruited from two distinct sources. The majority of fibroblast specific protein (FSP) positive and fibroblast activation protein (FAP) positive TAFs originate from mesenchymal stem/stromal cells (MSC) located in bone marrow sources, whereas most vascular and fibrovascular stroma (pericytes, α-SMA+ myofibroblasts, and endothelial cells) originates from neighboring adipose tissue. These results highlight the capacity for tumors to utilize multiple sources of structural cells in a systematic and discriminative manner.

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Author and article information

Journal

Journal ID (nlm-ta): Br J Cancer

Journal ID (iso-abbrev): Br. J. Cancer

Title: British Journal of Cancer

Publisher: Nature Publishing Group

ISSN (Print): 0007-0920

ISSN (Electronic): 1532-1827

Publication date (Print): 03 February 2015

Publication date (Electronic): 13 January 2015

Publication date PMC-release: 3 February 2015

Volume: 112

Issue: 3

Pages: 419-423

Affiliations

[1 ]Laboratory of Hematology-Oncology, European Institute of Oncology , Via Ripamonti 435, 20141, Milan, Italy

[2 ]Division of Plastic Surgery, European Institute of Oncology , 20141 Milan, Italy

[3 ]Institute of Molecular Medicine, University of Texas Health Science Center at Houston , Houston, TX, 77030, USA

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[* ]E-mail: francesco.bertolini@ 123456ieo.it

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Publisher Item ID: bjc2014657

DOI: 10.1038/bjc.2014.657

PMC ID: 4453662

PubMed ID: 25584493

SO-VID: 04c70bf2-03bf-4801-8c66-0d4453c6ede3

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This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/

Stem cells from adipose tissue and breast cancer: hype, risks and hope

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Karger: Oncology

Most cited references 23

Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival: a randomised placebo-controlled trial.

Risk of tumorigenicity in mesenchymal stromal cell-based therapies--bridging scientific observations and regulatory viewpoints.

Origins of the Tumor Microenvironment: Quantitative Assessment of Adipose-Derived and Bone Marrow–Derived Stroma

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