The Immunophenotype of Adipocyte Stromal Vascular Cells Varies between Patients with Breast Cancer, Lipodystrophy and Macromastia

BACKGROUND: Stromal vascular fraction (SVF) cells are embedded in adipose tissue and work synergistically when used in reconstructive and cosmetic breast procedures. SVF cells have been shown to promote tissue regeneration leading to improved wound healing and graft retention. SVF cells have become an attractive option for autologous applications in regenerative medicine due to easy access and processing. However, there is inherent variability in the therapeutic potential of SVF cells, and the clinical outcomes vary from for any one patient to another. Therefore, this study investigated the regenerative and immunomodulatory properties of thirteen medically diverse human donors.

METHODS: Primary lipoaspirate samples were derived from either thigh, abdominal, or axillary fat pads. The donors represented medical histories corresponding to breast cancer (donors 1-6, at least one year in remission), lipodystrophy (donors 7-10), or macromastia (donors 11-13). SVF cells were isolated using established protocols and assessed for yield, self-renewal capacity, viability, differentiation potential, proliferation, and immunomodulatory activity.

 RESULTS: Cell yield varied was on average 1-6 x 105 cells/ml lipoaspirate, and average post-thaw cell viability was 79% (median: 78%, range: 70-90%). The average self-renewal capacity of donor SVF cells was 3.6% (median: 3.6%, range: 1.6-7.0%). There was a strong trend towards increased clonogenic potential in breast cancer donors (p = 0.06). The differentiation potential for the osteogenic and adipogenic lineages in these samples was diminished (p > 0.05). Prior history of breast cancer did not appear to affect the immunomodulatory activity of donor SVF cells stimulated by pro-inflammatory conditions (p > 0.05). However, SVF cells derived from patients with breast cancer in remission had a higher baseline expression of IL-6, IL-8, MCP-1, and IFN-γ.

CONCLUSION: Correlation analyses of therapeutic parameters across all donors identified positive correlations for the expression of pro-inflammatory cytokines interleukin IL6, IL8, and monocyte chemoattractant protein with each other. Samples obtained from patients in remission from breast cancer showed increased self-renewal as well as decreased differentiation potential and increased inflammatory cytokine production. These results could be relevant for determining clinical treatment strategies for patients with a previous breast cancer diagnosis. The significant donor-to-donor variability observed for the measured parameters supports the need for standardizing both the source of cells for therapeutic procedures as well as the assessments used to predict clinical outcomes.