Regenerative Potential and Inflammation-Induced Secretion Profile of Human Adipose-Derived Stromal Vascular Cells Are Influenced by Donor Variability and Prior Breast Cancer Diagnosis
Adipose tissue contains a heterogeneous population of stromal vascular fraction (SVF) cells that work synergistically with resident cell types to enhance tissue healing. Ease of access and processing paired with therapeutic promise make SVF cells an attractive option for autologous applications in regenerative medicine. However, inherent variability in SVF cell therapeutic potential from one patient to another hinders prognosis determination for any one person. This study investigated the regenerative properties and inflammation responses of thirteen, medically diverse human donors. Using non-expanded primary lipoaspirate samples, SVF cells were assessed for robustness of several parameters integral to tissue regeneration, including yield, viability, self-renewal capacity, proliferation, differentiation potential, and immunomodulatory cytokine secretion. Each parameter was selected either for its role in regenerative potential, defined here as the ability to heal tissues through stem cell repopulation and subsequent multipotent differentiation, or for its potential role in wound healing through trophic immunomodulatory activity. These data were then analyzed for consistent and predictable patterns between and across measurements, while also investigating the influence of the donors’ relevant medical histories, particularly if the donor was in remission following breast cancer treatment. Analyses identified positive correlations among the expression of three cytokines: interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1. The expression of these cytokines also positively related to self-renewal capacity. These results are potentially relevant for establishing expectations in both preclinical experiments and targeted clinical treatment strategies that use stem cells from patients with diverse medical histories.
KeywordsAdipose-derived stromal cell Stem cell immunomodulation Breast cancer Inflammatory cytokines Heterogeneity Regenerative medicine Autologous cell therapy
This work was supported by the National Institutes of Health (R01 AR06304) and the National Science Foundation (EAGER CBET 1547819). The authors would like to thank Lisa White, Pa-C for aiding in the collection of donor samples and medical history data. Additionally, Christoph Schorl, PhD, of the Brown University genomics facility, provided assistance with microarray imaging and analysis software. Nicholas Labriola, PhD, produced the custom MATLAB program used to measure lineage-specific metabolite production. Vikram Mookerjee aided in proofreading and editing the manuscript.
AMP conducted experiments and analyses. DMC, PL, and EMD designed study. PL provided tissue samples. AMP, DMC, PL, and EMD contributed to writing and editing the manuscript.
Compliance with Ethical Standards
Conflict of Interest
The authors declare no potential conflict of interest.
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