Regenerative Secretoma of Adipose-Derived Stem Cells from Ischemic Patients

Abstract

Patients with terminal ischemia often reveal chronic limb and foot ulcers with subsequent risk of infection and/or amputation. Adipose-derived Stem Cells (ASC) may secrete angiogenic and regenerative factors. The autologous transplantation of such cells is considered to be an attractive therapeutic strategy, but their functional properties of ASC are influenced by many biochemical and biophysical stimuli of the microenvironment. Thus, patient-derived ASC might not be functionally competent. To study ASCs in ischemic disease, we have generated ASC lines from fat tissue of twelve ischemic patients. Lines were characterized for cell surface phenotype, multipotent capacities, and production of factors involved in wound healing. We succeeded to amplify ASC lines from all twelve patients and confirmed an ASC identity by their ability to: (i) adhere and grow on a plastic surface in standard culture conditions; (ii) express an ASC expression profile; (iii) differentiate in vitro into adipocytes, osteoblasts, and chondroblasts. Full transcriptome analysis of four selected lines showed a gene expression profile compatible with healing properties including all of the functional families involved in the wound healing process: extracellular matrix proteins, cell growth factors, pro-inflammatory cytokines, angiogenic factors, and matrix remodeling proteins. Our pilot study confirms that high-quality adipose stem cells can be easily derived from ischemic patients. Their transcriptome and secretome show a regenerative profile which makes them promising candidates for autologous therapy of chronic ulcers.