Abstract

Mesenchymal stem cells from adipose tissue (ADSCs) are an important source of cells for regenerative medicine. The therapeutic effect of culture-expanded adipose derived stem cells has been shown; however, optimal xeno-free culture conditions remain to be determined. Cancer patients, specifically those undergoing invasive surgery, constitute a subgroup of patients who could benefit from autologous stem cell transplantation. Although regenerative potential of their ADSCs could be affected by the disease and/or treatment, we are not aware of any study that has evaluated the therapeutic potential of ADSCs isolated from cancer patients in reference to that of ADSCs derived from healthy subjects. Here we report that ADSCs isolated from subabdominal adipose tissue of patients with urological neoplasms yielded similar growth kinetics, presented equivalent mesenchymal surface markers and showed similar differentiation potential into distinct mesodermal cell lineages: adipocytes, chondroblasts and osteoblasts than ADSCs isolated from adipose tissue of age-matched non-oncogenic participants, all under xeno-free growth culture conditions. Molecular karyotyping of patient expanded ADSCs genomes showed no disease-related alterations indicating their safety. In addition, vesicles <100 nm identified as exosomes (EXOs) which may be at least partly responsible for the attributed therapeutic paracrine effects of the ADSCs were effectively isolated from ADSCs and showed equivalent miRNA content regardless they were derived from cancer patients or non-oncogenic participants indicating that the repair capabilities of xeno-free expanded ADSCs are not compromised by patient condition and therefore their xeno-free culture expanded ADSCs should be suitable for autologous stem cell transplantation in a clinical setting.

Highlights

  • Human adipose tissue is an abundant and accessible source of multipotent mesenchymal stem cells (MSCs) which hold great potential for therapeutic applications in regenerative medicine and tissue engineering [1,2,3]

  • Growth potential and senescence To investigate cell growth potential of cells from either group of participants, population doublings (PD) of each sample were determined at every passage up to passage 6, equivalent to day 58 in culture on average (Figure 1)

  • Due to the therapeutic potential applications of Adipose-Derived Stem Cells (ADSCs) in regenerative medicine for cancer patients, a focus on detailed characterization of autologous samples, including efficacy of isolation, growth rates, differentiation potential and safe expansion for clinical use was at need

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Summary

Introduction

Human adipose tissue is an abundant and accessible source of multipotent mesenchymal stem cells (MSCs) which hold great potential for therapeutic applications in regenerative medicine and tissue engineering [1,2,3]. MSCs role in modulation of tissue repair and immunomodulation has been attributed to their paracrine factor secretion potential, mitochondrial transfer and exosome (EXO) secretion capacity [12,13,14]. Xeno-free culture could enhance the safety and quality of transplanted in vitro-expanded stem cells [20,21] and allow for the establishment of standard expansion methods, avoiding batch-to-batch variations. Their novelty and the big difference in price limit the number of studies that have used xeno-free medium until now

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