Abstract
Mesenchymal stromal cells are emerging as an extremely promising therapeutic agent for tissue regeneration due to their multi-potency, immune-modulation and secretome activities, but safety remains one of the main concerns, particularly when in vitro manipulation, such as cell expansion, is performed before clinical application. Indeed, it is well documented that in vitro expansion reduces replicative potential and some multi-potency and promotes cell senescence. Furthermore, during in vitro aging there is a decrease in DNA synthesis and repair efficiency thus leading to DNA damage accumulation and possibly inducing genomic instability. The European Research Project ADIPOA aims at validating an innovative cell-based therapy where autologous adipose stromal cells (ASCs) are injected in the diseased articulation to activate regeneration of the cartilage. The primary objective of this paper was to assess the safety of cultured ASCs. The maintenance of genetic integrity was evaluated during in vitro culture by karyotype and microsatellite instability analysis. In addition, RT-PCR array-based evaluation of the expression of genes related to DNA damage signaling pathways was performed. Finally, the senescence and replicative potential of cultured cells was evaluated by telomere length and telomerase activity assessment, whereas anchorage-independent clone development was tested in vitro by soft agar growth. We found that cultured ASCs do not show genetic alterations and replicative senescence during the period of observation, nor anchorage-independent growth, supporting an argument for the safety of ASCs for clinical use.
Highlights
Mesenchymal Stromal Cells (MSCs) are a population of adherent cells that are able to differentiate into mesenchymal lineages, as well as into other types of lineages not derived from the mesodermal layer [1]
MSCs obtained from bone marrow (BM) represent a standard in the field of adult stem cell biology and clinical applications; stromal cells obtained from adipose tissue are becoming an attractive alternative due to their minimally invasive accessibility and plentiful availability
The enzymatic digestion of adipose tissue releases a heterogeneous mix of cells, the stromal vascular fraction (SVF), which contains the stromal population of adipose derived stromal cells
Summary
Mesenchymal Stromal Cells (MSCs) are a population of adherent cells that are able to differentiate into mesenchymal lineages (cartilage, bone and fat tissue), as well as into other types of lineages not derived from the mesodermal layer [1].MSCs obtained from bone marrow (BM) represent a standard in the field of adult stem cell biology and clinical applications; stromal cells obtained from adipose tissue are becoming an attractive alternative due to their minimally invasive accessibility and plentiful availability.Adipose tissue originates from mesodermal germ layer and it is the most shared connective tissue in humans. The culture of the crude SVF allows the expansion of a relatively homogeneous fibroblastic-like population, adherent to plastic, with a wide proliferative capacity and a stromal surface phenotype [6,7], potentially differentiating in multiple lineages [8,9,10,11,12]. This population is identified as adipose-derived stromal/stem cells (ASCs), according to IFATS’s recommendations [13,14]. ASCs share a lot of similarities, such as morphology, distribution of surface antigens and multi-potency with other stem cells obtained, for example, from BM or umbilical cord blood [15]
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