Abstract
BackgroundMesenchymal stromal cells (MSCs) are considered potential candidates that hold great promise in the treatment of immune-related diseases. For therapeutic applications, it is necessary to isolate and expand MSCs with procedures complying with good manufacturing practice (GMP). Recent studies reported the use of human serum (HS) instead of fetal bovine serum (FBS) for the expansion of bone marrow-derived MSCs. Nevertheless, there are only limited data on HS as an alternative to FBS for the isolation and expansion of umbilical (UC-MSCs) and placenta-derived MSCs (PL-MSCs). In this study, we evaluate the effect of HS compared to FBS on the proliferative and immunosuppressive capacities of these MSCs.MethodsPL-MSCs and UC-MSCs were isolated and cultured in HS- or FBS-supplemented media. The MSC characteristics, including morphology, immunophenotype, and differentiation ability, were verified. The proliferative and immunosuppressive capacities were also examined. In addition, the proliferative-enhancing factors in both sera were explored using proteomic analysis.ResultsPL-MSCs and UC-MSCs proliferated faster in HS-supplemented medium than in equivalent levels of FBS-supplemented medium. Adipogenic and osteogenic differentiations occurred at nearly identical levels in HS- and FBS-supplemented media. Interestingly, MSCs cultured in HS-supplemented medium had a similar immunosuppressive effect as MSCs cultured in FBS-supplemented medium. Proteomic analysis revealed that Con-A binding glycoproteins with a molecular weight > 100 kDa in FBS could significantly enhance MSC proliferation. In contrast, the proliferative enhancing factors in HS were found in the Con-A non-binding fraction and WGA binding fraction with a molecular weight > 100 kDa.ConclusionsTaken together, our results suggest applications for the use of HS instead of FBS for the isolation and expansion of PL-MSCs and UC-MSCs for cell therapy in the future. Furthermore, this study identifies factors in HS that are responsible for its proliferative and immunosuppressive effects and might thus lead to the establishment of GMPs for the therapeutic use of MSCs.
Highlights
Mesenchymal stromal cells (MSCs) are considered potential candidates that hold great promise in the treatment of immune-related diseases
placenta-derived MSCs (PL-MSCs) could be expanded in human serum (HS)-supplemented medium for more than 20 passages without any noticeable changes in their morphology, similar to that of PL-MSCs expanded in fetal bovine serum (FBS)-supplemented medium
For umbilical cord-derived MSCs (UC-MSCs), the cells cultured in HS-supplemented medium exhibited an elongated, spindle-shaped morphology similar to that of the cells cultured in FBS-supplemented medium
Summary
Mesenchymal stromal cells (MSCs) are considered potential candidates that hold great promise in the treatment of immune-related diseases. PL-MSCs and UC-MSCs express low alloimmunogenicity, which allows their use as a human leucocyte antigen (HLA)-unmatched off-the-shelf product [17] This characteristic makes these cells an ideal candidate for a clinical approach in immunerelated diseases. Recent studies have addressed the effect of HS on the expansion of BM-MSCs and adipose tissue-derived MSCs. MSCs expanded in HScontaining media had a similar phenotype and functional properties as MSCs cultured in FBS-containing media [18, 25]. The aims of the study were first to compare the effect of HS- and FBS-supplemented media on the biological characteristics and immunosuppressive property of PL-MSCs and UC-MSCs. Secondly, we explored the proliferation enhancing factors in HS in comparison to FBS in order to establish xeno-free factors for therapeutic uses
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