Abstract
Quality evaluation of mesenchymal stem cells (MSCs) based on efficacy would be helpful for their clinical application. In this study, we aimed to find the factors of human bone marrow MSCs relating to cartilage repair. The expression profiles of humoral factors, messenger RNAs (mRNAs), and microRNAs (miRNAs) were analyzed in human bone marrow MSCs from five different donors. We investigated the correlations of these expression profiles with the capacity of the MSCs for proliferation, chondrogenic differentiation, and cartilage repair in vivo. The mRNA expression of MYBL1 was positively correlated with proliferation and cartilage differentiation. By contrast, the mRNA expression of RCAN2 and the protein expression of TIMP-1 and VEGF were negatively correlated with proliferation and cartilage differentiation. However, MSCs from all five donors had the capacity to promote cartilage repair in vivo regardless of their capacity for proliferation and cartilage differentiation. The mRNA expression of HLA-DRB1 was positively correlated with cartilage repair in vivo. Meanwhile, the mRNA expression of TMEM155 and expression of miR-486-3p, miR-148b, miR-93, and miR-320B were negatively correlated with cartilage repair. The expression analysis of these factors might help to predict the ability of bone marrow MSCs to promote cartilage repair.
Highlights
Mesenchymal stem cells (MSCs) have the capacity for selfrenewal [1] and differentiation into several mesoderm-type lineages, including osteoblasts, chondrocytes, adipocytes, myocytes, and vascular cells [2] and are considered to be nonimmunogenic [3, 4]
The human bone marrow MSCs (hMSCs) from five different donors were ranked from hMSC-1 to hMSC-5 in order of growth rate (GR), and the hMSC-1 to hMSC-5 were from a 22year-old black man, 20-year-old white man, 39-year-old black man, 29-year-old white woman, and 41-year-old white women, respectively
In the assessment of protein expression using enzyme-linked immunosorbent assay (ELISA), the anabolic factors tissue inhibitor of metalloproteinase- (TIMP-)1, TIMP-2, transforming growth factor- (TGF-)β1, TGF-β2, platelet-derived growth factor- (PDGF-)AA, hepatocyte growth factor (HGF), and insulin-like growth factor- (IGF-)1 and the catabolic factors IL6, IL8, stromal cell-derived factor- (SDF-)1a, MMP13, vascular endothelial growth factor (VEGF), monocyte chemotactic protein- (MCP-)1, MMP1, and matrix metalloproteinase- (MMP-)3 were detected in the culture supernatant for each donor (Table 2)
Summary
Mesenchymal stem cells (MSCs) have the capacity for selfrenewal [1] and differentiation into several mesoderm-type lineages, including osteoblasts, chondrocytes, adipocytes, myocytes, and vascular cells [2] and are considered to be nonimmunogenic [3, 4]. MSCs are one of the most promising cellular sources of stem cells that can be studied without using any immunosuppressive drugs, for both research and clinical purposes. We have started two clinical trials of intra-articular injection of autologous bone marrow MSCs for articular cartilage repair based on our previous animal experiments [5, 12, 13]. The functional quality of MSCs for cartilage regeneration might be diversified depending on the donor due to the heterogeneity of MSCs. There have been reports that differentiation and proliferation capacity decrease with age [14, 15] and, the use of autologous MSCs for tissue repair, which in some indications concerns elderly patients, has certain limits [16]. Quality evaluation confirming the properties of MSCs has been established and is based on cell surface markers (negative for CD14 or CD11b, CD19, CD34, CD45, CD79α, and HLA-DR and positive for CD73, CD90, CD105, CD166, and CD44 [17,18,19]) and
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