Abstract
BackgroundMesenchymal stem cells (MSCs) are widely used in cell-based therapy owing to their multilineage potential and low immunogenicity. However, low differentiation efficiency and unpredictable immunogenicity of allogeneic MSCs in vivo limit their success in therapeutic treatment. Herein, we evaluated the differentiation potential and immunogenicity of human placenta-derived MSCs manipulated with osteogenic priming and dedifferentiation process.MethodsMSCs from human placentas were subjected to osteogenic induction and then cultivated in osteogenic factor-free media; the obtained cell population was termed dedifferentiated mesenchymal stem cells (De-MSCs). De-MSCs were induced into osteo-, chondro- and adipo-differentiation in vitro. Cell proliferation was quantified by a Cell-Counting Kit-8 or tritiated thymidine ([3H]-TdR) incorporation. Meanwhile, the osteogenesis of De-MSCs in vivo was assayed by real-time PCR and histological staining. The expressions of stem cell markers and co-stimulatory molecules on De-MSCs and lymphocytes from primed BALB/c mouse with De-MSCs were determined by flow cytometry.ResultsDe-MSCs exhibited some properties similar to MSCs including multiple differentiation potential and hypoimmunogenicity. Upon re-osteogenic induction, De-MSCs exhibited higher differentiation capability than MSCs both in vitro and in vivo. Of note, De-MSCs had upregulated immunogenicity in association with their osteogenesis, reflected by the alternated expressions of co-stimulatory molecules on the surface and decreased suppression on T cell activation. Functionally, De-MSC-derived osteoblasts could prime lymphocytes of peripheral blood and spleen in BALB/c mice in vivo.ConclusionsThese data are of great significance for the potential application of De-MSCs as an alternative resource for regenerative medicine and tissue engineering. In order to avoid being rejected by the host during allogeneic De-MSC therapy, we suggest that immune intervention should be considered to boost the immune acceptance and integration because of the upregulated immunogenicity of De-MSCs with redifferentiation in clinical applications.
Highlights
Mesenchymal stem cells (MSCs) are widely used in cell-based therapy owing to their multilineage potential and low immunogenicity
Phenotypic analysis was conducted with MSCs, MSC-derived osteoblasts (Ob-MSCs), dedifferentiated mesenchymal stem cells (De-MSCs) and Osteoblasts derived from De-MSCs (Re-MSCs), which were derived from independent placenta samples
We showed that activated T cells, B cells, monocytes, and macrophages were found in Peripheral blood mononuclear cells (PBMCs) and splenocytes of mice immunized with Mitomycin C (MMC)-treated Ob-MSCs and Re-MSCs
Summary
Mesenchymal stem cells (MSCs) are widely used in cell-based therapy owing to their multilineage potential and low immunogenicity. Lohan et al further summarized that during osteogenic, chondrogenic and myocardial differentiation, the expressions of MHC-I, MHC-II, CD80 or CD86 on differentiated allo-MSCs increased, while the secretion of prostaglandin E2 (PGE2) or nitric oxide (NO) reduced [12]. It is indicative of the effect of induced differentiation on the decreased immunosuppressive ability, and increased immunogenicity of allo-MSCs is a potential obstacle when applying MSCs in tissue replacement therapies. The immunogenicity of differentiated MSCs needs to be fully considered
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