Background: Mesenchymal stem cells (MSCs) are widely used in cell-based therapy owing to their multilineage\npotential and low immunogenicity. However, low differentiation efficiency and unpredictable immunogenicity\nof allogeneic MSCs in vivo limit their success in therapeutic treatment. Herein, we evaluated the differentiation\npotential and immunogenicity of human placenta-derived MSCs manipulated with osteogenic priming and\ndedifferentiation process.\nMethods: MSCs from human placentas were subjected to osteogenic induction and then cultivated in osteogenic\nfactor-free media; the obtained cell population was termed dedifferentiated mesenchymal stem cells (De-MSCs).\nDe-MSCs were induced into osteo-, chondro- and adipo-differentiation in vitro. Cell proliferation was quantified by\na Cell-Counting Kit-8 or tritiated thymidine ([3H]-TdR) incorporation. Meanwhile, the osteogenesis of De-MSCs in\nvivo was assayed by real-time PCR and histological staining. The expressions of stem cell markers and costimulatory\nmolecules on De-MSCs and lymphocytes from primed BALB/c mouse with De-MSCs were determined\nby flow cytometry.\nResults: De-MSCs exhibited some properties similar to MSCs including multiple differentiation potential and\nhypoimmunogenicity. Upon re-osteogenic induction, De-MSCs exhibited higher differentiation capability than MSCs\nboth in vitro and in vivo. Of note, De-MSCs had upregulated immunogenicity in association with their osteogenesis,\nreflected by the alternated expressions of co-stimulatory molecules on the surface and decreased suppression on\nT cell activation. Functionally, De-MSC-derived osteoblasts could prime lymphocytes of peripheral blood and spleen\nin BALB/c mice in vivo.\nConclusions: These data are of great significance for the potential application of De-MSCs as an alternative\nresource for regenerative medicine and tissue engineering. In order to avoid being rejected by the host during\nallogeneic De-MSC therapy, we suggest that immune intervention should be considered to boost the immune\nacceptance and integration because of the upregulated immunogenicity of De-MSCs with redifferentiation in\nclinical applications.
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