Mesenchymal stem cells (MSCs) with self-renewing, multilineage differentiation and immunomodulatory properties, have been extensively studied in the field of regenerative medicine and proved to have significant therapeutic potential in many different pathological conditions. The role of MSCs mainly depends on their paracrine components, namely secretome. However, the components of MSC-derived secretome are not constant and are affected by the stimulation MSCs are exposed to. Therefore, the content and composition of secretome can be regulated by the pretreatment of MSCs. We summarize the effects of different pretreatments on MSCs and their secretome, focusing on their immunomodulatory properties, in order to provide new insights for the therapeutic application of MSCs and their secretome in inflammatory immune diseases.
Current bone defect treatment strategies are associated with several risks and have major limitations. Therefore, it is necessary to develop an inexpensive growth factor delivery system that can be easily produced in large quantities and can promote long-term bone regeneration. An osteogenic growth peptide (OGP) is a 14 amino acid peptide with a short peptide sequence active fragment. In this study, we developed two OGP-based self-assembling supramolecular hydrogels (F- and G-sequence hydrogels) and investigated the in vitro and in vivo effects on proliferation and osteogenesis, including the mechanism of hydrogel-mediated bone defect repair. The hydrogels presented excellent biocompatibility and cell proliferation-promoting properties (1.5–1.7-fold increase). The hydrogels could effectively upregulate the expression of osteogenic factors, including RUNX2, BMP2, OCN, and OPN, to promote osteogenesis differentiation. Interestingly, 353 differentially expressed genes were identified in hBMSCs treated with hydrogels. The hydrogels were proved to be involved in the inflammatory pathways and folate-related pathways to mediate the osteogenesis differentiation. Furthermore, the therapeutic efficiency (bone volume/total volume, trabecular number, and bone mineral density) of hydrogels on bone regeneration in vivo was evaluated. The results showed that the hydrogels promoted bone formation in the early stage of bone defect healing. Taken together, this study was the first to develop and evaluate the properties of OGP-based self-assembling supramolecular hydrogels. Our study will provide inspiration for the development of delivering OGP for bone regeneration.
An electrospun P34HB scaffold was prepared and coated with lecithin. As a scaffold for bone tissue engineering, the P34HB/lec scaffold could promote proliferation and osteogenesis of BMSCs in vitro, and also accelerate bone regeneration in vivo.
Phenotypic transformation of macrophages plays important immune response roles in the occurrence, development and regression of periodontitis. Under inflammation or other environmental stimulation, mesenchymal stem cells (MSCs) exert immunomodulatory effects through their secretome. It has been found that secretome derived from lipopolysaccharide (LPS)-pretreated or three-dimensional (3D)-cultured MSCs significantly reduced inflammatory responses in inflammatory diseases, including periodontitis, by inducing M2 macrophage polarization. In this study, periodontal ligament stem cells (PDLSCs) pretreated with LPS were 3D cultured in hydrogel (termed SupraGel) for a certain period of time and the secretome was collected to explore its regulatory effects on macrophages. Expression changes of immune cytokines in the secretome were also examined to speculate on the regulatory mechanisms in macrophages. The results indicated that PDLSCs showed good viability in SupraGel and could be separated from the gel by adding PBS and centrifuging. The secretome derived from LPS-pretreated and/or 3D-cultured PDLSCs all inhibited the polarization of M1 macrophages, while the secretome derived from LPS-pretreated PDLSCs (regardless of 3D culture) had the ability to promote the polarization of M1 to M2 macrophages and the migration of macrophages. Cytokines involved in the production, migration and polarization of macrophages, as well as multiple growth factors, increased in the PDLSC-derived secretome after LPS pretreatment and/or 3D culture, which suggested that the secretome had the potential to regulate macrophages and promote tissue regeneration, and that it could be used in the treatment of inflammation-related diseases such as periodontitis in the future.
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