Mesenchymal stem cells (MSC) are multipotential cells with utility in tissue engineering and regenerative medicine. However, the immunological properties and immunogenicity of allogeneic MSC remain poorly defined. Recent studies investigating their immunogenicity remain inconclusive and this has hampered their clinical application. This study investigated the (1) immunogenicity and (2) immunomodulatory properties of bone marrow-derived MSC using an allogeneic mouse model involving Balb/c (responder) and C3H (stimulator) mice. Dermal fibroblasts (DF) were used as controls for cells of mesenchymal origin. Adaptations of the lymphocyte transformation assay (LTA) and mixed lymphocyte reaction (MLR) were used to investigate the immunogenicity and immunomodulatory properties of allogeneic undifferentiated and chondrogenic-differentiated MSC and DF. Both MSC and DF displayed a similar phenotypic profile with the exception of lower expression of CD44 and CD105 in DF. Tri-lineage differentiation of MSC and DF into adipocytes, chondrocytes and osteocytes confirmed their multipotency. In LTA, both undifferentiated and chondrogenic-differentiated allogeneic MSC stimulated lymphocyte proliferation. Allogeneic DF were non-stimulatory but chondrogenic-differentiated DF triggered responder lymphocyte proliferation. In one-way MLR, both allogeneic MSC and DF significantly suppressed Balb/c lymphocyte proliferation. The current challenges in distinguishing between MSC and fibroblasts were apparent throughout the work. These findings support the notion that although MSC possess immunosuppressive properties, they may not be immunoprivileged. Thus, clinical application of allogeneic MSC should be taken with due consideration of their potential immunogenicity.
Human mesenchymal stem cells (hMSCs) are widely represented in ongoing regenerative medicine clinical trials due to their ease of autologous implantation. In bone regeneration, crosstalk between macrophages and hMSCs is critical with macrophages playing a key role in the recruitment and differentiation of hMSCs. However, engineered biomaterials able to both direct hMSC fate and modulate macrophage phenotype have not yet been identified. A novel combinatorial chemistry-microtopography screening platform, the ChemoTopoChip, is used to identify materials suitable for bone regeneration by screening with human immortalized mesenchymal stem cells (hiMSCs) and human macrophages. The osteoinduction achieved in hiMSCs cultured on the "hit" materials in basal media is comparable to that seen when cells are cultured in osteogenic media, illustrating that these materials offer a materials-induced alternative in bone-regenerative applications. These also exhibit immunomodulatory effects, concurrently polarizing macrophages towards a pro-healing phenotype. Control of cell response is achieved when both chemistry and topography are recruited to instruct the required cell phenotype, combining synergistically. The large library of materials reveals that the relative roles of microtopography and material chemistry are similar, and machine learning identifies key material and topographical features for cell-instruction.
Organogels prepared with vegetable oils as the liquid organic phase present an excellent platform for the controlled delivery of hydrophobic guest molecules.
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