Evaluation of 3D biomimetic microcarriers for enhancing therapeutic efficacy of human umbilical cord mesenchymal stem cells in psoriasis treatment

Mesenchymal stem cells (MSCs) hold promise for regenerative medicine due to their unique biological properties, including self-renewal and multi-lineage differentiation potential. Conventional two-dimensional (2D) culture systems may hinder therapeutic efficacy due to challenges in maintaining quality and producing a sufficient quantity of cells for clinical applications. This study aimed to evaluate the influence of a three-dimensional (3D) microcarrier-bioreactor system on the biological characteristics of human umbilical cord MSCs (hUC-MSCs) and their potential therapeutic efficacy in a psoriasis mouse model. The 3D microcarrier-bioreactor system was observed to improve hUC-MSCs attachment and proliferation while preserving genetic stability, characteristic surface marker expression, non-tumorigenic properties, and differentiation potential, consistent with outcomes from 2D cultures. Moreover, the 3D-hUC-MSCs demonstrated enhanced proliferation, stemness, immune function, and cell viability compared to those cultured in 2D systems.<i>In vitro</i> experiments demonstrated that 3D-hUC-MSCs supernatants effectively suppressed IL-17A-induced NF-κB signaling in keratinocytes. <i>In vivo</i>, 3D-hUC-MSCs significantly reduced IMQ+IL-23-induced psoriasis-like skin inflammation by reducing immune cell infiltration and inhibiting IL-17-associated inflammatory pathways. Transcriptomic analysis revealed that 3D-hUC-MSCs modulated signaling pathways associated with inflammation and innate immune responses. Our findings suggest that the 3D microcarrier-bioreactor system holds promise as a strategy to enhance the therapeutic potential of hUC-MSCs, particularly in the treatment of immune-mediated disorders such as psoriasis.