Fibrous scaffolds potentiate the paracrine function of mesenchymal stem cells: A new dimension in cell-material interaction

Abstract

While the studies on the material interaction with mesenchymal stem cells (MSCs) have been mainly focused on the ability of materials to provide environment to regulate cell viability, proliferation or differentiation, the therapeutic effects of MSC-material constructs may result from the secretion of immunomodulatory and angiogenic cytokines from MSCs. Here, electrospun scaffolds composed of fibers in random, aligned and mesh-like patterns were fabricated, and the paracrine behavior of adipose-derived MSCs (Ad-MSCs) on the scaffolds were investigated in comparison to the cell culture via conventional microplates. It was found that the Ad-MSCs on the electrospun fibers produced significantly higher levels of anti-inflammatory and pro-angiogenic cytokines compared to those cultured on microplates. The enhanced modulatory effects of the secreted products of Ad-MSCs on fibrous electrospun scaffolds were also proven in the cultures of endothelial cells and the LPS-stimulated macrophages, with three types of scaffolds showing distinct influences on the paracrine function of Ad-MSCs. In a skin excisional wound-healing model in rat, the conditioned medium collected from the MSC-scaffold system accelerated the wound closure, promoted the macrophage recruitment and enhanced the polarization of macrophages toward the pro-healing phenotype in the wound bed. Our study demonstrates that the fibrous topography of scaffolds is a key material property that modulates the paracrine function of cells. The discovery elucidates a new aspect of material functions, laying the foundation for developing scaffold materials to promote tissue regeneration/repair through guiding the paracrine signaling network.

Differential and Interactive Effects of Substrate Topography and Chemistry on Human Mesenchymal Stem Cell Gene Expression

“…It is crucial for understanding cell-biomaterial interactions in order to maximize the potential in the designed material since many cellular processes including adhesion, migration, and stem cell differentiation are governed by the non-soluble components of the matrix. To this end, enhanced cell biological activities and narrowed integrin usage of cells cultured on three-dimensional matrices compared to their two-dimensional counterparts was shown to highlight the importance of substrate topography in regulating cell behavior and paracrine functions [17,18]. Additionally, various studies have shown enhanced osteogenic capacities with three-dimensional fibrous culture surfaces [19,20,21,22,23] and have shown regulations of the differentiation potential of other lineages [24,25,26,27].…”

Construction of a dermis–fat composite in vivo: Optimizing heterogeneous acellular dermal matrix with in vitro pretreatment

“…Our previous experiments on ADM without laser perforating also confirmed this mechanism (Zhu et al, ). Scaffolds can produce specific microenvironments depending on their morphological, chemical, and mechanical properties, which can influence material‐cell interactions and affect the behavior of seed cells (Eichholz & Hoey, ); (Su et al, ). Our previous studies have found that PADM can provide rADSCs with a microenvironment that facilitates their paracrine function (Zhu et al, ).…”

Design of Polymeric Culture Substrates to Promote Proangiogenic Potential of Stem Cells

“…The MSC‐embedded fibrin patches thus can act predominantly as a reservoir of paracrine factors in chronic myocardial infarction. Recently, Luo and co‐workers also reported that ADSCs‐embedded electrospun fibers potentiated paracrine signaling network of ADSCs and promoted tissue regeneration . This study demonstrated that ADSCs on the electrospun scaffold enhanced secretion of anti‐inflammatory and proangiogenic cytokines and enhanced wound closure.…”