The Effect of Mesenchymal Stromal Cell–Hyaluronic Acid Hydrogel Constructs on Immunophenotype of Macrophages

Abstract

During the past several years, multipotent mesenchymal stromal cells (MSCs) have rapidly moved from in vitro and animal studies into clinical trials as a therapeutic modality potentially applicable to a wide range of disorders. It has been proposed that ex vivo culture-expanded MSCs exert their tissue regeneration potential through their immunomodulatory and anti-inflammatory properties, and paracrine effects more than their ability to differentiate into multiple tissue lineages. Since extracellular matrix (ECM) deposition and tissue support is also one of many physiological roles of MSCs, there is increasing interest in their potential use for tissue engineering, particularly in combination with ECM-based scaffolds such as hyaluronic acid (HA). We investigated the effect of MSCs on immunophenotype of macrophages in the presence of an HA-hydrogel scaffold using a unique 3D coculture system. MSCs were encapsulated in the hydrogel and peripheral blood CD14 + monocyte-derived macrophages plated in direct contact with the MSC-gel construct. To determine the immunophenotype of macrophages, we looked at the expression of cell surface markers CD14, CD16, CD206, and human leukocyte antigen (HLA)-DR by flow cytometry. MSCs and macrophages cultured on the HAhydrogel remained viable and were able to be recovered from the construct. There was a significant difference in the immunophenotype observed between monocyte-derived macrophages cultured on the HA scaffold compared to tissue culture polystyrene. Macrophages cultured on gels with MSCs expressed lower CD16 and HLA-DR with higher expression of CD206, indicating the least inflammatory profile overall, compatible with the immunophenotype of alternatively activated macrophages. Development of macrophages, with this immunophenotype, upon interaction with the MSC-hydrogel constructs may play a potentially significant role in tissue repair when using a cellular-biomaterial therapeutic approach.

Comparative Analysis of Adipose-Derived Mesenchymal Stem Cells Isolated From Abdominal and Breast Tissue

“…activation following culture with bone marrow-derived MSC, indicating an anti-inflammatory effect. 11,21 In this study, we demonstrated a similar effect when co-cultured with ADSC, with no statistical difference between abdominal and breast adipose tissues. Clinically, both CD16 and HLA-DR are measures of acute inflammation, particularly in systemic disease and trauma; reduction in these markers on circulating macrophages may be an indication in the resolution of inflammation.…”

Decellularized skin/adipose tissue flap matrix for engineering vascularized composite soft tissue flaps

“…hASCs contributed to adipose regeneration through direct differentiation and/or paracrine action. As others have posited [27–29, 33–35], we believe that hASCs and DSAF worked synergistically to activate M2 polarization and provide a pro-regenerative environment for adipose tissue formation in our model. Hence, our data suggest that the hASCs-DSAF 3D scaffold holds great promise in soft tissue engineering because each component not only directly participates in adipose tissue regeneration but also modulates the host immune response to the engineered constructs.…”

“…For example, certain surface peptides and ligands on the scaffold that have been exposed by the decellularization process may modulate the immune response [28, 30–32], and the ECM degradation products may have immunomodulatory activity [26]. hASCs, owing to their unique immunomodulatory properties, can also induce the M2 macrophage phenotype [33, 34]. One recent study suggested that 3D topography plays a key role in regulating mesenchymal stem cells’ immunomodulatory effects, which can push macrophages towards an anti-inflammatory phenotype [35].…”

Mesenchymal stromal cell injection promotes vocal fold scar repair without long-term engraftment

“…In pre-clinical investigations, bone marrow mesenchymal stromal cell (BM-MSC) and hyaluronic acid hydrogel therapies have shown promise for vocal fold regeneration through enhanced tissue viscoelasticity, extracellular matrix (ECM) profiles, and immunomodulation [3–10]. Prior to the development of a cell and/or gel-based therapy for clinical use, a number of practical considerations need to be addressed.…”