Alterations in the Secretome of Clinically Relevant Preparations of Adipose-Derived Mesenchymal Stem Cells Cocultured with Hyaluronan

Abstract

Osteoarthritis (OA) can be a debilitating degenerative disease and is the most common form of arthritic disease. There is a general consensus that current nonsurgical therapies are insufficient for younger OA sufferers who are not candidates for knee arthroplasties. Adipose-derived mesenchymal stem cells (MSCs) therapy for the treatment of OA can slow disease progression and lead to neocartilage formation. The mechanism of action is secretion driven. Current clinical preparations from adipose tissue for the treatment of OA include autologous stromal vascular fraction (SVF), SVF plus mature adipocytes, and culture-purified MSCs. Herein we have combined these human adipose-derived preparations with Hyaluronan (Hylan G-F 20: Synvisc) in vitro and measured alterations in cytokine profile. SVF plus mature adipocytes showed the greatest decreased in the proinflammatory cytokines IL-1β, IFN-γ, and VEGF. MCP-1 and MIP-1α decreased substantially in the SVF preparations but not the purified MSCs. The purified MSC preparation was the only one to show increase in MIF. Overall the SVF plus mature adipocytes preparation may be most suited of all the preparations for combination with HA for the treatment of OA, based on the alterations of heavily implicated cytokines in OA disease progression. This will require further validation using in vivo models.

Priming Adipose‐Derived Mesenchymal Stem Cells with Hyaluronan Alters Growth Kinetics and Increases Attachment to Articular Cartilage

“…Vascular endothelial growth factor (VEGF) decreased with increasing concentration of HA and significantly for the 2 mg/mL concentration. This was consistent with our previous investigations of HA and MSC coculture [ 29 ]. VEGF may play an active role in the pathogenesis of OA.…”

“…MIF is considered to be a proinflammatory mediator especially in OA and acts in local tissue to increase neutrophil and macrophage migration to regions of inflammation. Our previous investigations also showed increased secretion of MIF by MSCs cultured with HA [ 29 ]. Vascular endothelial growth factor (VEGF) decreased with increasing concentration of HA and significantly for the 2 mg/mL concentration.…”

“…Culturing MSCs with HA can alter the cytokine secretion profile. Investigations of the secretome of MSCs when combined with HA have been shown to increase the secretion of macrophage migration inhibitory factor (MIF) [ 29 ]. MIF secretion by MSCs in this study peaked significantly only for the 1 mg/mL treated cells.…”

Regenerative Medicine: A New Paradigm in Bone Regeneration

“…Previous studies have reported many growth factors and cytokines derived from the CM of various stem cells [19][20][21][85][86][87][88][89], which could be responsible for the paracrine protective effects of stem cells against several diseases. Consequently, the use of stem cells CM instead of direct implantation of stem cells may be a feasible approach to overcome the limitations of current cell-based therapy.…”

Patient-Specific Age: The Other Side of the Coin in Advanced Mesenchymal Stem Cell Therapy

“…MSC niche interactions appear to be of mutual benefit since MSC release a wide range of bioactive factors that confer trophic and immune-modulatory effects, such as cytokines and distinct forms of miRNA and tRNA species (Hsiao et al, 2012 ; Baglio et al, 2015 ). More and more reports have unraveled the potent features of the MSC secretome, which now is thought to become by itself a regenerative therapeutical tool (Sdrimas and Kourembanas, 2014 ; Gallina et al, 2015 ; Succar et al, 2015 ; Tran and Damaser, 2015 ).…”