Conditioned Serum Enhances the Chondrogenic and Immunomodulatory Behavior of Mesenchymal Stem Cells.

Rebeca Blázquez,Javier G Casado,Verónica Álvarez,Julio Reinecke,Esther López,Francisco Miguel Sánchez-Margallo,Federica Marinaro

doi:10.3389/fphar.2019.00699

Abstract

Osteoarthritis is one of the most common chronic health conditions associated with pain and disability. Advanced therapies based on mesenchymal stem cells have become valuable options for the treatment of these pathologies. Conditioned serum (CS, “Orthokine”) has been used intra-articularly for osteoarthritic patients. In this work, we hypothesized that the rich content on anti-inflammatory proteins and growth factors of CS may exert a beneficial effect on the biological activity of human adipose-derived mesenchymal stem cells (hAdMSCs). In vitro studies were designed using hAdMSCs cocultured with CS at different concentrations (2.5, 5, and 10%). Chondrogenic differentiation assays and immunomodulatory experiments using in vitro-stimulated lymphocytes were performed. Our results demonstrated that CS significantly enhanced the differentiation of hAdMSCs toward chondrocytes. Moreover, hAdMSCs pre-sensitized with CS reduced the lymphocyte proliferation as well as their differentiation toward activated lymphocytes. These results suggest that in vivo coadministration of CS and hAdMSCs may have a beneficial effect on the therapeutic potential of hAdMSCs. Moreover, these results indicate that intra-articular administration of CS might influence the biological behavior of resident stem cells increasing their chondrogenic differentiation and inherent immunomodulatory activity. To our knowledge, this is the first in vitro study reporting this combination.

Highlights

Osteoarthritis is one of the most common chronic health conditions associated with pain and disability (Allen and Golightly, 2015), being the most common form of arthritis followed by rheumatoid arthritis, gout, lupus, fibromyalgia, and others (Barbour et al, 2017)
In order to compare the phenotype of human adipose-derived mesenchymal stem cells (hAdMSCs) cultured in the presence of fetal bovine serum (FBS) with those cultured in the presence of CS, the expression of stem cell markers was analyzed by flow cytometry
The stem cell phenotype of hAdMSCs cultured with 2.5, 5, and 10% of FBS or CS was determined after 6 days by flow cytometry using commercially available monoclonal antibodies (mAbs) against CD44, CD45, CD73, CD90, and human leucocyte antigen DR (HLA-DR)

Summary

Introduction

Osteoarthritis is one of the most common chronic health conditions associated with pain and disability (Allen and Golightly, 2015), being the most common form of arthritis followed by rheumatoid arthritis, gout, lupus, fibromyalgia, and others (Barbour et al, 2017). CS Enhances the Immunomodulatory Potential of MSCs (Hunter, 2011) These treatments do not address the cause of the disease being frequently associated to renal, cardiovascular, and gastrointestinal secondary effects mainly due to the use of nonsteroidal anti-inflammatory drugs. Great efforts are being made to develop new therapeutic tools for arthritic diseases. In this sense, plateletrich plasma (PRP) has emerged in the last years as a promising therapeutic option for cartilage degeneration, demonstrating its chondroprotective effect (Andia and Maffulli, 2013; Moussa et al, 2017) and a temporal pain relief together with a functional improvement of the involved joint (Laver et al, 2017). The variation between different preparations makes difficult the establishment of its therapeutic potential (Richards et al, 2016), and postinjection pain seems to be more frequent after PRP intraarticular administration than with other treatments using the same route (Ornetti et al, 2016)

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