Optimization of Lyophilized Hyperacute Serum (HAS) as a Regenerative Therapeutic in Osteoarthritis.

Isabel Olmos Calvo,Zsombor Lacza,Szilvia Takács,Karina Kramer,Diána Simon,Timea Berki,Ágnes Madár,Andrea De Luna,Stefan Nehrer,Dorottya Kardos,Olga Kuten-Pella,Szabina Erdö-Bonyár

doi:10.3390/ijms22147496

Abstract

Hyperacute serum (HAS) is a blood derivative product that promotes the proliferation of various cell types and controls inflammation in vitro. The aim of this study is to investigate the regenerative potential of different formulations of HAS, including lyophilized and hyaluronic acid combined versions, to obtain a stable and standardized therapeutic in osteoarthritis (OA), which may be able to overcome the variability limitations of platelet-rich plasma (PRP). Primary human osteoarthritic chondrocytes were used for testing cellular viability and gene expression of OA-related genes. Moreover, a co-culture of human explants of cartilage, bone and synovium under inflammatory conditions was used for investigating the inflammatory control capacities of the different therapeutics. In this study, one formulation of lyophilized HAS achieved the high cell viability rates of liquid HAS and PRP. Gene expression analysis showed that HAS induced higher Col1a1 expression than PRP. Cytokine quantification from supernatant fluids revealed that HAS treatment of inflamed co-cultures significantly reduced levels of IL-5, IL-15, IL-2, TNFα, IL-7 and IL-12. To conclude, lyophilized HAS is a stable and standardized therapeutic with high potential in joint regeneration.

Highlights

Osteoarthritis (OA) is the most common joint degenerative disease, especially affecting the elderly population, which it is expected to increase in the decades [1]
Two concentrations of filtered lyophilized hyperacute serum (HAS) were compared to the known gold standard supplementation, fetal calf serum (FCS) (Figure 1A)
Statistical time-dependent analysis showed a significant increase in cell viability over time after supplementation with 10% FCS and 20% filtered lyophilized HAS (p = 0.0298, p = 0.0375, respectively)

Summary

Introduction

Osteoarthritis (OA) is the most common joint degenerative disease, especially affecting the elderly population, which it is expected to increase in the decades [1]. The lack of an effective current treatment to regenerate or impede joint destruction in the context of OA has left alleviating symptoms as the only therapeutic option until the joint is surgically replaced [2]. The aim is to isolate and concentrate specific components that may have a potential effect in the context of tissue engineering. Different preparation processes lead to different compositions and different potential outcomes in modulating cell proliferation and inflammation [4]. These blood derivative products are intraarticularly injected into osteoarthritic joints. The main disadvantage relates to its composition variability due to different production techniques and its relevant content of pro-inflammatory agents such as fibrin and leukocytes [9,10,11,12,13]

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Conclusion