Conditioned Medium – Is it an Undervalued Lab Waste with the Potential for Osteoarthritis Management?

Stem Cell Reviews and Reports https://doi.org/10.1007/s12015-023-10517-1 Conditioned Medium – Is it an Undervalued Lab Waste with the Potential for Osteoarthritis Management? Monika A. Rosochowicz1,2 · Michał S. Lach1,2 · Magdalena Richter1 · Wiktoria M. Suchorska2,3 · Tomasz Trzeciak1 Accepted: 6 February 2023 © The Author(s) 2023 Abstract Background The approaches currently used in osteoarthritis (OA) are mainly short-term solutions with unsatisfactory outcomes. Cell-based therapies are still controversial (in terms of the sources of cells and the results) and require strict culture protocol, quality control, and may have side-effects. A distinct population of stromal cells has an interesting secretome composition that is underrated and commonly ends up as biological waste. Their unique properties could be used to improve the existing techniques due to protective and anti-ageing properties. Scope of Review In this review, we seek to outline the advantages of the use of conditioned media (CM) and exosomes, which render them superior to other cell-based methods, and to summarise current information on the composition of CM and their effect on chondrocytes. Major Conclusions CM are obtainable from a variety of mesenchymal stromal cell (MSC) sources, such as adipose tissue, bone marrow and umbilical cord, which is significant to their composition. The components present in CMs include proteins, cytokines, growth factors, chemokines, lipids and ncRNA with a variety of functions. In most in vitro and in vivo studies CM from MSCs had a beneficial effect in enhance processes associated with chondrocyte OA pathomechanism. General Significance This review summarises the information available in the literature on the function of components most commonly detected in MSC-conditioned media, as well as the effect of CM on OA chondrocytes in in vitro culture. It also highlights the need to standardise protocols for obtaining CM, and to conduct clinical trials to transfer the effects obtained in vitro to human subjects. Keywords OA · Osteoarthritis · MSCs · CM · Stromal cells · Chondrocytes · Exosomes Background Hyaline cartilage is a subtype of connective tissue that provides a smooth surface reducing friction and resistance to compressive forces during movement [1–3]. Its function is Monika A. Rosochowicz and Michał S. Lach contributed equally to this work. * Monika A. Rosochowicz 1 Department of Orthopedics and Traumatology, Poznan University of Medical Sciences, 28 Czerwca 1956r. 135/147 Street, 61‑545 Poznan, Poland 2 Radiobiology Laboratory, Greater Poland Cancer Centre, Garbary 15 Street, 61‑866 Poznan, Poland 3 Department of Electroradiology, Poznan University of Medical Sciences, Garbary 15 Street, 61‑866 Poznan, Poland made possible due to a dense extracellular matrix (ECM) [1, 2, 4, 5], consisting of a network of collagen fibres, proteoglycans, and non-collagenous proteins [1, 4, 6]. Cartilage is basically composed of a single cell type –chondrocytes [1, 4], which once the organism has reached skeletal maturity, are unable to divide and maintain the quiescent state [6]. These cells are responsible for synthesising ECM components and proteolytic enzymes, that remodel surrounding tissue [4, 6]. The histological architecture of the cartilage also includes neither blood, lymphatic vessels nor neural tissue, which in general provides an ease of movement. The features of this tissue consequently preclude the regeneration of damaged tissue, which may lead to the development of osteoarthritis [7]. OA is a chronic degenerative disease, the development of which is affected by several factors, such as obesity, genetic predispositions, age and extensive stress on the joints [4, 8, 9]. This damages the dense ECM and affects the secretome 13 Vol.:(0123456789) Stem Cell Reviews and Reports of the local microenvironment, disrupting the balance between catabolic and anabolic actions in the metabolism of the chondrocytes. The primary causes of the idiopathic disease are yet to be fully explained, but it is thought to be closely related to the inflammatory process. Unlike any other arthritis, however, it is directly related to a severe inflammatory response with an autoimmune background [10]. The interleukin 1β (IL-1β) and tumour necrosis factor α (TNFα) are the most prominent cytokines involved in the progression of OA and the most commonly used during in vitro modelling [4, 5, 9]. The secretion of these inflammatory mediators leads to the release of even more chemokines and pro-inflammatory cytokines, as well as ECM-degrading enzymes: matrix metalloproteinases (MMPs) and aggrecanases [4, 9]. Among the ways of treating OA, we may distinguish methods consisting mainly in fighting the symptoms of the disease, such as the use of painkillers or joint injections, e.g. with hyaluronic acid (HA), corticosteroids or plateletrich plasma (PRP) [3, 5, 11–13]. In addition to symptomatic treatment, there is also surgical management, which involves: microfracture, the use of cells and tissue engineering (autologous chondrocyte implantation (ACI) or matrixinduced autologous implantation (MACI)), osteochondral autograft transplantation and alloplasty, the most invasive [1, 5, 11, 14]. Comparisons of these methods, together with their pros and cons have been already described in a number of reputable studies [5, 14, 15]. The main drawbacks of these procedures tend to be the formation of fibrocartilage, the lifespan of the implants and the invasiveness of these procedures. New sources of cells and materials for tissue engineering purposes are therefore necessary, as are alternative methods for preventing the development of OA or significantly retarding it [1, 11, 15, 16]. This would offer a better quality of life and delay extensive surgical interventions. Cell engineering has mainly been applied in ACI and MACI procedures [3–5, 13]. Initially, it involves collecting chondrocytes from the patient, cultivating them through cell culture and retransplanting them into the site of the defect [4]. The main advantage of cell-based therapies is that the cellular material needed can be taken from various sources, which is extremely hopeful for patients with degenerative diseases, elderly patients and those with genetic and metabolic dysfunctions [3, 15]. Neither do cell-based methods require complex surgery, reducing invasiveness [1, 15, 17]. Among the MSCs that may be used in therapy a variety may be distinguished, but not exclusively osteoblasts, chondrocytes, adipocytes, astrocytes and cardiomyocytes, and they exhibit anti-inflammatory outcomes. They may therefore make it possible to reconstruct the joint and, through immunomodulation, reduce the locally induced immune response [1, 4, 11, 18]. The availability of autologous material for the treatment minimises the risk of patients rejecting it [1, 4]. 13 The efficiency of cell therapy is to a great extent determined by the donor’s health and age, (...truncated)