Osteoarthritis (OA) is a degenerative inflammatory disease of multifactorial origin affecting the joints and is a major cause of pain and disability. Although the option of arthroplasty is highly effective, it is not suitable for younger patients. It is highly invasive with a number of well-recognised complications. Treatments using cell-based and biological substances are gaining popularity to delay the need for surgery. The complexity of both development of the disease and decisions on the correct patient pathways manifest themselves in the ultimate aims of optimization of novel potential biological cures following acute injury, tissue regeneration and protection in mild to moderate disease, and effective pain relief in the later stages.

In the coming years, a greater understanding of the interaction between individual contributing factors in the development of OA and the response to treatment will be a requirement in order to inform a data-driven, personalised, and precise approach, thereby optimizing pain relief, repair, and recovery through regenerative pathways. Stem cell-based therapies will undoubtedly form a key element of this armamentarium with growing clinical and laboratory-based evidence indicating that these cells can modulate the local OA micro-environment and can be provided through a minimally-invasive intra-articular injection, an effective alternative to invasive surgery. However, further evidence is required from more detailed biological characterization of the mechanisms of action of stem cells, their exosomes, and stem cell-containing materials such as micro-fragmented adipose tissue, together with the publication of more definitive clinical trials prior to gaining recognition and general licensing for use.

The aim of this Special Issue is to provide an up-to-date scientific and clinical database that can be used to inform both scientists and clinicians of the possible benefits of stem cell-based therapy in the treatment of OA. This Special Issue seeks articles that answer the above questions and look beyond current knowledge to perceive how novel primarily stem cell-based therapies can be incorporated into treatment regimens as part of a precision translational outlook. Original research and review articles are welcome, particularly those correlating stem cell-based treatment with outcomes. In addition, in vivo studies using models of OA, studies providing novel data on the biological mechanisms of action of stem cells, exosomes, and stem cell-containing biomaterials as well as the incorporation of artificial matrices and homing mechanisms for delivery will be of interest.

Potential topics include but are not limited to the following:

• Stem cell-related biological functions in OA
• The role of stem cell-derived exosomes in repair and regeneration
• Clinical studies/trials examining pain relief, repair, and regeneration after stem cell treatments
• The role of cell-based therapy as part of a precision medicine patient pathway
• Stem cell artificial and natural matrices, 3D printing, and tissue synthesis
• The role of genomics and proteomics in the monitoring of response to biological treatments of OA
• Use of stem cell-based therapies as an adjunct to surgical intervention for the treatment of arthritis
• Reasons and mechanisms of response and non-response to stem cell-based therapies for the treatment of OA
• Stem cell drug loading for targeted therapies
• Stem cell modification and homing in disease
• Stem cell-based combinational regenerative/reparative therapies
• iPS-MSC differentiation for therapeutic treatments