Advances in stem cell therapy for cartilage regeneration in osteoarthritis

ABSTRACT

Introduction: Osteoarthritis (OA) is a progressive joint disease that compromises the structural integrity of cartilage tissue. Conventional treatments based on medication or surgery are nowadays inefficient and cell-based therapy has emerged as one of the most promising methods for cartilage regeneration. The first therapy developed for cartilage defects was autologous chondrocyte implantation, but in the last few decades stem cells (SCs) from different sources have been proposed as a possible alternative for OA.

Areas covered: SC sources and available delivery procedures (scaffolds/hydrogels) are presented, along with the main issues arisen in this regard. Thereafter, preclinical and clinical trials performed in recent years are reviewed in order to take a glance toward the potential benefits that such therapies could deliver to the patients.

Expert opinion: SCs have proven their potential and safety for OA treatment. Nevertheless, there are still many questions to be resolved before their widespread used in clinical practice, such as the treatment mechanism, the best cell source, the most appropriate processing method, the most effective dose and delivery procedure, and their efficacy. In this sense, long-term follow-up and larger randomized controlled trials utilizing standardized and established outcome scores are mandatory to make objective conclusions.

KEYWORDS:

• Osteoarthritis
• cell therapy
• mesenchymal stem cells
• cartilage regeneration
• scaffolds/hydrogels
• growth factors

Article highlights

• Osteoarthritis (OA), a degenerative joint disease that provokes the loss of the cartilage and limits extremely the daily life of the patients, will become in the following decades a tremendous health and economic problem.

• Cartilage regeneration nowadays is still a challenge as it is one the most difficult tissues to heal due to its intrinsic characteristics and complex functional zonal structure with different cell density/morphology/organization.

• Stem cells-based therapy has emerged as a promising alternative for cartilage regeneration and OA treatment, nevertheless many efforts are still needed before clinical practice translation.

• Scaffolds/hydrogels are designed to improve the retention, viability, growth and differentiation of stem cells (SCs) and they can be loaded with bioactive molecules to enhance cartilage regeneration.

• Most of the clinical trials based on SCs therapy published in the last few years use mesenchymal stem cells as cell transplants in OA treatment.

• All clinical trials carried out to date have shown pain relief according to the different pain scales used in clinical practice and show no remarkable adverse events. Nevertheless, larger randomized controlled trials utilizing standardized outcome scores are needed.

This box summarizes key points contained in the article.

Declaration of interest

The authors wish to thank projects SAF2016-76150-R from the Spanish Ministry of Economy, Industry and Competitiveness and PRGF 3.0 ELKARTEK KK-2017/00063 from the Basque Country Government and intellectual and technical assistance from the ICTS ‘NANBIOSIS’, more specifically by the Drug Formulation Unit (U10) of the CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN) at the University of the Basque Country (UPV/EHU). We also appreciate grant support from the Basque Country Government (Grupos Consolidados, No ref: IT907-16). ADP would like to acknowledge the Danish Council for Independent Research (Technology and Production Sciences, 5054–00142B), Danish Council for Independent Research (Technology and Production Sciences, 8105–00003B), Gigtforeningen (R139-A3864) and the Villum Foundation (10103) for support. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.