A Comprehensive Review of Stem Cells for Cartilage Regeneration in Osteoarthritis
Osteoarthritis (OA) is an age related joint disease associated with degeneration and loss of articular cartilage. Consequently, OA patients suffer from chronic joint pain and disability. Weight bearing joints and joints that undergo repetitive stress and excessive ‘wear and tear’ are particularly prone to developing OA. Cartilage has a poor regenerative capacity and current pharmacological agents only provide symptomatic pain relief. OA patients that respond poorly to conventional therapies are ultimately treated with surgical procedures to promote cartilage repair by implantation of artificial joint structures (arthroplasty) or total joint replacement (TJR). In the last two decades, stem cells derived from various tissues with varying differentiation and tissue regeneration potential have been used for the treatment of OA either alone or in combination with natural or synthetic scaffolds to aid cartilage repair. Although stem cells can be differentiated into chondrocytes in vitro or aid cartilage regeneration in vivo, their potential for OA management remains limited as cartilage regenerated by stem cells fails to fully recapitulate the structural and biomechanical properties of the native tissue. Efficient tissue regeneration remains elusive despite the simple design of cartilage, which unlike most other tissues is avascular and aneural, consisting of a single cell type. In this article, we have comprehensively reviewed the types of stem cells that have been proposed or tested for the management of OA, their potential efficacy as well as their limitations. We also touch on the role of biomaterials in cartilage tissue engineering and examine the prospects for their use in cell-based therapies.
KeywordsChondrocytes In vitro In vivo Osteoarthritis Regenerative medicine Stem cells
Autologous chondrocyte implantation
Autologous chondrocyte transplantation
Bone marrow aspirate concentrate
Bone morphogenetic protein
Cluster of Differentiation
Embryonic stem cells
Food and drug administration
Haematopoietic stem cells
Induced pluripotent stem cells
International Society for Cellular Therapy
Mesenchymal stem cells
Nonsteroidal anti-inflammatory drug
Platelet rich plasma
Serotonin-norepinephrine reuptake inhibitors
Transforming growth factor beta
Total knee arthroplasty
The authors acknowledge the financial support provided by the “Sheikh Salem Bin Mahfouz Scientific Chair for Treatment of Osteoarthritis by Stem Cells” and the stem cell laboratory facility at CEGMR and King Abdulaziz University Hospital.
Conflicts of Interest
The authors declare no conflict of interests.
Competing Interests and Disclosures
The authors declare no competing interests.
G. Kalamegam and A. Memic were involved in intellectual contribution and manuscript writing. MA and EB were involved in intellectual contribution and editing of the manuscript. A. Mobasheri contributed to the synthesis and editing of the manuscript.
- Fong C-Y, Subramanian A, Gauthaman K, Venugopal J, Biswas A, Ramakrishna S, Bongso A (2012) Human umbilical cord Wharton’s jelly stem cells undergo enhanced chondrogenic differentiation when grown on nanofibrous scaffolds and in a sequential two-stage culture medium environment. Stem Cell Rev Rep 8:195–209CrossRefGoogle Scholar
- Foyt DA, Norman MDA, Yu TTL, Gentleman E (2018) Exploiting advanced hydrogel technologies to address key challenges in regenerative medicine. Adv Healthc Mater. https://doi.org/10.1002/adhm.201700939
- Gooding C, Bartlett W, Bentley G, Skinner J, Carrington R, Flanagan A (2006) A prospective, ranomised study comparing two techniques of autologous chondrocyte implantation for osteochondral defects in the knee: periosteum covered versus type I/III collagen covered. Knee 13:203–210CrossRefGoogle Scholar
- Huang W-N, Tso TK (2018) Etoricoxib improves osteoarthritis pain relief, joint function, and quality of life in the extreme elderly. Bosn J Basic Med Sci 18:87–94.Google Scholar
- Lee M et al (2017) A randomized, multicenter, phase III trial to evaluate the efficacy and safety of polmacoxib compared with celecoxib and placebo for patients with osteoarthritis clinics in orthopedic surgery 9:439–457Google Scholar
- Mathis DT, Kaelin R, Rasch H, Arnold MP, Hirschmann MT (2017) Good clinical results but moderate osseointegration and defect filling of a cell-free multi-layered nano-composite scaffold for treatment of osteochondral lesions of the knee. Knee Surg Sports Traumatol Arthrosc 26(4):1273–1280. https://doi.org/10.1007/s00167-017-4638-zCrossRefPubMedGoogle Scholar
- Mistry H et al (2017) Autologous chondrocyte implantation in the knee: systematic review and economic evaluation. National Institute for Health Research, SouthamptonGoogle Scholar
- Murphy C, Mobasheri A, Tancos Z, Kobolak J, Dinnyes A (2017) The Potency of induced pluripotent stem cells in cartilage regeneration and osteoarthritis treatment. In: Advances in experimental medicine and biology. Springer, Boston, pp 1–14. https://doi.org/10.1007/5584_2017_141
- Patrascu JM, Freymann U, Kaps C, Poenaru DV (2010) Repair of a post-traumatic cartilage defect with a cell-free polymer-based cartilage implant: a follow-up at two years by MRI and histological review. J Bone Joint Surg (Br) 92:1160–1163. https://doi.org/10.1302/0301-620X.92B8.24341CrossRefGoogle Scholar
- Patrascu JM et al (2013) Polyglycolic acid-hyaluronan scaffolds loaded with bone marrow-derived mesenchymal stem cells show chondrogenic differentiation in vitro and cartilage repair in the rabbit model. J Biomed Mater Res B Appl Biomater 101:1310–1320. https://doi.org/10.1002/jbm.b.32944CrossRefPubMedGoogle Scholar
- Suchorska WM, Augustyniak E, Richter M, Łukjanow M, Filas V, Kaczmarczyk J, Trzeciak T (2017) Modified methods for efficiently differentiating human embryonic stem cells into chondrocyte-like cells. Adv Hyg Exp Med/Postepy Higieny i Medycyny Doswiadczalnej 71:500–509Google Scholar