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Current Therapeutic Strategies for Stem Cell-Based Cartilage Regeneration - PubMed

  • ️Mon Jan 01 2018

Review

. 2018 Mar 25:2018:8490489.

doi: 10.1155/2018/8490489. eCollection 2018.

Affiliations

Review

Current Therapeutic Strategies for Stem Cell-Based Cartilage Regeneration

Yoojun Nam et al. Stem Cells Int. 2018.

Abstract

The process of cartilage destruction in the diarthrodial joint is progressive and irreversible. This destruction is extremely difficult to manage and frustrates researchers, clinicians, and patients. Patients often take medication to control their pain. Surgery is usually performed when pain becomes uncontrollable or joint function completely fails. There is an unmet clinical need for a regenerative strategy to treat cartilage defect without surgery due to the lack of a suitable regenerative strategy. Clinicians and scientists have tried to address this using stem cells, which have a regenerative potential in various tissues. Cartilage may be an ideal target for stem cell treatment because it has a notoriously poor regenerative potential. In this review, we describe past, present, and future strategies to regenerate cartilage in patients. Specifically, this review compares a surgical regenerative technique (microfracture) and cell therapy, cell therapy with and without a scaffold, and therapy with nonaggregated and aggregated cells. We also review the chondrogenic potential of cells according to their origin, including autologous chondrocytes, mesenchymal stem cells, and induced pluripotent stem cells.

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Figures

Figure 1
Figure 1

Techniques to regenerate cartilage. Microfracture involves penetrating the osteochondral bone at a depth of 3-4 mm, with each hole separated by 3-4 mm. MSCs migrate from bone marrow to the cartilage defect. ACI involves injecting a patient with their own chondrocytes. MACI involves placing 3D scaffolds, such as those composed of hyaluronic acid or collagen types I and III, into cartilage defects together with autologous chondrocytes. Biocompatible scaffolds have also been developed. There are also scaffold-free techniques that use chondrospheres or self-assembling processes. Smaller chondrospheres are expected to improve therapeutic access via intra-articular injection.

Figure 2
Figure 2

Somatic stem cells (adult stem cells) support healing in the body, for example, replace cells and repair defects. Adult stem cells used in culture are usually obtained from fat, umbilical cord, or bone marrow. ESCs isolated from early embryos can differentiate into various cell types. iPSCs can be artificially generated by reprogramming a patient's own cells and can also differentiate into several lineages.

Figure 3
Figure 3

A simple scheme of the various methods used to differentiate iPSCs into chondrocytes.

Figure 4
Figure 4

The clinical transplantation of hiPSCs homozygous for HLA-A, HLA-B, and HLA-DR, the three types closely related to immune rejection. Theoretically, a relatively small number of homozygous stem cell lines would cover the majority of the population.

Figure 5
Figure 5

A 3D culture method for tissue engineering. Cells cultured in a 3D system have considerably improved biological properties and a higher regeneration potential than cells cultured in a 2D system. Sophisticated techniques for mass production of spheroids are also being developed. “Micropellet” 3D culture may also improve therapeutic accessibility by reducing the size of the product.

Figure 6
Figure 6

Commercialization strategy to develop safer, more efficient, and less expensive therapeutic agents for cartilage repair using iPSCs.

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References

    1. Bhosale A. M., Richardson J. B. Articular cartilage: structure, injuries and review of management. British Medical Bulletin. 2008;87(1):77–95. doi: 10.1093/bmb/ldn025. - DOI - PubMed
    1. Li M. H., Xiao R., Li J. B., Zhu Q. Regenerative approaches for cartilage repair in the treatment of osteoarthritis. Osteoarthritis and Cartilage. 2017;25(10):1577–1587. doi: 10.1016/j.joca.2017.07.004. - DOI - PubMed
    1. Pap T., Korb-Pap A. Cartilage damage in osteoarthritis and rheumatoid arthritis—two unequal siblings. Nature Reviews Rheumatology. 2015;11(10):606–615. doi: 10.1038/nrrheum.2015.95. - DOI - PubMed
    1. Makris E. A., Gomoll A. H., Malizos K. N., Hu J. C., Athanasiou K. A. Repair and tissue engineering techniques for articular cartilage. Nature Reviews Rheumatology. 2015;11(1):21–34. doi: 10.1038/nrrheum.2014.157. - DOI - PMC - PubMed
    1. Caron M. M. J., Emans P. J., Coolsen M. M. E., et al. Redifferentiation of dedifferentiated human articular chondrocytes: comparison of 2D and 3D cultures. Osteoarthritis and Cartilage. 2012;20(10):1170–1178. doi: 10.1016/j.joca.2012.06.016. - DOI - PubMed

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