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Identifying an Optimal Meniscus‐derived Stem Cell Population for Regenerative Approaches

Review of “Characterization and comparison of post-natal rat meniscus stem cells at different developmental stages” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Injury to or removal of the meniscus, the cartilage that cushions the contact between the femur and tibia, can lead to the accelerated onset of long‐term degenerative joint changes, such as osteoarthritis, thereby highlighting the need for new therapies that preserve or repair the damaged meniscus [1]. Mesenchymal stem cells have been posited by many as a possible treatment option, although most sources associate with donor site morbidity and ectopic bone formation.

Researchers led by Weishan Chen and Weiliang Shen (Zhejiang University School of Medicine, Zhejiang Province, China) proposed the application of meniscus‐derived MSCs (MeSCs) [2, 3] to delay or reduce the progression of osteoarthritis induced by the loss of the meniscus [2-4]. However, studies have suggested that MeSCs derived from different developmental stages or different tissue regions may possess a varying stem-like potential; therefore, the team's new STEM CELLS Translational Medicinestudy sought to define an optimal population of rat meniscus tendon tissue-derived MeSCs for use in meniscus repair and osteoarthritis suppression [5].

He et al. characterized and compared postnatal rat meniscus tissue and MeSCs derived from different tissue regions and stages of development, finding that rat meniscus tissue exhibited evident changes to tissue morphology during development according to hematoxylin and eosin staining, polarized light microscopy, and collagen II immunohistochemical evaluation of rat meniscal tissues. These assessments highlighted day-seven as the most representative time point when compared to day-one or week-eight. Rat MeSCs derived from inner meniscus tissue at d-seven expressed markers for mesenchymal stem cells (CD29, CD44, CD90, and CD105) and displayed the highest self‐renewal capacity, cell proliferation, differentiation potential toward various mesenchymal lineage (with a preference towards chondrogenic differentiation), and expression of chondrogenic genes (e.g., Col I, Sox9, Mkx, and Scx) and proteins (e.g., Col II and Sox9).

Excitingly, the final part of this new study assessed the intra‐articular transplantation of day-seven rat MeSCs as a means to repair meniscal tissue in an experimental osteoarthritis rat model, finding that this approach led to neo‐tissue formation and more effective protection of the joint surface cartilage, thereby suggesting that this approach may serve to inhibit osteoarthritis progression.

While these intriguing data indicate MeSCs derived from seven-day inner meniscus tissue as a promising cell source for meniscus regeneration and osteoarthritis prevention, the authors do note some limitations to their study. To remedy these limitations, the team aim to further optimize and explore the optimal MeSCs more accurately and to widen their characterization and in vivo evaluations to human MeSCs at different stages and tissue regions.

For more on the identification of an optimal meniscus‐derived stem cell population for regenerative approaches, stay tuned to the Stem Cells Portal.

References

  1. Thorlund JB, Juhl CB, Ingelsrud LH, et al., Risk factors, diagnosis and non-surgical treatment for meniscal tears: evidence and recommendations: a statement paper commissioned by the Danish Society of Sports Physical Therapy (DSSF). British Journal of Sports Medicine 2018;52:557.
  2. Shen W, Chen J, Zhu T, et al., Intra-Articular Injection of Human Meniscus Stem/Progenitor Cells Promotes Meniscus Regeneration and Ameliorates Osteoarthritis Through Stromal Cell-Derived Factor-1/CXCR4-Mediated Homing. STEM CELLS Translational Medicine 2014;3:387-394.
  3. Shen W, Chen J, Zhu T, et al., Osteoarthritis Prevention Through Meniscal Regeneration Induced by Intra-Articular Injection of Meniscus Stem Cells. Stem Cells and Development 2013;22:2071-2082.
  4. Gui J, Zhang J, and Huang H, Isolation and characterization of meniscus derived stem cells from rabbit as a possible treatment for damaged meniscus. Current Stem Cell Research and Therapy 2015;10:353-63.
  5. He S, Ruan D, Chen Y, et al., Characterization and Comparison of Postnatal Rat Meniscus Stem Cells at Different Developmental Stages. STEM CELLS Translational Medicine 2019;8:1318-1329.