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MSC-mediated Cartilage Repair Moves a Step Closer to the Clinic

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Review of “Cartilage Repair Using Composites of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Hyaluronic Acid Hydrogel in a Minipig Model” from Stem Cells Translational Medicine by Stuart P. Atkinson.

While to some, the stiffening of the joints is merely a reminder of the passing of time, cartilage injury and disease can severely impair quality of life of many patients. Mesenchymal stem cell (MSC)-based strategies hold great promise for the treatment of cartilage injury and osteoarthritis and MSCs derived from human umbilical cord blood (hUCB-MSCs) seeded within a hyaluronic acid (HA) hydrogel composite have shown excellent results in small animal models [1, 2]. Now, in a new study from Stem Cells Translational Medicine, researchers have taken a further step towards MSC-based cartilage repair in humans, following the effective demonstration of this treatment modality in a more relevant large animal model [3].

The experimental scheme comprised the creation of 10-millimeter cartilage injuries in both knees of 6 minipigs followed three weeks later by the removal of fibrous scar tissue and the creation of bone defects of around 10 millimeters in depth in the middle of the cartilage injury area. The authors then placed the hUCB-MSC/HA hydrogel composite onto the injured area on one knee only, while the other knee remained untreated. After 12 weeks of normal farm life, an examination of the knees took place following sacrifice.

Macroscopically, the treated knees had a smoother articular surface with a less distinct defect borderline and they presented with a greater amount of cartilage formation in the treated knee. Microscopically, the treated knees presented with a higher cartilage regeneration, and cells resembled normal chondrocytes. Immunohistochemical staining for type II collagen indicated that the untreated knees did not regenerate articular joint cartilage (hyaline), but the treated knees presented with extensive and even collagen staining (See figure).

This study should provide a basis for the further study of differentiation, paracrine action, and immunomodulation following hUCB-MSC transplantation and the successful production of cartilage in this pre-clinical model. This extends the successful studies in small animal models and should allow this treatment modality to move closer to human patient trials.

References

  1. Park YB, Song M, Lee CH, et al. Cartilage repair by human umbilical cord blood-derived mesenchymal stem cells with different hydrogels in a rat model. J Orthop Res 2015;
  2. Chung JY, Song M, Ha CW, et al. Comparison of articular cartilage repair with different hydrogel-human umbilical cord blood-derived mesenchymal stem cell composites in a rat model. Stem Cell Res Ther 2014;5:39.
  3. Ha CW, Park YB, Chung JY, et al. Cartilage Repair Using Composites of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Hyaluronic Acid Hydrogel in a Minipig Model. Stem Cells Transl Med 2015;4:1044-1051.