Srabani Roy Chowdhury, MAKAUT, WB
Cartilage is considered to be a shock absorber in joints. It is also considered to be highly susceptible to damage due to any trauma or injuries from sports or falls or just daily wear and tear. Researchers at the University of Southampton have developed a novel method to harness human cartilage tissue from stem cells. This innovative technique can pave the way for the development of a new treatment for people who has any cartilage damage.
How were the Cartilage Tissues generated?
Laboratory generation of cartilage tissue has been carried out by the researchers from the Centre for Human Development, Stem Cells, and Regeneration. They have successfully differentiated embryonic stem cells into cartilage cells which are then used to create pieces of three-dimensional cartilage tissue without the support of any synthetic or natural materials. This method is called the “scaffold-free” cartilage tissue engineering technique. The artificially created cartilage tissue is structurally and mechanically similar to the normal human cartilage. Its potential to form a stable and longer-lasting repair gives high competition to the current treatment techniques availed by the patients. Initially, constructs (approximately 1 mm in size) were created by strategies using hESC-derived chondrocytes for scaffold-free cartilage tissue engineering.
However, the exploration of the mechanical properties of these constructs was limited. The present study has successfully generated three-dimensional scaffold-free cartilage tissue constructs from hESCs. These are analogous to human hyaline cartilage having mechanical properties comparable to the human articular cartilage. With scaling up the size of the scaffold-free cartilage tissue constructs, their suitability for clinical application has been improved as well. The significant modifications that led to the development of a robust and reproducible method yielding a homogeneous population of hESC-derived chondrocytes are:
- Firstly, the protocol was initiated with a hypoxic condition of a pure population of highly pluripotent hESCs maintained at 5% O2, and the entire differentiation protocol was also performed at 5% O2 instead of 20% O2. Due to this, a substantial improvement was observed in the efficiency of chondrocyte generation from 73% at 20% O2 to 95% at 5% O2. A significant increase in expression of COL2A1 in hESC-derived chondrocytes was observed. Hypoxic conditions are seen to enhance chondrogenesis and prevent terminal differentiation through PI3K/Akt/FoxO regulated anti-apoptotic pathways. Hypoxia also regulates the expression of the key chondrogenic transcription factor SOX9.
- Secondly, the cells culture was carried out on Matrigel, instead of gelatin/fibronectin coatings, and the passaging protocol was reduced to passage on days 4 and 9 only.
- Thirdly, the potent chondrogenic growth factor TGF-β3 was added between the 9th day and 14th day of differentiation.
Conclusion:
The creation of cartilage tissue from this scaffold-free technique was carried out for the first time by these researchers. It is scaled up beyond 1 mm without causing any adverse effects to its structural and mechanical properties. However, the team hopes for regular use of the cartilage in surgery to mend damaged cartilages but only after more research is conducted. In conclusion, a robust and reproducible protocol to culture and differentiate hESCs into hyaline cartilage has been developed by the researchers. They also scaled up the size of the 3D, scaffold-free cartilage tissue constructs.
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Reference:
Griffith, L. A., Arnold, K. M., Sengers, B. G., Tare, R. S., & Houghton, F. D. (2021). A scaffold-free approach to cartilage tissue generation using human embryonic stem cells. Scientific Reports, 11(1), 18921. https://doi.org/10.1038/s41598-021-97934-9
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