Cartilage regeneration cell therapy in ACI and MACI enhanced by hyaluronic acid enriched tissue engineered chondrocytes by Japanese Orthopedicians

·5-min read

The Edogawa Evolutionary Laboratory of Science (EELS) based in Tokyo, Japan headed by Dr. Shojiro Katoh, an orthopedic surgeon have developed a technology called EELS-TALC (Enriched with Essentials and Lapped in Scaffold Transplant-suitable Autologous Leveraged Chondrocytes) which is a novel human chondrocyte tissue engineering method in which the cells are grown employing a specialized tissue-culture platform for use in clinical therapies such as Autologous Chondrocyte Implantation (ACI) and Matrix Associated Chondrocyte Implantation (MACI) for treating cartilage damages. The major advantage of their technology isproduction of chondrocytes enriched with hyaluronic acid (HA) in the lab without addition of HA from external sources, which according to the authors is the first of its kind in the world, published in the journal,“The KNEE” (https://doi.org/10.1016/j.knee.2021.02.019).

Osteoarthritis (OA) or joint problems is a highly prevalent disease with every third person affected and with the average life span increasing, nearly 150 million people around the world are expected to be affected by this debilitating diseasein the near future.

The knee joint is the most commonly affected joint with OA. In OA, the cartilage which cushions the space in the knee joint gets damaged due to wear and tear and loses its cushioning effect making the bones rubbing against one another causing inflammation of the joint, bone damage and pain causing difficult to stand up and walk. OA becomes severe with advancing age, affecting a person’s mobility to a great extent andaffects the quality of life significantly also making the victim semi or fully dependent. While OA is common in elderly and obese individuals, younger age group people develop cartilage damage due to sports injuries and trauma to the cartilage due to road traffic accidents and fall.

While pain relivers work to a certain extent, joint replacement is the most common approach used by orthopedic surgeons who use artificial prosthesis in place of the affected cartilage. However, these artificial prostheseshave their own limitations. Advancements in surgical treatment procedures gave rise to arthroplasty in which the knee joint is reshaped to withstand the stress better or microscopic fracture wherein the bone underlying the cartilage in the joint is drilled to attract stem cells from the blood to the area of damage to induce healing. However, these procedures also have been relatively unsuccessful with the cartilage formed after the procedure being a fibrocartilage while another type of cartilage called hyaline cartilage is the native cartilage which is found in knee joint that can withstand the wear and tear of the joint better.

To overcome these hurdles,Autologous chondrocyte implantation (ACI) treatment is performed in which a portion of the cartilage from the non-weight bearing portion of the knee joint is obtained, cells of cartilage called chondrocytes areisolated and transplanted with or without further culture in the lab into the affected portion, which has become an accepted clinicaltreatmentfor knee OA. In this procedure too, the disadvantage of fibrocartilage formation both during culture andin vivo remains a bottle neck. Adding a matrix to ACI, the Matrix Associated Cartilage Implantation (MACI) in which a scaffold is used during the culture and transplantation, provides a three-dimensional environment to the chondrocytes similar to what exists in the native knee joint in the human body and the proper cues and signals for better regeneration of the cartilage. Several natural scaffolds like collagen, fibrin etc and synthetic scaffolds are used for MACI. Natural scaffolds have the problem of biological contamination and immune rejection while many synthetic scaffolds are not very bio-compatible.

The EELS-TALC is a unique scaffold-based technology which uses a novel synthetic polymer that has the following advantages in terms of knee cartilage repair and regeneration, says Dr. Katoh in his press statement, • EELS-TALC specifically promotes hyaline chondrocyte formation in culture with tissue-like morphology, preventing fibrocartilage de-differentiation without use of feeder layers or growth factors in the lab (Ref: https://doi.org/10.1089/ten.2006.12.1237/http://www.jortho.org/2011/8/3/e3/e3.htm) • The hyaline phenotype of the chondrocytes are maintained for a longer time in vitro and in vivo, proven by clinical transplantation (Ref: https://doi.org/10.1016/j.jor.2017.01.003) • This technology helps even chondrocytes obtained from severely inflamed and damaged OA tissue from knee joints of elderly patients over 65 years which are otherwise thrown away as biomedical waste, to be grown into hyaline cartilage tissue-construct (Ref: https://doi.org/10.1016/j.reth.2020.03.006).

• Such cartilage tissue, engineered in the lab using the EELS TALC has been found to be positive for the presence of pluripotent stem cells which will have enhanced regenerative potential, when used for human clinical studies (https://doi.org/10.1016/j.reth.2020.03.006) • Apart from pluripotent stem cells and mature chondrocytes, the lab grown tissue- construct has been shown to contain in it, chondroprogenitors and mesenchymal stem cells which will contribute to optimal regeneration (https://doi.org/10.1016/j.jor.2021.01.005).

• HA is essential for homoeostasis and development of the cartilage. For OA, HA is delivered as injection into the knee joint as therapy or HA containing scaffolds are used to culture the cartilage cells. However, EELS-TALC without artificial addition of HA, has been demonstrated to help the chondrocytes grown in it to secrete more HA which will help the neighboring cells as well in a paracrine manner to grow in unison to form a tissue in vitro and the scaffold has also been shown to retain the secreted HA (https://doi.org/10.1016/j.knee.2021.02.019) , thus providing a valuable culture and transplantation methodology to treat cartilage diseases and disorders.

Presently, Dr. Katoh’s team at Edogawa Hospital with the researchers of EELS, JBM and GN Corporation, Japan are working towards studying the technology’s capabilities in terms of promotingmicroRNA (miRNA) 140 (an important factor associated with cartilage formation and maintenance)apart from studying the anti-aging related potentials of the platform to enable healthy cartilage regeneration even in aged patients.

The EELS-TALC technology when applied for ACI and MACI will help in regenerating cartilage in an ideal manner and GN Corporation and JBM Inc is looking forward to potential collaborations and partnerships with stakeholders, institutes and organizations worldwide to promote this one of its kind technologiesto address the locomotion disabilities of millions of victims due to cartilage damage, globally.

PWR PWR