Advantage and Core Benefit
- A large number of chondrocytes can be induced from abundant fibroblasts and adipose-derived stem cells without time and culture costs
- The risk of tumorigenesis was reduced by using Sendai virus vector for introduction of reprogramming factors
- Combined with biocompatible substrates, development of cartilage regeneration devices is also possible
Background and Technology
The cartilage of joints is a tissue with low regenerative capacity due to the absence of blood vessels, nerves, and lymphatic vessels, which prevent the supply of new cells. For this reason, once damaged, it is difficult to heal spontaneously, and if the damage expands over time, it is said to be the cause of osteoarthritis. Although drug therapy and joint replacement surgery are used to treat articular cartilage damage and osteoarthritis, complete cartilage regeneration is difficult to achieve. In addition, autologous cartilage transplantation, in which the patient’s own normal cartilage is harvested, cultured, and transplanted into the cartilage defect, has been developed for the purpose of cartilage regeneration, but it has the problem of damaging normal cartilage tissue.
Direct reprogramming is a method of inducing chondrocytes for transplantation by gene transfer of KLF4, c-MYC, and SOX9 into fibroblasts or adipose-derived stem cells. The direct programming method has the advantages of abundant source cells, such as adipose-derived stem cells, and higher time efficiency than induction from iPS cells, but the induction efficiency of chondrocytes is low. The inventors found that the use of a modified of SOX9 improved the efficiency of chondrocyte induction. Furthermore, they established a protocol that avoids the risk of inserting programming factors into host genes by using Sendai virus vectors for gene transfer. Currently, they are in the process of inducing chondrocytes with a safer Sendai virus vector and demonstrating this in animal models while investigating combinations with grafting substrates for transplantation.
Data
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- KLF4, c-MYC, and SOX9 (wild type or mutant) were introduced into mouse embryonic-derived fibroblasts (MEFs) with retroviral vectors to check induced chondrocytes and secretion of cartilage matrix (A) expression of cartilage-related genes (B).
Patent & Publication
JPB 7265763 (Granted)
Researcher
Dr. Aya Fukuda (University of Tsukuba)
Expectations
We are interested in collaborating with companies developing cellular medicine and companies developing cartilage regenerative medicine. We are also interested in conducting joint research (in vivo) on cartilage regeneration in collaboration with companies developing biocompatible matrices or grafting substrates for regenerative medicine.
Project No. WL-04617