iPS cells: a new approach to treating intractable diseases

On August 29, 2019, a research team from Osaka University in Japan used corneal tissue induced by iPS cells to restore the sight of a female patient who suffered from corneal disease. As soon as this report came out, it immediately aroused strong curiosity and expectations from the public.

Induced pluripotent stem cells (iPS cells) are artificial pluripotent stem cells, which are made by introducing pluripotency inducing factors into human skin and other somatic cells, and culturing them to differentiate into various tissues and organs of the human body and have unlimited proliferation ability. At present, it has become a new idea for treating difficult and complicated diseases.

Fossilization ossification, also known as fossilization ossification progressive (FOP), is one of the rare diseases in the world. There are no more than a thousand cases worldwide, and only 80 patients in Japan. There is no effective treatment so far.

The main symptom of this disease is the formation of excess bone tissue in the muscles. Since childhood, the patient's muscles, including the membranes, tendons, ligaments and other parts of the body, have gradually hardened and calcified. Calcification of the muscles of the limbs will lead to a narrow range of motion of the joints of the hands and feet and bending of the fingers; calcification of the spine will lead to back deformation; calcification of the oral muscles and muscles related to breathing will lead to difficulty in eating and respiratory failure, and the patient will eventually die in pain.

On November 2, 2018, the iPS cell research team at Kyoto University in Japan reported that they had used iPS cell technology to screen out several candidate drugs that may have therapeutic effects on FOP. Although it is too early to declare that humans have defeated the disease FOP, for patients struggling in pain, this research is like a ray of light shining into the darkness.

This three-year study is the world's first successful attempt to use iPS cells to screen drugs that inhibit muscle calcification. Although a large number of experiments are still needed to obtain drugs that can be truly used in clinical practice, this is a major breakthrough in the research and treatment of muscular ossification.

In addition to being used to establish drug analysis and screening models, iPS cells can also be used in the field of organ transplantation and tissue transplantation. For example, iPS cells can be used to repair cartilage defects.

Cartilage tissue is composed of chondrocytes and matrix tissue, and is present in large quantities in joints in the human body. After being severely damaged, it is difficult for cartilage tissue to repair or regenerate itself, which is likely to lead to cartilage loss and seriously affect the patient's quality of life. Currently, the main method of treating cartilage defects is to transplant the patient's own healthy cartilage tissue. However, this method is likely to cause chondrocyte degeneration and generate fibrous structures, making the transplantation effect poor.

The bone tissue transplantation research team at the iPS Cell Research Institute of Kyoto University in Japan used iPS cells from healthy people to differentiate chondrocytes, which were then further formed into cartilage tissue, and finally the tissue pieces were transplanted into the cartilage defect of the patient. The advantage of this method is that the high quality of the transplanted chondrocytes can be strictly controlled, and the patient's own tissue does not need to be used as the source. Currently, the researchers are conducting experiments on mice.

In the field of regenerative medicine, in addition to using iPS cells to treat cartilage diseases, researchers are also trying to differentiate iPS cells into cardiac tissue, pancreatic tissue, retinal tissue, etc. In simple terms, this method is to first extract iPS cells from the patient's body, differentiate iPS cells into myocardial tissue, corneal tissue, neural tissue, platelets, pancreatic islets, etc. in vitro, and then transplant these tissues to the patient's affected area to ultimately make up for or replace the defective tissue. iPS cell therapy provides a new perspective for the treatment of difficult and complicated diseases such as congenital heart disease and retinal degeneration, and related research has made significant progress.

How iPS cells differ from stem cells

The biggest difference between iPS cells and stem cells is that iPS cells are not directly derived from human organs and tissues, but are a type of stem cells that are derived through gene editing. For example, Shinya Yamanaka, a Japanese scientist who first discovered iPS cells, used a viral vector to transfer a combination of four transcription factors into differentiated somatic cells to reprogram them into induced pluripotent stem cells similar to embryonic stem cells. Other methods discovered by different scientists around the world can also produce such cells. You only need to choose the corresponding preparation method according to their type.

What are the advantages of iPS cells?

First, it is similar to embryonic stem cells, with strong differentiation and regeneration capabilities, and can differentiate into various cell types required by various organs and tissues of the human body. Second, it is a stem cell derived through genetic editing, so there are no social ethical issues in terms of its source. Finally, it can produce isogenic control cell lines through CRISPR-Cas9 gene editing. This gene editing can change DNA to achieve the goal of using cells to treat human diseases.