「It started with a friend’s spinal cord injury.」
J-ARM（below J）：Dr. Kishigami is a pioneer in the field of veterinary regenerative medicine who has been a pioneer in promoting regenerative therapy in the veterinary community. Thank you very much for your cooperation.
Dr. Kishigami (hereinafter Kishigami)：Thank you for your time.
J：After graduating from Azabu University, you spent two years in the neurosurgery lab at the University of California, Davis. Did you do any research on regenerative medicine there?
Kishigami：At the time, I was not yet aware of such things. We were doing neurosurgery, so we were using canines to model spinal cord injury. As part of experiments on spinal cord neurotransmission, I was studying the electrophysiological progression of paralysis when a harpoon was dropped on the spinal cord and in what way. I then returned to Japan and after several years of training, I went to Osaka for clinical practice. Then I went to the Institute for Frontier Medical Sciences at Kyoto University. This is where I first encountered regenerative medicine.
It all started when a junior colleague of mine had a motorcycle accident that damaged his cervical spinal cord and paralyzed his limbs. He was bedridden, sitting on his bed with chopsticks in his mouth, typing on his computer. When I saw the horrific scene, I thought, “This is a disaster. I thought, “We have to regenerate the spinal cord. That was one of the reasons I attended the neurological society for human medicine. I went to the reception afterwards and asked around to see if there were any places that were doing spinal cord regeneration. Almost no one was doing it, but there was one place that was willing to do research, and that was Kyoto University.
I didn’t know anything at the time, but I was afraid to put my idea to Dr. Yoshihiko Shimizu and Dr. Tatsuo Nakamura, who are regarded as great authorities in the Institute for Regeneration Research at Kyoto University. I look back on it with a shudder (laughs). I asked if it would be possible to cut the nerve in a dog’s tail and transplant it into the affected area. The doctor snickered at me. He said, “Kishigami, at least for a newborn, but for an adult, even if you cut a fresh spinal cord and keep it together, you can’t connect it. The spinal cord is that difficult. That made me cringe. But I said, “I want to do research,” and they let me in. I stayed at Kyoto University for about seven years. During that time, I was making models of spinal cord injury and developing treatment methods. Nowadays, though, it is not possible to conduct experiments on dogs.
J：Were you the only veterinarian in the research environment at Kyoto University?
Kishigami：Yes, I was. At first I was like a handyman because I could perform surgeries and handle animals, but as I came up with various ideas on my own, both Dr. Shimizu and Dr. Nakamura recognized me as an interesting guy. During my tenure, I received a grant award from the Society for Prosthetic Organ Research in the orthopedic division, and gradually gained the recognition of those around me.
I finally quit Kyoto University because I realized that in the field of human medicine, I could not do anything because I could not get permission from the Ministry of Health, Labor and Welfare to do any research, even if I had tried. There were experiments that I wanted to do, but there was a tendency that such experiments would not be allowed in actual clinical practice in the human medical field. Even if they succeeded in their experiments and produced data, they would not be allowed to use stem cells in human medicine. It was uninteresting because all the people said it would be impossible to realize it. I thought that if that was the case, research would make more progress in the veterinary field, i.e., at my own hospital, so I devoted myself to research at the hospital.
J：At that time, you had expertise in bone marrow stem cell culture, didn’t you?
Kishigami：That’s right. At first, I bought a small clean bench in one of my hospital rooms and cobbled together a culture. One day, I hit a dead end due to contamination (contamination: bacterial contamination of the culture medium). At that time, I met Dr. Okada (current president of J-ARM) at the Society of Tissue Engineering. That was the beginning of immuno-cell therapy as well.
「There is a response that recurrence is being controlled. However, the number of cases is still needed.」
J：You mentioned immuno-cell therapy. How is the response to activated lymphocyte therapy at your hospital?
Kishigami：Overall, the response to QOL has been good and satisfactory, but I can’t say yet what type of cancer responds well to it. We still need to see more cases because we can’t express its effectiveness in objective terms, such as numbers. In terms of progression, I feel that there is nothing that can be done for cases that are in the terminal stage or have advanced stages, or have grown to a bumpy size. However, I strongly feel that we are preventing recurrence and metastasis. However, as long as I am in clinical practice, it is difficult to put a figure on it. My stance when treating cancer is that surgical resection is the first step, followed by the use of activated lymphocyte therapy as an adjuvant therapy.
There was a dog who had a lot of cancer in his liver. When he came to the hospital, it had metastasized to the spinal cord, and because of that, his hind legs were limping and he could no longer walk. After 3 or 4 doses, the family stopped coming to see me. I thought it was hopeless, but a year later, the child came to my hospital. She was fine and walking. I was surprised. I asked for a CT scan, but was told that her recovery was already good enough (laughs). (Laughs.) It is a wonder that he is still alive, but he was standing up and walking around fine. In my experience, if the cancer has metastasized that far and reached the bone, the tumor cells would have flowed into the bloodstream in a fountain.
J：Recently, some doctors are utilizing immuno-cell therapy in combination with various treatments including chemotherapy. Do you use immuno-cell therapy in combination with anticancer agents?
Kishigami：Basically, I don’t use anticancer drugs. Sometimes I have no choice but to use them in the case of lymphoma, but even if I do, I generally don’t use 99 out of 100. A survey was conducted on two doctors. The question was, “If you had cancer, would you use anti-cancer drugs? Ninety percent of the doctors answered that they would not use anticancer drugs for themselves.
As for cellular immunotherapy, I think it is troubling that there is no objective indicator that it has worked, so it is not clear whether it is working or not. However, there is a response that recurrence is under control. When I talk about this kind of thing out loud, I am sure to be told that the disease would not have recurred even if I had not done it, so I try not to say too much.