After a kidney transplant, the drugs don’t stop
Organ transplants do save lives, but at the same time as undergoing surgery, the recipient is put under the same straitjacket that tamed Son Gokū: “Lifelong immunosuppressant therapy.”.
The human body will reject the“New stranger” spontaneously, like strangers, and it is difficult to be like brothers at first sight. The relationship between the human body and the kidney transplant must begin with getting to know each other and adapting to each other, all unpleasant adaptations and minor discomforts during this period are rejections.
Nobody likes to take medicine.
Take medicine this matter, one to increase the economic burden, according to statistics, the global annual related medical expenses as high as zero million. The second is more troubling and frightening than the economic pressures-“Side effects of immunosuppressants”. Long-term use of immunosuppressants can lead to a general decrease in the body’s immunity after kidney transplantation, which may lead to a series of serious complications such as infections, cardiovascular diseases, diabetes, malignant tumors and drug toxicity, this affects the patient and the long-term survival of the transplanted organ.
Therefore, how to ensure the health and safety of post-transplant patients under the premise of making the transplanted organs can get along with the body, the professional term is“Organ transplant immune tolerance”, it has always been a common dream of doctors and patients in the field of transplantation to free organ transplant patients from the“Straitjacket” of lifelong use of immunosuppressants, and it is also one of the difficult problems that the international organ transplantation field has been striving to overcome.
To ensure a safe and peaceful living environment for transplanted organs
By“Organ transplant tolerance,” we mean that, without the use of immunosuppressants, the organ transplant recipient’s immune system can tell friend from foe, such as never attacking the new organ, but when there is an invasion can be immediately confronted, killing all threats to health and instability.
At present, the strategies of immune tolerance induction mainly include:
(1) induction of central immune tolerance by clonal clearance of T cells in thymus and B cells in bone marrow;
(2) to induce immune anergy of T and B cells, inhibit their proliferation or function, and induce peripheral immune tolerance by blocking costimulatory signaling pathway, infusion or induction of regulatory immune cell generation. Since the induction of immune tolerance in organ transplantation involves the complex process of immune system remodeling and immunomodulation maintenance, relevant theoretical and clinical studies are still needed to develop safe and effective induction strategies.
Exciting News: the dawn of clinical immune tolerance
In recent years, more than 10 cases of Hematopoietic stem cell infusion combined with kidney transplantation were studied in the department of Kidney Transplantation of Massachusetts General Hospital, Stanford University, Northwestern University and Sun Yat-sen hospital affiliated to Fudan University.
In this protocol, the recipient of a kidney transplant is first pre-irradiated with total lymph node radiation and is infused with the donor’s Hematopoietic stem cell. These clinical studies have achieved varying degrees of success. Some patients have completely stopped using immunosuppressants. While the cost of treatment has been greatly reduced, the quality of life has also been significantly improved.
The study found long-term“Donor-recipient chimeras” in the peripheral blood and bone marrow of kidney transplant recipients, with the recipients showing Hapten or low responses to the donor organs. In layman’s terms, this involves injecting the recipient with the donor’s Hematopoietic stem cell and“Engineering” the recipient’s immune system so that it no longer sees the organ as a“Foreign object.”, no longer“Attack” it, and eventually make the transplant recipient off of immunosuppressant.
According to the Department of Kidney Transplantation, Zhongshan hospital, fudan university, “Donor Hematopoietic stem cell infusion” may be a major breakthrough in the induction of immune tolerance in clinical kidney transplantation.
Possible mechanism of immune tolerance: remodeling of the recipient’s lymphatic system by Hematopoietic stem cell
The possible mechanism of immune tolerance is that the donor’s Hematopoietic stem cell is infused into the recipient so that it can develop, differentiate and evolve in the recipient. Mutual education changes the pattern of the recipient’s immune system response, eventually Hapten tolerance.
Specific mechanisms include:
1. T and B cell precursors from donor and recipient Hematopoietic stem cell induce tolerance in central immune organs such as bone marrow and thymus by immunorecognition, clonal selection and elimination, and formation of cell-in-cell structure
Hematopoietic stem cell mature T and B cells from donor and recipient migrate from central immune organs to peripheral lymphoid tissues, inducing regulatory immune cells to form a chimeric state and achieving peripheral immune tolerance
The donor Hematopoietic stem cell or the donor-educated recipient Hematopoietic stem cell directly exert local immunosuppression by secreting inhibitory cytokines or microvesicles to promote peripheral immune tolerance.
Hope for the future: the promotion of Hematopoietic stem cell induced immune tolerance
The clinical research of the Kidney Transplantation Department of Zhongshan Hospital affiliated to Fudan University has achieved an important breakthrough in the induction of immune tolerance in some kidney transplant patients, but the overall success rate has not yet reached our expected goal, there is still a lot of room for improvement to improve the success rate of immune tolerance induction through optimization schemes.
We believe that with the promotion of Hematopoietic stem cell immune tolerance, the rapid application of the new method in the clinic will bring a better future to kidney transplant patients.
Article | Zhu Tongyu, photography |
Elliott C.Mei、Grace
Brief introduction of famous doctors
Zhu Tongyu
He graduated from Qingdao Medical College in 1989 and graduated from Graduate School of Fudan University Shanghai Medical College in 1994 with a doctor’s degree in surgery. From 1999 to 2000, he worked as a postdoctoral researcher at the University of Hong Kong School of Medicine.
He has published more than one hundred and fifty academic papers, including more than 40 SCI papers, and participated in the compilation of more than 10 academic monographs. Shanghai leading talent, Shanghai Outstanding Principal Investigator, Shanghai Health System New 100-person plan.
We performed the first living related kidney transplantation for a child with Denys-Drash syndrome in China, the difficult fourth kidney transplantation and the first sequential heart-liver-kidney Multi-organ transplantation in Asia, it has been reported by many media such as CCTV science and Technology Light and Xinhua News Agency.
He is currently the Vice President of Zhongshan Hospital of Fudan University, the executive president of Xiamen Hospital of Zhongshan Hospital of Fudan University, the president of Qingpu District Branch of Zhongshan Hospital of Fudan University, and the professor, chief physician and doctoral supervisor of the Department of Urology of Zhongshan Hospital of Fudan University.
He is currently in charge of the national key clinical specialty of organ transplantation, member of the organ transplantation branch of the Chinese Medical Association and vice-chairman of the Kidney Transplantation Group, vice-chairman of the kidney transplantation group of the organ transplantation physicians branch of the Chinese Medical Association, vice-chairman of the organ transplantation branch of the Shanghai Medical Association, Director of the Shanghai Key Laboratory of organ transplantation, and vice-director of the Fudan University organ transplantation center.
As The editorial board member of The International Journal of Clinical Pratiace and more than 10 other domestic and foreign academic journals, he has undertaken more than 10 scientific research projects under the National Natural Science Foundation of China, the 11th five-year plan for tackling key scientific and technological problems, and major key projects in Shanghai. He has maintained good communication and cooperation with well-known international organ transplantation centers, and has been invited to speak or co-chair international academic conferences for more than 10 times.
Healing is my life’s work
Relieving pain and innovating medical knowledge
Training medical talents is the pursuit of a lifetime
