Chapters authored
A Novel Strategy for Xeno-Regenerative Therapy
The shortage of organs for transplantation is of critical importance worldwide. Xenotransplantation or xeno-embryonic organ transplantation can stably supply organs and is considered to be an established alternative treatment. Regenerative medicine is another option, and recent advances in stem cell research have enabled the reproduction of miniature organs, called organoids, derived in vitro from human induced pluripotent stem cells. However, the in vitro production of large and complex organs that can efficiently function in vivo is not yet accomplished. We proposed a novel strategy for xenotransplantation in which a chimeric kidney is constructed by injecting human nephron progenitor cells into a porcine embryonic kidney, thereby eliminating pig nephron progenitor cells and allowing transplantation into a human and long-term survival. In this chapter, we discussed advantages and pitfalls of xenotransplantation and xeno-embryonic kidney transplantation. Recent attempts of human organoids and blastocyst complementation were reviewed. Finally, we proposed our novel xeno-regenerative therapeutic strategy.
Part of the book: Xenotransplantation
Controllable Immunosuppression in Pigs as a Basis for Preclinical Studies on Human Cell Therapy
Along with a growing interest in regenerative medicine, pigs are becoming a popular model for preclinical studies on human cell therapy. Due to pharmaceutical species difference and inability to self-medicate, specific modification and care are necessary in immunosuppressive regimen for pigs. Here, we summarize recent literature on immunosuppression in pigs for experimental transplantation. Based on literature and our own experiences, a practical protocol has been proposed in this report. In early studies of allogeneic organ transplantation, recipient pigs were administered cyclosporine or tacrolimus, and mycophenolate mofetil at slightly higher dose than that in human cases, because of relatively poor effectiveness of the drugs in pigs. Steroids may be effective but sometimes can cause debilitating side effects. Cell transplantation studies follow the basic protocol, but it remains to be clarified whether the smaller graft mass, even if it is xenogeneic, requires the same scale of immunosuppression as organ transplantation. To obtain reliable results, the use of gastrostomy tube and blood trough level monitoring are highly recommended. Nonpharmaceutical immunosuppression such as thymic intervention and the use of severe combined immunodeficient pigs have also been discussed.
Part of the book: Xenotransplantation
Pigs as Models of Preclinical Studies and In Vivo Bioreactors for Generation of Human Organs
Pigs are valuable and essential large animal models for human medical applications, including for stem cell therapy. Moreover, substantial effort has been made to directly engraft genetically engineered pig organs in the human body and to use pigs as in vivo bioreactors for the growth and development of human cells, tissue, or organs. However, engraftment of human cells in pigs has not yet been achieved. Although severe combined immunodeficient pigs have been developed, which can accept human biological materials, these pigs do not have practical value at present owing to difficulty in their care. To overcome these current limitations, we have proposed the generation of operational immunodeficient pig models by simply removing the thymus and spleen, enabling the long-term accommodation of human tissue. In this review, we summarize research progress on xenotransplantation animal models that accept human cells, tissues, or organs.
Part of the book: Xenotransplantation