An enterprising approach is being developed to address the issue of absolute donor organ shortages. A team led by Professor Hiromitsu Nakauchi of Tokyo University and Professor Hiroshi Nagashima of Meiji University has successfully “grown” a functional pancreas inside a pig. Central to this success laid two important concepts. Firstly “designer” pig embryos (fertilized eggs) were derived, which had been genetically modified so that it lacked the ability to develop a pancreas. This created a “niche” or “space” that could be occupied later. Theoretically, modifications can be designed for a number of different organs. The other important concept is the use of stem cells. Embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) have the potential to become almost any cell type in the body. It is this potential that allows it to occupy the “space” created in designer embryos. These two cell types are not yet available in pigs hence in this highlighted example characteristically similar “embryonic cells” from a normal donor pig were injected into modified pig embryos. The resulting offsprings each had a functional pancreas made up of donor cell origin. Eventually the goal is to generate transplantable human organs in a similar way by injecting patient iPSCs into designer host embryos. Professor Nakauchi’s team was the first to demonstrate these principals through generating rat pancreas and kidney in mice. Further demonstration in larger host animals represents an important advancement in applying this technique to treat patients.
Organ regeneration has been an important goal in regenerative medicine. In recent times, the possibility of generating iPSCs from patients has created a unique opportunity for more personalized treatments. Previously stem cell therapy targeted conditions such as spinal cord injuries, Parkinson’s disease or retinal degenerative diseases that may be treated by transplanting certain types of stem cells without any further complex modifications. Although ESCs and iPSCs can be manipulated to become almost any cell type, further development into functional organs requires growth conditions that are impractical to replicate out of the body.
In 2010, a team led by Professor Hiromitsu Nakauchi working on the Exploratory Research for Advanced Technology (ERATO) Nakauchi Stem Cell and Organ Regeneration Project at the Institute of Medical Science, The University of Tokyo, reported generation of rat pancreas in mouse. It was achieved by creating “designer” mouse embryos that lacked the ability to develop a functional pancreas followed by an injection of rat iPSCs. The reported generation of rat kidney by similar methods was reported soon after. However, if transplantable human organs are to be grown in this way, the same principals must first be demonstrated in larger livestock animals capable of accommodating larger organ sizes. Pancreas generation in pigs by this method represents an important step forward. The resulting offsprings survived to adulthood and the functional pancreas was found to be composed almost entirely of donor cells. If the donor cells were to be replaced by human stem cells then the resulting organ would be human in origin.
The achievement of this research brings the possibility of using human stem cells to grow functional organs inside animals closer to reality. The adult form of these designer animals may also provide sperm that can be used to produce large numbers of embryos that are incapable of forming a specific organ like the pancreas. These may then be used to grow organs for many different patients.
It is currently prohibited to inject human ESCs or iPSCs into animal embryo then transfer into a surrogate female. If this legislative barrier can be overcome then there is every confidence that human organs can be “grown” in the same way. Ultimately the aim is to address the critical issue of absolute shortages of donor organs.
Title: Blastocyst complementation generates exogenic pancreas in vivo in apancreatic cloned pigs
Authors Hitomi Matsunari, Hiroshi Nagashima, Masahito Watanabe, Kazuhiro Umeyama, Kazuaki Nakano, Masaki Nagaya, Toshihiro Kobayashi, Tomoyuki Yamaguchi, Ryo Sumazaki, Leonard A. Herzenberg and Hiromitsu Nakauchi
Proc. Natl. Acad. Sci. U.S.A.
Hiromitsu Nakauchi M.D.,Ph.D.
Professor and Director, Center for Stem Cell Biology and Medicine,
The Institute of Medical Science, The University of Tokyo
Department of Research Project
Japan Science and Technology Agency (JST)