Compensation of Disabled Organogeneses in Genetically Modified Pig Fetuses by Blastocyst Complementation

Matsunari, Hitomi; Watanabe, Masaru; Hasegawa, Koki; Uchikura, Ayuko; Nakano, K.; Umeyama, Kazuhiro; Hara, Masaki; Hamanaka, Sanae; Yamaguchi, Tomoyuki; Nagaya, Masaki; Nishinakamura, Ryuichi; Nakauchi, Hiromitsu; Nagashima, Hiroshi

doi:10.1016/j.stemcr.2019.11.008

Cited by 51 publications

(51 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Following injection of mouse iPS cells into the blastocysts of Sall1‐null mice, which lack both kidneys, most of the metanephroi consisted of iPS cell–derived differentiated cells. Similar results were reported in the interspecies condition in rodents 13 as well as in the allo‐condition in bigger animals such as pig 14 . However, these embryos die soon after birth for unknown reasons.…”

Section: Regenerative Medicine For Solid Organssupporting

confidence: 84%

Xeno‐regenerative medicine: A novel concept for donor kidney fabrication

Yokoo

Yamanaka

Kobayashi

2020

Xenotransplantation

View full text Add to dashboard Cite

show abstract

Section: Regenerative Medicine For Solid Organssupporting

confidence: 84%

Xeno‐regenerative medicine: A novel concept for donor kidney fabrication

Yokoo

Yamanaka

Kobayashi

2020

Xenotransplantation

View full text Add to dashboard Cite

show abstract

“…Using this methodology, the entire pancreas of a rat was grown in a mouse [ 145 ], kidney in rodents [ 146 ], and pancreas in pigs [ 147 ]. More recently, pancreas, kidney and the liver were produced in pigs using this approach [ 148 ].…”

Section: Potential Uses For Marmoset Escs In Liver Regeneration Anmentioning

confidence: 99%

Utility of Common Marmoset (Callithrix jacchus) Embryonic Stem Cells in Liver Disease Modeling, Tissue Engineering and Drug Metabolism

Aravalli

Steer

2020

Genes

View full text Add to dashboard Cite

The incidence of liver disease is increasing significantly worldwide and, as a result, there is a pressing need to develop new technologies and applications for end-stage liver diseases. For many of them, orthotopic liver transplantation is the only viable therapeutic option. Stem cells that are capable of differentiating into all liver cell types and could closely mimic human liver disease are extremely valuable for disease modeling, tissue regeneration and repair, and for drug metabolism studies to develop novel therapeutic treatments. Despite the extensive research efforts, positive results from rodent models have not translated meaningfully into realistic preclinical models and therapies. The common marmoset Callithrix jacchus has emerged as a viable non-human primate model to study various human diseases because of its distinct features and close physiologic, genetic and metabolic similarities to humans. C. jacchus embryonic stem cells (cjESC) and recently generated cjESC-derived hepatocyte-like cells (cjESC-HLCs) could fill the gaps in disease modeling, liver regeneration and metabolic studies. They are extremely useful for cell therapy to regenerate and repair damaged liver tissues in vivo as they could efficiently engraft into the liver parenchyma. For in vitro studies, they would be advantageous for drug design and metabolism in developing novel drugs and cell-based therapies. Specifically, they express both phase I and II metabolic enzymes that share similar substrate specificities, inhibition and induction characteristics, and drug metabolism as their human counterparts. In addition, cjESCs and cjESC-HLCs are advantageous for investigations on emerging research areas, including blastocyst complementation to generate entire livers, and bioengineering of discarded livers to regenerate whole livers for transplantation.

show abstract

“…The development of technology for farming human organs in xenogeneic animals such as pigs is hindered by a number of factors. There is a risk of zoonosis and the risk of contamination of human organs with cells or proteins of the recipient animal (Rashid et al, 2014;Matsunari et al, 2020). One problem is that retroviruses integrated into the genome of chimeric animals can be transferred to humans when growing human organs.…”

Section: The Main Problems Hindering the Development Of Technologiesmentioning

confidence: 99%

“…For the successful transplantation of human organs grown in animals, it is necessary for the organ's circulatory system, like the organ, to be formed from human cells in order to minimize the xenogenic component during transplantation. Many researchers are working on this problem (Hamanaka et al, 2018;Matsunari et al, 2020). To solve all these problems, the factors influencing the success of the colonization of pluripotent donor cells into the organism of the recipient animal, and the mechanisms underlying the differentiation of these cells in the conditions of the "free niche" are still to be determined and investigated.…”

Section: The Main Problems Hindering the Development Of Technologiesmentioning

confidence: 99%

Generation of donor organs in chimeric animals via blastocyst complementation

2020

View full text Add to dashboard Cite

The lack of organs for transplantation is an important problem in medicine today. The growth of organs in chimeric animals may be the solution of this. The proposed technology is the interspecific blastocyst complementation method in combination with genomic editing for obtaining “free niches” and pluripotent stem cell production methods. The CRISPR/Cas9 method allows the so-called “free niches” to be obtained for blastocyst complementation. The technologies of producing induced pluripotent stem cells give us the opportunity to obtain human donor cells capable of populating a “free niche”. Taken together, these technologies allow interspecific blastocyst complementation between humans and other animals, which makes it possible in the future to grow human organs for transplantations inside chimeric animals. However, in practice, in order to achieve successful interspecific blastocyst complementation, it is necessary to solve a number of problems: to improve methods for producing “chimeric competent” cells, to overcome specific interspecific barriers, to select compatible cell developmental stages for injection and the corresponding developmental stage of the host embryo, to prevent apoptosis of donor cells and to achieve effective proliferation of the human donor cells in the host animal. Also, it is very important to analyze the ethical aspects related to developing technologies of chimeric organisms with the participation of human cells. Today, many researchers are trying to solve these problems and also to establish new approaches in the creation of interspecific chimeric organisms in order to grow human organs for transplantation. In the present review we described the historical stages of the development of the blastocyst complementation method, examined in detail the technologies that underlie modern blastocyst complementation, and analyzed current progress that gives us the possibility to grow human organs in chimeric animals. We also considered the barriers and issues preventing the successful implementation of interspecific blastocyst complementation in practice, and discussed the further development of this method.

show abstract

Compensation of Disabled Organogeneses in Genetically Modified Pig Fetuses by Blastocyst Complementation

Cited by 51 publications

References 44 publications

Xeno‐regenerative medicine: A novel concept for donor kidney fabrication

Xeno‐regenerative medicine: A novel concept for donor kidney fabrication

Utility of Common Marmoset (Callithrix jacchus) Embryonic Stem Cells in Liver Disease Modeling, Tissue Engineering and Drug Metabolism

Generation of donor organs in chimeric animals via blastocyst complementation

Contact Info

Product

Resources

About