scholarly journals The road to generating transplantable organs: from blastocyst complementation to interspecies chimeras

Development ◽  
2021 ◽  
Vol 148 (12) ◽  
Author(s):  
Canbin Zheng ◽  
Emily B. Ballard ◽  
Jun Wu
Keyword(s):  
Science Fiction ◽  
Pluripotent Stem Cells ◽  
Current Status ◽  
Divergent Evolution ◽  
Closely Related Species ◽  
The Road ◽  
Human Organs ◽  
Blastocyst Complementation ◽  
Donor Cells ◽  
Host Embryo

ABSTRACT Growing human organs in animals sounds like something from the realm of science fiction, but it may one day become a reality through a technique known as interspecies blastocyst complementation. This technique, which was originally developed to study gene function in development, involves injecting donor pluripotent stem cells into an organogenesis-disabled host embryo, allowing the donor cells to compensate for missing organs or tissues. Although interspecies blastocyst complementation has been achieved between closely related species, such as mice and rats, the situation becomes much more difficult for species that are far apart on the evolutionary tree. This is presumably because of layers of xenogeneic barriers that are a result of divergent evolution. In this Review, we discuss the current status of blastocyst complementation approaches and, in light of recent progress, elaborate on the keys to success for interspecies blastocyst complementation and organ generation.

scholarly journals Generation of donor organs in chimeric animals via blastocyst complementation

2020 ◽  
Vol 24 (8) ◽  
pp. 913-921
Author(s):  
T. I. Babochkina ◽  
L. A. Gerlinskaya ◽  
M. P. Moshkin
Keyword(s):  
Developmental Stages ◽  
Successful Implementation ◽  
Host Animal ◽  
Human Donor ◽  
Human Organs ◽  
Blastocyst Complementation ◽  
Donor Cells ◽  
Induced Pluripotent ◽  
Medicine Today ◽  
Genomic Editing

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.

scholarly journals Umbilical Cord Tissue as a Source of Young Cells for the Derivation of Induced Pluripotent Stem Cells Using Non-Integrating Episomal Vectors and Feeder-Free Conditions

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 49
Author(s):  
Aisha Mohamed ◽  
Theresa Chow ◽  
Jennifer Whiteley ◽  
Amanda Fantin ◽  
Kersti Sorra ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Umbilical Cord ◽  
Pluripotent Stem Cells ◽  
Blood Cells ◽  
Growth Media ◽  
Donor Cells ◽  
Episomal Vectors ◽  
Umbilical Cord Tissue ◽  
Induced Pluripotent

The clinical application of induced pluripotent stem cells (iPSC) needs to balance the use of an autologous source that would be a perfect match for the patient against any safety or efficacy issues that might arise with using cells from an older patient or donor. Drs. Takahashi and Yamanaka and the Office of Cellular and Tissue-based Products (PMDA), Japan, have had concerns over the existence of accumulated DNA mutations in the cells of older donors and the possibility of long-term negative effects. To mitigate the risk, they have chosen to partner with the Umbilical Cord (UC) banks in Japan to source allogeneic-matched donor cells. Production of iPSCs from UC blood cells (UCB) has been successful; however, reprogramming blood cells requires cell enrichment with columns or flow cytometry and specialized growth media. These requirements add to the cost of production and increase the manipulation of the cells, which complicates the regulatory approval process. Alternatively, umbilical cord tissue mesenchymal stromal cells (CT-MSCs) have the same advantage as UCB cells of being a source of young donor cells. Crucially, CT-MSCs are easier and less expensive to harvest and grow compared to UCB cells. Here, we demonstrate that CT-MSCs can be easily isolated without expensive enzymatic treatment or columns and reprogramed well using episomal vectors, which allow for the removal of the reprogramming factors after a few passages. Together the data indicates that CT-MSCs are a viable source of donor cells for the production of clinical-grade, patient matched iPSCs.

i1-net: The Iran Strong Motion Network

2021 ◽  
Author(s):  
Mohammad Pourmohammad Shahvar ◽  
Esmaeil Farzanegan ◽  
Attiyeh Eshaghi ◽  
Hossein Mirzaei
Keyword(s):  
Earthquake Engineering ◽  
Strong Motion ◽  
Current Status ◽  
Primary Input ◽  
The Road ◽  
Leading Position ◽  
Hazard And Risk ◽  
Ground Motion Records ◽  
Strong Motion Network ◽  
Strong Ground

Abstract Strong ground-motion records are the primary input data in earthquake engineering studies to improve understanding of seismic hazard and risk. As the overseer of the Iran Strong Motion Network (i1-net), the Road, Housing, and Urban Development Research Center occupies the leading position in this field in the country. With more than 1260 active accelerometers and a collection of over 14,129 earthquake recordings since 1973, the Iran Strong Motion Network is the major Iranian source of information for engineering seismology and earthquake engineering. The present article describes the current status and developments of the i1-net in the last 46 yr.

Immunological Attack by Adult Cells in the Developing Chick Embryo: Influence of the Vascularity of the Host Spleen and of Homograft Rejection by the Embryo on Splenomegaly

Development ◽  
1963 ◽  
Vol 11 (1) ◽  
pp. 119-134
Author(s):  
J. B. Solomon ◽  
D. F. Tucker
Keyword(s):  
Chick Embryo ◽  
Donor Cells ◽  
Host Embryo ◽  
Immunological Attack ◽  
Adult Cells

The immunological attack by adult cells introduced into the embryo is first manifest by splenomegaly. The extent of this splenomegaly depends upon many factors. There must be antigenic differences between the donor and host in that the host must possess antigens absent in the donor (Cock & Simonsen, 1958; Mun, Kosin & Sato, 1959; Burnet & Boyer, 1961; Jaffe & Payne, 1961). The degree of splenomegaly also depends upon the immunological maturity of the donor cells (Ebert, 1951; Simonsen, 1957; Solomon, 1960, 1961a), the number of donor cells injected into the embryo (Isacson, 1959; Terasaki, 1959a; Solomon, 1962) and, in some cases, upon the sex of the host (Solomon, 1962). In this paper two further factors are shown to affect splenomegaly—the age of the host embryo and the method of administration of the donor cells. Danchakoff (1916) first showed that the histology of the spleen during splenomegaly varied with the age of the host without being aware of the nature of the transplantation reactions involved.

scholarly journals Human Pluripotent Stem Cell Culture: Current Status, Challenges, and Advancement

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Sushrut Dakhore ◽  
Bhavana Nayer ◽  
Kouichi Hasegawa
Keyword(s):  
Stem Cells ◽  
Cell Culture ◽  
Pluripotent Stem Cells ◽  
Large Scale ◽  
Embryonic Stem ◽  
Current Status ◽  
Specific Cell ◽  
Therapeutic Applications ◽  
Proliferative Ability

Over the past two decades, human embryonic stem cells (hESCs) have gained attention due to their pluripotent and proliferative ability which enables production of almost all cell types in the human body in vitro and makes them an excellent tool to study human embryogenesis and disease, as well as for drug discovery and cell transplantation therapies. Discovery of human-induced pluripotent stem cells (hiPSCs) further expanded therapeutic applications of human pluripotent stem cells (PSCs). hPSCs provide a stable and unlimited original cell source for producing suitable cells and tissues for downstream applications. Therefore, engineering the environment in which these cells are grown, for stable and quality-controlled hPSC maintenance and production, is one of the key factors governing the success of these applications. hPSCs are maintained in a particular niche using specific cell culture components. Ideally, the culture should be free of xenobiotic components to render hPSCs suitable for therapeutic applications. Substantial efforts have been put to identify effective components, and develop culture conditions and protocols, for their large-scale expansion without compromising on quality. In this review, we discuss different media, their components and functions, including specific requirements to maintain the pluripotent and proliferative ability of hPSCs. Understanding the role of culture components would enable the development of appropriate conditions to promote large-scale, quality-controlled expansion of hPSCs thereby increasing their potential applications.

Research Commentary—The Digital Transformation of Healthcare: Current Status and the Road Ahead

2010 ◽  
Vol 21 (4) ◽  
pp. 796-809 ◽  
Author(s):  
Ritu Agarwal ◽  
Guodong (Gordon) Gao ◽  
Catherine DesRoches ◽  
Ashish K. Jha
Keyword(s):  
Digital Transformation ◽  
Current Status ◽  
The Road

scholarly journals Preventing Emergency Vehicle Crashes: Status and Challenges of Human Factors Issues

2018 ◽  
Vol 60 (7) ◽  
pp. 1048-1072 ◽  
Author(s):  
Hongwei Hsiao ◽  
Joonho Chang ◽  
Peter Simeonov
Keyword(s):  
Risk Factors ◽  
Human Factors ◽  
Red Light ◽  
Control Measures ◽  
Current Status ◽  
Emergency Vehicle ◽  
Vehicle Crashes ◽  
Contributing Factors ◽  
The Road ◽  
On The Road

Objective: This study reports current status of knowledge and challenges associated with the emergency vehicle (police car, fire truck, and ambulance) crashes, with respect to the major contributing risk factors. Background: Emergency vehicle crashes are a serious nationwide problem, causing injury and death to emergency responders and citizens. Understanding the underlying causes of these crashes is critical for establishing effective strategies for reducing the occurrence of similar incidents. Method: We reviewed the broader literature associated with the contributing factors for emergency vehicle crashes: peer-reviewed journal papers; and reports, policies, and manuals published by government agencies, universities, and research institutes. Results: Major risk factors for emergency vehicle crashes identified in this study were organized into four categories: driver, task, vehicle, and environmental factors. Also, current countermeasures and interventions to mitigate the hazards of emergency vehicle crashes were discussed, and new ideas for future studies were suggested. Conclusion: Risk factors, control measures, and knowledge gaps relevant to emergency vehicle crashes were presented. Six research concepts are offered for the human factors community to address. Among the topics are emergency vehicle driver risky behavior carryover between emergency response and return from a call, distraction in emergency vehicle driving, in-vehicle driver assistance technologies, vehicle red light running, and pedestrian crash control. Application: This information is helpful for emergency vehicle drivers, safety practitioners, public safety agencies, and research communities to mitigate crash risks. It also offers ideas for researchers to advance technologies and strategies to further emergency vehicle safety on the road.

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