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Cellular reprogramming for understanding and treating human disease.

Kanherkar RR, Bhatia-Dey N, Makarev E, Csoka AB - Front Cell Dev Biol (2014)

Bottom Line: We propose that cellular reprogramming will have an equally profound impact on understanding and curing human disease, because it allows us to perceive and study molecular biological processes such as differentiation, epigenetics, and chromatin in ways that were likewise previously impossible.While the technology of reprogramming is being developed and refined there have also been significant ongoing developments in other complementary technologies such as gene editing, progenitor cell production, and tissue engineering.These technologies are the foundations of what is becoming a fully-functional field of regenerative medicine and are converging to a point that will allow us to treat almost any disease.

View Article: PubMed Central - PubMed

Affiliation: Epigenetics Laboratory, Department of Anatomy, Howard University Washington, DC, USA.

ABSTRACT
In the last two decades we have witnessed a paradigm shift in our understanding of cells so radical that it has rewritten the rules of biology. The study of cellular reprogramming has gone from little more than a hypothesis, to applied bioengineering, with the creation of a variety of important cell types. By way of metaphor, we can compare the discovery of reprogramming with the archeological discovery of the Rosetta stone. This stone slab made possible the initial decipherment of Egyptian hieroglyphics because it allowed us to see this language in a way that was previously impossible. We propose that cellular reprogramming will have an equally profound impact on understanding and curing human disease, because it allows us to perceive and study molecular biological processes such as differentiation, epigenetics, and chromatin in ways that were likewise previously impossible. Stem cells could be called "cellular Rosetta stones" because they allow also us to perceive the connections between development, disease, cancer, aging, and regeneration in novel ways. Here we present a comprehensive historical review of stem cells and cellular reprogramming, and illustrate the developing synergy between many previously unconnected fields. We show how stem cells can be used to create in vitro models of human disease and provide examples of how reprogramming is being used to study and treat such diverse diseases as cancer, aging, and accelerated aging syndromes, infectious diseases such as AIDS, and epigenetic diseases such as polycystic ovary syndrome. While the technology of reprogramming is being developed and refined there have also been significant ongoing developments in other complementary technologies such as gene editing, progenitor cell production, and tissue engineering. These technologies are the foundations of what is becoming a fully-functional field of regenerative medicine and are converging to a point that will allow us to treat almost any disease.

No MeSH data available.


Related in: MedlinePlus

Disease modeling. iPSCs are an excellent source for modeling genetic, epigenetic, and environmental diseases. Such cellular models representing diseased phenotypes can be used for understanding the interplay between the genetics, epigenetics and environment involved in the disease, and can expose unknown details about disease pathophysiology, and can be used for screening drugs. In the figure all green cells represent diseased cells, and all pink cells represent healthy cells. (A) Genetic diseases can be modeled by reprogramming diseased cells to iPSCs and then re-differentiating them to produce a diseased phenotype. Additionally, these iPSCs can be corrected for the genetic mutation involved in the disease using gene-editing technology. On re-differentiation, corrected iPSCs produce healthy cells that can be used as isogenic controls. (B) Epigenetic diseases can be modeled using healthy cells that are reprogrammed to iPSCs and then induced toward an epigenetic disease state by recapitulating an environment containing the epigenetic factor(s) contributing to the disease. If iPSCs retain an epigenetic mark when in culture, or after being redifferentiated to the desired cell type, it indicates that the epigenetic mark is permanent and is likely to be passed on to offspring or carried by germ-line cells. It can also mean that the particular cell type is predisposed to retaining that epigenetic mark. Patient-specific models can be used as special models, as they can involve known epigenetic factors contributing to the disease. (C) Acute environmental diseases can be modeled using healthy cells by exposing them to a disease-causing environment that results in genetic damage or instability in the cells. For disease modeling, such cells can be reprogrammed to iPSCs and redifferentiated to diseased phenotypes. All of the above models can help us gain better insight into the diverse factors affecting a complex disease in terms of susceptibility, prognosis as well outcomes.
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Figure 4: Disease modeling. iPSCs are an excellent source for modeling genetic, epigenetic, and environmental diseases. Such cellular models representing diseased phenotypes can be used for understanding the interplay between the genetics, epigenetics and environment involved in the disease, and can expose unknown details about disease pathophysiology, and can be used for screening drugs. In the figure all green cells represent diseased cells, and all pink cells represent healthy cells. (A) Genetic diseases can be modeled by reprogramming diseased cells to iPSCs and then re-differentiating them to produce a diseased phenotype. Additionally, these iPSCs can be corrected for the genetic mutation involved in the disease using gene-editing technology. On re-differentiation, corrected iPSCs produce healthy cells that can be used as isogenic controls. (B) Epigenetic diseases can be modeled using healthy cells that are reprogrammed to iPSCs and then induced toward an epigenetic disease state by recapitulating an environment containing the epigenetic factor(s) contributing to the disease. If iPSCs retain an epigenetic mark when in culture, or after being redifferentiated to the desired cell type, it indicates that the epigenetic mark is permanent and is likely to be passed on to offspring or carried by germ-line cells. It can also mean that the particular cell type is predisposed to retaining that epigenetic mark. Patient-specific models can be used as special models, as they can involve known epigenetic factors contributing to the disease. (C) Acute environmental diseases can be modeled using healthy cells by exposing them to a disease-causing environment that results in genetic damage or instability in the cells. For disease modeling, such cells can be reprogrammed to iPSCs and redifferentiated to diseased phenotypes. All of the above models can help us gain better insight into the diverse factors affecting a complex disease in terms of susceptibility, prognosis as well outcomes.

Mentions: We can group human diseases into three broad categories: genetic, epigenetic and acute environmental (Cherry and Daley, 2012). Modeling of all three types is possible in vitro using stem cells, and an excellent way to study the intricate mechanisms and pathways underlying the etiology and pathophysiology of disease (Figure 4). Stem cells in general are ideal for creating “disease-in-a-dish” models because of their capacity for self-renewal and differentiation, their potential for recapitulating disease pathogenesis, and also their amenability for developing and testing therapeutics (Sterneckert et al., 2014).


Cellular reprogramming for understanding and treating human disease.

Kanherkar RR, Bhatia-Dey N, Makarev E, Csoka AB - Front Cell Dev Biol (2014)

Disease modeling. iPSCs are an excellent source for modeling genetic, epigenetic, and environmental diseases. Such cellular models representing diseased phenotypes can be used for understanding the interplay between the genetics, epigenetics and environment involved in the disease, and can expose unknown details about disease pathophysiology, and can be used for screening drugs. In the figure all green cells represent diseased cells, and all pink cells represent healthy cells. (A) Genetic diseases can be modeled by reprogramming diseased cells to iPSCs and then re-differentiating them to produce a diseased phenotype. Additionally, these iPSCs can be corrected for the genetic mutation involved in the disease using gene-editing technology. On re-differentiation, corrected iPSCs produce healthy cells that can be used as isogenic controls. (B) Epigenetic diseases can be modeled using healthy cells that are reprogrammed to iPSCs and then induced toward an epigenetic disease state by recapitulating an environment containing the epigenetic factor(s) contributing to the disease. If iPSCs retain an epigenetic mark when in culture, or after being redifferentiated to the desired cell type, it indicates that the epigenetic mark is permanent and is likely to be passed on to offspring or carried by germ-line cells. It can also mean that the particular cell type is predisposed to retaining that epigenetic mark. Patient-specific models can be used as special models, as they can involve known epigenetic factors contributing to the disease. (C) Acute environmental diseases can be modeled using healthy cells by exposing them to a disease-causing environment that results in genetic damage or instability in the cells. For disease modeling, such cells can be reprogrammed to iPSCs and redifferentiated to diseased phenotypes. All of the above models can help us gain better insight into the diverse factors affecting a complex disease in terms of susceptibility, prognosis as well outcomes.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
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Figure 4: Disease modeling. iPSCs are an excellent source for modeling genetic, epigenetic, and environmental diseases. Such cellular models representing diseased phenotypes can be used for understanding the interplay between the genetics, epigenetics and environment involved in the disease, and can expose unknown details about disease pathophysiology, and can be used for screening drugs. In the figure all green cells represent diseased cells, and all pink cells represent healthy cells. (A) Genetic diseases can be modeled by reprogramming diseased cells to iPSCs and then re-differentiating them to produce a diseased phenotype. Additionally, these iPSCs can be corrected for the genetic mutation involved in the disease using gene-editing technology. On re-differentiation, corrected iPSCs produce healthy cells that can be used as isogenic controls. (B) Epigenetic diseases can be modeled using healthy cells that are reprogrammed to iPSCs and then induced toward an epigenetic disease state by recapitulating an environment containing the epigenetic factor(s) contributing to the disease. If iPSCs retain an epigenetic mark when in culture, or after being redifferentiated to the desired cell type, it indicates that the epigenetic mark is permanent and is likely to be passed on to offspring or carried by germ-line cells. It can also mean that the particular cell type is predisposed to retaining that epigenetic mark. Patient-specific models can be used as special models, as they can involve known epigenetic factors contributing to the disease. (C) Acute environmental diseases can be modeled using healthy cells by exposing them to a disease-causing environment that results in genetic damage or instability in the cells. For disease modeling, such cells can be reprogrammed to iPSCs and redifferentiated to diseased phenotypes. All of the above models can help us gain better insight into the diverse factors affecting a complex disease in terms of susceptibility, prognosis as well outcomes.
Mentions: We can group human diseases into three broad categories: genetic, epigenetic and acute environmental (Cherry and Daley, 2012). Modeling of all three types is possible in vitro using stem cells, and an excellent way to study the intricate mechanisms and pathways underlying the etiology and pathophysiology of disease (Figure 4). Stem cells in general are ideal for creating “disease-in-a-dish” models because of their capacity for self-renewal and differentiation, their potential for recapitulating disease pathogenesis, and also their amenability for developing and testing therapeutics (Sterneckert et al., 2014).

Bottom Line: We propose that cellular reprogramming will have an equally profound impact on understanding and curing human disease, because it allows us to perceive and study molecular biological processes such as differentiation, epigenetics, and chromatin in ways that were likewise previously impossible.While the technology of reprogramming is being developed and refined there have also been significant ongoing developments in other complementary technologies such as gene editing, progenitor cell production, and tissue engineering.These technologies are the foundations of what is becoming a fully-functional field of regenerative medicine and are converging to a point that will allow us to treat almost any disease.

View Article: PubMed Central - PubMed

Affiliation: Epigenetics Laboratory, Department of Anatomy, Howard University Washington, DC, USA.

ABSTRACT
In the last two decades we have witnessed a paradigm shift in our understanding of cells so radical that it has rewritten the rules of biology. The study of cellular reprogramming has gone from little more than a hypothesis, to applied bioengineering, with the creation of a variety of important cell types. By way of metaphor, we can compare the discovery of reprogramming with the archeological discovery of the Rosetta stone. This stone slab made possible the initial decipherment of Egyptian hieroglyphics because it allowed us to see this language in a way that was previously impossible. We propose that cellular reprogramming will have an equally profound impact on understanding and curing human disease, because it allows us to perceive and study molecular biological processes such as differentiation, epigenetics, and chromatin in ways that were likewise previously impossible. Stem cells could be called "cellular Rosetta stones" because they allow also us to perceive the connections between development, disease, cancer, aging, and regeneration in novel ways. Here we present a comprehensive historical review of stem cells and cellular reprogramming, and illustrate the developing synergy between many previously unconnected fields. We show how stem cells can be used to create in vitro models of human disease and provide examples of how reprogramming is being used to study and treat such diverse diseases as cancer, aging, and accelerated aging syndromes, infectious diseases such as AIDS, and epigenetic diseases such as polycystic ovary syndrome. While the technology of reprogramming is being developed and refined there have also been significant ongoing developments in other complementary technologies such as gene editing, progenitor cell production, and tissue engineering. These technologies are the foundations of what is becoming a fully-functional field of regenerative medicine and are converging to a point that will allow us to treat almost any disease.

No MeSH data available.


Related in: MedlinePlus