The Experts below are selected from a list of 72000 Experts worldwide ranked by ideXlab platform
Hans Clevers - One of the best experts on this subject based on the ideXlab platform.
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Translational applications of Adult Stem Cell-derived organoids
Development (Cambridge England), 2017Co-Authors: Jarno Drost, Hans CleversAbstract:Adult Stem Cells from a variety of organs can be expanded long-term in vitro as three-dimensional organotypic structures termed organoids. These Adult Stem Cell-derived organoids retain their organ identity and remain genetically stable over long periods of time. The ability to grow organoids from patient-derived healthy and diseased tissue allows for the study of organ development, tissue homeostasis and disease. In this Review, we discuss the generation of Adult Stem Cell-derived organoid cultures and their applications in in vitro disease modeling, personalized cancer therapy and regenerative medicine.
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what is an Adult Stem Cell
Science, 2015Co-Authors: Hans CleversAbstract:The paradigm of the hematopoietic Stem Cell (HSC) has become deeply engrained in our minds, ever since bone marrow transplantation technology narrowed in on this almost magical multipotent entity that gives rise to all blood Cells. The HSC's ability to “self-renew” as well as to proceed down hierarchical differentiation pathways involves a rigidly choreographed flow of events. The HSC paradigm currently serves as a template to interpret experimental observations on any other mammalian tissue. Yet, it is not obvious why evolution would have come up with the very same solution for the renewal of all tissues. Attempts to fit observations on solid tissues into the HSC hierarchy mold have led to confusing theories, terminologies, experimental approaches, and heated debates, many of which remain unresolved. Organs differ in size, architecture, and function, and are subject to markedly different biological and physical challenges. It therefore appears plausible that tissues, with their different regenerative demands, have evolved different ways to restore Cell numbers.
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human intestinal tissue with Adult Stem Cell properties derived from pluripotent Stem Cells
Stem cell reports, 2014Co-Authors: Ryan Forster, Hans Clevers, Kunitoshi Chiba, Lorian Schaeffer, Samuel G Regalado, Christine S Lai, Qing Gao, Samira Kiani, Henner F FarinAbstract:Genetically engineered human pluripotent Stem Cells (hPSCs) have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many applications are limited due to the lack of robust differentiation paradigms that allow for the isolation of defined functional tissues. Here, using an endogenous LGR5-GFP reporter, we derived Adult Stem Cells from hPSCs that gave rise to functional human intestinal tissue comprising all major Cell types of the intestine. Histological and functional analyses revealed that such human organoid cultures could be derived with high purity and with a composition and morphology similar to those of cultures obtained from human biopsies. Importantly, hPSC-derived organoids responded to the canonical signaling pathways that control self-renewal and differentiation in the Adult human intestinal Stem Cell compartment. This Adult Stem Cell syStem provides a platform for studying human intestinal disease in vitro using genetically engineered hPSCs.
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Tissue-Resident Adult Stem Cell Populations of Rapidly Self-Renewing Organs
Cell stem cell, 2010Co-Authors: Nick Barker, Sina Bartfeld, Hans CleversAbstract:The epithelial lining of the intestine, stomach, and skin is continuously exposed to environmental assault, imposing a requirement for regular self-renewal. Resident Adult Stem Cell populations drive this renewal, and much effort has been invested in revealing their identity. Reliable Adult Stem Cell biomarkers would accelerate our understanding of Stem Cell roles in tissue homeostasis and cancer. Membrane-expressed markers would also facilitate isolation of these Adult Stem Cell populations for exploitation of their regenerative potential. Here, we review recent advances in Adult Stem Cell biology, highlighting the promise and pitfalls of the candidate biomarkers of the various Stem Cell populations.
Malcolm R Alison - One of the best experts on this subject based on the ideXlab platform.
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Adult Stem Cell plasticity will engineered tissues be rejected
International Journal of Experimental Pathology, 2004Co-Authors: T C Fang, N A Wright, Malcolm R Alison, Richard PoulsomAbstract:Summary The dogma that Adult tissue-specific Stem Cells remain committed to supporting only their own tissue has been challenged; a new hypothesis, that Adult Stem Cells demonstrate plasticity in their repertoires, is being tested. This is important because it seems possible that haematopoietic Stem Cells, for example, could be exploited to generate and perhaps deliver Cell-based therapies deep within existing nonhaematopoietic organs. Much of the evidence for plasticity derives from histological studies of tissues from patients or animals that have received grafts of Cells or whole organs, from a donor bearing (or lacking) a definitive marker. Detection in the recipient of appropriately differentiated Cells bearing the donor marker is indicative of a switch in phenotype of a Stem Cell or a member of a transit amplifying population or of a differentiated Cell. In this review, we discuss evidence for these changes occurring but do not consider the molecular basis of Cell commitment. In general, the extent of engraftment is low but may be increased if tissues are damaged. In model syStems of liver regeneration, the repeated application of a selection pressure increases levels of engraftment considerably; how this occurs is unclear. Cell fusion plays a part in regeneration and remodelling of the liver, skeletal muscle and even regions of the brain. Genetic disease may be amenable to some forms of Cell therapy, yet immune rejection will present challenges. Graft-vs.-host disease will continue to present problems, although this may be avoided if the Cells were derived from the recipient or they were tolerized. Despite great expectations for Cellular therapies, there are indications that attempts to replace missing proteins could be confounded simply by the development of specific immunity that rejects the new phenotype.
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recipes for Adult Stem Cell plasticity fusion cuisine or readymade
Journal of Clinical Pathology, 2004Co-Authors: Natalie C Direkze, M Lovell, T C Fang, S L Preston, William R. Otto, Richard Poulsom, Mairi Brittan, Malcolm R Alison, N A WrightAbstract:A large body of evidence supports the idea that certain Adult Stem Cells, particularly those of bone marrow origin, can engraft at alternative locations, particularly when the recipient organ is damaged. Under strong and positive selection pressure these Cells will clonally expand/differentiate, making an important contribution to tissue replacement. Similarly, bone marrow derived Cells can be amplified in vitro and differentiated into many types of tissue. Despite seemingly irrefutable evidence for Stem Cell plasticity, a veritable chorus of detractors has emerged, some doubting its very existence, motivated perhaps by more than a little self interest. The issues that have led to this situation include the inability to reproduce certain quite startling observations, and extrapolation from the behaviour of embryonic Stem Cells to suggest that Adult bone marrow Cells simply fuse with other Cells and adopt their phenotype. Although these issues need resolving and, accepting that Cell fusion does appear to allow reprogramming of haemopoietic Cells in special circumstances, criticising this whole new field because some areas remain unclear is not good science.
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Adult Stem Cell plasticity new pathways of tissue regeneration become visible
Clinical Science, 2002Co-Authors: S J Forbes, N A Wright, Richard Poulsom, Malcolm R AlisonAbstract:There has recently been a significant change in the way we think about organ regeneration. In the Adult, organ formation and regeneration was thought to occur through the action of organ-or tissue-restricted Stem Cells (i.e. haematopoietic Stem Cells making blood; gut Stem Cells making gut, etc.). However, there is a large body of recent work that has extended this model. Thanks to lineage tracking techniques, we now believe that Stem Cells from one organ syStem, for example the haematopoietic compartment, can develop into the differentiated Cells within another organ syStem, such as liver, brain or kidney. This Cellular plasticity not only occurs under experimental conditions, but has also been shown to take place in humans following bone marrow and organ transplants. This trafficking is potentially bi-directional, and even differentiated Cells from different organ syStems can interchange, with pancreatic Cells able to form hepatocytes, for example. In this review we will detail some of these findings and attempt to explain their biological significance.
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Adult Stem Cell plasticity
The Journal of Pathology, 2002Co-Authors: Richard Poulsom, S J Forbes, N A Wright, Malcolm R AlisonAbstract:Observations made in the last few years support the existence of pathways, in Adult humans and rodents, that allow Adult Stem Cells to be surprisingly flexible in their differentiation repertoires. Termed plasticity, this property allows Adult Stem Cells, assumed, until now, to be committed to generating a fixed range of progeny, to switch, when they have been relocated, to make other specialized sets of Cells appropriate to their new niche. Reprogramming of some Adult Stem Cells can occur in vivo; the Stem Cells normally resident in bone marrow appear particularly flexible and are able to contribute usefully to multiple recipient organs. This process produces Cells with specialized structural and metabolic adaptations commensurate with their new locations. In a few examples, the degree of support is sufficient to assist or even rescue recipient mice from genetic defects. Some studies provide evidence for the expansion of the reprogrammed Cells locally, but in most it remains possible that Cells arrive and redifferentiate, but are no longer Stem Cells. Nevertheless, the fact that appropriately differentiated Cells are delivered deep within organs simply by injection of bone marrow Cells should make us think differently about the way that organs regenerate and repair. Migratory pathways for Stem Cells in Adult organisms may exist that could be exploited to effect repairs using an individual's own Stem Cells, perhaps after gene therapy. Logical extensions of this concept are that a transplanted organ would become affected by the genetic susceptibilities of the recipient, alleles that re-express themselves via marrow-derived Stem Cells, and that plasticity after bone marrow transplantation would also transfer different phenotypes, affecting important parameters such as susceptibility to long-term complications of diabetes, or the ability to metabolize drugs in the liver. This article reviews some of the evidence for Stem Cell plasticity in rodents and man. Copyright © 2002 John Wiley & Sons, Ltd.
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Adult Stem Cell plasticity.
The Journal of pathology, 2002Co-Authors: Richard Poulsom, S J Forbes, Malcolm R Alison, N A WrightAbstract:Observations made in the last few years support the existence of pathways, in Adult humans and rodents, that allow Adult Stem Cells to be surprisingly flexible in their differentiation repertoires. Termed plasticity, this property allows Adult Stem Cells, assumed, until now, to be committed to generating a fixed range of progeny, to switch, when they have been relocated, to make other specialized sets of Cells appropriate to their new niche. Reprogramming of some Adult Stem Cells can occur in vivo; the Stem Cells normally resident in bone marrow appear particularly flexible and are able to contribute usefully to multiple recipient organs. This process produces Cells with specialized structural and metabolic adaptations commensurate with their new locations. In a few examples, the degree of support is sufficient to assist or even rescue recipient mice from genetic defects. Some studies provide evidence for the expansion of the reprogrammed Cells locally, but in most it remains possible that Cells arrive and redifferentiate, but are no longer Stem Cells. Nevertheless, the fact that appropriately differentiated Cells are delivered deep within organs simply by injection of bone marrow Cells should make us think differently about the way that organs regenerate and repair. Migratory pathways for Stem Cells in Adult organisms may exist that could be exploited to effect repairs using an individual's own Stem Cells, perhaps after gene therapy. Logical extensions of this concept are that a transplanted organ would become affected by the genetic susceptibilities of the recipient, alleles that re-express themselves via marrow-derived Stem Cells, and that plasticity after bone marrow transplantation would also transfer different phenotypes, affecting important parameters such as susceptibility to long-term complications of diabetes, or the ability to metabolize drugs in the liver. This article reviews some of the evidence for Stem Cell plasticity in rodents and man.
N A Wright - One of the best experts on this subject based on the ideXlab platform.
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Adult Stem Cell plasticity will engineered tissues be rejected
International Journal of Experimental Pathology, 2004Co-Authors: T C Fang, N A Wright, Malcolm R Alison, Richard PoulsomAbstract:Summary The dogma that Adult tissue-specific Stem Cells remain committed to supporting only their own tissue has been challenged; a new hypothesis, that Adult Stem Cells demonstrate plasticity in their repertoires, is being tested. This is important because it seems possible that haematopoietic Stem Cells, for example, could be exploited to generate and perhaps deliver Cell-based therapies deep within existing nonhaematopoietic organs. Much of the evidence for plasticity derives from histological studies of tissues from patients or animals that have received grafts of Cells or whole organs, from a donor bearing (or lacking) a definitive marker. Detection in the recipient of appropriately differentiated Cells bearing the donor marker is indicative of a switch in phenotype of a Stem Cell or a member of a transit amplifying population or of a differentiated Cell. In this review, we discuss evidence for these changes occurring but do not consider the molecular basis of Cell commitment. In general, the extent of engraftment is low but may be increased if tissues are damaged. In model syStems of liver regeneration, the repeated application of a selection pressure increases levels of engraftment considerably; how this occurs is unclear. Cell fusion plays a part in regeneration and remodelling of the liver, skeletal muscle and even regions of the brain. Genetic disease may be amenable to some forms of Cell therapy, yet immune rejection will present challenges. Graft-vs.-host disease will continue to present problems, although this may be avoided if the Cells were derived from the recipient or they were tolerized. Despite great expectations for Cellular therapies, there are indications that attempts to replace missing proteins could be confounded simply by the development of specific immunity that rejects the new phenotype.
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recipes for Adult Stem Cell plasticity fusion cuisine or readymade
Journal of Clinical Pathology, 2004Co-Authors: Natalie C Direkze, M Lovell, T C Fang, S L Preston, William R. Otto, Richard Poulsom, Mairi Brittan, Malcolm R Alison, N A WrightAbstract:A large body of evidence supports the idea that certain Adult Stem Cells, particularly those of bone marrow origin, can engraft at alternative locations, particularly when the recipient organ is damaged. Under strong and positive selection pressure these Cells will clonally expand/differentiate, making an important contribution to tissue replacement. Similarly, bone marrow derived Cells can be amplified in vitro and differentiated into many types of tissue. Despite seemingly irrefutable evidence for Stem Cell plasticity, a veritable chorus of detractors has emerged, some doubting its very existence, motivated perhaps by more than a little self interest. The issues that have led to this situation include the inability to reproduce certain quite startling observations, and extrapolation from the behaviour of embryonic Stem Cells to suggest that Adult bone marrow Cells simply fuse with other Cells and adopt their phenotype. Although these issues need resolving and, accepting that Cell fusion does appear to allow reprogramming of haemopoietic Cells in special circumstances, criticising this whole new field because some areas remain unclear is not good science.
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Adult Stem Cell plasticity new pathways of tissue regeneration become visible
Clinical Science, 2002Co-Authors: S J Forbes, N A Wright, Richard Poulsom, Malcolm R AlisonAbstract:There has recently been a significant change in the way we think about organ regeneration. In the Adult, organ formation and regeneration was thought to occur through the action of organ-or tissue-restricted Stem Cells (i.e. haematopoietic Stem Cells making blood; gut Stem Cells making gut, etc.). However, there is a large body of recent work that has extended this model. Thanks to lineage tracking techniques, we now believe that Stem Cells from one organ syStem, for example the haematopoietic compartment, can develop into the differentiated Cells within another organ syStem, such as liver, brain or kidney. This Cellular plasticity not only occurs under experimental conditions, but has also been shown to take place in humans following bone marrow and organ transplants. This trafficking is potentially bi-directional, and even differentiated Cells from different organ syStems can interchange, with pancreatic Cells able to form hepatocytes, for example. In this review we will detail some of these findings and attempt to explain their biological significance.
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Adult Stem Cell plasticity
The Journal of Pathology, 2002Co-Authors: Richard Poulsom, S J Forbes, N A Wright, Malcolm R AlisonAbstract:Observations made in the last few years support the existence of pathways, in Adult humans and rodents, that allow Adult Stem Cells to be surprisingly flexible in their differentiation repertoires. Termed plasticity, this property allows Adult Stem Cells, assumed, until now, to be committed to generating a fixed range of progeny, to switch, when they have been relocated, to make other specialized sets of Cells appropriate to their new niche. Reprogramming of some Adult Stem Cells can occur in vivo; the Stem Cells normally resident in bone marrow appear particularly flexible and are able to contribute usefully to multiple recipient organs. This process produces Cells with specialized structural and metabolic adaptations commensurate with their new locations. In a few examples, the degree of support is sufficient to assist or even rescue recipient mice from genetic defects. Some studies provide evidence for the expansion of the reprogrammed Cells locally, but in most it remains possible that Cells arrive and redifferentiate, but are no longer Stem Cells. Nevertheless, the fact that appropriately differentiated Cells are delivered deep within organs simply by injection of bone marrow Cells should make us think differently about the way that organs regenerate and repair. Migratory pathways for Stem Cells in Adult organisms may exist that could be exploited to effect repairs using an individual's own Stem Cells, perhaps after gene therapy. Logical extensions of this concept are that a transplanted organ would become affected by the genetic susceptibilities of the recipient, alleles that re-express themselves via marrow-derived Stem Cells, and that plasticity after bone marrow transplantation would also transfer different phenotypes, affecting important parameters such as susceptibility to long-term complications of diabetes, or the ability to metabolize drugs in the liver. This article reviews some of the evidence for Stem Cell plasticity in rodents and man. Copyright © 2002 John Wiley & Sons, Ltd.
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Adult Stem Cell plasticity.
The Journal of pathology, 2002Co-Authors: Richard Poulsom, S J Forbes, Malcolm R Alison, N A WrightAbstract:Observations made in the last few years support the existence of pathways, in Adult humans and rodents, that allow Adult Stem Cells to be surprisingly flexible in their differentiation repertoires. Termed plasticity, this property allows Adult Stem Cells, assumed, until now, to be committed to generating a fixed range of progeny, to switch, when they have been relocated, to make other specialized sets of Cells appropriate to their new niche. Reprogramming of some Adult Stem Cells can occur in vivo; the Stem Cells normally resident in bone marrow appear particularly flexible and are able to contribute usefully to multiple recipient organs. This process produces Cells with specialized structural and metabolic adaptations commensurate with their new locations. In a few examples, the degree of support is sufficient to assist or even rescue recipient mice from genetic defects. Some studies provide evidence for the expansion of the reprogrammed Cells locally, but in most it remains possible that Cells arrive and redifferentiate, but are no longer Stem Cells. Nevertheless, the fact that appropriately differentiated Cells are delivered deep within organs simply by injection of bone marrow Cells should make us think differently about the way that organs regenerate and repair. Migratory pathways for Stem Cells in Adult organisms may exist that could be exploited to effect repairs using an individual's own Stem Cells, perhaps after gene therapy. Logical extensions of this concept are that a transplanted organ would become affected by the genetic susceptibilities of the recipient, alleles that re-express themselves via marrow-derived Stem Cells, and that plasticity after bone marrow transplantation would also transfer different phenotypes, affecting important parameters such as susceptibility to long-term complications of diabetes, or the ability to metabolize drugs in the liver. This article reviews some of the evidence for Stem Cell plasticity in rodents and man.
Margaret T. Fuller - One of the best experts on this subject based on the ideXlab platform.
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The Histone Variant His2Av is Required for Adult Stem Cell Maintenance in the Drosophila Testis
PLoS genetics, 2013Co-Authors: Jose Rafael Morillo Prado, Shrividhya Srinivasan, Margaret T. FullerAbstract:Many tissues are sustained by Adult Stem Cells, which replace lost Cells by differentiation and maintain their own population through self-renewal. The mechanisms through which Adult Stem Cells maintain their identity are thus important for tissue homeostasis and repair throughout life. Here, we show that a histone variant, His2Av, is required Cell autonomously for maintenance of germline and cyst Stem Cells in the Drosophila testis. The ATP-dependent chromatin-remodeling factor Domino is also required in this tissue for Adult Stem Cell maintenance possibly by regulating the incorporation of His2Av into chromatin. Interestingly, although expression of His2Av was ubiquitous, its function was dispensable for germline and cyst Cell differentiation, suggesting a specific role for this non-canonical histone in maintaining the Stem Cell state in these lineages.
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accumulation of a differentiation regulator specifies transit amplifying division number in an Adult Stem Cell lineage
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Megan L Insco, Arlene Leon, Dennis M Mckearin, Margaret T. FullerAbstract:A key feature of many Adult Stem Cell lineages is that Stem Cell daughters destined for differentiation undergo several transit amplifying (TA) divisions before initiating terminal differentiation, allowing few and infrequently dividing Stem Cells to produce many differentiated progeny. Although the number of progenitor divisions profoundly affects tissue (re)generation, and failure to control these divisions may contribute to cancer, the mechanisms that limit TA proliferation are not well understood. Here, we use a model Stem Cell lineage, the Drosophila male germ line, to investigate the mechanism that counts the number of TA divisions. The Drosophila Bag of Marbles (Bam) protein is required for male germ Cells to cease spermatogonial TA divisions and initiate spermatocyte differentiation [McKearin DM, et al. (1990) Genes Dev 4:2242–2251]. Contrary to models involving dilution of a differentiation repressor, our results suggest that the switch from proliferation to terminal differentiation is triggered by accumulation of Bam protein to a critical threshold in TA Cells and that the number of TA divisions is set by the timing of Bam accumulation with respect to the rate of Cell cycle progression.
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Asymmetric Stem Cell Division and function of the Niche in the Drosophila Male Germ Line
International Journal of Hematology, 2005Co-Authors: Yukiko M. Yamashita, Margaret T. FullerAbstract:The balance between Stem Cell and differentiating Cell populations is critical for the long-term maintenance of tissue renewal for Cell types derived from Adult Stem Cell lineages such as blood, skin, intestinal epithelium, and sperm. To keep this balance, Stem Cells have the potential to divide asymmetrically, producing one daughter Cell that maintains Stem Cell identity and one daughter Cell that initiates differentiation. In many Adult Stem Cell syStems, the maintenance, proliferation, and number of Stem Cells appear to be controlled by the microenvironment, or niche. The Drosophila male and female germ line provide exCellent model syStems in which to study asymmetric Stem Cell divisions within the Stem Cell niche. In addition to signals from the niche that specify Stem Cell self-renewal, the Stem Cells themselves have elaborate Cellular mechanisms to ensure the asymmetric outcome of Cell division.
Richard Poulsom - One of the best experts on this subject based on the ideXlab platform.
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Adult Stem Cell plasticity will engineered tissues be rejected
International Journal of Experimental Pathology, 2004Co-Authors: T C Fang, N A Wright, Malcolm R Alison, Richard PoulsomAbstract:Summary The dogma that Adult tissue-specific Stem Cells remain committed to supporting only their own tissue has been challenged; a new hypothesis, that Adult Stem Cells demonstrate plasticity in their repertoires, is being tested. This is important because it seems possible that haematopoietic Stem Cells, for example, could be exploited to generate and perhaps deliver Cell-based therapies deep within existing nonhaematopoietic organs. Much of the evidence for plasticity derives from histological studies of tissues from patients or animals that have received grafts of Cells or whole organs, from a donor bearing (or lacking) a definitive marker. Detection in the recipient of appropriately differentiated Cells bearing the donor marker is indicative of a switch in phenotype of a Stem Cell or a member of a transit amplifying population or of a differentiated Cell. In this review, we discuss evidence for these changes occurring but do not consider the molecular basis of Cell commitment. In general, the extent of engraftment is low but may be increased if tissues are damaged. In model syStems of liver regeneration, the repeated application of a selection pressure increases levels of engraftment considerably; how this occurs is unclear. Cell fusion plays a part in regeneration and remodelling of the liver, skeletal muscle and even regions of the brain. Genetic disease may be amenable to some forms of Cell therapy, yet immune rejection will present challenges. Graft-vs.-host disease will continue to present problems, although this may be avoided if the Cells were derived from the recipient or they were tolerized. Despite great expectations for Cellular therapies, there are indications that attempts to replace missing proteins could be confounded simply by the development of specific immunity that rejects the new phenotype.
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recipes for Adult Stem Cell plasticity fusion cuisine or readymade
Journal of Clinical Pathology, 2004Co-Authors: Natalie C Direkze, M Lovell, T C Fang, S L Preston, William R. Otto, Richard Poulsom, Mairi Brittan, Malcolm R Alison, N A WrightAbstract:A large body of evidence supports the idea that certain Adult Stem Cells, particularly those of bone marrow origin, can engraft at alternative locations, particularly when the recipient organ is damaged. Under strong and positive selection pressure these Cells will clonally expand/differentiate, making an important contribution to tissue replacement. Similarly, bone marrow derived Cells can be amplified in vitro and differentiated into many types of tissue. Despite seemingly irrefutable evidence for Stem Cell plasticity, a veritable chorus of detractors has emerged, some doubting its very existence, motivated perhaps by more than a little self interest. The issues that have led to this situation include the inability to reproduce certain quite startling observations, and extrapolation from the behaviour of embryonic Stem Cells to suggest that Adult bone marrow Cells simply fuse with other Cells and adopt their phenotype. Although these issues need resolving and, accepting that Cell fusion does appear to allow reprogramming of haemopoietic Cells in special circumstances, criticising this whole new field because some areas remain unclear is not good science.
-
Adult Stem Cell plasticity new pathways of tissue regeneration become visible
Clinical Science, 2002Co-Authors: S J Forbes, N A Wright, Richard Poulsom, Malcolm R AlisonAbstract:There has recently been a significant change in the way we think about organ regeneration. In the Adult, organ formation and regeneration was thought to occur through the action of organ-or tissue-restricted Stem Cells (i.e. haematopoietic Stem Cells making blood; gut Stem Cells making gut, etc.). However, there is a large body of recent work that has extended this model. Thanks to lineage tracking techniques, we now believe that Stem Cells from one organ syStem, for example the haematopoietic compartment, can develop into the differentiated Cells within another organ syStem, such as liver, brain or kidney. This Cellular plasticity not only occurs under experimental conditions, but has also been shown to take place in humans following bone marrow and organ transplants. This trafficking is potentially bi-directional, and even differentiated Cells from different organ syStems can interchange, with pancreatic Cells able to form hepatocytes, for example. In this review we will detail some of these findings and attempt to explain their biological significance.
-
Adult Stem Cell plasticity
The Journal of Pathology, 2002Co-Authors: Richard Poulsom, S J Forbes, N A Wright, Malcolm R AlisonAbstract:Observations made in the last few years support the existence of pathways, in Adult humans and rodents, that allow Adult Stem Cells to be surprisingly flexible in their differentiation repertoires. Termed plasticity, this property allows Adult Stem Cells, assumed, until now, to be committed to generating a fixed range of progeny, to switch, when they have been relocated, to make other specialized sets of Cells appropriate to their new niche. Reprogramming of some Adult Stem Cells can occur in vivo; the Stem Cells normally resident in bone marrow appear particularly flexible and are able to contribute usefully to multiple recipient organs. This process produces Cells with specialized structural and metabolic adaptations commensurate with their new locations. In a few examples, the degree of support is sufficient to assist or even rescue recipient mice from genetic defects. Some studies provide evidence for the expansion of the reprogrammed Cells locally, but in most it remains possible that Cells arrive and redifferentiate, but are no longer Stem Cells. Nevertheless, the fact that appropriately differentiated Cells are delivered deep within organs simply by injection of bone marrow Cells should make us think differently about the way that organs regenerate and repair. Migratory pathways for Stem Cells in Adult organisms may exist that could be exploited to effect repairs using an individual's own Stem Cells, perhaps after gene therapy. Logical extensions of this concept are that a transplanted organ would become affected by the genetic susceptibilities of the recipient, alleles that re-express themselves via marrow-derived Stem Cells, and that plasticity after bone marrow transplantation would also transfer different phenotypes, affecting important parameters such as susceptibility to long-term complications of diabetes, or the ability to metabolize drugs in the liver. This article reviews some of the evidence for Stem Cell plasticity in rodents and man. Copyright © 2002 John Wiley & Sons, Ltd.
-
Adult Stem Cell plasticity.
The Journal of pathology, 2002Co-Authors: Richard Poulsom, S J Forbes, Malcolm R Alison, N A WrightAbstract:Observations made in the last few years support the existence of pathways, in Adult humans and rodents, that allow Adult Stem Cells to be surprisingly flexible in their differentiation repertoires. Termed plasticity, this property allows Adult Stem Cells, assumed, until now, to be committed to generating a fixed range of progeny, to switch, when they have been relocated, to make other specialized sets of Cells appropriate to their new niche. Reprogramming of some Adult Stem Cells can occur in vivo; the Stem Cells normally resident in bone marrow appear particularly flexible and are able to contribute usefully to multiple recipient organs. This process produces Cells with specialized structural and metabolic adaptations commensurate with their new locations. In a few examples, the degree of support is sufficient to assist or even rescue recipient mice from genetic defects. Some studies provide evidence for the expansion of the reprogrammed Cells locally, but in most it remains possible that Cells arrive and redifferentiate, but are no longer Stem Cells. Nevertheless, the fact that appropriately differentiated Cells are delivered deep within organs simply by injection of bone marrow Cells should make us think differently about the way that organs regenerate and repair. Migratory pathways for Stem Cells in Adult organisms may exist that could be exploited to effect repairs using an individual's own Stem Cells, perhaps after gene therapy. Logical extensions of this concept are that a transplanted organ would become affected by the genetic susceptibilities of the recipient, alleles that re-express themselves via marrow-derived Stem Cells, and that plasticity after bone marrow transplantation would also transfer different phenotypes, affecting important parameters such as susceptibility to long-term complications of diabetes, or the ability to metabolize drugs in the liver. This article reviews some of the evidence for Stem Cell plasticity in rodents and man.
