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Adult Stem Cell

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Hans Clevers – One of the best experts on this subject based on the ideXlab platform.

  • Translational applications of Adult Stem Cell-derived organoids
    Development (Cambridge England), 2017
    Co-Authors: Jarno Drost, Hans Clevers

    Abstract:

    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.

  • what is an Adult Stem Cell
    Science, 2015
    Co-Authors: Hans Clevers

    Abstract:

    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.

  • human intestinal tissue with Adult Stem Cell properties derived from pluripotent Stem Cells
    Stem cell reports, 2014
    Co-Authors: Ryan Forster, Hans Clevers, Kunitoshi Chiba, Lorian Schaeffer, Samuel G Regalado, Christine S Lai, Qing Gao, Samira Kiani, Henner F Farin

    Abstract:

    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.

Malcolm R Alison – One of the best experts on this subject based on the ideXlab platform.

  • Adult Stem Cell plasticity will engineered tissues be rejected
    International Journal of Experimental Pathology, 2004
    Co-Authors: T C Fang, Malcolm R Alison, N A Wright, Richard Poulsom

    Abstract:

    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.

  • recipes for Adult Stem Cell plasticity fusion cuisine or readymade
    Journal of Clinical Pathology, 2004
    Co-Authors: Richard Poulsom, Malcolm R Alison, William R. Otto, Mairi Brittan, Natalie C Direkze, M Lovell, T C Fang, S L Preston, N A Wright

    Abstract:

    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, 2002
    Co-Authors: S J Forbes, Richard Poulsom, N A Wright, Malcolm R Alison

    Abstract:

    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.

N A Wright – One of the best experts on this subject based on the ideXlab platform.

  • Adult Stem Cell plasticity will engineered tissues be rejected
    International Journal of Experimental Pathology, 2004
    Co-Authors: T C Fang, Malcolm R Alison, N A Wright, Richard Poulsom

    Abstract:

    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.

  • recipes for Adult Stem Cell plasticity fusion cuisine or readymade
    Journal of Clinical Pathology, 2004
    Co-Authors: Richard Poulsom, Malcolm R Alison, William R. Otto, Mairi Brittan, Natalie C Direkze, M Lovell, T C Fang, S L Preston, N A Wright

    Abstract:

    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, 2002
    Co-Authors: S J Forbes, Richard Poulsom, N A Wright, Malcolm R Alison

    Abstract:

    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.