The Experts below are selected from a list of 2193 Experts worldwide ranked by ideXlab platform

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

  • Stem Cell Plasticity and tumour formation
    European Journal of Cancer, 2006
    Co-Authors: Malcolm R Alison, Matthew J Lovell, Natalie C Direkze, N A Wright, Richard Poulsom
    Abstract:

    Stem Cell Plasticity refers to the ability of certain Stem Cells to switch lineage determination and generate unexpected Cell types. This review applies largely to bone marrow Cells (BMCs), which appear to contribute positively to the regeneration of several damaged non-haematopoietic tissues. This beneficial effect on regeneration may be a direct result of BMCs giving rise to organ parenchymal Cells. Alternatively, it could be due to BMCs fusing with existing parenchymal Cells, or providing paracrine growth factor support, or contributing to neovascularisation. In the context of oncology, BMC derivation of the tumour stroma and vasculature has profound biological and therapeutic implications, and there are several examples of carcinomas seemingly being derived from BMCs.

  • 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: Malcolm R Alison, Richard Poulsom, William R Otto, M Brittan, N 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.

  • adult Stem Cell Plasticity
    The Journal of Pathology, 2002
    Co-Authors: Richard Poulsom, Malcolm R Alison, N A Wright, S J Forbes
    Abstract:

    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.

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

  • Stem Cell Plasticity and tumour formation
    European Journal of Cancer, 2006
    Co-Authors: Malcolm R Alison, Matthew J Lovell, Natalie C Direkze, N A Wright, Richard Poulsom
    Abstract:

    Stem Cell Plasticity refers to the ability of certain Stem Cells to switch lineage determination and generate unexpected Cell types. This review applies largely to bone marrow Cells (BMCs), which appear to contribute positively to the regeneration of several damaged non-haematopoietic tissues. This beneficial effect on regeneration may be a direct result of BMCs giving rise to organ parenchymal Cells. Alternatively, it could be due to BMCs fusing with existing parenchymal Cells, or providing paracrine growth factor support, or contributing to neovascularisation. In the context of oncology, BMC derivation of the tumour stroma and vasculature has profound biological and therapeutic implications, and there are several examples of carcinomas seemingly being derived from BMCs.

  • 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: Malcolm R Alison, Richard Poulsom, William R Otto, M Brittan, N 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.

  • adult Stem Cell Plasticity
    The Journal of Pathology, 2002
    Co-Authors: Richard Poulsom, Malcolm R Alison, N A Wright, S J Forbes
    Abstract:

    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.

Mariusz Z Ratajczak - One of the best experts on this subject based on the ideXlab platform.

  • The developmental deposition of epiblast/germ Cell-line derived Cells in various organs as a hypothetical explanation of Stem Cell Plasticity?
    Acta Neurobiologiae Experimentalis, 2006
    Co-Authors: Magda Kucia, Bogusław Machaliński, Mariusz Z Ratajczak
    Abstract:

    The embryo develops from germ Cell line (fertilized oocyte) and precursors of primordial germ Cells (PGC) are the first population of Stem Cells that are specified in mice at the beginning of gastrulation in proximal primitive ectoderm (epiblast) - region adjacent to the extraembryonic ectoderm. These founder Cells subsequently move through the primitive streak and give rise to several extra-embryonic mesodermal lineages and to germ Cells. By day 7.25 of embryonic development, a cluster of PGC is visible at the basis of allantois. Subsequently PGC migrate through the embryo proper and colonize genital ridges, where they finally differentiate into sperm and oocytes. We hypothesize that during early development epiblast/germ line-derived Cells including PGC become a founder populations of pluripotent Stem Cells (PSC). These Cells are deposited during embryogenesis in various organs and may persist in these locations into adulthood - for example in bone marrow (BM). To support this, we recently identified in BM a population of very small embryonic-like (VSEL) Stem Cells that express epiblast/germ line-derived Cells transcription factor Oct-4 and several other PGC markers. Similarly, Cells expressing Oct-4 were also identified in several adult tissues by other investigators. Thus, pluripotent epiblast/PGC may persist beyond embryogenesis in neonatal and adult tissues. Their fate is defined by several mechanisms which regulate Cell proliferation and affect status of somatic imprint on selected genes responsible for pluripotency. We hypothesize that these Cells play an important role in tissue/organ regeneration and their presence in adult tissues may explain phenomenon of Stem Cell Plasticity. In pathological situations, however they may undergo malignant transformation and give rise to tumors.

  • the developmental deposition of epiblast germ Cell line derived Cells in various organs as a hypothetical explanation of Stem Cell Plasticity
    Acta Neurobiologiae Experimentalis, 2006
    Co-Authors: Magda Kucia, Boguslaw Machalinski, Mariusz Z Ratajczak
    Abstract:

    The embryo develops from germ Cell line (fertilized oocyte) and precursors of primordial germ Cells (PGC) are the first population of Stem Cells that are specified in mice at the beginning of gastrulation in proximal primitive ectoderm (epiblast) - region adjacent to the extraembryonic ectoderm. These founder Cells subsequently move through the primitive streak and give rise to several extra-embryonic mesodermal lineages and to germ Cells. By day 7.25 of embryonic development, a cluster of PGC is visible at the basis of allantois. Subsequently PGC migrate through the embryo proper and colonize genital ridges, where they finally differentiate into sperm and oocytes. We hypothesize that during early development epiblast/germ line-derived Cells including PGC become a founder populations of pluripotent Stem Cells (PSC). These Cells are deposited during embryogenesis in various organs and may persist in these locations into adulthood - for example in bone marrow (BM). To support this, we recently identified in BM a population of very small embryonic-like (VSEL) Stem Cells that express epiblast/germ line-derived Cells transcription factor Oct-4 and several other PGC markers. Similarly, Cells expressing Oct-4 were also identified in several adult tissues by other investigators. Thus, pluripotent epiblast/PGC may persist beyond embryogenesis in neonatal and adult tissues. Their fate is defined by several mechanisms which regulate Cell proliferation and affect status of somatic imprint on selected genes responsible for pluripotency. We hypothesize that these Cells play an important role in tissue/organ regeneration and their presence in adult tissues may explain phenomenon of Stem Cell Plasticity. In pathological situations, however they may undergo malignant transformation and give rise to tumors.

  • Stem Cell Plasticity revisited cxcr4 positive Cells expressing mrna for early muscle liver and neural Cells hide out in the bone marrow
    Leukemia, 2004
    Co-Authors: Mariusz Z Ratajczak, Magdalena Kucia, Ryan Reca, Marcin Majka, Anna Janowskawieczorek, Janina Ratajczak
    Abstract:

    Stem Cell Plasticity revisited: CXCR4-positive Cells expressing mRNA for early muscle, liver and neural Cells ‘hide out’ in the bone marrow

  • Circulating CXCR4-positive Stem-progenitor Cells compete for SDF-1-positive niches in bone marrow, muscle and naural tissues: an alternative hypothesis to Stem Cell Plasticity
    Folia Histochemica Et Cytobiologica, 2003
    Co-Authors: A Pituch-noworolska, Marcin Majka, Anna Janowska-wieczorek, Monika Baj-krzyworzeka, Barbara Urbanowicz, E Malec, Mariusz Z Ratajczak
    Abstract:

    The trans-differentiation hypothesis of adult tissue-specific Stem Cells has been recently questioned because of insufficient proof that the so-called Plasticity experiments were performed on pure populations of tissue-specific Stem Cells. It was shown recently, for example, that the formation of haematopoietic colonies by muscle Cells depended on the presence of haematopoietic Stem/progenitor Cells residing within the muscle tissue and hence was not related to the Plasticity of the muscle Stem Cells. The explanation for the presence in, or homing into, muscles of haematopoietic Stem Cells is, however, not clear. In our study, we hypothesised that muscle tissues secrete stromal-derived factor (SDF)- 1, an alpha-chemokine for haematopoietic Stem Cells (HSC), which could attract HSC circulating in peripheral blood into muscle tissue. We found, using RT-PCR and immunocytochemistry, that SDF-1 was expressed in human heart and skeletal muscles. Moreover, muscle satellite Cells, which are pivotal for regeneration of muscle, highly expressed on their surface CXCR4, a G-protein-coupled receptor that binds SDF-1. To determine whether the CXCR4 receptor is functional on muscle satellite/progenitor Cells, we stimulated murine satellite Cells (the C2C12 Cell line) with SDF-1 and demonstrated the phosphorylation of p42/44 MAPK and AKT serine-threonine kinase in these Cells. Moreover, we showed that SDF-1 gradient chemoattracts these Cells. We postulate that the CXCR4-positive muscle satellite and CXCR4-positive HSC circulating in the peripheral blood compete for occupancy of SDF-1-positive Stem Cell niches that are present in bone marrow and muscle tissues. Thus, we suggest that competition for common niches by various circulating CXCR4-positive Stem Cells and their ability to home to the SDF-1-positive niches in various organs, is a better explanation than Stem Cell Plasticity of why (i) haematopoietic colonies can be cultured from muscles and (ii) early muscle progenitors could be cultured from bone marrow.

Richard Poulsom - One of the best experts on this subject based on the ideXlab platform.

  • Stem Cell Plasticity and tumour formation
    European Journal of Cancer, 2006
    Co-Authors: Malcolm R Alison, Matthew J Lovell, Natalie C Direkze, N A Wright, Richard Poulsom
    Abstract:

    Stem Cell Plasticity refers to the ability of certain Stem Cells to switch lineage determination and generate unexpected Cell types. This review applies largely to bone marrow Cells (BMCs), which appear to contribute positively to the regeneration of several damaged non-haematopoietic tissues. This beneficial effect on regeneration may be a direct result of BMCs giving rise to organ parenchymal Cells. Alternatively, it could be due to BMCs fusing with existing parenchymal Cells, or providing paracrine growth factor support, or contributing to neovascularisation. In the context of oncology, BMC derivation of the tumour stroma and vasculature has profound biological and therapeutic implications, and there are several examples of carcinomas seemingly being derived from BMCs.

  • 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: Malcolm R Alison, Richard Poulsom, William R Otto, M Brittan, N 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.

  • adult Stem Cell Plasticity
    The Journal of Pathology, 2002
    Co-Authors: Richard Poulsom, Malcolm R Alison, N A Wright, S J Forbes
    Abstract:

    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.

Margaret A Goodell - One of the best experts on this subject based on the ideXlab platform.

  • Stem Cell Plasticity in muscle and bone marrow
    Annals of the New York Academy of Sciences, 2006
    Co-Authors: Margaret A Goodell, Kathyjo A Jackson, Susan M Majka, Tiejuan Mi, H Wang, Jennifer Pocius, Craig J Hartley, Mark W Majesky, Mark L Entman, Lloyd H Michael
    Abstract:

    : Recent discoveries have demonstrated the extraordinary Plasticity of tissue-derived Stem Cells, raising fundamental questions about Cell lineage relationships and suggesting the potential for novel Cell-based therapies. We have examined this phenomenon in a potential reciprocal relationship between Stem Cells derived from the skeletal muscle and from the bone marrow. We have discovered that Cells derived from the skeletal muscle of adult mice contain a remarkable capacity for hematopoietic differentiation. Cells prepared from muscle by enzymatic digestion and 5 day in vitro culture were harvested and introduced into each of six lethally irradiated recipients together with distinguishable whole bone marrow Cells. Six and twelve weeks later, all recipients showed high-level engraftment of muscle-derived Cells representing all major adult blood lineages. The mean total contribution of muscle Cell progeny to peripheral blood was 56%, indicating that the cultured muscle Cells generated approximately 10- to 14-fold more hematopoietic activity than whole bone marrow. Although the identity of the muscle-derived hematopoietic Stem Cells is still unknown, they may be identical to muscle satellite Cells, some of which lack myogenic regulators and could respond to hematopoietic signals. We have also found that Stem Cells in the bone marrow can contribute to cardiac muscle repair and neovascularization after ischemic injury. We transplanted highly purified bone marrow Stem Cells into lethally irradiated mice that subsequently were rendered ischemic by coronary artery occlusion and reperfusion. The engrafted Stem Cells or their progeny differentiated into cardiomyocytes and endothelial Cells and contributed to the formation of functional tissue.

  • Stem Cell Plasticity from transdifferentiation to macrophage fusion
    Cell Proliferation, 2004
    Co-Authors: Fernando D Camargo, Stuart M Chambers, Margaret A Goodell
    Abstract:

    Abstract.   The past 5 years have witnessed an explosion of interest in using adult-derived Stem Cells for Cell and gene therapy. This has been driven by a number of findings, in particular, the possibility that some adult Stem Cells can differentiate into non-autologous Cell types, and also the discovery of multipotential Stem Cells in adult bone marrow. These discoveries suggested a quasi-alchemical nature of Cells derived from adult organs, thus raising new and exciting therapeutic possibilities. Recent data, however, argue against the whole idea of Stem Cell ‘Plasticity’, and bring into question the therapeutic strategies based upon this concept. Here, we will review the current state of knowledge in the field and discuss some of the clinical implications.

  • Stem Cell Plasticity befuddled by the muddle
    Current Opinion in Hematology, 2003
    Co-Authors: Margaret A Goodell
    Abstract:

    In the past 4 years, multiple reports have suggested that Stem Cells derived from adult tissues can differentiate outside their tissue of origin, challenging long-accepted tenets of developmental biology. This concept of Stem-Cell “Plasticity” has helped to galvanize research on Stem Cells due to the myriad therapeutic possibilities. However, there are wide discrepancies in the reported frequencies of so-called transdifferentiation events, from recent reports of negative data to reports of the contribution in some tissues and syStems reaching as much as 20%. The evidence for and against Stem-Cell Plasticity is reviewed here as well as some of the possible sources of the experimental variation.

  • somatic Stem Cell Plasticity current evidence and emerging concepts
    Experimental Hematology, 2001
    Co-Authors: Gerald Wulf, Kathyjo A Jackson, Margaret A Goodell
    Abstract:

    In the 19 th century, mammalian tissues were first described to be composed of Cells, leading to the claim that Cells originate exclusively from other Cells (“omnis Cellula a Cellula”) formulated by Virchow and Schwann, respectively [1,2]. At the beginning of the 20 th century, the concept of tissue Stem Cells as the basis for tissue regeneration was introduced: analyzing the phylogeny of hematopoiesis in the bone marrow solely based on morphological observations, Pappenheim postulated the existence of an undifferentiated Stem Cell (“gemeinsame Stammzelle”) giving rise to the plethora of blood Cells via an intermediate state of progenitor Cells (Fig. 1, [3]). In the 1950s, several groups corroborated the existence of the hematopoietic Stem Cell in the bone marrow by showing hematopoietic recovery from transplanted bone marrow after irradiation damage [4–6]. Till and McCulloch later traced hematopoietic repopulation capacity to clonogenic Cells establishing spleen colony-forming units [7]. Subsequently, the concept of tissue regeneration from a small population of resident tissue Stem Cells was generally accepted, was extended to nonhematopoietic tissues such as gut and skin [8], and still is our understanding of adult tissue regeneration today, enriched by an immense body of descriptive data. In parallel, the principle of directed Cellular proliferation underlay the understanding of the early stages in embryogenesis and, together with the Cellular movement, led to the discovery of morphogenesis via germ layers in the early embryo [9]. With emerging technologies, it was 33 and 3 years ago that Stem Cells with the capacity to differentiate into all tissues of the adult organism were functionally isolated from preimplantation embryos in mice and humans, respectively, and were called embryonic Stem (ES) Cells [10–13]. Although the concept of Stem Cells in embryogenesis and Stem Cells in adult tissue regeneration were initially pursued in conceptually separate approaches, they merged again with the successful cloning of a mammal from the nucleus of an adult tissue Cell 4 years ago [14]. These experiments established that the nuclei of at least some adult Cells were capable of being reprogrammed and spurred several groups to reevaluate the differentiation capacity of adult tissue Stem Cells, leading to a number of reports on somatic Stem Cell Plasticity over the last 3 years. Here, we will review the current evidence for Stem Cell Plasticity. Following the chronology of discoveries, we will start from the broadening developmental potential of bone marrow–derived Stem Cells leading to the differentiation capacities of Stem Cells from nonhematopoietic tissues. We will discuss some of the potential caveats to the current work, and finally will speculate about the potential underlying mechanisms of transdifferentiation.