Adult stem cell plasticity: Will engineered tissues be rejected?

Te Chao Fang, Malcolm R. Alison, Nicholas A. Wright, Richard Poulsom

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)115-124
Number of pages10
JournalInternational Journal of Experimental Pathology
Volume85
Issue number3
DOIs
Publication statusPublished - Jun 2004
Externally publishedYes

Fingerprint

Adult Stem Cells
Liver Regeneration
Cell- and Tissue-Based Therapy
Stem Cells
Tissue Donors
Transplants
Phenotype
Inborn Genetic Diseases
Cell Fusion
Hematopoietic Stem Cells
Immunity
Skeletal Muscle
Cell Plasticity
Pressure
Brain
Population
Proteins

Keywords

  • Adult stem cells
  • Cell fusion
  • Cell therapy
  • Immune rejection
  • Plasticity
  • Tissue regeneration

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Adult stem cell plasticity : Will engineered tissues be rejected? / Fang, Te Chao; Alison, Malcolm R.; Wright, Nicholas A.; Poulsom, Richard.

In: International Journal of Experimental Pathology, Vol. 85, No. 3, 06.2004, p. 115-124.

Research output: Contribution to journalArticle

Fang, Te Chao ; Alison, Malcolm R. ; Wright, Nicholas A. ; Poulsom, Richard. / Adult stem cell plasticity : Will engineered tissues be rejected?. In: International Journal of Experimental Pathology. 2004 ; Vol. 85, No. 3. pp. 115-124.
@article{b44c2c69f2564f12964ba739fb2ffb91,
title = "Adult stem cell plasticity: Will engineered tissues be rejected?",
abstract = "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.",
keywords = "Adult stem cells, Cell fusion, Cell therapy, Immune rejection, Plasticity, Tissue regeneration",
author = "Fang, {Te Chao} and Alison, {Malcolm R.} and Wright, {Nicholas A.} and Richard Poulsom",
year = "2004",
month = "6",
doi = "10.1111/j.0959-9673.2004.00380.x",
language = "English",
volume = "85",
pages = "115--124",
journal = "International Journal of Experimental Pathology",
issn = "0959-9673",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Adult stem cell plasticity

T2 - Will engineered tissues be rejected?

AU - Fang, Te Chao

AU - Alison, Malcolm R.

AU - Wright, Nicholas A.

AU - Poulsom, Richard

PY - 2004/6

Y1 - 2004/6

N2 - 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.

AB - 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.

KW - Adult stem cells

KW - Cell fusion

KW - Cell therapy

KW - Immune rejection

KW - Plasticity

KW - Tissue regeneration

UR - http://www.scopus.com/inward/record.url?scp=3843055848&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3843055848&partnerID=8YFLogxK

U2 - 10.1111/j.0959-9673.2004.00380.x

DO - 10.1111/j.0959-9673.2004.00380.x

M3 - Article

C2 - 15255965

AN - SCOPUS:3843055848

VL - 85

SP - 115

EP - 124

JO - International Journal of Experimental Pathology

JF - International Journal of Experimental Pathology

SN - 0959-9673

IS - 3

ER -