A model of the control of cellular regeneration in the intestinal crypt after perturbation based solely on local stem cell regulation.

2.50
Hdl Handle:
http://hdl.handle.net/10541/109003
Title:
A model of the control of cellular regeneration in the intestinal crypt after perturbation based solely on local stem cell regulation.
Authors:
Paulus, U; Potten, Christopher S; Loeffler, M
Abstract:
The control mechanisms involved in regeneration of murine intestinal crypts after perturbations are presently not well understood. The existence of some feedback signals from the cells on the villus to the cells in the crypt has been suggested. However, some recent experimental data point to the fact that regeneration in the crypt starts very early after perturbation, at a time when the villus cell population has hardly changed. In particular, this early cell proliferative activity is seen specifically at the bottom of the crypt, i.e. in the presumed stem cell zone and furthest from the villus. The objective of this study was to investigate whether a new concept of regulation operating solely at the stem cell level could explain the present mass of accumulated data on the post-irradiation recovery, which is an extensively studied perturbation from the experimental point of view. In order to check its validity, the new concept was formalized as a mathematical simulation model thus enabling comparison with experimental data. The model describes the cellular development from stem cells to the mature villus cells. As a basic feature it is assumed that the self-maintenance and the cell cycle activity of the stem cells are controlled by the number of these cells in an autoregulatory fashion. The essential features of the experimental data (i.e. the recovery with time and the consistency between different types of measurements) can be very well reproduced by simulations using a range of model parameters. Thus, we conclude that stem cell autoregulation is a valid concept which could replace the villus crypt feedback concept in explaining the early changes after irradiation when the damage primarily affects the crypt. The question of the detailed nature of the control process requires further investigation.
Affiliation:
Department of Biometry, Medizinische Universitaetsklinik I, Cologne, Germany.
Citation:
A model of the control of cellular regeneration in the intestinal crypt after perturbation based solely on local stem cell regulation. 1992, 25 (6):559-78 Cell Prolif.
Journal:
Cell Proliferation
Issue Date:
Nov-1992
URI:
http://hdl.handle.net/10541/109003
DOI:
10.1111/j.1365-2184.1992.tb01460.x
PubMed ID:
1457605
Type:
Article
Language:
en
ISSN:
0960-7722
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorPaulus, Uen
dc.contributor.authorPotten, Christopher Sen
dc.contributor.authorLoeffler, Men
dc.date.accessioned2010-08-04T10:02:05Z-
dc.date.available2010-08-04T10:02:05Z-
dc.date.issued1992-11-
dc.identifier.citationA model of the control of cellular regeneration in the intestinal crypt after perturbation based solely on local stem cell regulation. 1992, 25 (6):559-78 Cell Prolif.en
dc.identifier.issn0960-7722-
dc.identifier.pmid1457605-
dc.identifier.doi10.1111/j.1365-2184.1992.tb01460.x-
dc.identifier.urihttp://hdl.handle.net/10541/109003-
dc.description.abstractThe control mechanisms involved in regeneration of murine intestinal crypts after perturbations are presently not well understood. The existence of some feedback signals from the cells on the villus to the cells in the crypt has been suggested. However, some recent experimental data point to the fact that regeneration in the crypt starts very early after perturbation, at a time when the villus cell population has hardly changed. In particular, this early cell proliferative activity is seen specifically at the bottom of the crypt, i.e. in the presumed stem cell zone and furthest from the villus. The objective of this study was to investigate whether a new concept of regulation operating solely at the stem cell level could explain the present mass of accumulated data on the post-irradiation recovery, which is an extensively studied perturbation from the experimental point of view. In order to check its validity, the new concept was formalized as a mathematical simulation model thus enabling comparison with experimental data. The model describes the cellular development from stem cells to the mature villus cells. As a basic feature it is assumed that the self-maintenance and the cell cycle activity of the stem cells are controlled by the number of these cells in an autoregulatory fashion. The essential features of the experimental data (i.e. the recovery with time and the consistency between different types of measurements) can be very well reproduced by simulations using a range of model parameters. Thus, we conclude that stem cell autoregulation is a valid concept which could replace the villus crypt feedback concept in explaining the early changes after irradiation when the damage primarily affects the crypt. The question of the detailed nature of the control process requires further investigation.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshCell Death-
dc.subject.meshCell Division-
dc.subject.meshComputer Simulation-
dc.subject.meshGamma Rays-
dc.subject.meshIntestinal Mucosa-
dc.subject.meshMathematics-
dc.subject.meshMice-
dc.subject.meshMice, Inbred Strains-
dc.subject.meshModels, Biological-
dc.subject.meshStem Cells-
dc.titleA model of the control of cellular regeneration in the intestinal crypt after perturbation based solely on local stem cell regulation.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biometry, Medizinische Universitaetsklinik I, Cologne, Germany.en
dc.identifier.journalCell Proliferationen

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