Bone Marrow Cells in Murine Colitis: Multi-Signal Analysis Confirms Pericryptal Myofibroblast Engraftment without Epithelial Involvement

Lee, Chung-Yin; Jeffery, Rosemary; Hutchinson, Gillian; Alison, Malcolm R.; Poulsom, Richard; Wright, Nicholas; Otto, W

doi:10.1371/journal.pone.0026082

Cited by 5 publications

(4 citation statements)

References 45 publications

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“…Susceptibly of DSS to induce colitis differs amongst different mouse strains [24,25]. Therefore, we used 3% DSS in our experiments with C57BL/6J based on our previous work [8,19], and 5% DSS [26] for the germ free mouse experiment. The animals were weighed daily and colonic length measurements were performed at the end of the experiments following CO 2 asphyxiation.…”

Section: Methodsmentioning

confidence: 99%

Prenatal Methyl-Donor Supplementation Augments Colitis in Young Adult Mice

Mir

Nagy‐Szakal

Dowd³

et al. 2013

PLoS ONE

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Inflammatory bowel diseases (IBD) have become highly prevalent in developed countries. Environmentally triggered exaggerated immune responses against the intestinal microbiome are thought to mediate the disorders. The potential dietary origins of the disease group have been implicated. However, the effects of environmental influences on prenatal developmental programming in respect to orchestrating postnatal microbiome composition and predilection towards mammalian colitis have not been examined. We tested how transient prenatal exposure to methyl donor micronutrient (MD) supplemented diets may impact predilection towards IBD in a murine dextran sulfate sodium (DSS) colitis model. Prenatal MD supplementation was sufficient to modulate colonic mucosal Ppara expression (3.2 fold increase; p=0.022) and worsen DSS colitis in young adulthood. The prenatal dietary exposure shifted the postnatal colonic mucosal and cecal content microbiomes. Transfer of the gut microbiome from prenatally MD supplemented young adult animals into germ free mice resulted in increased colitis susceptibility in the recipients compared to controls. Therefore, the prenatal dietary intervention induced the postnatal nurturing of a colitogenic microbiome. Our results show that prenatal nutritional programming can modulate the mammalian host to harbor a colitogenic microbiome. These findings may be relevant for the nutritional developmental origins of IBD.

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Section: Methodsmentioning

confidence: 99%

Prenatal Methyl-Donor Supplementation Augments Colitis in Young Adult Mice

Mir

Nagy‐Szakal

Dowd³

et al. 2013

PLoS ONE

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“…Bone marrow-derived cells contributing to the (myo)fibroblast population in the stomach, small intestine, and colon of rats and mice were shown in all seven included studies [ 5 , 32 , 33 , 34 , 35 , 36 , 37 ]. Lee et al [ 37 ] observed pericryptal engraftment in the stomach but no epithelial engraftment. Several models of inflammation/damage induction reported an increase in engrafted (myo)fibroblasts in gastrointestinal tissues.…”

Section: Resultsmentioning

confidence: 99%

A Systematic Review of the Evidence of Hematopoietic Stem Cell Differentiation to Fibroblasts

et al. 2022

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Fibroblasts have an important role in the maintenance of the extracellular matrix of connective tissues by producing and remodelling extracellular matrix proteins. They are indispensable for physiological processes, and as such also associate with many pathological conditions. In recent years, a number of studies have identified donor-derived fibroblasts in various tissues of bone marrow transplant recipients, while others could not replicate these findings. In this systematic review, we provide an overview of the current literature regarding the differentiation of hematopoietic stem cells into fibroblasts in various tissues. PubMed, Embase, and Web of Science (Core Collection) were systematically searched for original articles concerning fibroblast origin after hematopoietic stem cell transplantation in collaboration with a medical information specialist. Our search found 5421 studies, of which 151 were analysed for full-text analysis by two authors independently, resulting in the inclusion of 104 studies. Only studies in animals and humans, in which at least one marker was used for fibroblast identification, were included. The results were described per organ of fibroblast engraftment. We show that nearly all mouse and human organs show evidence of fibroblasts of hematopoietic stem cell transfer origin. Despite significant heterogeneity in the included studies, most demonstrate a significant presence of fibroblasts of hematopoietic lineage in non-hematopoietic tissues. This presence appears to increase after the occurrence of tissue damage.

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“…The fate of bone marrow derived cells migrated to colons during colitis is an active and controversial area of research. After bone marrow transplantation and induction of murine colitis, it is likely that some of bone marrow derived cells exist as lymphoid cells and myofibroblasts in the colons 5 . Another report suggested that bone marrow derived cells serve as endothelial progenitor cells for neovascularization in recovery process 6 .…”

Section: Discussionmentioning

confidence: 99%

Differentiating Functional Roles of Gene Expression from Immune and Non-immune Cells in Mouse Colitis by Bone Marrow Transplantation

Koon

Cheng

et al. 2012

JoVE

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To understand the role of a gene in the development of colitis, we compared the responses of wild-type mice and gene-of-interest deficient knockout mice to colitis. If the gene-of-interest is expressed in both bone marrow derived cells and non-bone marrow derived cells of the host; however, it is possible to differentiate the role of a gene of interest in bone marrow derived cells and non-bone marrow derived cells by bone marrow transplantation technique. To change the bone marrow derived cell genotype of mice, the original bone marrow of recipient mice were destroyed by irradiation and then replaced by new donor bone marrow of different genotype. When wild-type mice donor bone marrow was transplanted to knockout mice, we could generate knockout mice with wild-type gene expression in bone marrow derived cells. Alternatively, when knockout mice donor bone marrow was transplanted to wild-type recipient mice, wild-type mice without gene-of-interest expressing from bone marrow derived cells were produced. However, bone marrow transplantation may not be 100% complete. Therefore, we utilized cluster of differentiation (CD) molecules (CD45.1 and CD45.2) as markers of donor and recipient cells to track the proportion of donor bone marrow derived cells in recipient mice and success of bone marrow transplantation. Wild-type mice with CD45.1 genotype and knockout mice with CD45.2 genotype were used. After irradiation of recipient mice, the donor bone marrow cells of different genotypes were infused into the recipient mice. When the new bone marrow regenerated to take over its immunity, the mice were challenged by chemical agent (dextran sodium sulfate, DSS 5%) to induce colitis. Here we also showed the method to induce colitis in mice and evaluate the role of the gene of interest expressed from bone-marrow derived cells. If the gene-of-interest from the bone derived cells plays an important role in the development of the disease (such as colitis), the phenotype of the recipient mice with bone marrow transplantation can be significantly altered. At the end of colitis experiments, the bone marrow derived cells in blood and bone marrow were labeled with antibodies against CD45.1 and CD45.2 and their quantitative ratio of existence could be used to evaluate the success of bone marrow transplantation by flow cytometry. Successful bone marrow transplantation should show a vast majority of donor genotype (in term of CD molecule marker) over recipient genotype in both the bone marrow and blood of recipient mice. Video LinkThe video component of this article can be found at http://www.jove.com/video/4208/ Protocol 1. Before-you-start Technical Considerations 1. We recommend using both C57/BL6 wild-type mice and knockout mice for experiment because mice with corresponding CD molecules can be purchased from major mouse vendors. 2. Since it is difficult to track the wild-type mice and knockout mice derived donor cells after bone marrow transplantation, it is necessary to use CD45.1 mice to represent wild-type mice. (CD45.1 C57...

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Bone Marrow Cells in Murine Colitis: Multi-Signal Analysis Confirms Pericryptal Myofibroblast Engraftment without Epithelial Involvement

Cited by 5 publications

References 45 publications

Prenatal Methyl-Donor Supplementation Augments Colitis in Young Adult Mice

Prenatal Methyl-Donor Supplementation Augments Colitis in Young Adult Mice

A Systematic Review of the Evidence of Hematopoietic Stem Cell Differentiation to Fibroblasts

Differentiating Functional Roles of Gene Expression from Immune and Non-immune Cells in Mouse Colitis by Bone Marrow Transplantation

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