Small intestinal stem cells

King, Stephanie L.; Dekaney, Christopher M.

doi:10.1097/mog.0b013e32835cf253

Cited by 12 publications

(5 citation statements)

References 52 publications

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“…Maintenance of the intestinal stem cell niche, including Paneth cells and mesenchymal cells such as intestinal subepithelial myofibroblasts, is believed to be critical to intestinal stem cell health. 43 In support of this hypothesis we previously identified preserved epithelialmesenchymal relationships during TESI formation. 12 Based on our published observations in TESI, 12 we expected to observe conservation of original epithelial-mesenchymal spatial relationships in TEE (Fig.…”

Section: Ck13supporting

confidence: 58%

Murine and Human Tissue-Engineered Esophagus Form from Sufficient Stem/Progenitor Cells and Do Not Require Microdesigned Biomaterials

Spurrier

Speer

Hou

et al. 2015

Tissue Engineering Part A

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Purpose: Tissue-engineered esophagus (TEE) may serve as a therapeutic replacement for absent foregut. Most prior esophagus studies have favored microdesigned biomaterials and yielded epithelial growth alone. None have generated human TEE with mesenchymal components. We hypothesized that sufficient progenitor cells might only require basic support for successful generation of murine and human TEE. Materials and Methods: Esophageal organoid units (EOUs) were isolated from murine or human esophagi and implanted on a polyglycolic acid/poly-l-lactic acid collagen-coated scaffold in adult allogeneic or immunedeficient mice. Alternatively, EOU were cultured for 10 days in vitro prior to implantation. Results: TEE recapitulated all key components of native esophagus with an epithelium and subjacent muscularis. Differentiated suprabasal and proliferative basal layers of esophageal epithelium, muscle, and nerve were identified. Lineage tracing demonstrated that multiple EOU could contribute to the epithelium and mesenchyme of a single TEE. Cultured murine EOU grew as an expanding sphere of proliferative basal cells on a neuromuscular network that demonstrated spontaneous peristalsis in culture. Subsequently, cultured EOU generated TEE. Conclusions: TEE forms after transplantation of mouse and human organ-specific stem/progenitor cells in vivo on a relatively simple biodegradable scaffold. This is a first step toward future human therapies.

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Section: Ck13supporting

confidence: 58%

Murine and Human Tissue-Engineered Esophagus Form from Sufficient Stem/Progenitor Cells and Do Not Require Microdesigned Biomaterials

Spurrier

Speer

Hou

et al. 2015

Tissue Engineering Part A

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“…Current literature suggests there are two broad categories of ISCs: an actively cycling population found at the crypt base and marked by Lgr5; and one (or more) relatively quiescent population(s) located a little higher in the crypt (Barker, et al, 2012, Carlone and Breault, 2012, King and Dekaney, 2013, Potten, et al, 2009, Shaker and Rubin, 2010). The former, herein designated “active ISCs”, are believed to be primarily responsible for daily turnover of the epithelium under homeostatic conditions, whereas the latter, designated “reserve ISCs”, appear to function as a source of epithelial replacement and crypt regeneration after intestinal damage.…”

Section: Introductionmentioning

confidence: 99%

Tissue underlying the intestinal epithelium elicits proliferation of intestinal stem cells following cytotoxic damage

et al. 2015

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The goals of this study were to document the proliferative response of intestinal stem cells (ISCs) during regeneration after damage from doxorubicin (DXR) and to characterize the signals responsible for ISC activation. To this end, jejuni from DXR-treated mice were harvested for histology, assessment of ISC numbers and proliferation by flow cytometry, crypt culture, and RNA analyses. Histology showed that crypt depth and width were increased 4 days after DXR. At this time point, flow cytometry on tissue collected 1 hour after EdU administration revealed increased numbers of CD24loUEA− ISCs and increased percentage of ISCs cycling. In culture, crypts harvested from DXR-treated mice were equally proliferative as those of control mice. Addition of subepithelial intestinal tissue (SET) collected 4 days after DXR elicited increased budding (1.4 ± 0.3 vs. 5.1 ± 1.0 buds per enteroid). Microarray analysis of SET collected 4 days after DXR revealed 1,030 differentially expressed transcripts. Cross comparison of Gene Ontology terms considered relevant to ISC activation pointed to 10 candidate genes. Of these the epidermal growth factor (EGF) family member amphiregulin and the BMP antagonist chordin-like 2 were chosen for further study. In crypt culture, amphiregulin alone did not elicit significant budding, but amphiregulin in combination with BMP antagonism showed marked synergism (yielding 6.3 ± 0.5 buds per enteroid). These data suggest a critical role for underlying tissue in regulating ISC behavior after damage, and point to synergism between amphiregulin and chordin-like 2 as factors which may account for activation of ISCs in the regenerative phase.

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“…There have been recent strides in the characterization of both ISC biology, and the niche they occupy (Barker et al, 2012; King and Dekaney, 2013; Lund, 2012; Noah et al, 2011). These advances have in large part been a product of transgenic reporter mice.…”

Section: Introductionmentioning

confidence: 99%

Side population sorting separates subfractions of cycling and non-cycling intestinal stem cells

et al. 2014

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Small intestinal stem cells

Abstract: This brief review provides a general historical perspective of our understanding of the delineation of the two ISC populations. Furthermore, it discusses the known ISC markers and how these markers have been used to isolate and characterize ISC populations.

Cited by 12 publications

References 52 publications

Murine and Human Tissue-Engineered Esophagus Form from Sufficient Stem/Progenitor Cells and Do Not Require Microdesigned Biomaterials

Murine and Human Tissue-Engineered Esophagus Form from Sufficient Stem/Progenitor Cells and Do Not Require Microdesigned Biomaterials

Tissue underlying the intestinal epithelium elicits proliferation of intestinal stem cells following cytotoxic damage

Side population sorting separates subfractions of cycling and non-cycling intestinal stem cells

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