Evidence map›Paper›PMID 21463628›Full record

ArticleGastroenterology2011

Successful implantation of bioengineered, intrinsically innervated, human internal anal sphincter.

Shreya Raghavan, Robert R Gilmont, Eiichi A Miyasaka, Sita Somara, Shanthi Srinivasan, Daniel H Teitelbaum, Khalil N Bitar

Open access · greenAbstract read
In one paragraph

Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
7.7field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 77 citations in OpenAlex.

  1. Trial
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  8. Review
  9. Stromal cell derived factor 1 plasmid to regenerate the anal sphincters.Journal of tissue engineering and regenerative medicine · 2022
    Article
  10. Review
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  18. Bioengineering the gut: future prospects of regenerative medicine.Nature reviews. Gastroenterology & hepatology · 2016
    Review
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  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Shreya RaghavanGI Molecular Motors Lab, Department of Pediatrics-Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0658, USA.
Robert R Gilmont
Eiichi A Miyasaka
Sita Somara
Shanthi Srinivasan
Daniel H Teitelbaum
Khalil N Bitar
University of Michigan–Ann Arbor · USEmory University · US

Funding

TRAINING PROGRAM IN ORGANOGENESIST32HD007505 · NICHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PASCA DI MAGLIANO, MARINA, SPENCE, JASON · 1997 to 2021
$6.9M
Mechanism of Enteric NeuropathyR01DK080684 · NIDDK · EMORY UNIVERSITY · PI Shanthi K Srinivasan · 2009 to 2026
$6.1M
Restoration of Fecal Continence in Aging IASR01DK071614 · NIDDK · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI BITAR, KHALIL N · 2008 to 2012
$1.6M
Implantation of physiologically functional bioengineered innervated IAS constructRC1DK087151 · NIDDK · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI BITAR, KHALIL N · 2009 to 2010
$994k
NICHD NIH HHS T32 HD007505NICHD NIH HHS T32HD007505NIDDK NIH HHS 1RC1DK087151NIDDK NIH HHS R01 DK071614NIDDK NIH HHS R01DK071614NIDDK NIH HHS R01 DK080684NIDDK NIH HHS R01DK080684NIDDK NIH HHS RC1 DK087151
6 · The paper itself

Abstract

BACKGROUND &

aimsTo restore fecal continence, the weakened pressure of the internal anal sphincter (IAS) must be increased. We bioengineered intrinsically innervated human IAS to emulate sphincteric physiology in vitro.

methodsWe cocultured human IAS circular smooth muscle with immortomouse fetal enteric neurons. We investigated the ability of bioengineered innervated human IAS, implanted in RAG1-/- mice, to undergo neovascularization and preserve the physiology of the constituent myogenic and neuronal components.

resultsThe implanted IAS was neovascularized in vivo; numerous blood vessels were observed with no signs of inflammation or infection. Real-time force acquisition from implanted and preimplant IAS showed distinct characteristics of IAS physiology. Features included the development of spontaneous myogenic basal tone; relaxation of 100% of basal tone in response to inhibitory neurotransmitter vasoactive intestinal peptide (VIP) and direct electrical field stimulation of the intrinsic innervation; inhibition of nitrergic and VIPergic electrical field-induced relaxation (by antagonizing nitric oxide synthesis or receptor interaction); contraction in response to cholinergic stimulation with acetylcholine; and intact electromechanical coupling (evidenced by direct response to potassium chloride). Implanted, intrinsically innervated bioengineered human IAS tissue preserved the integrity and physiology of myogenic and neuronal components.

conclusionsIntrinsically innervated human IAS bioengineered tissue can be successfully implanted in mice. This approach might be used to treat patients with fecal incontinence.

Indexed as

Bioartificial OrgansGraft SurvivalAnal CanalAnimalsCells, CulturedCholinergic AgonistsCoculture TechniquesElectric StimulationEnzyme InhibitorsGastrointestinal MotilityHomeodomain ProteinsHormone AntagonistsHumansMiceMice, KnockoutMuscle ContractionCholinergic AgonistsEnzyme InhibitorsHomeodomain ProteinsHormone AntagonistsNitric Oxide SynthaseRAG-1 proteinReceptors, Vasoactive Intestinal PeptideVasoactive Intestinal Peptide

Identifiers

PMID21463628
PMCPMC3129458
OpenAlexW2022716403

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.