Evidence map›Paper›PMID 26378976›Full record

ArticleBiomaterials2015

Hyaluronic acid-serum hydrogels rapidly restore metabolism of encapsulated stem cells and promote engraftment.

Angel T Chan, Mehmet F Karakas, Styliani Vakrou, Junaid Afzal, Andrew Rittenbach, Xiaoping Lin, Richard L Wahl, Martin G Pomper, Charles J Steenbergen, Benjamin M W Tsui and 2 more

Abstract read
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In one paragraph

Article in Biomaterials, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.4field-weighted citation impact, top 21% 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

11 citing papers in PubMed, 43 citations in OpenAlex.

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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

12 authors at 1 institution in 1 country.

Angel T ChanDepartment of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Mehmet F KarakasDepartment of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Styliani VakrouDepartment of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Junaid AfzalDepartment of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Andrew RittenbachDepartment of Radiology, Johns Hopkins University, Baltimore, MD, USA.
Xiaoping LinDepartment of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Richard L WahlDepartment of Radiology, Johns Hopkins University, Baltimore, MD, USA.
Martin G PomperDepartment of Radiology, Johns Hopkins University, Baltimore, MD, USA.
Charles J SteenbergenDepartment of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Benjamin M W TsuiDepartment of Radiology, Johns Hopkins University, Baltimore, MD, USA.
Jennifer H ElisseeffDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
M Roselle AbrahamDepartment of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Johns Hopkins University · US

Funding

Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8M
PATHOPHYSIOLOGY OF MYOCARDIAL DISEASEST32HL007227 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI Chulan Kwon, WENDY S POST · 1985 to 2026
$21.2M
Imaging of the Myocardial Microenvironment to Facilitate Stem Cell EngraftmentR01HL092985 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI ABRAHAM, MARIA ROSELLE, WAHL, RICHARD LEO · 2010 to 2014
$2.3M
NCRR NIH HHS UL1 RR 025005NCRR NIH HHS UL1 RR025005NHLBI NIH HHS R01 HL092985NHLBI NIH HHS T32 HL007227NHLBI NIH HHS T32HL07227
6 · The paper itself

Abstract

backgroundCell death due to anoikis, necrosis and cell egress from transplantation sites limits functional benefits of cellular cardiomyoplasty. Cell dissociation and suspension, which are a pre-requisite for most cell transplantation studies, lead to depression of cellular metabolism and anoikis, which contribute to low engraftment.

objectiveWe tissue engineered scaffolds with the goal of rapidly restoring metabolism, promoting viability, proliferation and engraftment of encapsulated stem cells.

methodsThe carboxyl groups of HA were functionalized with N-hydroxysuccinimide (NHS) to yield HA succinimidyl succinate (HA-NHS) groups that react with free amine groups to form amide bonds. HA-NHS was cross-linked by serum to generate HA:Serum (HA:Ser) hydrogels. Physical properties of HA:Ser hydrogels were measured. Effect of encapsulating cardiosphere-derived cells (CDCs) in HA:Ser hydrogels on viability, proliferation, glucose uptake and metabolism was assessed in vitro. In vivo acute intra-myocardial cell retention of (18)FDG-labeled CDCs encapsulated in HA:Ser hydrogels was quantified. Effect of CDC encapsulation in HA:Ser hydrogels on in vivo metabolism and engraftment at 7 days was assessed by serial, dual isotope SPECT-CT and bioluminescence imaging of CDCs expressing the Na-iodide symporter and firefly luciferase genes respectively. Effect of HA:Ser hydrogels ± CDCs on cardiac function was assessed at 7 days & 28 days post-infarct.

resultsHA:Ser hydrogels are highly bio-adhesive, biodegradable, promote rapid cell adhesion, glucose uptake and restore bioenergetics of encapsulated cells within 1 h of encapsulation, both in vitro and in vivo. These metabolic scaffolds can be applied epicardially as a patch to beating hearts or injected intramyocardially. HA:Ser hydrogels markedly increase acute intramyocardial retention (∼6 fold), promote in vivo viability, proliferation, engraftment of encapsulated stem cells and angiogenesis.

conclusionHA:Ser hydrogels serve as 'synthetic stem cell niches' that rapidly restore metabolism of encapsulated stem cells, promote stem cell engraftment and angiogenesis. These first ever, tissue engineered metabolic scaffolds hold promise for clinical translation in conjunction with CDCs and possibly other stem cell types.

Indexed as

AnimalsBiocompatible MaterialsCell AdhesionCell ProliferationCell SurvivalCell TransplantationEchocardiographyElastic ModulusEmbryonic Stem CellsFemaleFluorodeoxyglucose F18GlucoseHeartHumansHyaluronic AcidHydrogelsBiocompatible MaterialsFluorodeoxyglucose F18GlucoseHyaluronic AcidHydrogelsIntercellular Signaling Peptides and ProteinsAngiogenesisEngraftmentHA:Serum hydrogelsMetabolismMolecular imagingStem cells

Identifiers

PMID26378976
PMCPMC4980097
OpenAlexW1679277848

What OpenQuestion holds

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Registered trials

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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.