Evidence map›Paper›PMID 32417266›Full record

ArticleActa biomaterialia2020

Extracellular matrix mechanics regulate transfection and SOX9-directed differentiation of mesenchymal stem cells.

Adriana M Ledo, Kyle H Vining, Maria J Alonso, Marcos Garcia-Fuentes, David J Mooney

Open access · greenAbstract read
In one paragraph

Article in Acta biomaterialia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 7% 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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.

  1. Advances in Engineering Human Tissue Models.Frontiers in bioengineering and biotechnology · 2020
    Pooled it
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  7. [Preparation of collagen-polysaccharide composite hydrogels and research progress in biomedical applications].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2024
    Review
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  13. Article
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  16. Matrices Activated with Messenger RNA.Journal of functional biomaterials · 2023
    Review
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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

5 authors at 2 institutions in 2 countries.

Adriana M LedoDepartment of Pharmacy and Pharmaceutical Technology, IDIS Research Institute, CIMUS Research Institute, University of Santiago de Compostela, Santiago de Compostela 15782, Spain. Electronic address: adriana.martinez_ledo@novartis.com.
Kyle H ViningWyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA. Electronic address: kvining@g.harvard.edu.
Maria J AlonsoDepartment of Pharmacy and Pharmaceutical Technology, IDIS Research Institute, CIMUS Research Institute, University of Santiago de Compostela, Santiago de Compostela 15782, Spain. Electronic address: mariaj.alonso@usc.es.
Marcos Garcia-FuentesDepartment of Pharmacy and Pharmaceutical Technology, IDIS Research Institute, CIMUS Research Institute, University of Santiago de Compostela, Santiago de Compostela 15782, Spain. Electronic address: marcos.garcia@usc.es.
David J MooneyWyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA. Electronic address: mooneyd@seas.harvard.edu.
Universidade de Santiago de Compostela · ESHarvard University · US

Funding

POLYMERIC MATRICES WITH DEFINED CELL ADHESION AND MECHANR01DE013033 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MOONEY, DAVID J · 1998 to 2018
$3.0M
Anti-Inflammatory Mesenchymal Stem Cell Therapy for Dental ApplicationsK08DE025292 · NIDCR · HARVARD UNIVERSITY · PI VINING, KYLE HOLMBERG · 2016 to 2020
$635k
NIDCR NIH HHS K08 DE025292NIDCR NIH HHS R01 DE013033
6 · The paper itself

Abstract

Gene delivery within hydrogel matrices can potentially direct mesenchymal stem cells (MSCs) towards a chondrogenic fate to promote regeneration of cartilage. Here, we investigated whether the mechanical properties of the hydrogel containing the gene delivery systems could enhance transfection and chondrogenic programming of primary human bone marrow-derived MSCs. We developed collagen-I-alginate interpenetrating polymer network hydrogels with tunable stiffness and adhesion properties. The hydrogels were activated with nanocomplexed SOX9 polynucleotides to direct chondrogenic differentiation of MSCs. MSCs transfected within the hydrogels showed higher expression of chondrogenic markers compared to MSCs transfected in 2D prior to encapsulation. The nanocomplex uptake and resulting expression of transfected SOX9 were jointly enhanced by increased stiffness and cell-adhesion ligand density in the hydrogels. Further, transfection of SOX9 effectively induced MSCs chondrogenesis and reduced markers of hypertrophy compared to control matrices. These findings highlight the importance of matrix stiffness and adhesion as design parameters in gene-activated matrices for regenerative medicine. STATEMENT OF SIGNIFICANCE: Gene-activated matrices (GAMs) are biodegradable polymer networks integrating gene therapies, and they are promising technologies for supporting tissue regeneration. Despite this interest, there is still limited information on how to rationally design these systems. Here, we provide a systematic study of the effect of matrix stiffness and cell adhesion ligands on gene transfer efficiency. We show that high stiffness and the presence of cell-binding sites promote transfection efficiency and that this result is related to more efficient internalization and trafficking of the gene therapies. GAMs with optimized mechanical properties can induce cartilage formation and result in tissues with better characteristics for articular cartilage tissue engineering as compared to previously described standard methods.

Indexed as

Mesenchymal Stem CellsSOX9 Transcription FactorCell DifferentiationChondrogenesisExtracellular MatrixHumansHydrogelsTransfectionHydrogelsSOX9 protein, humanSOX9 Transcription Factor3D transfectionGAMsIPNsSOX9Tissue engineering

Identifiers

PMID32417266
PMCPMC7291356
OpenAlexW3024067848

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.