Dataset Information

Mesenchymal stromal cells protect human cardiomyocytes from amyloid fibril damage.

ABSTRACT:

Background aims

Light chain (AL) amyloidosis is a protein misfolding disease characterized by extracellular deposition of immunoglobulin light chains (LC) as amyloid fibrils. Patients with LC amyloid involvement of the heart have the worst morbidity and mortality. Current treatments target the plasma cells to reduce further production of amyloid proteins. There is dire need to understand the mechanisms of cardiac tissue damage from amyloid to develop novel therapies. We recently reported that LC soluble and fibrillar species cause apoptosis and inhibit cell growth in human cardiomyocytes. Mesenchymal stromal cells (MSCs) can promote wound healing and tissue remodeling. The objective of this study was to evaluate MSCs to protect cardiomyocytes affected by AL amyloid fibrils.

Methods

We used live cell imaging and proteomics to analyze the effect of MSCs in the growth arrest caused by AL amyloid fibrils.

Results

We evaluated the growth of human cardiomyocytes (RFP-AC16 cells) in the presence of cytotoxic LC amyloid fibrils. MSCs reversed the cell growth arrest caused by LC fibrils. We also demonstrated that this effect requires cell contact and may be mediated through paracrine factors modulating cell adhesion and extracellular matrix remodeling. To our knowledge, this is the first report of MSC protection of human cardiomyocytes in amyloid disease.

Conclusions

This important proof of concept study will inform future rational development of MSC therapy in cardiac LC amyloid.

SUBMITTER: Lin Y

PROVIDER: S-EPMC6456258 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Publications

Mesenchymal stromal cells protect human cardiomyocytes from amyloid fibril damage.

Lin Yi Y Marin-Argany Marta M Dick Christopher J CJ Redhage Keely R KR Blancas-Mejia Luis M LM Bulur Peggy P Butler Greg W GW Deeds Michael C MC Madden Benjamin J BJ Williams Angela A Wall Jonathan S JS Dietz Allan A Ramirez-Alvarado Marina M

Cytotherapy 20171014 12

<h4>Background aims</h4>Light chain (AL) amyloidosis is a protein misfolding disease characterized by extracellular deposition of immunoglobulin light chains (LC) as amyloid fibrils. Patients with LC amyloid involvement of the heart have the worst morbidity and mortality. Current treatments target the plasma cells to reduce further production of amyloid proteins. There is dire need to understand the mechanisms of cardiac tissue damage from amyloid to develop novel therapies. We recently reported ...[more]

PMID: 29037943

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Dataset Information

Mesenchymal stromal cells protect human cardiomyocytes from amyloid fibril damage.

Background aims

Methods

Results

Conclusions

Publications

Mesenchymal stromal cells protect human cardiomyocytes from amyloid fibril damage.

Similar Datasets

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