Mesenchymal stromal cells protect human cardiomyocytes from amyloid fibril damage

Yi Lin, Marta Marin-Argany, Christopher J. Dick, Keely R. Redhage, Luis M. Blancas-Mejia, Peggy Bulur, Greg W. Butler, Michael C. Deeds, Benjamin J. Madden, Angela Williams, Jonathan S. Wall, Allan B Dietz, Marina Ramirez-Alvarado

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
JournalCytotherapy
DOIs
StateAccepted/In press - 2017

Keywords

  • Amyloid
  • Cellular toxicity
  • Immunoglobulin light chain
  • Light chain amyloidosis
  • Mesenchymal stromal cells
  • Stem cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Transplantation
  • Cancer Research

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    Lin, Y., Marin-Argany, M., Dick, C. J., Redhage, K. R., Blancas-Mejia, L. M., Bulur, P., Butler, G. W., Deeds, M. C., Madden, B. J., Williams, A., Wall, J. S., Dietz, A. B., & Ramirez-Alvarado, M. (Accepted/In press). Mesenchymal stromal cells protect human cardiomyocytes from amyloid fibril damage. Cytotherapy. https://doi.org/10.1016/j.jcyt.2017.08.021