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Can Systems Proteomics Boost Cardiopoietic Stem Cell Therapy Translation?

Review of “Cardiopoietic stem cell therapy restores infarction-altered cardiac proteome” from NPJ Regenerative Medicine by Stuart P. Atkinson

Following successful preclinical studies [1, 2], cardiopoietic stem cell therapy has now been evaluated in clinical trials as a means to treat heart failure [3, 4]; however, the molecular impact of cardiopoietic stem cell transplantation in the heart remains relatively unexplored. To remedy this knowledge gap, a team of researchers led by Andre Terzic (Mayo Clinic, Rochester, MN, USA) recently analyzed the molecular consequences of transplanting cardiopoietic stem cells derived from human bone marrow-derived mesenchymal stem cells [3, 4] into the infarcted mouse heart using a systems proteomics approach [5]. This fascinating study now reveals extensive proteome remodeling within the infarcted heart and establishes that cardiopoietic stem cell therapy reverses disease-associated proteomic changes. Can systems proteomics help to boost the translational potential of cardiopoietic stem cell therapy and other regenerative approaches?

Arrell et al. employed multidimensional label-free tandem mass spectrometry to identify a healthy mouse cardiac proteome of around 4000 proteins and highlight the alteration of some 450 proteins following myocardial infarction. Fascinatingly, human cardiopoietic stem cell transplantation significantly reversed infarction-provoked proteome alterations and mediated a functional reorganization that promoted vasculogenesis, cardiac development, organ regeneration, and differentiation. Furthermore, the reversion of infarction-provoked proteomic alterations by human cardiopoietic stem cell transplantation also ameliorated the adverse ischemic effects associated with infarction, as evidenced by improved cardiac chamber size, reduced QT prolongation, and augmented ejection fraction.

While this study highlights cardiopoietic stem cell therapy as an effective means to treat myocardial infarctions, these findings also underscore how systems proteomics can delineate and interpret complex regenerative outcomes. Indeed, the authors state that the future integration of high-throughput, high-resolution systems readouts to further dissect and interpret complex molecular outcomes [6, 7] may significantly contribute to the translation of regenerative technologies.

For more on systems proteomics-based analyses of regenerative stem cell therapies, stay tuned to the Stem Cells Portal!

 

References

  1. Behfar A, Yamada S, Crespo-Diaz R, et al., Guided Cardiopoiesis Enhances Therapeutic Benefit of Bone Marrow Human Mesenchymal Stem Cells in Chronic Myocardial Infarction. Journal of the American College of Cardiology 2010;56:721-734.
  2. Emmert MY, Wolint P, Jakab A, et al., Safety and efficacy of cardiopoietic stem cells in the treatment of post-infarction left-ventricular dysfunction – From cardioprotection to functional repair in a translational pig infarction model. Biomaterials 2017;122:48-62.
  3. Bartunek J, Behfar A, Dolatabadi D, et al., Cardiopoietic Stem Cell Therapy in Heart Failure: The C-CURE (Cardiopoietic stem Cell therapy in heart failURE) Multicenter Randomized Trial With Lineage-Specified Biologics. Journal of the American College of Cardiology 2013;61:2329-2338.
  4. Bartunek J and Wojakowski W, Intracoronary autologous bone marrow cell transfer after acute myocardial infarction: abort and refocus. European Heart Journal 2017;38:2944-2947.
  5. Arrell DK, Rosenow CS, Yamada S, et al., Cardiopoietic stem cell therapy restores infarction-altered cardiac proteome. NPJ Regenerative Medicine 2020;5:5.
  6. Lau E and Wu Joseph C, Omics, Big Data, and Precision Medicine in Cardiovascular Sciences. Circulation Research 2018;122:1165-1168.
  7. Leopold Jane A and Loscalzo J, Emerging Role of Precision Medicine in Cardiovascular Disease. Circulation Research 2018;122:1302-1315.