The DOI matches its Crossref record; 75 of the 75 references it cites were found in a registry or an index.
An acute immune response underlies the benefit of cardiac stem cell therapy
Open accessAbstract
Clinical trials using adult stem cells to regenerate damaged heart tissue continue to this day 1 , 2 , despite ongoing questions of efficacy and a lack of mechanistic understanding of the underlying biological effect 3 . The rationale for these cell therapy trials is derived from animal studies that show a modest but reproducible improvement in cardiac function in models of cardiac ischaemic injury 4 , 5 . Here we examine the mechanistic basis for cell therapy in mice after ischaemia–reperfusion injury, and find that—although heart function is enhanced—it is not associated with the production of new cardiomyocytes. Cell therapy improved heart function through an acute sterile immune response characterized by the temporal and regional induction of CCR2 + and CX3CR1 + macrophages. Intracardiac injection of two distinct types of adult stem cells, cells killed by freezing and thawing or a chemical inducer of the innate immune response all induced a similar regional accumulation of CCR2 + and CX3CR1 + macrophages, and provided functional rejuvenation to the heart after ischaemia–reperfusion injury. This selective macrophage response altered the activity of cardiac fibroblasts, reduced the extracellular matrix content in the border zone and enhanced the mechanical properties of the injured area. The functional benefit of cardiac cell therapy is thus due to an acute inflammatory-based wound-healing response that rejuvenates the infarcted area of the heart. Cardiac stem cell therapy in mouse models of ischaemia–reperfusion injury demonstrates that improvement in heart function is linked to an immune response characterized by the induction of CCR2 + and CX3CR1 + macrophages.
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Cites
Bone marrow cells regenerate infarcted myocardium
Orlic, D., Kajstura, J., Chimenti, S., Jakoniuk, I., Anderson, S. M., Li, B., Pickel, J., McKay, R., Nadal-Ginard, B., Bodine, D. M., et al. (2001) · Nature · doi:10.1038/35070587 · Cited by 5,155
Macrophages in Tissue Repair, Regeneration, and Fibrosis
Wynn, T. A., & Vannella, K. M. (2016) · Immunity · doi:10.1016/j.immuni.2016.02.015 · Cited by 4,481
Adult Cardiac Stem Cells Are Multipotent and Support Myocardial Regeneration
Beltrami, A. P., Barlucchi, L., Torella, D., Baker, M., Limana, F., Chimenti, S., Kasahara, H., Rota, M., Musso, E., Urbanek, K., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00687-1 · Cited by 3,534
Fate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis
Yona, S., Kim, K.-W., Wolf, Y., Mildner, A., Varol, D., Breker, M., Strauss-Ayali, D., Viukov, S., Guilliams, M., Misharin, A., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.12.001 · Cited by 3,245
Jung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.4106-4114.2000 · Cited by 2,632
Nahrendorf, M., Swirski, F. K., Aikawa, E., Stangenberg, L., Wurdinger, T., Figueiredo, J.-L., Libby, P., Weissleder, R., & Pittet, M. J. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070885 · Cited by 2,300
Self-citationThe Biological Basis for Cardiac Repair After Myocardial Infarction: From Inflammation to Fibrosis
Prabhu, S. D., & Frangogiannis, N. G. (2016) · Circulation Research · doi:10.1161/circresaha.116.303577 · Cited by 2,224
Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts
Murry, C. E., Soonpaa, M. H., Reinecke, H., Nakajima, H., Nakajima, H. O., Rubart, M., Pasumarthi, K. B. S., Ismail Virag, J., Bartelmez, S. H., Poppa, V., et al. (2004) · Nature · doi:10.1038/nature02446 · Cited by 2,154
Davies, L. C., Jenkins, S. J., Allen, J. E., & Taylor, P. R. (2013) · Nature Immunology · doi:10.1038/ni.2705 · Cited by 2,096
Paracrine Mechanisms in Adult Stem Cell Signaling and Therapy
Gnecchi, M., Zhang, Z., Ni, A., & Dzau, V. J. (2008) · Circulation Research · doi:10.1161/circresaha.108.176826 · Cited by 2,027
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Pang, S. H. M., D’Rozario, J., Mendonca, S., Bhuvan, T., Payne, N. L., Zheng, D., Hisana, A., Wallis, G., Barugahare, A., Powell, D., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26834-3 · Cited by 245
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Metadata
- Authors
- Vagnozzi, R. J., Maillet, M., Sargent, M. A., Khalil, H., Johansen, A. K. Z., Schwanekamp, J. A., York, A. J., Huang, V., Nahrendorf, M., Sadayappan, S., & Molkentin, J. D.
- Venue
- Nature
- Published
- 2019-11-27
- Volume
- 577
- Issue
- 7790
- Pages
- 405-409
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2990914781
- Cited by
- 554
- References
- 75
- FWCI
- 50.04
- Type
- journal article
- Language
- en
- Open access
- green
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- Vagnozzi, R. J., Maillet, M., Sargent, M. A., Khalil, H., Johansen, A. K. Z., Schwanekamp, J. A., York, A. J., Huang, V., Nahrendorf, M., Sadayappan, S., & Molkentin, J. D. (2020). An acute immune response underlies the benefit of cardiac stem cell therapy. Nature. https://doi.org/10.1038/s41586-019-1802-2
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