Next Article in Journal
In Vitro Characterization of Dental Pulp Stem Cells Cultured in Two Microsphere-Forming Culture Plates
Next Article in Special Issue
Eph/ephrin Signaling and Biology of Mesenchymal Stromal/Stem Cells
Previous Article in Journal
Potential Salivary mRNA Biomarkers for Early Detection of Oral Cancer
Previous Article in Special Issue
HCMV Infection in a Mesenchymal Stem Cell Niche: Differential Impact on the Development of NK Cells versus ILC3
Open AccessReview

Immune Dysregulation in HFpEF: A Target for Mesenchymal Stem/Stromal Cell Therapy

1
Center for Regenerative Medicine, University of Florida, Gainesville, FL 32610, USA
2
Cardiology Department, Elias Emergency University Hospital, 011461 Bucharest, Romania
3
Division of Cardiovascular Medicine, Department of Medicine, University of Florida, Gainesville, FL 32610, USA
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(1), 241; https://doi.org/10.3390/jcm9010241 (registering DOI)
Received: 23 December 2019 / Revised: 12 January 2020 / Accepted: 14 January 2020 / Published: 16 January 2020
(This article belongs to the Special Issue Mesenchymal Stem/Stromal Cells in Immunity and Disease)
Over 26 million people worldwide suffer from heart failure, a disease associated with a 1 year mortality rate of 22%. Half of these patients present heart failure with preserved ejection fraction (HFpEF), for which there is no available therapy to improve prognosis. HFpEF is strongly associated with aging, inflammation, and comorbid burden, which are thought to play causal roles in disease development. Mesenchymal stromal/stem cells (MSCs) have potent immunomodulatory actions and promote tissue healing, thus representing an attractive therapeutic option in HFpEF. In this review, we summarize recent data suggesting that a two-hit model of immune dysregulation lies at the heart of the HFpEF. A first hit is represented by genetic mutations associated with clonal hematopoiesis of indeterminate potential (CHIP), which skew immune cells toward a pro-inflammatory phenotype, are associated with HFpEF development in animal models, and with immune dysregulation and risk of HF hospitalization in patients. A second hit is induced by cardiovascular risk factors, which cause subclinical cardiac dysfunction and production of danger signals. In mice, these attract proinflammatory macrophages, Th1 and Th17 cells into the myocardium, where they are required for the development of HFpEF. MSCs have been shown to reduce the pro-inflammatory activity of immune cell types involved in murine HFpEF in vitro, and to reduce myocardial fibrosis and improve diastolic function in vivo, thus they may efficiently target immune dysregulation in HFpEF and stop disease progression. View Full-Text
Keywords: HFpEF; immune dysregulation; inflammation; mesenchymal stromal/stem cells; MSC; CHIP HFpEF; immune dysregulation; inflammation; mesenchymal stromal/stem cells; MSC; CHIP
Show Figures

Graphical abstract

MDPI and ACS Style

Sava, R.I.; Pepine, C.J.; March, K.L. Immune Dysregulation in HFpEF: A Target for Mesenchymal Stem/Stromal Cell Therapy. J. Clin. Med. 2020, 9, 241.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop