Convergences of Life Sciences and Engineering in Understanding and Treating Heart Failure

Abstract

On March 1 and 2, 2018, the National Institutes of Health 2018 Progenitor Cell Translational Consortium (PCTC) and Cardiovascular Bioengineering Symposium (CVBE) was held at the University of Alabama at Birmingham. Convergence of life sciences and engineering to advance the understanding and treatment of heart failure was the theme of the meeting. Over 150 attendees were present for more than 40 scientists presenting their latest works on engineering human functional myocardium for disease modeling, drug development, and heart failure research. The scientists, engineers and physicians in the field of cardiovascular sciences, met and discussed on the most recent advances in their works and propose future strategies in overcoming the major roadblocks of cardiovascular bioengineering and therapy. Particular emphasis was given for manipulation and using of stem/progenitor cells, biomaterials, and methods to provide molecular, chemical and mechanical cues to cells in order to influence their identity and fate in vitro and in vivo. Collectively, these works are profoundly impacting and progressing toward deciphering the mechanisms and developing novel treatments for left ventricular dysfunction of failing hearts. Here we present some important perspectives that emerged from this meeting.

Extracellular vesicles from human embryonic stem cell-derived cardiovascular progenitor cells promote cardiac infarct healing through reducing cardiomyocyte death and promoting angiogenesis

“…Cell therapy by transplantation of stem/progenitor cells and their derived cardiovascular cells is one of the most notable alternative therapeutic approaches under exploration [12][13][14][15][16][17][18] . Among them, human pluripotent stem cells (hPSCs), including both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), hold promise for promoting cardiac infarct healing because they can be theoretically produced in unlimited quantities of cells of any lineages, including cardiomyocytes 17,[19][20][21][22][23][24] .…”

Human embryonic stem cell-derived cardiomyocyte therapy in mouse permanent ischemia and ischemia-reperfusion models

“…Thus, the strategy of cell transplantation needs to be further optimized. Previous studies have shown the combination of biomaterial and cytokines can promote cell survival and retention in the infarct area [32, 33], and these methods should further benefit the heart function in both PI and IR models. Due to the comparable characteristics between ESCs and induced pluripotent stem cells (iPSCs) [34–36], the same therapeutic effects of ESC- and iPSC-derived cardiomyocytes in these two heart ischemia models would be expected.…”

Perspective on human pluripotent stem cell-derived cardiomyocytes in heart disease modeling and repair

“…Low cell survival and long‐term retention are major obstacles hampering cell therapy, especially at the acute phase of MI, which represents one of the most important therapeutic windows to reduce acute cell death and activate the endogenous repair mechanisms 2,7,23,25,28,51 . To solve this problem, several strategies targeting the following aspects have been developed or under examination: (a) pretreating/engineering the cells before the transplantation to enhance their resistance to stress (eg, treating cells with hypoxic preconditioning and the prosurvival cocktail to induce endogenous cellular survival mechanisms and inhibits major cell death pathways) or genetic engineering of cell‐cycle genes to enhance proliferation of hPSC‐CMs 2,7,22,52 ; (b) codelivery of supportive biomaterials (such as biodegradable microparticles 53 ) and/or cells (hPSC‐derived ECs and SMCs, 15,54,55 epicardial cells, 56 MSCs 57 ), or CFs, 16,17,58 as well as the EHT (cell‐loaded patches and cardiac tissues) to enhance the graft survival, retention, and vascularization 2,47,49,50,57 . Similar obstacles exist for cell‐free strategies.…”

“…Thus, Li and colleagues 60 developed an anti‐IL‐1β antibody‐platelet conjugate with the infarcted heart‐homing ability and used it as an anti‐inflammatory agent to treat acute MI. Interestingly, some recent studies have shown that the inflammatory responses also promote infarct healing, including those modulated by the transplanted cells through secreted cytokines 7,23,61 . In the near future, combining the hPSC‐CM transplantation with the cardiac‐specific immunomodulation approaches need to be tested in both small and larger animal I/R models.…”

“…HDs encompass a broad range of disorders extending from myocardial infarction (MI) to heritable cardiomyopathies and heart failure (HF), either caused by pathological insults or inherited DNA sequence variants 3‐5 . Rapid advances in the stem cell field have lightened the hope of regenerating the heart by transplantation of stem cell‐derived cardiomyocytes (CMs) 1,2,6,7 . To date, the only robust source for efficient generation of authentic human cardiomyocytes is human pluripotent stem cells (hPSCs), including embryonic stem cells (hESCs), and induced pluripotent stem cells (hiPSCs) 8‐10 .…”