Stem cell-derived sheet engineering has been developed as the next-generation treatment for myocardial infarction (MI) and offers attractive advantages in comparison with direct stem cell transplantation and scaffold tissue engineering. Furthermore, induced pluripotent stem cell-derived cell sheets have been indicated to possess higher potential for MI therapy than other stem cell-derived sheets because of their capacity to form vascularized networks for fabricating thickened human cardiac tissue and their long-term therapeutic effects after transplantation in MI. To date, stem cell sheet transplantation has exhibited a dramatic role in attenuating cardiac dysfunction and improving clinical manifestations of heart failure in MI. In this review, we retrospectively summarized the current applications and strategy of stem cell-derived cell sheet technology for heart tissue repair in MI.
Stem cell-based therapy has been used to treat ischaemic heart diseases for two decades. However, optimal cell types and transplantation methods remain unclear. This study evaluated the therapeutic effects of human umbilical cord mesenchymal stem cell (hUCMSC) sheet on myocardial infarction (MI).
Methods
hUCMSCs expressing luciferase were generated by lentiviral transduction for
in vivo
bio-luminescent imaging tracking of cells. We applied a temperature-responsive cell culture surface-based method to form the hUCMSC sheet. Cell retention was evaluated using an
in vivo
bio-luminescent imaging tracking system. Unbiased transcriptional profiling of infarcted hearts and further immunohistochemical assessment of monocyte and macrophage subtypes were used to determine the mechanisms underlying the therapeutic effects of the hUCMSC sheet. Echocardiography and pathological analyses of heart sections were performed to evaluate cardiac function, angiogenesis and left ventricular remodelling.
Results
When transplanted to the infarcted mouse hearts, hUCMSC sheet significantly improved the retention and survival compared with cell suspension. At the early stage of MI, hUCMSC sheet modulated inflammation by decreasing Mcp1-positive monocytes and CD68-positive macrophages and increasing Cx3cr1-positive non-classical macrophages, preserving the cardiomyocytes from acute injury. Moreover, the extracellular matrix produced by hUCMSC sheet then served as bioactive scaffold for the host cells to graft and generate new epicardial tissue, providing mechanical support and routes for revascularsation. These effects of hUCMSC sheet treatment significantly improved the cardiac function at days 7 and 28 post-MI.
Conclusions
hUCMSC sheet formation dramatically improved the biological functions of hUCMSCs, mitigating adverse post-MI remodelling by modulating the inflammatory response and providing bioactive scaffold upon transplantation into the heart.
Translational perspective
Due to its excellent availability as well as superior local cellular retention and survival, allogenic transplantation of hUCMSC sheets can more effectively acquire the biological functions of hUCMSCs, such as modulating inflammation and enhancing angiogenesis. Moreover, the hUCMSC sheet method allows the transfer of an intact extracellular matrix without introducing exogenous or synthetic biomaterial, further improving its clinical applicability.
IntroductionMinimally invasive direct coronary artery bypass (MIDCAB) grafting is performed via small, left anterolateral thoracotomy. The left internal mammary artery was grafted to the left anterior descending (LAD) artery in 300 consecutive patients.AimIn-hospital results were evaluated and compared with the conventional, off-pump coronary artery bypass graft procedure.Material and methodsOne hundred and sixty-three (54.33%) of 300 patients underwent staged hybrid coronary revascularization, 93 (31%) were treated for a single LAD lesion, and 44 (14.67%) were treated for multi-vessel disease with reasonably incomplete revascularization. Major in-hospital cardiac adverse events and postoperative data were compared between groups.ResultsPreoperative data were similar between groups. However, the difference in left ventricular ejection fraction (p < 0.001) was significant. No conversions to sternotomy occurred during the primary MIDCAB procedures. Shorter operation time (p < 0.001), shorter postoperative mechanical ventilation time (p < 0.001), shorter intensive care unit stay (p < 0.001), and less red blood cell transfusion (p < 0.001) were noted in the MIDCAB group. Postoperative coronary angiography conducted in the MIDCAB group within one week after the operation showed that 2 of 163 patients developed graft occlusion. These patients underwent conventional CABG and recovered well. No significant differences were observed in postoperative MI, delayed wound healing or 30-day in-hospital mortality between the two groups.ConclusionsThe use of a chest wall lifting system and modified stabilizer makes the MIDCAB procedure safer and easier. The MIDCAB procedure is demonstrated to be a feasible and minimally invasive alternative for patients with coronary artery disease involving LAD lesions.
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