Background Stanford type B-acute aortic dissection (type B-AAD) is often life-threatening without invasive surgery. Multilineage-differentiating stress enduring cell (Muse cells), which comprise several percent of mesenchymal stem cells (MSCs), are endogenous pluripotent-like stem cells that selectively home to damaged tissue and replace damaged/apoptotic cells by in-vivo differentiation. Methods Mortality, aortic diameter expansion, cell localization, cell differentiation, and inflammation of the dissected aorta were evaluated in type B-AAD model mice intravenously injected with human-Muse cells, -elastin-knockdown (KD)-Muse cells, -human leukocyte antigen-G (HLA-G)-KD-Muse cells, or MSCs, all without immunosuppressant. Results Here, we show the Muse (50,000 cells) group has a lower incidence of aortic rupture and mortality of AAD compared with the MSC-50K (50,000 human-MSCs) and vehicle groups. Spectrum computed tomography in-vivo dynamics and 3-dimensional histologic analyses demonstrate that Muse cells more effectively home to the AAD tissue and survive for 8 weeks in the Muse group than in the MSC-750K (750,000 human-MSCs containing 50,000 Muse cells) group. Homing of Muse cells is impeded in the HLA-G-KD-Muse (50,000 cells) group. Differentiation of homed Muse cells into CD31(+) and alpha-smooth muscle actin (+) cells, production and reorganization of elastic fibers in the AAD tissue, and suppression of diameter expansion are greater in the Muse group than in the MSC-750K and elastin-KD-Muse (50,000 cells) groups. Conclusions Intravenously administered Muse cells reconstruct the dissected aorta and improve mortality and diameter enlargement rates. Moreover, small doses of purified Muse cells are more effective than large doses of MSCs. HLA-G is suggested to contribute to the successful survival and homing of Muse cells.
Stanford type B acute aortic dissection (Stanford-B AAD) is often fatal. Endogenous pluripotent-like Muse cells selectively home to damaged tissue via sphingosine-1-phosphate, phagocytose damaged cells to differentiate into the damaged cell type and ultimately repair the tissue. Here we show the therapeutic efficacy of a single dose (50,000 cells) intravenous injection of human Muse cells in a Stanford-B AAD mouse model without immunosuppression. Homing to the AAD tissue, on-site differentiation into aorta constituent cells, elastin production, elastic fiber reorganization, alleviation of inflammatory cell migration, mitigation of aortic diameter expansion, aortic rupture avoidance, and survival rate improvement were superior in the Muse group when compared to the human mesenchymal stem cell (750,000 cells, containing 50,000 Muse cells) group. HLA-G expression was found to be integral for protecting Muse cells from immunorejection. Therefore, a small dose of purified Muse cells might be more effective than a large dose of MSCs for AAD.
Medical intervention for ischemic heart disease began approximately 150 years ago with nitrates, and for nearly a century thereafter, little fundamental progress was made. With the advent of the left internal thoracic artery to the left anterior descending artery (LITA-LAD) bypass in the 1960s, treatment entered a new stage; however, its essential significance remained insufficiently recognized for many years. Numerous studies were subsequently conducted to evaluate alternative or parallel treatment strategies, but these investigations also helped bring the durable capacity of LITA-LAD to perfuse ischemic myocardium into sharper focus. Over the past quarter century, the treatment of ischemic heart disease has remained in a state of uncertainty, and its central prognostic foundation has often been obscured, although in recent years this uncertainty has begun to resolve. In this review, we reexamine the historical process by which the significance of LITA-LAD remained incompletely appreciated in parts of the cardiology and cardiac surgical communities. We further outline how the principal basis of the long-term prognostic benefit conferred by LITA-LAD gradually became evident and define the contemporary roles of medical therapy and percutaneous coronary intervention in relation to LITA-LAD-based coronary artery bypass grafting (CABG).
Significant progress has been achieved in the treatment of acute aortic dissection over the past 90 years, following the first surgical intervention. This review pays tribute to the dedication of pioneers and innovators who developed advanced medical devices and therapeutic strategies to address this challenging condition. While navigating uncertainties in treatment optimization, the primary focus of the therapeutic strategies has been to save lives by increasing survival rates during the acute phase and to prevent aorta-related lethal events and late-stage thoracoabdominal aortic replacements. From a neutral standpoint, this review traces over 90 years of progress in treating acute aortic dissection. We hope that as many patients as possible will receive treatment rationally, without over- or under-treatment.
Significant progress has been achieved in the treatment of acute aortic dissection over the past 90 years, following the first surgical intervention. This review pays tribute to the dedication of pioneers and innovators who developed advanced medical devices and therapeutic strategies to address this challenging condition. While navigating uncertainties in treatment optimization, the primary focus remains on saving lives by increasing survival rates during the acute phase and preventing aorta-related lethal events and late thoracoabdominal aortic replacements. A strategy for managing this disease was established in 2013, demonstrating excellent early and long-term outcomes. From a fair and neutral standpoint, this review traces over 90 years of progress in treating acute aortic dissection. It outlines the journey that led to the establishment of the Oda strategy as the optimal approach and provides valuable insights for exceptional cardiovascular surgeons who will be utilizing this strategy in the future. We hope that as many patients as possible will benefit from this strategy and will receive treatment rationally, without over- or under-treatment.