• BMB Reports
• /
• v.49 no.1
• /
• pp.26-36
• /
• 2016

Emerging trends for cardiac tissue engineering are focused on increasing the biocompatibility and tissue regeneration ability of artificial heart tissue by incorporating various cell sources and bioactive molecules. Although primary cardiomyocytes can be successfully implanted, clinical applications are restricted due to their low survival rates and poor proliferation. To develop successful cardiovascular tissue regeneration systems, new technologies must be introduced to improve myocardial regeneration. Electrospinning is a simple, versatile technique for fabricating nanofibers. Here, we discuss various biodegradable polymers (natural, synthetic, and combinatorial polymers) that can be used for fiber fabrication. We also describe a series of fiber modification methods that can increase cell survival, proliferation, and migration and provide supporting mechanical properties by mimicking micro-environment structures, such as the extracellular matrix (ECM). In addition, the applications and types of nanofiber-based scaffolds for myocardial regeneration are described. Finally, fusion research methods combined with stem cells and scaffolds to improve biocompatibility are discussed. [BMB Reports 2016; 49(1): 26-36]

• 한국생물공학회:학술대회논문집
• /
• 2003.04a
• /
• pp.95-97
• /
• 2003

Despite recent advances in the treatment of acute myocardial infarction, the ability to repair extensive myocardial damage is limited. To develop a new therapy for myocardial infarction, we examined the possibility of regenerating myocardium by implanting bone marrow-derived mononuclear cells(BM-MNC) . Histological and immunohistochemical examination showed myocardium regeneration and angiogenesis in the cell transplantation site. Isolated perfused (Langendorff) heart experiments revealed enhanced functions of heart. These results suggest that BM-MNC transplantation induce cardiac muscle regeneration and that this approach could be applied as a possible treatment for myocardial infarction.

• BMB Reports
• /
• v.54 no.7
• /
• pp.356-367
• /
• 2021

Cell-based therapy is a promising approach in the field of regenerative medicine. As cells are formed into spheroids, their survival, functions, and engraftment in the transplanted site are significantly improved compared to single cell transplantation. To improve the therapeutic effect of cell spheroids even further, various biomaterials (e.g., nano- or microparticles, fibers, and hydrogels) have been developed for spheroid engineering. These biomaterials not only can control the overall spheroid formation (e.g., size, shape, aggregation speed, and degree of compaction), but also can regulate cell-to-cell and cell-to-matrix interactions in spheroids. Therefore, cell spheroids in synergy with biomaterials have recently emerged for cell-based regenerative therapy. Biomaterials-assisted spheroid engineering has been extensively studied for regeneration of bone or/and cartilage defects, critical limb ischemia, and myocardial infarction. Furthermore, it has been expanded to pancreas islets and hair follicle transplantation. This paper comprehensively reviews biomaterials-assisted spheroid engineering for regenerative therapy.

• Experimental and Molecular Medicine
• /
• v.50 no.11
• /
• pp.1.1-1.10
• /
• 2018

Bone marrow-derived mesenchymal stem cells (BMMSCs) are used extensively for cardiac repair and interact with immune cells in the damaged heart. Macrophages are known to be modulated by stem cells, and we hypothesized that priming macrophages with BMMSCs would enhance their therapeutic efficacy. Rat bone marrow-derived macrophages (BMDMs) were stimulated by lipopolysaccharide (LPS) with or without coculture with rat BMCs. In the LPS-stimulated BMDMs, induction of the inflammatory marker iNOS was attenuated, and the anti-inflammatory marker Arg1 was markedly upregulated by coculture with BMMSCs. Myocardial infarction (MI) was induced in rats. One group was injected with BMMSCs, and a second group was injected with MIX (a mixture of BMMSCs and BMDMs after coculture). The reduction in cardiac fibrosis was greater in the MIX group than in the BMC group. Cardiac function was improved in the BMMSC group and was substantially improved in the MIX group. Angiogenesis was better in the MIX group, and anti-inflammatory macrophages were more abundant in the MIX group than in the BMMSC group. In the BMMSCs, interferon regulatory factor 5 (IRF5) was exclusively induced by coculture with macrophages. IRF5 knockdown in BMMSCs failed to suppress inflammatory marker induction in the macrophages. In this study, we demonstrated the successful application of BMDMs primed with BMMSCs as an adjuvant to cell therapy for cardiac repair.

• Biomedical Science Letters
• /
• v.30 no.1
• /
• pp.10-16
• /
• 2024

Oxidative stress caused by elevated reactive oxygen species (ROS) in the heart causes various heart diseases. Oxidative stress is known as a factor that causes diseases in various organs as well as the heart. Diseases such as heart failure, myocardial infarction, and cardiomyopathy caused by oxidative stress in the heart can be treated with medication or surgery. Recently, blood cells concentrate (BCC) is used in various treatment areas such as orthopedics, gynecology, and urology. BCC therapy is applied to treatment by concentrating platelets and white blood cells necessary for regeneration through simple centrifugation using autologous blood. As the platelets are activated, many growth factors are released from alpha granules of the platelets. Growth factors such as TGF-β1, PDGF, VEGF, and EGF derived from platelets are involved in various cell signaling pathway. Due to these growth factors, BCC can contribute to tissue regeneration and can treat various diseases. CD34+ cells contained in BCC may also play an important role in tissue regeneration. In this study, we investigated whether BCC has a regenerative effect on heart disease, and if so, what mechanism causes the effect. To observe this, cardiomyocyte cells were treated with H₂O₂ to induce oxidative stress. And the effect was confirmed in the presence or absence of BCC. As a result, in the presence of BCC, the oxidative stress of cardiomyocyte cells was reduced and cell damage was also reduced. These results suggest that BCC therapy can be a new treatment alternative for heart disease.

• Journal of Periodontal and Implant Science
• /
• v.47 no.2
• /
• pp.96-105
• /
• 2017

Purpose: The National Health Insurance Service-National Sample Cohort and medical checkup data from 2002 to 2013 were used to evaluate the association between periodontal surgery for the treatment of periodontitis (PSTP) and vasculogenic erectile dysfunction (VED). Methods: Bivariate and multivariate logistic regression analyses were applied to a longitudinal retrospective database to assess the association between PSTP and VED while adjusting for the potential confounding effects of sociodemographic factors (age, household income, insurance status, health status, residence area, and smoking status) and comorbidities (diabetes mellitus, angina pectoris, cerebral infarction, and myocardial infarction). Results: Among the 7,148 PSTP within the 268,296 recruited subjects, the overall prevalence of VED in PSTP was 1.43% (n=102). The bivariate analysis showed that VED was significantly related to PSTP (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.38-2.06; P<0.001), and this was confirmed in the multivariate analysis after adjusting for sociodemographic factors and comorbidities (OR, 1.29; 95% CI, 1.06-1.58; P=0.002). Conclusions: Subjects with a history of periodontal flap surgery had a significantly higher risk of VED, after adjusting for potential confounding factors. Further studies are required to identify the key mechanisms underlying the association between severe periodontal disease and VED.

• BMB Reports
• /
• v.53 no.2
• /
• pp.118-123
• /
• 2020

Cardiac regeneration with adult stem-cell (ASC) therapy is a promising field to address advanced cardiovascular diseases. In addition, extracellular vesicles (EVs) from ASCs have been implicated in acting as paracrine factors to improve cardiac functions in ASC therapy. In our work, we isolated human cardiac mesenchymal stromal cells (h-CMSCs) by means of three-dimensional organ culture (3D culture) during ex vivo expansion of cardiac tissue, to compare the functional efficacy with human bone-marrow derived mesenchymal stem cells (h-BM-MSCs), one of the actively studied ASCs. We characterized the h-CMSCs as CD90^low, c-kit^negative, CD105^positive phenotype and these cells express NANOG, SOX2, and GATA4. To identify the more effective type of EVs for angiogenesis among the different sources of ASCs, we isolated EVs which were derived from CMSCs with either normoxic or hypoxic condition and BM-MSCs. Our in vitro tube-formation results demonstrated that the angiogenic effects of EVs from hypoxia-treated CMSCs (CMSC-Hpx EVs) were greater than the well-known effects of EVs from BM-MSCs (BM-MSC EVs), and these were even comparable to human vascular endothelial growth factor (hVEGF), a potent angiogenic factor. Therefore, we present here that CD90^lowc-kit^negativeCD105^positive CMSCs under hypoxic conditions secrete functionally superior EVs for in vitro angiogenesis. Our findings will allow more insights on understanding myocardial repair.

• Korean Circulation Journal
• /
• v.53 no.6
• /
• pp.367-386
• /
• 2023

Ischemic heart disease remains the primary cause of morbidity and mortality worldwide. Despite significant advancements in pharmacological and revascularization techniques in the late 20th century, heart failure prevalence after myocardial infarction has gradually increased over the last 2 decades. After ischemic injury, pathological remodeling results in cardiomyocytes (CMs) loss and fibrosis, which leads to impaired heart function. Unfortunately, there are no clinical therapies to regenerate CMs to date, and the adult heart's limited turnover rate of CMs hinders its ability to self-regenerate. In this review, we present novel therapeutic strategies to regenerate injured myocardium, including (1) reconstruction of cardiac niche microenvironment, (2) recruitment of functional CMs by promoting their proliferation or differentiation, and (3) organizing 3-dimensional tissue construct beyond the CMs. Additionally, we highlight recent mechanistic insights that govern these strategies and identify current challenges in translating these approaches to human patients.

• BMB Reports
• /
• v.45 no.12
• /
• pp.742-747
• /
• 2012

Granulocyte colony-stimulating factor (G-CSF) is used for heart failure therapy and promotes myocardial regeneration by inducing mobilization of bone marrow stem cells to the injured heart after myocardial infarction; however, this treatment has one weakness in that its biological effect is transient. In our previous report, we generated 5 mutants harboring N-linked glycosylation to improve its antiapoptotic activities. Among them, one mutant (Phe140Asn) had higher cell viability than wild-type hG-CSF in rat cardiomyocytes, even after treatment with an apoptotic agent ($H_2O_2$). Cells treated with this mutant significantly upregulated the antiapoptotic proteins, and experienced reductions in caspase 3 activity and PARP cleavage. Moreover, the total number of apoptotic cells was dramatically lower in cultures treated with mutant hG-CSF. Taken together, these results suggest that the addition of an N-linked glycosylation was successful in improving the antiapoptotic activity of hG-CSF, and that this mutated product will be a feasible therapy for patients who have experienced heart failure.

• Journal of Life Science
• /
• v.30 no.7
• /
• pp.651-659
• /
• 2020

Cardiovascular disease is one of the leading causes of death across the world, and gold-standard treatments such as percutaneous coronary intervention and artery bypass grafting have various limitations including myocardial damage and subsequent maladaptive cardiac remodeling. To overcome this, stem-cell therapies are emerging as a promising strategy for cardiovascular regeneration. Endothelial progenitor cells (EPCs) have high potential to proliferate and differentiate into endothelial cells for vascularization and tissue regeneration, and several clinical trials have explored EPC function in tissue repair in relation to clinical safety and improving cardiac function. Consequently, EPC has been suggested as a feasible stem-cell therapy. However, autologous EPC transplantation in cardiovascular disease patients is restricted by risk factors such as age, smoking status, and hypertension that lead to reduced bioactivity in the EPCs. New approaches for improving EPC function and stem-cell efficacy have therefore been suggested, including cell priming, organoid culture systems, and enhancing transplantation efficiency through 3D bioprinting methods. In this review, we provide a comprehensive understanding of EPC characteristics, therapeutic approaches, and the current state of clinical research into EPCs as stem-cell therapy for cardiovascular disease.