Stanford Advisors

Current Research and Scholarly Interests

Cardiovascular surgery, Translational research, Regenerative research, Heart failure, Tissue engineering, Heart transplant, Spinal cord ischemia, iPS cell,

All Publications

  • Seamless and non-destructive monitoring of extracellular microRNAs during cardiac differentiation from human pluripotent stem cells. Stem cell reports Sekine, O., Kanaami, S., Masumoto, K., Aihara, Y., Morita-Umei, Y., Tani, H., Soma, Y., Umei, T. C., Haga, K., Moriwaki, T., Kawai, Y., Ohno, M., Kishino, Y., Kanazawa, H., Fukuda, K., Ieda, M., Tohyama, S. 2023; 18 (10): 1925-1939


    Monitoring cardiac differentiation and maturation from human pluripotent stem cells (hPSCs) and detecting residual undifferentiated hPSCs are indispensable for the development of cardiac regenerative therapy. MicroRNA (miRNA) is secreted from cells into the extracellular space, and its role as a biomarker is attracting attention. Here, we performed an miRNA array analysis of supernatants during the process of cardiac differentiation and maturation from hPSCs. We demonstrated that the quantification of extracellular miR-489-3p and miR-1/133a-3p levels enabled the monitoring of mesoderm and cardiac differentiation, respectively, even in clinical-grade mass culture systems. Moreover, extracellular let-7c-5p levels showed the greatest increase with cardiac maturation during long-term culture. We also verified that residual undifferentiated hPSCs in hPSC-derived cardiomyocytes (hPSC-CMs) were detectable by measuring miR-302b-3p expression, with a detection sensitivity of 0.01%. Collectively, we demonstrate that our method of seamlessly monitoring specific miRNAs secreted into the supernatant is non-destructive and effective for the quality evaluation of hPSC-CMs.

    View details for DOI 10.1016/j.stemcr.2023.08.011

    View details for PubMedID 37738969

    View details for PubMedCentralID PMC10656301

  • Clinical outcome of intraoperative hemodialysis using a hemoconcentrator during cardiopulmonary bypass for dialysis-dependent patients. General thoracic and cardiovascular surgery Ohtsubo, S., Itoh, T., Kawai, Y., Kobayashi, K., Yoshitake, S., Fujimura, N., Shoji, Y., Ishii, S. 2023; 71 (9): 515-524


    The basic materials and structure of a hemoconcentrator incorporated into cardiopulmonary bypass (CPB) circuits are similar to those of hemodialyzers. Gravity drainage hemodiafiltration (GHDF) is an easy-to-use intraoperative renal replacement therapy (RRT) that utilizes a hemoconcentrator. This study aimed to verify whether GHDF can correct electrolyte imbalance and remove uremic toxins in dialysis-dependent patients and to evaluate the clinical outcomes of GHDF by comparing it with a conventional method of dilutional ultrafiltration (DUF).This study retrospectively compared perioperative clinical values of 41 dialysis-dependent patients (21 patients with GHDF and 20 patients with DUF) who underwent open-heart surgery. Changes in serum parameters before and after passing through the hemoconcentrator were also compared.Compared to DUF, GHDF significantly lowered potassium, blood urea nitrogen, and creatinine levels at the outflow of the hemoconcentrator. Less catecholamine was needed to wean CPB in GHDF than in DUF. The P/F ratio (arterial blood oxygen pressure/inhaled oxygen concentration) at the end of surgery was significantly higher in GHDF than in DUF (450.8 ± 149.7 vs. 279.3 ± 153.5; p < 0.001). Postoperative intubation time was shorter in GHDF than in DUF (8.3 ± 5.9 vs. 18.7 ± 16.1 h; p = 0.006). The major morbidity and mortality rates were comparable in both groups.GHDF removed both potassium and uremic toxins more efficiently than DUF in dialysis-dependent patients. Less catecholamine was needed to wean CPB using GHDF. It improved the immediate postoperative respiratory function and enabled earlier extubation. GHDF is a novel and effective option for intraoperative RRT in dialysis-dependent patients undergoing open-heart surgery.

    View details for DOI 10.1007/s11748-023-01922-x

    View details for PubMedID 36907942

    View details for PubMedCentralID 459998

  • Reoperative Aortic Valve Replacement for Structural Valve Deterioration through a Lower Hemisternotomy after a Previous Bentall Procedure in a Patient with Tracheostomy. The Keio journal of medicine Katsumata, K., Kawai, Y., Ito, T., Shimizu, H. 2023; 72 (1): 21-25


    Patients with tracheostomy who undergo a full sternotomy have an increased risk of mediastinitis and sternal infection. This report describes a reoperative aortic valve replacement (re-AVR) for structural valve deterioration (SVD) through a lower hemisternotomy. This procedure was performed on a 71-year-old man with a tracheostomy who had previously undergone a Bentall procedure with a bioprosthetic valve to replace an enlarged ascending aortic aneurysm. Comorbidities included chronic renal failure requiring hemodialysis. Fourteen months after the Bentall procedure, the patient presented with sudden dyspnea and was transferred to another hospital. Upon suffering acute heart failure, the patient required mechanical ventilation and was transferred to our hospital for intubation. The patient subsequently developed severe pneumonia. As a result of prolonged ventilation, the patient underwent tracheostomy and was administered antibiotic medication (piperacillin/tazobactam) for pneumonia. Echocardiography revealed severe aortic regurgitation caused by SVD. There was a risk that a full sternotomy in a patient with tracheostomy could cause mediastinitis; therefore, we performed a re-AVR through a lower hemisternotomy (second T incision). The re-AVR surgery proceeded without complications, and the bioprosthetic valve was removed while preserving the vascular graft from the previous Bentall procedure. The postoperative course was uneventful, and the patient was discharged from hospital 31 days after the tracheostomy was closed. The success of this procedure demonstrates the viability of re-AVR through a lower hemisternotomy in patients with SVD who are at risk of additional surgical complications.

    View details for DOI 10.2302/kjm.2022-0009-CR

    View details for PubMedID 36653143

  • Acute Pulmonary Embolism With a Left Atrial Thrombus Passing Through a Patent Foramen Ovale. Circulation journal : official journal of the Japanese Circulation Society Kawai, Y., Ohtsubo, S., Itoh, T., Kobayashi, K. 2023; 87 (3): 463

    View details for DOI 10.1253/circj.CJ-22-0398

    View details for PubMedID 36450520

  • Intramyocardial Transplantation of Human iPS Cell-Derived Cardiac Spheroids Improves Cardiac Function in Heart Failure Animals. JACC. Basic to translational science Kawaguchi, S., Soma, Y., Nakajima, K., Kanazawa, H., Tohyama, S., Tabei, R., Hirano, A., Handa, N., Yamada, Y., Okuda, S., Hishikawa, S., Teratani, T., Kunita, S., Kishino, Y., Okada, M., Tanosaki, S., Someya, S., Morita, Y., Tani, H., Kawai, Y., Yamazaki, M., Ito, A., Shibata, R., Murohara, T., Tabata, Y., Kobayashi, E., Shimizu, H., Fukuda, K., Fujita, J. 2021; 6 (3): 239-254


    The severe shortage of donor hearts hampered the cardiac transplantation to patients with advanced heart failure. Therefore, cardiac regenerative therapies are eagerly awaited as a substitution. Human induced pluripotent stem cells (hiPSCs) are realistic cell source for regenerative cardiomyocytes. The hiPSC-derived cardiomyocytes are highly expected to help the recovery of heart. Avoidance of teratoma formation and large-scale culture of cardiomyocytes are definitely necessary for clinical setting. The combination of pure cardiac spheroids and gelatin hydrogel succeeded to recover reduced ejection fraction. The feasible transplantation strategy including transplantation device for regenerative cardiomyocytes are established in this study.

    View details for DOI 10.1016/j.jacbts.2020.11.017

    View details for PubMedID 33778211

    View details for PubMedCentralID PMC7987543

  • Scaffold-Free Tubular Engineered Heart Tissue From Human Induced Pluripotent Stem Cells Using Bio-3D Printing Technology in vivo. Frontiers in cardiovascular medicine Kawai, Y., Tohyama, S., Arai, K., Tamura, T., Soma, Y., Fukuda, K., Shimizu, H., Nakayama, K., Kobayashi, E. 2021; 8: 806215


    Engineered heart tissues (EHTs) that are fabricated using human induced pluripotent stem cells (hiPSCs) have been considered as potential cardiac tissue substitutes in case of heart failure. In the present study, we have created hiPSC-derived cardiac organoids (hiPSC-COs) comprised of hiPSC-derived cardiomyocytes, human umbilical vein endothelial cells, and human fibroblasts. To produce a beating conduit for patients suffering from congenital heart diseases, we constructed scaffold-free tubular EHTs (T-EHTs) using hiPSC-COs and bio-3D printing with needle arrays. The bio-3D printed T-EHTs were cut open and transplanted around the abdominal aorta as well as the inferior vena cava (IVC) of NOG mice. The transplanted T-EHTs were covered with the omentum, and the abdomen was closed after completion of the procedure. Additionally, to compare the functionality of hiPSC-COs with that of T-EHTs, we transplanted the former around the aorta and IVC as well as injecting them into the subcutaneous tissue on the back of the mice. After 1 m of the transplantation procedures, we observed the beating of the T-EHTs in the mice. In histological analysis, the T-EHTs showed clear striation of the myocardium and vascularization compared to hiPSC-COs transplanted around the aorta or in subcutaneous tissue. Based on these results, bio-3D-printed T-EHTs exhibited a better maturation in vivo as compared to the hiPSC-COs. Therefore, these beating T-EHTs may form conduits for congenital heart disease patients, and T-EHT transplantation can form a treatment option in such cases.

    View details for DOI 10.3389/fcvm.2021.806215

    View details for PubMedID 35127867

    View details for PubMedCentralID PMC8811174

  • Mobile Thrombus in the Ascending Aorta. Annals of vascular diseases Kawai, Y., Koizumi, K., Itoh, T., Iio, M., Shimizu, H. 2020; 13 (1): 69-71


    A 65-year-old male who presented with dizziness, dysarthria, and disability of his left hand was admitted to our hospital. Magnetic resonance imaging of the head revealed cerebral infarction and enhanced computed tomography revealed a suspicious thrombus in the ascending aorta. He did not have a coagulation disorder. We performed ascending aortic replacement and removed the thrombus with the aortic wall in order to avoid any recurrences. Here we report the successful treatment of the case from clinical and pathological points of view with some findings.

    View details for DOI 10.3400/

    View details for PubMedID 32273925

    View details for PubMedCentralID PMC7140152

  • Transplantation of a decellularized mitral valve complex in pigs. Surgery today Inaba, Y., Yagi, H., Kuroda, K., Kato, J., Kawai, Y., Kasai, M., Kitahara, H., Ito, T., Osako, M., Kitagawa, Y., Shimizu, H. 2020; 50 (3): 298-306


    Conventional mitral valve replacement is associated with the loss of natural continuity of the mitral valve complex. This study evaluated the morphologic/histological characteristics and function of a decellularized mitral valve used as a transplantable graft.Hearts excised from pigs were decellularized by perfusion using detergent. Grafts with the mitral annulus, valve, chordae, and papillary muscle isolated from the decellularized heart were then transplanted into recipient pigs. After transplantation, the function of the graft was analyzed through echocardiography. A histological analysis was performed to evaluate the postoperative features of the decellularized graft.The decellularized graft was successfully transplanted in all cases but one. The remaining grafts maintained their morphology and function. They did not exhibit mitral regurgitation or stenosis. Only one animal survived for 3 weeks, and a histological analysis was able to be performed in this case. The transplanted valve was re-covered with endothelial cells. The microvessels in the papillary muscle were recellularized with vascular endothelial cells, and the papillary muscle was completely attached to the papillary muscle of the recipient.The early outcome of decellularized mitral graft transplantation was acceptable. This native organ-derived acellular scaffold is a promising candidate for the replacement of the mitral valve complex.

    View details for DOI 10.1007/s00595-019-01869-8

    View details for PubMedID 31468150

  • Adult Case of Parachute-Like Asymmetrical Mitral Valve Complicated by Mitral Stenosis and Thrombus Formation. Circulation journal : official journal of the Japanese Circulation Society Kawai, Y., Yokoyama, T., Hama, G., Toyoda, Y., Horigome, M., Tsuda, Y., Yazaki, Y., Takemura, T. 2018; 82 (4): 1208-1209

    View details for DOI 10.1253/circj.CJ-17-0209

    View details for PubMedID 28804106