التفاصيل البيبلوغرافية
| العنوان: |
Directed cardiomyogenesis of autologous human induced pluripotent stem cells recruited to infarcted myocardium with bioengineered antibodies |
| المؤلفون: |
Malecki, Marek, Putzer, Emily, Sabo, Chelsea, Foorohar, Afsoon, Quach, Carol, Stampe, Chris, Beauchaine, Michael, Tombokan, Xenia, Malecki, Raf, Anderson, Mark |
| بيانات النشر: |
BioMed Central Ltd. |
| سنة النشر: |
2014 |
| المجموعة: |
BioMed Central |
| مصطلحات موضوعية: |
Myocardial infarction, Cardiac regeneration, Stem cell therapy, Recruitment and retention of stem cells, Autologous human induced pluripotent stem cell, Heterospecific, Tetravalent antibodies, Stage specific embryonic antigen, Tumor related antigen, Induced pluripotent stem cell tumorigenicity |
| الوصف: |
Objective Myocardial infarctions constitute a major factor contributing to non-natural mortality world-wide. Clinical trials ofmyocardial regenerative therapy, currently pursued by cardiac surgeons, involve administration of stem cells into the hearts of patients suffering from myocardial infarctions. Unfortunately, surgical acquisition of these cells from bone marrow or heart is traumatic, retention of these cells to sites of therapeutic interventions is low, and directed differentiation of these cells in situ into cardiomyocytes is difficult. The specific aims of this work were: (1) to generate autologous, human, pluripotent, induced stem cells (ahiPSCs) from the peripheral blood of the patients suffering myocardial infarctions; (2) to bioengineer heterospecific tetravalent antibodies (htAbs) and use them for recruitment of the ahiPSCs to infarcted myocardium; (3) to initiate in situ directed cardiomyogenesis of the ahiPSCs retained to infarcted myocardium. Methods Peripheral blood was drawn from six patients scheduled for heart transplants. Mononuclear cells were isolated and reprogrammed, with plasmids carrying six genes ( NANOG, POU5F1, SOX2, KLF4, LIN28A, MYC ), to yield the ahiPSCs. Cardiac tissues were excised from the injured hearts of the patients, who received transplants during orthotopic surgery. These tissues were used to prepare in vitro model of stem cell therapy of infarcted myocardium. The htAbs were bioengineered, which simultaneously targeted receptors displayed on pluripotent stem cells (SSEA-4, SSEA-3, TRA-1-60, TRA-1-81) and proteins of myocardial sarcomeres (myosin, α-actinin, actin, titin). They were used to bridge the ahiPSCs to the infarcted myocardium. The retained ahiPSCs were directed with bone morphogenetic proteins and nicotinamides to differentiate towards myocardial lineage. Results The patients’ mononuclear cells were efficiently reprogrammed into the ahiPSCs. These ahiPSCs were administered to infarcted myocardium in in vitro models. They were recruited to and ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| العلاقة: |
http://www.molcelltherapies.com/content/2/1/13Test |
| الإتاحة: |
http://www.molcelltherapies.com/content/2/1/13Test |
| حقوق: |
Copyright 2014 Malecki et al.; licensee BioMed Central Ltd. |
| رقم الانضمام: |
edsbas.C945AD71 |
| قاعدة البيانات: |
BASE |
