Reprogramming and transdifferentiation for cardiovascular development and regenerative medicine: where do we stand?

Heart disease remains a leading cause of mortality and a major worldwide healthcare burden. Recent advances in stem cell biology have made it feasible to derive large quantities of cardiomyocytes for disease modeling, drug development, and regenerative medicine. The discoveries of reprogramming and transdifferentiation as novel biological processes have significantly contributed to this paradigm. This review surveys the means by which reprogramming and transdifferentiation can be employed to generate induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and induced cardiomyocytes (iCMs). The application of these patient-specific cardiomyocytes for both in vitro disease modeling and in vivo therapies for various cardiovascular diseases will also be discussed. We propose that, with additional refinement, human disease-specific cardiomyocytes will allow us to significantly advance the understanding of cardiovascular disease mechanisms and accelerate the development of novel therapeutic options

Digitizing marginal objects – amateur films from the GDR in color

[Blog-Beitrag im Vorfeld des an der Konferenz gehaltenen Vortrages mit Diskussionsrunde]. The Film Colors projects of the University of Zurich and the Filmmuseum Potsdam joined forces, in order to digitize selected color films from the Filmmuseum’s holdings. This blog post focuses on the results of a cooperation between the SNSF project Film Colors : Technologies, Cultures, Institutionslocated at the University of Zurich (Switzerland) and the Filmmuseum Potsdam (Germany), established by Josephine Dieckeand Dennis Basaldella. The aim is to present an innovative collaboration that brings together specialized knowledge in the realms of film production and film technology with a particular focus on typically marginalized topics, such as amateur filmmaking and film stock manufacturing in selected historical contexts. How can both approaches enrich the debates about the preservation, digitization and circulation of marginal objects

Farbfilmverfahren und Historiografie(n). Ein interdisziplinärer Ansatz

Technologien repräsentieren einen elementaren Knotenpunkt zwischen theoretisch und praktisch orientierten Disziplinen und Ansätzen, so auch in der Filmwissenschaft. Wie überbrücken wir aber die Kluft zwischen Theorie und Praxis in der Beschäftigung mit Film- und Technikgeschichte? Welche Zugänge bieten sich an, um bei der wissenschaftlichen Aufarbeitung nicht in die Falle von linearen und teleologischen Schlussfolgerungen zu tappen? Unsere vorgestellte Methodik erzielt die Verschränkung von Technologie und Gesellschaft durch die Koppelung von sozialkonstruktivistischen Ansätzen der Technikgeschichte mit kulturwissenschaftlicher Kontextualisierung. In diesem Aufsatz wenden wir unser theoretisches und methodologisches Gerüst am konkreten Fallbeispiel der Herstellung von Rohfilm in Japan in den 1930er Jahren an. Multidirektionale Netzwerke visualisieren die Ergebnisse zusätzlich

E-cadherin is crucial for embryonic stem cell pluripotency and can replace OCT4 during somatic cell reprogramming

We report new functions of the cell-adhesion molecule E-cadherin in murine pluripotent cells. E-cadherin is highly expressed in mouse embryonic stem cells, and interference with E-cadherin causes differentiation. During cellular reprogramming of mouse fibroblasts by OCT4, SOX2, KLF4 and c-MYC, fully reprogrammed cells were exclusively observed in the E-cadherin-positive cell population and could not be obtained in the absence of E-cadherin. Moreover, reprogrammed cells could be established by viral E-cadherin in the absence of exogenous OCT4. Thus, reprogramming requires spatial cues that cross-talk with essential transcription factors. The cell-adhesion molecule E-cadherin has important functions in pluripotency and reprogramming

Recent technological updates and clinical applications of induced pluripotent stem cells

Induced pluripotent stem cells (iPSCs) were first described in 2006 and have since emerged as a promising cell source for clinical applications. The rapid progression in iPSC technology is still ongoing and directed toward increasing the efficacy of iPSC production and reducing the immunogenic and tumorigenic potential of these cells. Enormous efforts have been made to apply iPSC-based technology in the clinic, for drug screening approaches and cell replacement therapy. Moreover, disease modeling using patient-specific iPSCs continues to expand our knowledge regarding the pathophysiology and prospective treatment of rare disorders. Furthermore, autologous stem cell therapy with patient-specific iPSCs shows great propensity for the minimization of immune reactions and the provision of a limitless supply of cells for transplantation. In this review, we discuss the recent updates in iPSC technology and the use of iPSCs in disease modeling and regenerative medicine

Generation of functional cardiomyocytes from the synoviocytes of patients with rheumatoid arthritis via induced pluripotent stem cells

Cardiovascular disease is a leading cause of morbidity in rheumatoid arthritis (RA) patients. This study aimed to generate and characterise cardiomyocytes from induced pluripotent stem cells (iPSCs) of RA patients. Fibroblast-like synoviocytes (FLSs) from patients with RA and osteoarthritis (OA) were successfully reprogrammed into RA-iPSCs and OA-iPSCs, respectively. The pluripotency of iPSCs was confirmed by quantitative reverse transcription-polymerase chain reaction and immunofluorescence staining. Established iPSCs were differentiated into cardiomyocytes using a small molecule-based monolayer differentiation protocol. Within 12 days of cardiac differentiation from patient-specific and control-iPSCs, spontaneously beating cardiomyocytes (iPSC-CMs) were observed. All iPSC-CMs exhibited a reliable sarcomeric structure stained with antibodies against cardiac markers and similar expression profiles of cardiac-specific genes. Intracellular calcium signalling was recorded to compare calcium-handling properties among cardiomyocytes differentiated from the three groups of iPSCs. RA-iPSC-CMs had a lower amplitude and a shorter duration of calcium transients than the control groups. Peak tangential stress and the maximum contractile rate were also decreased in RA-iPSC-CMs, suggesting that contractility was reduced. This study demonstrates the successful generation of functional cardiomyocytes from pathogenic synovial cells in RA patients through iPSC reprogramming. Research using RA-iPSC-CMs might provide an opportunity to investigate the pathophysiology of cardiac involvement in RA