Juni 2022


High-efficient serum-free differentiation of endothelial cells from human iPS cells


Stem Cell Res Ther. 2022 Jun 11;13(1):251


Sarkawt Hamad, Daniel Derichsweiler, John Antonydas Gaspar, Konrad Brockmeier, Jürgen Hescheler, Agapios Sachinidis, Kurt Paul Pfannkuche


Introduction: Endothelial cells (ECs) form the inner lining of all blood vessels of the body play important roles in vascular tone regulation, hormone secretion, anticoagulation, regulation of blood cell adhesion and immune cell extravasation. Limitless ECs sources are required to further in vitro investigations of ECs' physiology and pathophysiology as well as for tissue engineering approaches. Ideally, the differentiation protocol avoids animal-derived components such as fetal serum and yields ECs at efficiencies that make further sorting obsolete for most applications.

Method: Human induced pluripotent stem cells (hiPSCs) are cultured under serum-free conditions and induced into mesodermal progenitor cells via stimulation of Wnt signaling for 24 h. Mesodermal progenitor cells are further differentiated into ECs by utilizing a combination of human vascular endothelial growth factor A165 (VEGF), basic fibroblast growth factor (bFGF), 8-Bromoadenosine 3',5'-cyclic monophosphate sodium salt monohydrate (8Bro) and melatonin (Mel) for 48 h.

Result: This combination generates hiPSC derived ECs (hiPSC-ECs) at a fraction of 90.9 ± 1.5% and is easily transferable from the two-dimensional (2D) monolayer into three-dimensional (3D) scalable bioreactor suspension cultures. hiPSC-ECs are positive for CD31, VE-Cadherin, von Willebrand factor and CD34. Furthermore, the majority of hiPSC-ECs express the vascular endothelial marker CD184 (CXCR4).

Conclusion: The differentiation method presented here generates hiPSC-ECs in only 6 days, without addition of animal sera and at high efficiency, hence providing a scalable source of hiPSC-ECs.


To read the full text follow this LINK



Juni 2022


Generation of cardiac microtissues by microfluidic cell encapsulation


Watch the video to see how it works: click

Mai 2022


Generation of cardiac microtissues: Novel technology released


Engineering of cardiac microtissues by microfluidic cell encapsulation in thermoshrinking non-crosslinked PNIPAAm gels


Accepted manuscript, BIOFABRICATION



Philipp Jahn, Rebecca Katharina Karger, Shahab Soso Khalaf, Sarkawt Hamad, Gabriel Peinkofer, Raja Ghazanfar Ali Sahito, Stephanie Pieroth, Frank Nitsche, Junqi Lu, Daniel Derichsweiler, Konrad Brockmeier, Jürgen Hescheler, Annette Schmidt, Kurt Paul Pfannkuche



Multicellular agglomerates in form of irregularly shaped or spherical clusters can recapitulate cell-cell interactions and are referred to as microtissues. Microtissues gain increasing attention in several fields including cardiovascular research. Cardiac microtissues are evolving as excellent model systems for drug testing in vitro (organ-on-a-chip), are used as tissue bricks in 3D printing processes and pave the way for improved cell replacement therapies in vivo. Microtissues are formed for example in hanging drop culture or specialized microwell plates; truly scalable methods are not yet available. In this study, a novel method of encapsulation of cells in Poly-N-isopropylacrylamid (PNIPAAm) spheres is introduced. Murine induced pluripotent stem cell-derived cardiomyocytes (CMs) and bone marrow-derived mesenchymal stem cells (MSCs) were encapsulated in PNIPAAm by raising the temperature of droplets formed in a microfluidics setup above the lower critical solute temperature (LCST) of 32°C. PNIPAAM precipitates to a water-insoluble physically linked gel above the LCST and shrinks by the expulsion of water, thereby trapping the cells in a collapsing polymer network and increasing the cell density by one order of magnitude. Within 24 hours, stable cardiac microtissues were first formed and later released from their polymer shell by washout of PNIPAAm at temperatures below the LCST. Rhythmically contracting microtissues showed homogenous cell distribution, age-dependent sarcomere organizations and action potential generation. The novel approach is applicable for microtissue formation from various cell types and can be implemented into scalable workflows.


Download accepted Manuscript (external link)

März 2022


See our colleagues working at the Marga-and-Walter-Boll Laboratory


Video contains product advertising/ Video enthält Werbung

Video production: Rebecca K. Karger & Sarkawt Hamad

(Thanks to Yrii Semchyshyn, Coma Media for providing free music)


February 2022


Sarkawt is making progress in the field of human multicellular cardiac organoids. Watch the video and notice how long the cardiomyocytes contract before they relax. Pretty similar to human heart beats.

January 2022


Many thanks to Arthur Ziegler, Boris Christoffel, and Cedric Wolff from the Central Workshop of the Medical Faculty for building this novel device for us. We will explain later what it will be used for ,-)


Foto: MedizinFotoKöln, Dorothea Hensen


December 2021


Karim Daliri from our group has contributed to a recent manuscript about the pathology of human coenzyme Q4 deficiency.


Read the full text HERE


Human COQ4 deficiency: delineating the clinical, metabolic and neuroimaging phenotypes


Lucia Laugwitz et al.: Journal of Medical Genetics 2021. doi: 10.1136/jmedgenet-2021-107729


Background: Human coenzyme Q4 (COQ4) is essential for coenzyme Q10 (CoQ10) biosynthesis. Pathogenic variants in COQ4 cause childhood-onset neurodegeneration. We aimed to delineate the clinical spectrum and the cellular consequences of COQ4 deficiency.

Methods: Clinical course and neuroradiological findings in a large cohort of paediatric patients with COQ4 deficiency were analysed. Functional studies in patient-derived cell lines were performed.

Results: We characterised 44 individuals from 36 families with COQ4 deficiency (16 newly described). A total of 23 different variants were identified, including four novel variants in COQ4. Correlation analyses of clinical and neuroimaging findings revealed three disease patterns: type 1: early-onset phenotype with neonatal brain anomalies and epileptic encephalopathy; type 2: intermediate phenotype with distinct stroke-like lesions; and type 3: moderate phenotype with non-specific brain pathology and a stable disease course. The functional relevance of COQ4 variants was supported by in vitro studies using patient-derived fibroblast lines. Experiments revealed significantly decreased COQ4 protein levels, reduced levels of cellular CoQ10 and elevated levels of the metabolic intermediate 6-demethoxyubiquinone.

Conclusion: Our study describes the heterogeneous clinical presentation of COQ4 deficiency and identifies phenotypic subtypes. Cell-based studies support the pathogenic characteristics of COQ4 variants. Due to the insufficient clinical response to oral CoQ10 supplementation, alternative treatment strategies are warranted.


Keywords: early diagnosis; epilepsy; nervous system diseases; pediatrics.



November 2021


Priv-Doz. Dr. Nguemo from the Institute of Neurophysiologie, Cologne awarded among the most influential Africans worldwide. Congratulations!


November  2021


Dr. Leo Kurian from the Institute of Neurophysiologie, Cologne, CMMC and CEDAD awarded with the Binder award. Congratulation Leo!


Read the full story here

Oktober 2021


Scalable Generation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes


Sarkawt Hamad, Daniel Derichsweiler, Jürgen Hescheler and Kurt Pfannkuche


Methods in Molecular Biology 2021 Oct 19.doi: 10.1007/7651_2021_395. Online ahead of print.


Human induced pluripotent stem cells (hiPSCs) can be expanded at limitless scale in vitro and give rise to various organotypic cells, cardiomyocytes (CMs) among them. Advanced protocols shape the differentiation process of pluripotent stem cells by controlled growth factor application. Modulating the Wnt signaling pathway is effective to direct hiPSCs to CMs (hiPSC-CMs) and native growth factors were replaced by small chemical compounds. Here, we describe a refined protocol for scalable generation of hiPSC-CMs that manipulates porcupine and tankyrase sub-pathways of Wnt signaling for tight inhibition of non-canonical Wnt signaling. The approach results in a differentiation efficiency toward hiPSC-CMs of 87 ± 0.9% in stirred bioreactor cultures and yields about 70 million hiPSC-CMs per 100 mL serum free cardiac differentiation medium. The differentiation protocol is easily adapted from 3D to 2D culture and vice versa and has been demonstrated to work with different hiPSC lines.



Keywords: 3D culture; Bioreactor; Cardiomyocytes; Human induced pluripotent stem cells; Scalable differentiation process.


August 2021


Cologne - Karachi - Tandojam


My PostDoc Raja Sahito has travelled to Karachi, PK and Tandojam, PK for face-to-face discussion of our ongoing collaboration. The Sindh Agriculture University, Tandojam is already a partner of our Institute since 2014 and we are happy to add the renowned Sindh Madressatul Islam (SMI) University, Karachi to our network. SMI scientists hold deep knowledge in the field of artificial intelligence. We are looking forward to a fruitful collaboration.


April 2021

Upcoming event: Bio-Convergence – The Future of Health


Are you a researcher or entrepreneur in Pharma, Medical-tech, or AI? Have you ever heard of Bio-Convergence? Want to learn more about the existing nexus point between engineering, biology and medicine, which will revolutionize the future of health? Are you interested in German-Israeli collaborations?
If you answered YES to any of these questions, join us for Bio-Convergence – The Future of Health: Opportunities for German-Israeli Collaborations
We will discuss Bio-Convergence, display how cutting-edge research can lead to successful companies, and present potential funding opportunities for German-Israeli collaborations.


The event will take place on May 4th, 2021 at 11:00 (IST) | 10:00 (CET)


We will present two pitches on recent projects in this meeting.

April 2021


VEGF Contributes to Mesenchymal Stem Cell-Mediated Reversion of Nor1-Dependent Hypertrophy in iPS Cell-Derived Cardiomyocytes


Denise Philipp, Michelle Holthaus, Vida Basoah, Kurt Pfannkuche, Laura Suhr, Thorsten Wahlers, and Adnana Paunel-Görgülü


Myocardial hypertrophy is present in many heart diseases, representing a strong predictor of adverse cardiovascular outcomes. Regarding therapeutic intervention, mesenchymal stem cells (MSCs) have been suggested to significantly reduce cardiac hypertrophy and progression to heart failure. Preconditioning of MSCs was previously demonstrated to highly improve their paracrine activity resulting in modulation of immune responses and the progression of diseases. Here, we studied the effects of bone marrow-derived preconditioned MSCs on hypertrophied induced pluripotent stem cell-derived cardiomyocytes (iPS-CM) and also sought to identify MSC-derived antihypertrophic molecules. Phenylephrine (PE) was used to induce hypertrophy in murine iPS-CM, and markers of hypertrophy were identified by microarray analysis. Murine MSCs were treated with IFN-γ and IL-1β to enhance their paracrine activity, and transcriptional profiling was performed by microarray analysis. Hypertrophied iPS-CM were subsequently cocultured with preconditioned MSCs or MSC-conditioned medium (CM), respectively. Effects on hypertrophied iPS-CM were studied by cell area quantification, real-time PCR, and western blot. In some experiments, cells were incubated with fractions of MSC-CM obtained by ultrafiltration or by MSC-CM supplemented with inhibitory antibodies. Intracellular and extracellular levels of vascular endothelial growth factor (VEGF) were evaluated by western blot and ELISA. PE-induced hypertrophy in iPS-CM was associated with an upregulation of neuron-derived orphan receptor (Nor1) expression, activation of Akt, and inhibition of both strongly prevented hypertrophy induction in iPS-CM. VEGF secreted by preconditioned MSCs provoked hypertrophy regression in iPS-CM, and a negative correlation between Nor1 expression and hypertrophic growth could be evidenced. Our results demonstrate that Nor1 expression strongly supports hypertrophy in iPS-CM. Moreover, the secretome of preconditioned MSCs triggered regression of hypertrophy in iPS-CM in a VEGF-dependent manner. We suggest that the delivery of the MSC-derived secretome may represent a therapeutic strategy to limit cardiac hypertrophy. However, additional in vivo studies are needed to prove this hypothesis.


Read the full text HERE

March 2021


Impact of Poly(dimethylsiloxane) Surface Modification with Conventional and Amino Acid-Conjugated Self-Assembled Monolayers on the Differentiation of Induced Pluripotent Stem Cells into Cardiomyocytes


M. Özgen Öztürk-Öncel, Carlos O. Heras-Bautista, Lokman Uzun, Deniz Hür, Jürgen Hescheler, Kurt Pfannkuche, Bora Garipcan


Cardiomyocytes, differentiated from induced pluripotent stem cells (iPSCs), have the potential to produce patient- and disease-specific pharmacological and toxicological platforms, in addition to their cardiac cell therapy applications. However, the lack of both a robust and a simple procedure for scalable cell substrate production is one of the major limitations in this area. Mimicking the natural healthy myocardium extracellular matrix (ECM) properties by altering the cell substrate properties, such as stiffness and chemical/biochemical composition, can significantly affect cell substrate interfacial characteristics and potentially influence cellular behavior and differentiation of iPSCs to cardiomyocytes. Here, we propose a systematic and biomimetic approach, based on the preparation of poly(dimethylsiloxane) (PDMS) substrates having the similar stiffness as healthy heart tissue and a well-defined surface chemistry obtained by conventional [(3-aminopropyl)triethoxysilane (APTES) and octadecyltrimethoxysilane (OTS)] and amino acid (histidine and leucine)-conjugated self-assembled monolayers (SAMs). Among a wide range of different concentrations, the 50:1 prepolymer cross-linker ratio of PDMS allowed adaptation of the myocardium stiffness with a Young’s modulus of 23.79 ± 0.61 kPa. Compared with conventional SAM modification, amino acid-conjugated SAMs greatly improved iPSC adhesion, viability, and cardiac marker expression by increasing surface biomimetic properties, whereas all SAMs enhanced cell behavior, with respect to native PDMS. Furthermore, leucine-conjugated SAM modification provided the best environment for cardiac differentiation of iPSCs. This optimized approach can be easily adapted for cardiac differentiation of iPSCs in vitro, rendering a very promising tool for microfluidics, drug screening, and organ-on-chip platforms.


Read the full manuscript here:

March 2021


Transposon for fluorescent labelling and puromycin selection of human stem cell derived cardiomyocytes


As a service to our colleagues working in the field of human pluripotent stem cell derived cardiomyocytes the Marga and Walter Boll Laboratory for Cardiac Tissue Engineering releases a transposon free of charge via


To access and order the plasmid go to


You will receive a plasmid that contains a transposable element. A piggyBac transposase needs to be co-transfected for active insertion of the transposon in the genome. Selection of transfected human iPS cells is performed by Zeocin. Resistant clones need to be differentiated and screened for lines that show bright expression of the red fluorescent protein mCherry. As the coding sequence of mCherry is linked to the coding sequence of puromycin-N-acetyltransferase, red fluorescent cardiomyocytes exhibit resistance to puromycin and can be selected for experiments that require pure cells. Contact us if you need assistance.

10th International Meeting of the Stem Cell Network NRW



Dear all,



On March 29-30, 2021 the 10th International Meeting of the Stem Cell Network NRW “From Fundamental Biology to Translational Concepts” will take place – this year for the first time as a virtual event! The congress chairman Professor Oliver Bruestle of Bonn University/ University Hospital Bonn is looking forward to welcoming inspiring international stem cell experts, basic and clinical researchers as well as young talents and would like to invite you to join the conference.



The highlights include:

  • 16 lectures from internationally renowned stem cell researchers
  • Participation opportunities for all: Present your own research as a talk in one of the sessions or as an interactive pitch in a separate "room"! 
    Abstract submission is possible until February 15th, 2021
  • Opportunities for further exchange and discussions with the speakers in specific “breakout-sessions” directly after each session
  • Meet the speaker events for junior scientists
  • Virtual industry exhibition
  • Networking (almost) like at a normal conference: direct contact between participants via (video)chat
  • Access to recordings of all presentations until April 30th.



The deadline for abstract submission is February 15, 2021!



The preliminary program and further information about the event can be found on our homepage.



We look forward to seeing you on March 29 & 30, 2021!

Best regards from the Stem Cell Network NRW

Januar 2021



Burkert K, Taheri H, Hamad S, Oliverio M, Peinkofer G, Kornfeld JW, Harnying W, Pfannkuche K, Hescheler J, Berkessel A, Šarić T.



Salicylic diamines selectively eliminate residual undifferentiated cells from pluripotent stem cell-derived cardiomyocyte preparations



Sci Rep. 2021 Jan 27;11(1):2391. doi: 10.1038/s41598-021-81351-z.



Clinical translation of pluripotent stem cell (PSC) derivatives is hindered by the tumorigenic risk from residual undifferentiated cells. Here, we identified salicylic diamines as potent agents exhibiting toxicity to murine and human PSCs but not to cardiomyocytes (CMs) derived from them. Half maximal inhibitory concentrations (IC50) of small molecules SM2 and SM6 were, respectively, 9- and 18-fold higher for human than murine PSCs, while the IC50 of SM8 was comparable for both PSC groups. Treatment of murine embryoid bodies in suspension differentiation cultures with the most effective small molecule SM6 significantly reduced PSC and non-PSC contamination and enriched CM populations that would otherwise be eliminated in genetic selection approaches. All tested salicylic diamines exerted their toxicity by inhibiting the oxygen consumption rate (OCR) in PSCs. No or only minimal and reversible effects on OCR, sarcomeric integrity, DNA stability, apoptosis rate, ROS levels or beating frequency were observed in PSC-CMs, although effects on human PSC-CMs seemed to be more deleterious at higher SM-concentrations. Teratoma formation from SM6-treated murine PSC-CMs was abolished or delayed compared to untreated cells. We conclude that salicylic diamines represent promising compounds for PSC removal and enrichment of CMs without the need for other selection strategies.


Read the full text HERE



Januar 2021


Dr. Sarkawt Hamad from our group has contributed to a recent manuscript about the interpretation of statistic data.


Read the full text HERE



Salem Alawbathani, Mehreen Batool, Jan Fleckhaus, Sarkawt Hamad, Floyd Hassenrück, Yanhong Hou, Xia Li, Jon Salmanton-García, Sami Ullah, Frederique Wieters & Martin C. Michel



Naunyn-Schmiedeberg's Archives of Pharmacology (2021)



A teaching tool about the fickle p value and other statistical principles based on real-life data


A poor understanding of statistical analysis has been proposed as a key reason for lack of replicability of many studies in experimental biomedicine. While several authors have demonstrated the fickleness of calculated p values based on simulations, we have experienced that such simulations are difficult to understand for many biomedical scientists and often do not lead to a sound understanding of the role of variability between random samples in statistical analysis. Therefore, we as trainees and trainers in a course of statistics for biomedical scientists have used real data from a large published study to develop a tool that allows scientists to directly experience the fickleness of p values. A tool based on a commonly used software package was developed that allows using random samples from real data. The tool is described and together with the underlying database is made available. The tool has been tested successfully in multiple other groups of biomedical scientists. It can also let trainees experience the impact of randomness, sample sizes and choice of specific statistical test on measured p values. We propose that live exercises based on real data will be more impactful in the training of biomedical scientists on statistical concepts.

Januar 2021



Effects of physicochemical properties of polyacrylamide (PAA) and (polydimethylsiloxane) PDMS on cardiac cell behavior



Karim Daliri , Kurt Pfannkuche, Bora Garipcan





In vitro cell culture is commonly applied in laboratories around the world. Cultured cells are either of primary origin or established cell lines. Such transformed cell lines are increasingly replaced by pluripotent stem cell derived organotypic cells with more physiological properties. The quality of the culture conditions and matrix environment is of considerable importance in this regard. In fact, mechanical cues of the extracellular matrix have substantial effects on the cellular physiology. This is especially true if contractile cells such as cardiomyocytes are cultured. Therefore, elastic biomaterials have been introduced as scaffolds in 2D and 3D culture models for different cell types, cardiac cells among them. In this review, key aspects of cell-matrix interaction are highlighted with focus on cardiomyocytes and chemical properties as well as strengths and potential pitfalls in using two commonly applied polymers for soft matrix engineering, polyacrylamide (PAA) and polydimethylsiloxane (PDMS) are discussed.



Soft Matter. 2021 Jan 11.



Link to full text: LINK


November 2020


New Technology in the lab: PlasmaFecto 30


Our lab equipment has just been upgraded with a vacuum plasma device from Plasma Technologie. We are using argon and oxygen plasmas for plasma cleaning, plasma sterilization and surface activation and modification.


August 2020


August-24 Congratulation Sarkawt for obtaining the PhD in Health Sciences.


Today, Sarkawt has defended his PhD thesis in the graduate school PhD Health Sciences at the Medical Faculty of the University of Cologne. "An outstanding presentation for an outstanding thesis" as one of the reviewers told. That´s definitively true.



August 2020


Following the adverse outcome pathway from micronucleus to cancer using H2B-eGFP transgenic healthy stem cells.


Hölzel BN, Pfannkuche K, Allner B, Allner HT, Hescheler J, Derichsweiler D, Hollert H, Schiwy A, Brendt J, Schaffeld M, Froschauer A, Stahlschmidt-Allner P.
Arch Toxicol. 2020 Sep;94(9):3265-3280. doi: 10.1007/s00204-020-02821-3. Epub 2020 Jul 22.
In vitro assessment of genotoxicity as an early warning tool for carcinogenicity mainly relies on recording cytogenetic damages (micronuclei, nucleoplasmic bridges) in tumour-derived mammalian cell lines like V79 or CHO. The forecasting power of the corresponding standardised test is based on epidemiological evidence between micronuclei frequencies and cancer incidence. As an alternative to destructive staining of nuclear structures a fish stem cell line transgenic for a fusion protein of histone 2B (H2B) and enhanced green fluorescent protein (eGFP) was established. The cells are derived from koi carp brain (KCB) and distinguish from mammalian culturable cells by non-tumour-driven self-renewal. This technology enables the analysis of genotoxic- and malign downstream effects in situ in a combined approach. In proof-of concept-experiments, we used known carcinogens (4-Nitroquinoline 1-oxide, colchicine, diethylstilbestrol, ethyl methanesulfonate) and observed a significant increase in micronuclei (MNi) frequencies in a dose-dependent manner. The concentration ranges for MNi induction were comparable to human/mammalian cells (i.e. VH-16, CHL and HepG2). Cannabidiol caused the same specific cytogenetic damage pattern as observed in human cells, in particular nucleoplasmic bridges. Metabolic activation of aflatoxin B1 and cyclophosphamide could be demonstrated by pre-incubation of the test compounds using either conventional rat derived S9 mix as well as an in vitro generated biotechnological alternative product ewoS9R. The presented high throughput live H2B-eGFP imaging technology using non-transformed stem cells opens new perspectives in the field of in vitro toxicology. The technology offers experimental access to investigate the effects of carcinogens on cell cycle control, gene expression pattern and motility in the course of malign transformation. The new technology enables the definition of Adverse Outcome Pathways leading to malign cell transformation and contributes to the replacement of animal testing. Summary: Complementation of genotoxicity testing by addressing initiating events leading to malign transformation is suggested. A vertebrate cell model showing "healthy" stemness is recommended, in contrast to malign transformed cells used in toxicology/oncocology.
The study was supported by a BMWi Central Innovation Program for SMEs (ZIM; no. ZF4066801MD5) and BMBF for KMU-Innovative BioChance (PLUG; no. 031A263A)
Read the full article: Link to Journal
This manuscript results from our ongoing collaboration with Gobio GmbH and EWOMIS GmbH.

April 2020

April-28 Congratulation Raja for obtaining your doctorate!


Today my team member Raja Sahito has successfully defended his thesis and obtained the doctor title.


Congratulations Raja and good luck with your next projects!

March 2020




The laboratory is almost down due to the restrictions associated with the spreading of the Corona virus. However, we are still making progress and Daniel has succeeded to derive a seahorse from human stem cells. 


January 2020


Supercritical carbondioxide sterilizer from Novasterilis


New technology has arrived! Thanks to funding by the Marga-and-Walter-Boll Foundation we are now installing a Novasterilis device in our laboratory. The device can be used to sterilize sensitive biological materials with supercritical carbon dioxide. Furthermore, it can decellularize tissues by the same approach but at higher pressures. 

October 2019


Marga-and-Walter-Boll Laboratory for Cardiac Tissue Engineering


The Marga-and-Walter-Boll Foundation has decided to support my group with a new laboratory for cardiac tissue engineering. A room at the Center for Physiology and Pathophysiology is already found and we will soon start with renovations and purchasing the equipment. The Marga and Walter Boll Laboratory for Cardiac Tissue Engineering will allow us to intensify research on human iPS cell-derived cardiomyocytes for cardiac tissue engineering and cell therapy. Thanks a lot for this great opportunity!


August 2019


2nd Cologne Conference on Cardiac Regeneration and Therapy (26./27.9.2019)


Our conference is coming closer and we have finalized the conference program. Registration is open as well.

Please visit the conference page

August 2019

(updated October 2019)


Generation of human induced pluripotent stem cell-derived cardiomyocytes in 2D monolayer and scalable 3D suspension bioreactor cultures with reduced batch-to-batch variations

Sarkawt Hamad, Daniel Derichsweiler, Symeon Papadopolous, Filomain Nguemo, Tomo Saric, Agapios Sachinidis, Jürgen Hescheler, Bastiaan Boukens, Kurt Pfannkuche

Theranostics online date 2019-7-18; doi:10.7150/thno.32058; accepted


To download the PDF version click here


Mai 2019


On March 21st the 7th "Forschungsbörse" took place at the Medical Faculty Cologne. This event is organized by the students and allows research groups of the faculty to present their current work and discuss project opportunities with the students. 

I had a lot of interesting discussions with our highly motivated students that inquire for information on scientific projects and seek to inform themselves on current progress in cardiac tissue engineering and stem cell technologies.


(Foto: Dorothea Hensen, Medizinfoto Köln)

Mai 2019

First Cologne Conference on Cardiac Repair


Save the date: Sept. 26-27, 2019


Organizers: Kurt Pfannkuche and Tomo Saric

Further infos will appear soon on our conference website

Sponsor: Fritz-Thyssen-Foundation, Cologne


Confirmed speakers


  • Gabriele Pfitzer (Universität Köln, Deutschland)
  • Egbert Flory (Paul Ehrlich Institute, Cell Therapy and Tissue Engineering, Langen, Deutschland)
  • Jürgen Hescheler (Universität Köln, Deutschland)
  • Leo Kurian (Zentrum für molekulare Medizin Köln, Deutschland)
  • Christoph Dieterich (Heidelberg, Deutschland)
  • Felix Engel (Erlangen, Deutschland)
  • Hossein Baharvand (Royan Institute, Teheran, Iran)
  • Francisco Fernandez-Aviles (Hospital Gregorio Marañon, Madrid, Spanien)
  • Marcel Halbach (UKK, Cologne)
  • Peter Ertl (TU Wien, Österreich)
  • Wolfram Zimmermann (Göttingen, Deutschland)
  • Joost Sluijter (UMC Utrecht, Niederlande)
  • Marie Jose Goumans (Leiden, Niederlande)
  • Bernd K. Fleischmann (Uni Bonn, Deutschland)
  • Vitaliy Khlebnikov (UMC Utrecht, Niederlande)
  • Felipe Prósper (Hematology and Cell Therapy, Clínica Univ. de Navarra, Pamplona, Spain)


Mai 2019

Leitmarkt NRW: Vaskularisierter, bioartifizieller Herzmuskel aus induziert-pluripotenten Stammzellen


We proudly announce that the project proposal "Vaskularisierter, bioartifizieller Herzmuskel aus induziert-pluripotenten Stammzellen" has been selected by the "Leitmarkt-Agentur" for funding.


In the frame of this project the project consortium will employ a radically novel approach to generate vascularized engineered tissues for therapeutical approaches.


Consortium partners:


LightFab GmbH, Aachen

Miltenyi Biotech GmbH, Bergisch Gladbach

Taros Chemicals GmbH und Co KG, Dortmund

Fraunhofer-Institut für Lasertechnik ILT, Aachen (Dr. Elke Bremus-Koebberling, Dr. Nadine Nottrodt, Dr. Martin Wehner)

Universitätsklinik Köln (AG PD Dr. Kurt Pfannkuche)

Universität zu Köln, Institut für physikalische Chemie (AG Prof. Annette Schmidt)


Follow this link to see a list with all granted projects: Pressemitteilung

Mai 2019

"In vitro grown micro-tissues for cardiac cell replacement therapy in vivo"


Raja Ghazanfar Ali Sahito, Xiaowu Sheng, Martina Maass, Nelly Mikhael,l Sarkawt Hamad, Carlos O. Heras-Bautista, Daniel Derichsweiler, Dimitry Spitkovsky, Frank Suhr, Markus Khalil, Konrad Brockmeier, Marcel Halbach, Tomo Saric, Jürgen Hescheler, Benjamin Krausgrill, Kurt Pfannkuche


Background/Aims: Different approaches have been considered to improve heart reconstructive medicine and direct delivery of pluripotent stem cell-derived cardiomyocytes (PSC-CMs) appears to be highly promising in this context. However, low cell persistence post-transplantation remains a bottleneck hindering the approach. Here, we present a novel strategy to overcome the low engraftment of PSC-CMs during the early post-transplantation phase into the myocardium of both healthy and cryoinjured syngeneic mice. 

Methods: Adult murine bone marrow mesenchymal stem cells (MSCs) and PSC-CMs were co-cultured on thermo-responsive polymers and later detached through temperature reduction, resulting in the protease-free generation of cell clusters (micro-tissues) composed of both cells types. Micro-tissues were transplanted into healthy and cryo-injured murine hearts. Short term cell retention was quantified by real-time-PCR. Longitudinal cell tracking was performed by bioluminescence imaging for four weeks. Transplanted cells were further detected by immunofluorescence staining of tissue sections. 

Results: We demonstrated that in vitro grown micro-tissues consisting of PSC-CMs and MSCs can increase cardiomyocyte retention by >10-fold one day post-transplantation, but could not fully rescue a further cell loss between day 1 and day 2. Neutrophil infiltration into the transplanted area was detected in healthy hearts and could be attributed to the cellular implantation rather than tissue damage exerted by the transplantation cannula. Injected PSC-CMs were tracked and successfully detected for up to four weeks by bioluminescence imaging. 

Conclusion: This approach demonstrated that in vitro grown micro-tissues might contribute to the development of cardiac cell replacement therapies.


Read the full text:


Fig. 5. Histological observation of transplanted micro-tissues. Micro-tissues of low-dose MSC/iPS-CM were transplanted into cryoinjured cardiac tissue. Trichrome staining revealed fibrotic areas of myocardial damage after one week (A) and two weeks (E). Transplanted cells were stained with antibodies against luciferase (green) and nuclei were co-stained by Hoechst dye (blue). Tissue autofluorescence (red) was recorded to visualize the endogenous cardiac tissue. Panel A/B and C/D show results for two individual animals one week after cryoinjury and cell transplantation. Panel E/F show engrafted cells from one animal two weeks after cell transplantation. Panel G/H display magnified regions from the section shown in F.

Mai 2019

CCCR: First Cologne Conference on Cardiac Repair: 26./27. September 2019


Together with Tomo Saric at the Institute of Neurophysiology, Cologne we are organizing the first Cologne Conference on Cardiac Repair. The Event will take place on the 26st and 27th Sept. 2019 at the Center of Physiology, Cologne. We gratefully aknowledge support of the Fritz-Thyssen-Foundation to organize the meeting. I am comming back with more detailed information on topics, invited and confirmed speakers soon. This will be a great chance for networking, I am happy to be part of it!


March 2019

“Cardiomyocytes facing fibrotic conditions re-express extracellular matrix transcripts”


Carlos O.Heras Bautista*,  Nelly Mikhael*, Jennifer Lam, Vaibhav Shinde, Alisa Katsen-Globa, Sabine Dieluweit, 

Marek Molcanyi, Vladimir Uvarov, Peter Jütten, Raja G.A. Sahito, Francisco Mederos Henry, Alexander Piechot, 

Konrad Brockmeier, Jürgen Hescheler, Agapios Sachinidis, Kurt Pfannkuche

*both authors contributed equally


Pathophysiological conditions, such as myocardial infarction and mechanical overload affect the mammalian heart integrity, leading to a stiffened fibrotic tissue. With respect to the pathophysiology of cardiac fibrosis but also in the limelight of upcoming approaches of cardiac cell therapy it is of interest to decipher the interaction of cardiomyocytes with fibrotic matrix. Therefore, we designed a hydrogel-based model to engineer fibrotic tissue in vitro as an approach to predict the behavior of cardiomyocytes facing increased matrix rigidity. Here, we generated pure induced pluripotent stem cell-derived cardiomyocytes and cultured them on engineered polyacrylamide hydrogels matching the elasticities of healthy as well as fibrotic cardiac tissue. Only in cardiomyocytes cultured on matrices with fibrotic-like elasticity, transcriptional profiling revealed a substantial up-regulation of a whole panel of cardiac fibrosis-associated transcripts, including collagen I and III, decorin, lumican, and periostin. In addition, matrix metalloproteinases and their inhibitors, known to be essential in cardiac remodeling, were found to be elevated as well as insulin-like growth factor 2. Control experiments with primary cardiac fibroblasts were analyzed and did not show comparable behavior. In conclusion, we do not only present a snapshot on the transcriptomic fingerprint alterations in cardiomyocytes under pathological conditions but also provide a new reproducible approach to study the effects of fibrotic environments to various cell types.



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February 2019

Mobility Grant for MSc. Sarkawt Hamad


Congratulations to Sarkawt for winning a mobility grant (IPaK: Promoting international students at the University of Cologne) supported by the DAAD and selected by the medical faculty, Cologne. The grant will allow Sarkawt to stay for 2 months in the laboratory of Dr. Carolina Galvez-Monton located at Badalona, Spain. The aim of this visit is to initate first experiments of cardiac cell replacement therapy using human induced pluripotent stem cell derived cardiomyocytes in a large animal model.

February 2019

Novel project granted by the Elisabeth and Rudolf Hirsch-Foundation


We have just received the good news that the Elisabeth and Rudolf Hirsch Foundation gives support to the team thereby allowing us to conduct initial experiment of cardiac cell replacement therapy in a porcine model. This project is handled mainly by Daniel Derichsweiler and Msc. Sarkawt Hamad in the laboratory with support by Karina Neumann. Cell production technologies are established and experimental permissions were granted.

January 2019

Collaboration News Gobio GmbH


Our group has supported the SME Gobio GmbH (Aarbergen, Germany) in the develop of a stem cell-based cell assays for toxicity measurements. The collaborative work was funded by the German Federal Ministry for Economic Affairs and Energy within a "ZIM project" and has now resulted in the application of patents in Europe and US

("Indicator stem cell line/living organism (non human) and a method for detection of the genotoxic potential of aquatic samples or aqueous solutions of test compounds.")

December 2018

Networking Event Badalona - Spain


In preparation for the upcoming projects in the field of cardiac cell replacement therapy we have visited the IGTP Institute in Badalona, Spain to meet our collaboration partners Dr. Carolina Galvez-Monton and Prof. Bas Boukens (Amsterdam) for a brain storming. The novel facility at IGTP provides the best possible environment for our research with state of the art facilities and instrumentation.

October 2018

Networking Event Tandojam - Cologne Initiative


In the follow up of our first online course in cell culture technologies for students at our partner University SAU in Tandojam, PK  vicechancelor Prof. Memon is guest in Cologne to report on the ongoing initiative to establish a new institute for stem cell research. The building is now ready to use and we are planning the next steps.





July 2018

Novel project granted by the German Research Foundation (DFG)

Our team has now received a novel grant to optimize the early retention of transplanted stem cell-derived cardiomyocytes in a rodent model of cardiac infarction. In the frame of the project our successful strategy of micro-tissue transplantation will be further developed to enhance the efficiency of the approach. Magnetic targeting is among the strategies that appear attractive to boost the cell transplantation success.

June 2018

Generation of human induced pluripotent stem cell derived cardiomyocytes (HiPS-CMs) optimized

Sarkawt and Daniel from my team have made a hell of effort to optimize the differentiation of HiPS-CMs for reproducible generation of cardiac differentiation, high differentiation efficiencies of up to 95%, high yields of maximally 100 million cardiomyocytes per 100 ml suspension culture and controlled costs. Alltogether, we are now moving forward to plan preclinical studies in the porcine model together with Dr. Gálvez Montón in Badalona, Spain. Pall Corporation has just offered support for the bioreactor technology - hope to getting started soon.

June 2018

Tandojam Laboratory of Regenerative Medicine

Our team supports the SAU to rise a own stem cell laboratory at Tandojam, Pakistan. This collaboration has arisen from a project ("KAZE" project) funded by the BMBF in the frame of scientific collaborations with partners in Pakistan in 2014. Raja is busy in networking and keeping everybody in the consortium busy. The Vice-chancellor of SAU Prof. Mujeeb-u-ddin Sahrai has visited Cologne on several occasions to keep the business rolling.  Efforts have already payed-off and the Pakistan Ministry has just granted about 3.5 Mio. Euro to raise a stem cell laboratory at SAU. We are involved in the planning and help the SAU to get started in the field of stem cell technology. The online lecture series in April will be followed by further and more specific training measures in the future.

April 2018

Online course on basic stem cell culturing techniques at Sindh Agricultural University (SAU)

Together with our colleagues at the Institute of Neurophysiology Cologne we have prepared an online course for cell culturing technologies for students at the SAU in Tandojam, Pakistan. The lecture was attended by nearly 50 persons from student to principal investigator level. We are planning further activities in the future to intensify our collaboration with the SAU in the field of Stem Cell Research. Many thanks to the Vice Chancellor Prof. Mujeeb-u-ddin Sahrai for his great support of the project.