Medical Research.com Interview with:
Katrin Streckfuss-Boemeke, PhD
Department of Cardiology and Pneumology
Heart Research Center Göttingen (HRCG)
University Medical Center Göttingen
37075 Göttingen Germany
Medical ResearcH.com: What are the main findings of the study?
Answer: The main finding is that human induced pluripotent stem cells (hiPSCs) can be generated from different somatic cell sources including bone marrow mesenchymal stem cells (MSCs), hair keratinocytes, and skin fibroblasts, but MSCs and fibroblasts are more easily reprogrammed than keratinocytes.
All generated hiPSCs can differentiate into cardiomyocytes with an efficiency ranging from 3 to 42%. However, the highest cardiac differentiation efficiency was achieved from MSC-derived hiPSCs.
Although the cardiac differentiation efficiency varied among different cell lines, there is no significant difference in the functionalities of cardiomyocytes derived from different hiPSC lines.
Medical Research.com: Were any of the findings unexpected?
Answer: We find that the Oct and Nanog promoters in keratinocytes are significantly higher methylated than those in MSCs and fibroblasts, possibly explaining the lower reprogramming efficiencies in keratinocytes.
Medical Research.com: What should clinicians and patients take away from your report?
Answer: It is known that hiPSCs are a promising cell source for investigating cardiac diseases, and performing drug screenings on a patient-specific level.
Our study shows that different somatic cell sources can be used for the generation of hiPSCs with different advantages and disadvantages. For the patient plucked hairs as the cell source for reprogramming still offer significant advantages over skin biopsies and bone marrow aspirates, because they can be easily obtained in contrast to the other two cell types, where clinical specialists are needed. Therefore, it is possible to generate hair keratinocyte cultures from many patients who cannot undergo a skin biopsy or a bone marrow aspiration.
Nevertheless, before clinicians start to use hiPSCs in disease modeling and in regenerative medicine, they have to address many aspects including which donor cell source would be the best regarding the accessibility, the most efficient differentiation into certain cell types they need, and how to use the cells afterwards.
Although not demonstrated yet, it appears predictable that patient-specific hiPSC-derived cells can be used soon for clinical application. Whether this will be of therapeutic value remains to be studied.
Medical Research.com: What recommendations do you have for future research as a result of this study?
Answer: In this study we show that MSC-iPSCs differentiate into cardiomyocytes with higher efficiency than hiPSCs from fibroblasts or keratinocytes. To analyze the molecular mechanisms for this higher efficiency of cardiac differentiation of MSC-iPSCs a genome-wide transcriptional profiling and DNA methylation profiling in iPSCs from all cell sources is necessary.
Furthermore, it has to be addressed whether it is possible to generate hiPSCs from different cell sources without viral particles for further clinical applications.
Comparative study of human-induced pluripotent stem cells derived from bone marrow cells, hair keratinocytes, and skin fibroblasts.
Streckfuss-Bömeke K, Wolf F, Azizian A, Stauske M, Tiburcy M, Wagner S, Hübscher D, Dressel R, Chen S, Jende J, Wulf G, Lorenz V, Schön MP, Maier LS, Zimmermann WH, Hasenfuss G, Guan K.
Department of Cardiology and Pneumology, Georg-August-University Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.
Eur Heart J. 2012 Jul 12. [Epub ahead of print]