In Vitro Grown Micro-Tissues for Cardiac Cell Replacement Therapy in Vivo
| Autor: | Jürgen Hescheler, Tomo Saric, Raja Ghazanfar Ali Sahito, Nelly Mikhael, Carlos O Heras-Bautista, Sarkawt Hamad, Benjamin Krausgrill, Markus Khalil, Frank Suhr, Martina Maass, Kurt Pfannkuche, Konrad Brockmeier, Dimitry Spitkovsky, Marcel Halbach, Daniel Derichsweiler, Xiaowu Sheng |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Pathology Physiology Polymers Cell Myocardial Infarction Regenerative medicine lcsh:Physiology Mice 0302 clinical medicine lcsh:QD415-436 Myocytes Cardiac Induced pluripotent stem cell Cardiomyocytes lcsh:QP1-981 Optical Imaging Cardiac cell therapy Induced pluripotent stem cells medicine.anatomical_structure Neutrophil Infiltration Cell Tracking 030220 oncology & carcinogenesis Pluripotent Stem Cells Embryonic stem cells medicine.medical_specialty Bone Marrow Cells Mesenchymal Stem Cell Transplantation Cell Line lcsh:Biochemistry 03 medical and health sciences In vivo medicine Thermo-responsive polymer Bioluminescence imaging Animals business.industry Myocardium Mesenchymal stem cell Reconstructive medicine Mesenchymal Stem Cells Embryonic stem cell Coculture Techniques Immunity Innate Transplantation 030104 developmental biology Microscopy Fluorescence business |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 52, Iss 6, Pp 1309-1324 (2019) |
| ISSN: | 1421-9778 |
| Popis: | 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 >10fold 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. ispartof: Cell Physiol Biochem vol:52 issue:6 pages:1309-1324 ispartof: location:Germany status: published |
| Databáze: | OpenAIRE |
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