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Endovascular transp...
Endovascular transplantation of mRNA-enhanced mesenchymal stromal cells results in superior therapeutic protein expression in swine heart
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- Al-Saadi, Jonathan (författare)
- Department of Clinical Neuroscience, Karolinska Institute, Tomtebodavagen 18A, 171 65 Stockholm, Sweden, Tomtebodavägen 18A; Department of Neuroradiology, Karolinska University Hospital, 171 64, Stockholm, Sweden; MedTechLabs, Stockholm, Sweden
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- Waldén, Mathias (författare)
- Department of Clinical Neuroscience, Karolinska Institute, Tomtebodavagen 18A, 171 65 Stockholm, Sweden, Tomtebodavägen 18A
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- Sandell, Mikael (författare)
- KTH,Mikro- och nanosystemteknik,Department of Clinical Neuroscience, Karolinska Institute, Tomtebodavagen 18A, 171 65 Stockholm, Sweden, Tomtebodavägen 18A; MedTechLabs, Stockholm, Sweden
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- Sohlmér, Jesper (författare)
- Department of Cell and Molecular Biology, Karolinska Institute, Solnavagen 9, 171 65 Stockholm, Sweden, Solnavägen 9
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- Grankvist, Rikard (författare)
- Karolinska Institutet,Department of Clinical Neuroscience, Karolinska Institute, Tomtebodavagen 18A, 171 65 Stockholm, Sweden, Tomtebodavägen 18A
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- Friberger, Ida (författare)
- Department of Clinical Neuroscience, Karolinska Institute, Tomtebodavagen 18A, 171 65 Stockholm, Sweden, Tomtebodavägen 18A
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- Andersson, Agneta (författare)
- Department of Medicine, Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden
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- Carlsten, Mattias (författare)
- Karolinska Institutet,Department of Medicine, Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden; Center for Cell Therapy and Allogeneic Stem Cell Transplantation, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Stockholm, Sweden
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- Chien, Kenneth (författare)
- Karolinska Institutet,Department of Cell and Molecular Biology, Karolinska Institute, Solnavagen 9, 171 65 Stockholm, Sweden, Solnavägen 9
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- Lundberg, Johan (författare)
- Karolinska Institutet,Department of Clinical Neuroscience, Karolinska Institute, Tomtebodavagen 18A, 171 65 Stockholm, Sweden, Tomtebodavägen 18A; Department of Neuroradiology, Karolinska University Hospital, 171 64, Stockholm, Sweden; MedTechLabs, Stockholm, Sweden
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- Witman, Nevin (författare)
- Department of Clinical Neuroscience, Karolinska Institute, Tomtebodavagen 18A, 171 65 Stockholm, Sweden, Tomtebodavägen 18A
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- Holmin, Staffan (författare)
- Karolinska Institutet,Department of Clinical Neuroscience, Karolinska Institute, Tomtebodavagen 18A, 171 65 Stockholm, Sweden, Tomtebodavägen 18A; Department of Neuroradiology, Karolinska University Hospital, 171 64, Stockholm, Sweden; MedTechLabs, Stockholm, Sweden
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(creator_code:org_t)
- Elsevier BV, 2024
- 2024
- Engelska.
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Ingår i: Molecular therapy. Methods & clinical development. - : Elsevier BV. - 2399-6951 .- 2329-0501. ; 32:2
- Relaterad länk:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Heart failure has a poor prognosis and no curative treatment exists. Clinical trials are investigating gene- and cell-based therapies to improve cardiac function. The safe and efficient delivery of these therapies to solid organs is challenging. Herein, we demonstrate the feasibility of using an endovascular intramyocardial delivery approach to safely administer mRNA drug products and perform cell transplantation procedures in swine. Using a trans-vessel wall (TW) device, we delivered chemically modified mRNAs (modRNA) and mRNA-enhanced mesenchymal stromal cells expressing vascular endothelial growth factor A (VEGF-A) directly to the heart. We monitored and mapped the cellular distribution, protein expression, and safety tolerability of such an approach. The delivery of modRNA-enhanced cells via the TW device with different flow rates and cell concentrations marginally affect cell viability and protein expression in situ. Implanted cells were found within the myocardium for at least 3 days following administration, without the use of immunomodulation and minimal impact on tissue integrity. Finally, we could increase the protein expression of VEGF-A over 500-fold in the heart using a cell-mediated modRNA delivery system compared with modRNA delivered in saline solution. Ultimately, this method paves the way for future research to pioneer new treatments for cardiac disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Nyckelord
- cardiology
- cell transplantation
- endovascular intervention
- endovascular intramyocardial transplantation
- heart failure
- mesenchymal stromal cells
- modRNA
- mRNA drug products
- trans-vessel wall device
- vascular endothelial growth factor
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Al-Saadi, Jonath ...
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Waldén, Mathias
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Sandell, Mikael
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Sohlmér, Jesper
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Grankvist, Rikar ...
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Friberger, Ida
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visa fler...
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Andersson, Agnet ...
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Carlsten, Mattia ...
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Chien, Kenneth
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Lundberg, Johan
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Witman, Nevin
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Holmin, Staffan
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Kardiologi
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinsk biotek ...
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och Medicinsk biotek ...
- Artiklar i publikationen
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Molecular therap ...
- Av lärosätet
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Kungliga Tekniska Högskolan
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Karolinska Institutet