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Protein-encapsulated doxorubicin reduces cardiotoxicity in hiPSC-cardiomyocytes and cardiac spheroids while maintaining anticancer efficacy.
Arzt, Madelyn; Gao, Bowen; Mozneb, Maedeh; Pohlman, Stephany; Cejas, Romina B; Liu, Qizhi; Huang, Faqing; Yu, Changjun; Zhang, Yi; Fan, Xuemo; Jenkins, Amelia; Giuliano, Armando E; Burridge, Paul W; Cui, Xiaojiang; Sharma, Arun.
Afiliação
  • Arzt M; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Samuel Oschin Comprehensive Cancer In
  • Gao B; Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Mozneb M; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Samuel Oschin Comprehensive Cancer In
  • Pohlman S; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Samuel Oschin Comprehensive Cancer In
  • Cejas RB; Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Center for Pharmacogenomics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Liu Q; Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Huang F; Department of Chemistry and Biochemistry, University of Southern Mississippi, Hattiesburg, MS, USA.
  • Yu C; Division of Chemistry & Chemical Engineering, California Institute of Technology, Pasadena, CA, USA; Sunstate Biosciences LLC, Monrovia, CA, USA.
  • Zhang Y; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Fan X; Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Jenkins A; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Samuel Oschin Comprehensive Cancer In
  • Giuliano AE; Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Burridge PW; Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Center for Pharmacogenomics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Cui X; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Electronic address: xiaojiang.cui@cshs.org.
  • Sharma A; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Samuel Oschin Comprehensive Cancer In
Stem Cell Reports ; 18(10): 1913-1924, 2023 10 10.
Article em En | MEDLINE | ID: mdl-37657447
ABSTRACT
The chemotherapeutic doxorubicin (DOX) detrimentally impacts the heart during cancer treatment. This necessitates development of non-cardiotoxic delivery systems that retain DOX anticancer efficacy. We used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), endothelial cells (hiPSC-ECs), cardiac fibroblasts (hiPSC-CFs), multi-lineage cardiac spheroids (hiPSC-CSs), patient-specific hiPSCs, and multiple human cancer cell lines to compare the anticancer efficacy and reduced cardiotoxicity of single protein encapsulated DOX (SPEDOX-6), to standard unformulated (UF) DOX. Cell viability assays and immunostaining in human cancer cells, hiPSC-ECs, and hiPSC-CFs revealed robust uptake of SPEDOX-6 and efficacy in killing these proliferative cell types. In contrast, hiPSC-CMs and hiPSC-CSs exhibited substantially lower cytotoxicity during SPEDOX-6 treatment compared with UF DOX. SPEDOX-6-treated hiPSC-CMs and hiPSC-CSs maintained their functionality, as indicated by sarcomere contractility assessment, calcium imaging, multielectrode arrays, and RNA sequencing. This study demonstrates the potential of SPEDOX-6 to alleviate cardiotoxic side effects associated with UF DOX, while maintaining its anticancer potency.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Miócitos Cardíacos / Células-Tronco Pluripotentes Induzidas Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
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PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Miócitos Cardíacos / Células-Tronco Pluripotentes Induzidas Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article