Tumorigenicity assay essential for facilitating safety studies of hiPSC-derived cardiomyocytes for clinical application

Transplantation of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC-CMs) is a promising treatment for heart failure, but residual undifferentiated hiPSCs and malignant transformed cells may lead to tumor formation. Here we describe a highly sensitive tumorigenicity assay...

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Published inScientific reports Vol. 9; no. 1; p. 1881
Main Authors Ito, Emiko, Miyagawa, Shigeru, Takeda, Maki, Kawamura, Ai, Harada, Akima, Iseoka, Hiroko, Yajima, Shin, Sougawa, Nagako, Mochizuki-Oda, Noriko, Yasuda, Satoshi, Sato, Yoji, Sawa, Yoshiki
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 13.02.2019
Nature Publishing Group
Subjects
13
13/100
13/31
13/51
38
38/77
631/532/1360
631/532/2064/2158
64
64/60
Animals
Carcinogenicity Tests - methods
Cardiomyocytes
Cell Differentiation
Cell Proliferation
Cells, Cultured
Congestive heart failure
Humanities and Social Sciences
Humans
Induced Pluripotent Stem Cells - cytology
Induced Pluripotent Stem Cells - metabolism
Karyotype
Membrane Glycoproteins - metabolism
multidisciplinary
Myocytes, Cardiac - cytology
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - transplantation
Neoplasms - etiology
Pluripotency
Rats
Rats, Nude
RNA-Binding Proteins - metabolism
Science
Science (multidisciplinary)
Stem cells
Subculture
Transformed cells
Transplantation
Transplantation - adverse effects
Tumorigenicity
Tumors
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Abstract Transplantation of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC-CMs) is a promising treatment for heart failure, but residual undifferentiated hiPSCs and malignant transformed cells may lead to tumor formation. Here we describe a highly sensitive tumorigenicity assay for the detection of these cells in hiPSC-CMs. The soft agar colony formation assay and cell growth analysis were unable to detect malignantly transformed cells in hiPSC-CMs. There were no karyotypic abnormalities during hiPSCs subculture and differentiation. The hiPSC markers TRA1-60 and LIN28 showed the highest sensitivity for detecting undifferentiated hiPSCs among primary cardiomyocytes. Transplantation of hiPSC-CMs with a LIN28-positive fraction > 0.33% resulted in tumor formation in nude rats, whereas no tumors were formed when the fraction was < 0.1%. These findings suggested that combination of these in vitro and in vivo tumorigenecity assays can verify the safety of hiPSC-CMs for cell transplantation therapy.
AbstractList Transplantation of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC-CMs) is a promising treatment for heart failure, but residual undifferentiated hiPSCs and malignant transformed cells may lead to tumor formation. Here we describe a highly sensitive tumorigenicity assay for the detection of these cells in hiPSC-CMs. The soft agar colony formation assay and cell growth analysis were unable to detect malignantly transformed cells in hiPSC-CMs. There were no karyotypic abnormalities during hiPSCs subculture and differentiation. The hiPSC markers TRA1-60 and LIN28 showed the highest sensitivity for detecting undifferentiated hiPSCs among primary cardiomyocytes. Transplantation of hiPSC-CMs with a LIN28-positive fraction > 0.33% resulted in tumor formation in nude rats, whereas no tumors were formed when the fraction was < 0.1%. These findings suggested that combination of these in vitro and in vivo tumorigenecity assays can verify the safety of hiPSC-CMs for cell transplantation therapy.
Transplantation of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC-CMs) is a promising treatment for heart failure, but residual undifferentiated hiPSCs and malignant transformed cells may lead to tumor formation. Here we describe a highly sensitive tumorigenicity assay for the detection of these cells in hiPSC-CMs. The soft agar colony formation assay and cell growth analysis were unable to detect malignantly transformed cells in hiPSC-CMs. There were no karyotypic abnormalities during hiPSCs subculture and differentiation. The hiPSC markers TRA1-60 and LIN28 showed the highest sensitivity for detecting undifferentiated hiPSCs among primary cardiomyocytes. Transplantation of hiPSC-CMs with a LIN28-positive fraction > 0.33% resulted in tumor formation in nude rats, whereas no tumors were formed when the fraction was < 0.1%. These findings suggested that combination of these in vitro and in vivo tumorigenecity assays can verify the safety of hiPSC-CMs for cell transplantation therapy.
Abstract Transplantation of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC-CMs) is a promising treatment for heart failure, but residual undifferentiated hiPSCs and malignant transformed cells may lead to tumor formation. Here we describe a highly sensitive tumorigenicity assay for the detection of these cells in hiPSC-CMs. The soft agar colony formation assay and cell growth analysis were unable to detect malignantly transformed cells in hiPSC-CMs. There were no karyotypic abnormalities during hiPSCs subculture and differentiation. The hiPSC markers TRA1-60 and LIN28 showed the highest sensitivity for detecting undifferentiated hiPSCs among primary cardiomyocytes. Transplantation of hiPSC-CMs with a LIN28-positive fraction > 0.33% resulted in tumor formation in nude rats, whereas no tumors were formed when the fraction was < 0.1%. These findings suggested that combination of these in vitro and in vivo tumorigenecity assays can verify the safety of hiPSC-CMs for cell transplantation therapy.
ArticleNumber 1881
Author Sawa, Yoshiki
Kawamura, Ai
Yasuda, Satoshi
Mochizuki-Oda, Noriko
Takeda, Maki
Yajima, Shin
Miyagawa, Shigeru
Sougawa, Nagako
Sato, Yoji
Ito, Emiko
Harada, Akima
Iseoka, Hiroko
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/30760836$$D View this record in MEDLINE/PubMed
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Snippet Transplantation of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC-CMs) is a promising treatment for heart failure, but residual...
Abstract Transplantation of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC-CMs) is a promising treatment for heart failure, but...
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13/100
13/31
13/51
38
38/77
631/532/1360
631/532/2064/2158
64
64/60
Animals
Carcinogenicity Tests - methods
Cardiomyocytes
Cell Differentiation
Cell Proliferation
Cells, Cultured
Congestive heart failure
Humanities and Social Sciences
Humans
Induced Pluripotent Stem Cells - cytology
Induced Pluripotent Stem Cells - metabolism
Karyotype
Membrane Glycoproteins - metabolism
multidisciplinary
Myocytes, Cardiac - cytology
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - transplantation
Neoplasms - etiology
Pluripotency
Rats
Rats, Nude
RNA-Binding Proteins - metabolism
Science
Science (multidisciplinary)
Stem cells
Subculture
Transformed cells
Transplantation
Transplantation - adverse effects
Tumorigenicity
Tumors
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Title Tumorigenicity assay essential for facilitating safety studies of hiPSC-derived cardiomyocytes for clinical application
URI https://link.springer.com/article/10.1038/s41598-018-38325-5
https://www.ncbi.nlm.nih.gov/pubmed/30760836
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Volume 9
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