Selective elimination of human pluripotent stem cells by Anti-Dsg2 antibody-doxorubicin conjugates

Lee, Na Geum; Oh, Mihee; Song, Jinhoi; Kim, Wooil; Kwon, Min‐Gi; Kim, Seul Gi; Han, Baek Soo; Bae, Kwang‐Hee; Lee, Dong Gwang; Lee, Sang‐Hyun; Park, Jong‐Gil; Kim, Jae Ho; Min, Jeong‐Ki

doi:10.1016/j.biomaterials.2020.120265

Cited by 7 publications

(5 citation statements)

References 46 publications

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“…Teratoma formation assays were performed following a conventional method 20,26,40,41,47,48 after hPSCs were cultured on PVAI hydrogels conjugated with designed peptides for 10 passages. Briefly, after 6–8 weeks of subcutaneously transplanting hPSCs into nonobese diabetic/severe combined immunodeficiency (NOD.CB17-Prkdcscid/JNarl NOD/SCID) mice, teratomas were commonly generated, isolated and fixed in a formaldehyde solution.…”

Section: Methodsmentioning

confidence: 99%

Designed peptide-grafted hydrogels for human pluripotent stem cell culture and differentiation

et al. 2023

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Section: Methodsmentioning

confidence: 99%

Designed peptide-grafted hydrogels for human pluripotent stem cell culture and differentiation

et al. 2023

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“…Teratomas were excised 8 weeks from injection, and their weights and sizes were measured. For histology, tissue fixation, paraffin processing, embedding, sectioning, and hematoxylin and eosin staining were performed as described previously ( 20 ).…”

Section: Methodsmentioning

confidence: 99%

“…Total RNA was extracted from mice testicle tissues using TRIzol reagent (iNtRON Biotechnology) and cDNA was synthesized as described previously ( 20 ). For RT-PCR, primers to detect GATA6 , FN1 , AMY2A , HAND1 , MSX1 , MAP2 , NESTIN , TUBB3 , and GAPDH gene expression were used with primer sequences obtained from a previous study ( 19 ).…”

Section: Methodsmentioning

confidence: 99%

Monoclonal antibody K312-based depletion of pluripotent cells from differentiated stem cell progeny prevents teratoma formation

Lee¹,

Lee²,

Kwon³

et al. 2022

BMB Rep

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Human pluripotent stem cells (PSCs) have been utilized as a promising source in regenerative medicine. However, the risk of teratoma formation that comes with residual undifferentiated PSCs in differentiated cell populations is most concerning in the clinical use of PSC derivatives. Here, we report that a monoclonal antibody (mAb) targeting PSCs could distinguish undifferentiated PSCs, with potential teratoma-forming activity, from differentiated PSC progeny. A panel of hybridomas generated from mouse immunization with H9 human embryonic stem cells (hESCs) was screened for ESC-specific binding using flow cytometry. A novel mAb, K312, was selected considering its high stem cell-binding activity, and this mAb could bind to several human induced pluripotent stem cells and PSC lines. Cell-binding activity of K312 was markedly decreased as hESCs were differentiated into embryoid bodies or by retinoic acid treatment. In addition, a cell population negatively isolated from undifferentiated or differentiated H9 hESCs via K312 targeting showed a significantly reduced expression of pluripotency markers, including Oct4 and Nanog. Furthermore, K312-based depletion of pluripotent cells from differentiated PSC progeny completely prevented teratoma formation. Therefore, our findings suggest that K312 is utilizable in improving stem cell transplantation safety by specifically distinguishing residual undifferentiated PSCs.

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“…Another significant consideration is the potential off-target effects of targeting DSG2 [116]. While DSG2 is primarily expressed in epithelial tissues and plays a critical role in cell-cell adhesion, therapies designed to modulate DSG2 may inadvertently affect tissue integrity, cell adhesion and physiological function.…”

Section: Limitations Of Current Research On Dsg2 and Covid-19mentioning

confidence: 99%

Desmoglein-2 and COVID-19 complications: insights into its role as a biomarker, pathogenesis and clinical implications

Uchechukwu,

Anyaduba,

Udekwu

et al. 2023

Journal of General Virology

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Desmoglein-2 (DSG2) has emerged as a potential biomarker for coronavirus disease 2019 (COVID-19) complications, particularly cardiac and cardiovascular involvement. The expression of DSG2 in lung tissues has been detected at elevated levels, and circulating DSG2 levels correlate with COVID-19 severity. DSG2 may contribute to myocardial injury, cardiac dysfunction and vascular endothelial dysfunction in COVID-19. Monitoring DSG2 levels could aid in risk stratification, early detection and prognostication of COVID-19 complications. However, further research is required to validate DSG2 as a biomarker. Such research will aim to elucidate its precise role in pathogenesis, establishing standardized assays for its measurement and possibly identifying therapeutic targets.

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Selective elimination of human pluripotent stem cells by Anti-Dsg2 antibody-doxorubicin conjugates

Cited by 7 publications

References 46 publications

Designed peptide-grafted hydrogels for human pluripotent stem cell culture and differentiation

Designed peptide-grafted hydrogels for human pluripotent stem cell culture and differentiation

Monoclonal antibody K312-based depletion of pluripotent cells from differentiated stem cell progeny prevents teratoma formation

Desmoglein-2 and COVID-19 complications: insights into its role as a biomarker, pathogenesis and clinical implications

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