Tumorigenicity risk of iPSCs <i>in vivo</i>: nip it in the bud

Zhong, Chaoliang; Liu, Miao; Pan, Xinghua; Zhu, Haiying

doi:10.1093/pcmedi/pbac004

Cited by 22 publications

(12 citation statements)

References 107 publications

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“…Pluripotent stem cells, including embryonic stem (ES) cells, have immense potential in regenerative medicine 27 – 29 . The ability of ES cells to differentiate into any cell type comes with a risk of teratoma formation in the event of undesired, uncontrolled differentiation of cells in patients 30 . To demonstrate that the PRSIM-based kill switch can eliminate this type of cell, stable cell lines containing the kill switch were made in the ES cell line Sa121.…”

Section: Resultsmentioning

confidence: 99%

A simeprevir-inducible molecular switch for the control of cell and gene therapies

Chin,

Schindler,

Vinall

et al. 2023

Nat Commun

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Chemical inducer of dimerization (CID) modules can be used effectively as molecular switches to control biological processes, and thus there is significant interest within the synthetic biology community in identifying novel CID systems. To date, CID modules have been used primarily in engineering cells for in vitro applications. To broaden their utility to the clinical setting, including the potential to control cell and gene therapies, the identification of novel CID modules should consider factors such as the safety and pharmacokinetic profile of the small molecule inducer, and the orthogonality and immunogenicity of the protein components. Here we describe a CID module based on the orally available, approved, small molecule simeprevir and its target, the NS3/4A protease from hepatitis C virus. We demonstrate the utility of this CID module as a molecular switch to control biological processes such as gene expression and apoptosis in vitro, and show that the CID system can be used to rapidly induce apoptosis in tumor cells in a xenograft mouse model, leading to complete tumor regression.

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Section: Resultsmentioning

confidence: 99%

A simeprevir-inducible molecular switch for the control of cell and gene therapies

Chin,

Schindler,

Vinall

et al. 2023

Nat Commun

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“…Finally, iPSCs technology needs to be standardised to ensure safe and effective sources of autologous cells for 3D bioprinting. Human iPSCs have provided massive potentials for use in regenerative and personalised medicine 70–72 . IPSCs have ability to effectively culture and expand in vitro and can be committed to differentiate into specific cells for cell therapy.…”

Section: The Prospect Of 3d Skin Bioprinting In Treatment Of Cutaneou...mentioning

confidence: 99%

3D skin bioprinting as promising therapeutic strategy for radiation‐associated skin injuries

Lv,

Zhao,

Long

et al. 2024

Wound Repair Regeneration

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Both cutaneous radiation injury and radiation combined injury (RCI) could have serious skin traumas, which are collectively referred to as radiation‐associated skin injuries in this paper. These two types of skin injuries require special managements of wounds, and the therapeutic effects still need to be further improved. Cutaneous radiation injuries are common in both radiotherapy patients and victims of radioactive source accidents, which could lead to skin necrosis and ulcers in serious conditions. At present, there are still many challenges in management of cutaneous radiation injuries including early diagnosis, lesion assessment, and treatment prognosis. Radiation combined injuries are special and important issues in severe nuclear accidents, which often accompanied by serious skin traumas. Mass victims of RCI would be the focus of public health concern. Three‐dimensional (3D) bioprinting, as a versatile and favourable technique, offers effective approaches to fabricate biomimetic architectures with bioactivity, which provides potentials for resolve the challenges in treating radiation‐associated skin injuries. Combining with the cutting‐edge advances in 3D skin bioprinting, the authors analyse the damage characteristics of skin wounds in both cutaneous radiation injury and RCI and look forward to the potential value of 3D skin bioprinting for the treatments of radiation‐associated skin injuries.

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“…While considering speed and volume, attention also needs to be paid to purity, as residual iPSCs or partially differentiated iPSCs could lead to tumorigenicity, which mainly includes teratoma formation and oncogene c-MYC expression-induced tumor formation [44]. Apart from using surface markers to isolate myogenic populations, it is critical to confirm if any iPSCs or partially differentiated iPSCs remain in the cell product [45]. Flow cytometry to detect pluripotency surface markers like SSEA4 and TRA-1-60 and quantitative PCR to detect gene expression of pluripotent genes like OCT4, Lin28, and ESRG have been employed to verify the cell product [46,47].…”

Section: Lineage Specification Efficiency Purification Process and Tu...mentioning

confidence: 99%

Challenges and Considerations of Preclinical Development for iPSC-Based Myogenic Cell Therapy

Sun,

Serra,

Kalicharan

et al. 2024

Cells

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Cell therapies derived from induced pluripotent stem cells (iPSCs) offer a promising avenue in the field of regenerative medicine due to iPSCs’ expandability, immune compatibility, and pluripotent potential. An increasing number of preclinical and clinical trials have been carried out, exploring the application of iPSC-based therapies for challenging diseases, such as muscular dystrophies. The unique syncytial nature of skeletal muscle allows stem/progenitor cells to integrate, forming new myonuclei and restoring the expression of genes affected by myopathies. This characteristic makes genome-editing techniques especially attractive in these therapies. With genetic modification and iPSC lineage specification methodologies, immune-compatible healthy iPSC-derived muscle cells can be manufactured to reverse the progression of muscle diseases or facilitate tissue regeneration. Despite this exciting advancement, much of the development of iPSC-based therapies for muscle diseases and tissue regeneration is limited to academic settings, with no successful clinical translation reported. The unknown differentiation process in vivo, potential tumorigenicity, and epigenetic abnormality of transplanted cells are preventing their clinical application. In this review, we give an overview on preclinical development of iPSC-derived myogenic cell transplantation therapies including processes related to iPSC-derived myogenic cells such as differentiation, scaling-up, delivery, and cGMP compliance. And we discuss the potential challenges of each step of clinical translation. Additionally, preclinical model systems for testing myogenic cells intended for clinical applications are described.

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Tumorigenicity risk of iPSCs in vivo: nip it in the bud

Cited by 22 publications

References 107 publications

A simeprevir-inducible molecular switch for the control of cell and gene therapies

A simeprevir-inducible molecular switch for the control of cell and gene therapies

3D skin bioprinting as promising therapeutic strategy for radiation‐associated skin injuries

Challenges and Considerations of Preclinical Development for iPSC-Based Myogenic Cell Therapy

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