Stem Cell Therapy Becomes Safer... Only Teratomas Are Eliminated

Development of Antibody Complex-Based Multipotent Cell Control Technology
Selective Removal of Multipotent Stem Cells
Expected Development of Safe Functional Cell Therapeutics

A) Schematic diagram of undifferentiated stem cell-targeting antibody-drug conjugate production (B-D) Molecular weight and drug release behavior of the antibody-drug conjugate

[Asia Economy Reporter Junho Hwang] A technology has been developed that can selectively remove undifferentiated stem cells remaining after differentiation of pluripotent stem cells capable of differentiating into all cells that make up our body. Undifferentiated stem cells can differentiate into teratomas during stem cell therapy, potentially causing cancer. The research team expects this technology to be useful in clinical trials of stem cell therapeutics and new drug development.

The research team led by Dr. Jangwook Lee from the Bio New Drug Translational Research Center at the Korea Research Institute of Bioscience and Biotechnology announced on the 26th that their research results were recently published in the international journal Biomaterials.

Selective Isolation and Removal of Teratoma-Inducing Cells from Cells Differentiated into Specific Cell Types

Confirmation of Selective Removal Efficiency of Residual Pluripotent Stem Cells within Neural Cell Aggregates Derived from Induced Pluripotent Stem Cells

The research team secured a technology that can selectively isolate and remove the group causing teratoma formation from cells induced to differentiate into specific cell types, based on the marker Dsg2 that recognizes only pluripotent stem cells and its antibody (K6-1). What the team developed is an antibody-drug conjugate combining the K6-1 antibody and the cell death inducer DOX; when Dsg2 selectively targets undifferentiated stem cells, the internalized DOX kills them.

Through animal model experiments, the research team also demonstrated that pluripotent function is lost in undifferentiated stem cells treated with the conjugate, preventing differentiation into teratomas.

Enhancing the Safety of Stem Cell Therapeutics

Verification of teratoma formation inhibition efficacy. (A) Image of the extracted testis 8 weeks after injection of undifferentiated stem cells into mouse testis, (B) quantitative analysis of testis size, and (C) weight, (D & E) confirmation of endoderm, mesoderm, and ectoderm formation (H&E staining & Western blot).

The research team stated, "We effectively removed remaining undifferentiated stem cells without dissociating/detaching differentiated cells into single-cell forms, and this did not affect the functionality of differentiated cells." This suggests the possibility of solving safety issues caused by residual undifferentiated stem cells after differentiation while maintaining the therapeutic efficacy and functionality of many pluripotent stem cell-based cell therapies currently under development.

Dr. Jangwook Lee, the principal investigator, said, "This research outcome is a meaningful result applying antibody-based targeted control technology to enhance the safety of stem cell therapy. By broadly utilizing undifferentiated stem cell targets already discovered or newly identified and antibodies binding to them, it will greatly contribute not only to effective cell therapies for intractable and degenerative diseases but also to stem cell regenerative medicine research capable of differentiating into specific tissues or organs."

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