Assessing Tumorigenicity in Stem Cell-Derived Therapeutic Products: A Critical Step in Safeguarding Regenerative Medicine

Abstract

Stem cells hold promise in regenerative medicine due to their ability to proliferate and differentiate into various cell types. However, their self-renewal and multipotency also raise concerns about their tumorigenicity during and post-therapy. Indeed, multiple studies have reported the presence of stem cell-derived tumors in animal models and clinical administrations. Therefore, the assessment of tumorigenicity is crucial in evaluating the safety of stem cell-derived therapeutic products. Ideally, the assessment needs to be performed rapidly, sensitively, cost-effectively, and scalable. This article reviews various approaches for assessing tumorigenicity, including animal models, soft agar culture, PCR, flow cytometry, and microfluidics. Each method has its advantages and limitations. The selection of the assay depends on the specific needs of the study and the stage of development of the stem cell-derived therapeutic product. Combining multiple assays may provide a more comprehensive evaluation of tumorigenicity. Future developments should focus on the optimization and standardization of microfluidics-based methods, as well as the integration of multiple assays into a single platform for efficient and comprehensive evaluation of tumorigenicity.

iPSCs chondrogenic differentiation for personalized regenerative medicine: a literature review

“…This heterogeneity might complicate result interpretation and compromise the validity and reproducibility of experimental results [ 22 ]. Due to the potential of iPSCs to form teratomas, residual undifferentiated iPSCs in iPSC-derived cartilage grafts may pose a risk of tumor formation in transplantation studies [ 88 ]. Another main challenge is the variability in the efficiency of chondrogenic differentiation among different iPSC lines and even among clones of the same line [ 31 ].…”

Understanding the heterogeneous immune repertoire of brain metastases for designing next‐gen therapeutics

“…[107] However, it is crucial to note the financial and safety challenges involved in translating cellular therapies. Current issues include extended turnaround times, [108] potential tumorigenicity, [109] and the high costs associated with manufacturing. [110]…”

Cancer Spheroids Embedded in Tissue-Engineered Skin Substitutes: A New Method to Study Tumorigenicity In Vivo

“…In vivo tumorigenic assays are widely used to evaluate the safety of cell-based therapies [1][2][3]. These assays usually rely on the ability of cells to develop local tumors when injected in an animal.…”