Therapeutic potential and impact of nanoengineered patient-derived mesenchymal stem cells in a murine resection and recurrence model of human glioblastoma

Several human studies show positive signals, while research methods and sample sizes continue to develop.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Confounding results of engineered mesenchymal stem cells (MSCs) used as cellular vehicles has plagued technologies whereby success or failure of novel approaches may be dismissed or inaccurately ascribed solely to the biotechnology platform rather than suitability of the human donor. Polymeric materials were screened for non-viral engineering of MSCs from multiple human donors to deliver bone morphogenic protein-4 (BMP4), a protein previously investigated in clinical trials for glioblastoma (GBM) to combat a subpopulation of highly invasive and tumorigenic clones. A "smart technology" that target the migratory and stem-like nature of GBM will require: (1) a cellular vehicle (MSC) which can scavenge and target residual cells left behind after surgical debulking and deliver; (2) anti-glioma cargo (BMP4). Multiple MSC donors are safely engineered, though varied in susceptibility to accept BMP4 due to intrinsic characteristics revealed by their molecular signatures. Efficiency is compared via secretion, downstream signaling, differentiation, and anti-proliferative properties across all donors. In a clinically relevant resection and recurrence model of patient-derived human GBM, we demonstrate that nanoengineered MSCs are not "donor agnostic" and efficacy is influenced by the inherent suitability of the MSC to the cargo. Therefore, donor profiles hold greater influence in determinin

Evidence level

Several human studies show positive signals, while research methods and sample sizes continue to develop.

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