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

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 mater...

Full description

Saved in:
Bibliographic Details
Published in:Bioengineering & translational medicine 2024-11, Vol.9 (6), p.e10675-n/a
Main Authors: Al‐Kharboosh, Rawan, Bechtle, Alex, Tzeng, Stephany Y., Zheng, Jiaying, Mondal, Sujan Kumar, Wilson, David R., Perez‐Vega, Carlos, Green, Jordan J., Quiñones‐Hinojosa, Alfredo
Format: Article
Language:English
Subjects:
Bioengineering
Brain cancer
Cancer therapies
Cargo
Engineering
GBM
Glioma
Influence
Medical prognosis
MSC
nanoengineering
Nanoparticles
Patients
Proteins
Regenerative medicine
resection
Stem cells
Success
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 determining downstream outcomes than the technical capabilities of the engineering technology.
ISSN:2380-6761
2380-6761
DOI:10.1002/btm2.10675