Part 1 preclinical: Safety of MSC-EV testing on monkeys

Project Title: Investigating the safety of mesenchymal stem cell-derived extracellular vesicles in non-human primates

Project Description:

The study evaluates the safety of MSC-EVs derived from two sources: umbilical cord and adipose tissue mesenchymal stem cells. Each animal received 4 injections at doses of 4 billion, 20 billion, or 100 billion EV particles/kg over 1 month. Safety was assessed via adverse event frequency, vital signs monitoring pre-, during-, and post-injection, and at follow-up end. Blood parameters—including complete blood count, liver/kidney function, and inflammation markers—were measured and thoroughly evaluated.

Significance:

Nonhuman primates (NHPs) are critical for MSC-EV safety testing because they closely resemble humans in anatomy, physiology, gene behavior, cognition, and aging, making results more predictive before clinical trials. They are particularly relevant for osteoporosis/osteoarthritis studies, where rodent bone and cartilage structure differs markedly from humans. NHPs also have a human-like central nervous system and can show age-related cognitive decline and amyloid-related pathology, supporting evaluation of neurological safety. Finally, human clinical equipment and monitoring methods can often be used in NHPs, enabling clinically relevant safety assessment and improving translational readiness.

Goals

-Develop a standard operating procedure (SOP) for isolating and characterizing MSC-derived EVs using the TFF system.

-Systematic data set for evaluation of the safety of injecting AD- and UC-MSC EVs in monkeys.

Innovation:

We developed an innovative TFF-based method to isolate EVs with higher yield and quality than conventional differential ultracentrifugation, while being suitable for large sample volumes. This single, streamlined TFF workflow efficiently concentrates EVs and removes soluble contaminants, improving purity and preserving vesicle integrity. The process is GMP-compatible, scalable, and cost-effective, enabling the production of clinical-grade EVs for therapeutic applications. We conduct one of the first MSC-EV safety studies in macaques regionally, generating crucial translational data in non-human primates to bridge the gap between rodent experiments and human clinical trials.