Table 3.

Preclinical studies of alternative forms of donor antigen delivery

Reference	Model	Treatment	Outcomes
Rodent models
Bryant et al 2014109	Islet allograft Mouse	Treatment: Donor antigen-coupled poly(d,l-lactide-co-glycolide) (PLG) particles infused 7 days prior and 1 day after transplantation without other IS Methods: PLG coupled by ECDI to donor spleen lysate to create donor antigen-couple PLG particles Control: Multiple dose groups, primary comparator sham injection of carrier molecule without donor antigen coupling	Median survival <20 days in control group vs >20 days in nanoparticle-treated group (p = 0.0099; exact values not reported)
Shah et al 201992	Skin allograft Mouse	Treatment: Donor antigen-coupled PLG infused 7 days prior and 1 day after transplantation without other IS Methods: PLG coupled by ECDI to donor protein to create donor antigen-coupled PLG particles Control: Multiple dose groups, primary comparator sham injection of carrier molecule without donor antigen coupling	Median survival <20 days in control group vs >20 days in nanoparticle-treated group (p < 0.001; exact values not reported)
Luo et al 2023110	Heart allograft Mouse	Treatment: Donor BMDC-derived exosomes injected daily from 0 days to 3 days after transplantation without other IS Methods: BM-derived donor DCs genetically altered to create high PD-L1 expression, with supernatant collected when cell fusion rate reached 80% Control: Multiple groups, primary comparator no injection of exosomes	Mean survival approximately 6 days in control group vs 12 days in exosome-treated group (p = 0.001; exact values not reported)
Pêche et al2003111	Heart allograft Rat	Treatment: Donor BMDC-derived exosomes 10μg injected 14 days and 7 days prior to transplantation without other IS Methods: BM-derived donor cells co-cultured with GM-CSF and IL-4 with supernatant collected at day 10 Control: Multiple dose groups, primary comparator no injection of exosomes	Median survival 6 days in control group vs 25 days in exosome-treated group (p < 0.01)
Pêche et al 200690	Heart allograft Rat	Treatment: Donor BMDC-derived exosomes 25μg injected 0 days and 6 days after transplantation without other IS Methods: BM-derived donor cells co-cultured with GM-CSF and IL-4 with supernatant collected at day 10 Control: Multiple dose groups, primary comparator no injection of exosomes	Median survival 6 days in control group vs 25.5 days in exosome-treated group (p < 0.05)
Ma et al 201691	Liver allograft Rat	Treatment: Donor BMDC-derived exosomes 25μg injected 7 days prior, 0 days and 7 days after transplantation without other IS Methods: BM-derived donor (syngeneic) cells co-cultured with GM-CSF and IL-4 with supernatant collected at days 6 and 11 Control: Multiple dose groups, primary comparator no injection of exosomes	Median survival 10 days in control group vs 37 days in exosome-treated group (p < 0.0001)