TY - JOUR
T1 - Donor-specific mesenchymal stem cell infusion in human and nonhuman primate kidney transplantation
AU - Anwar, Imran J.
AU - Li, Shu
AU - Mulvihill, Michael
AU - Schmitz, Robin
AU - Shaw, Brian
AU - Gao, Qimeng
AU - Swan-Nesbit, Sherri
AU - Cheatham, Lynn A.
AU - How, Tam
AU - Miller, Allison
AU - Williams, Kyha
AU - Yin, Fang Fang
AU - Giles, William
AU - Kurtzberg, Joanne
AU - Chandran, Sindhu
AU - Bridges, Nancy
AU - Lyakh, Lyudmila
AU - Breeden, Cynthia
AU - Gandhi, Krupa
AU - Sever, Michelle
AU - Song, Mingqing
AU - He, Xu
AU - Kirk, Allan D.
N1 - Publisher Copyright:
© 2025 American Society of Transplantation & American Society of Transplant Surgeons
PY - 2025
Y1 - 2025
N2 - We report the results of 2 independent, concurrently performed studies evaluating the safety and efficacy of donor-derived mesenchymal stromal cell (MSC) infusions in inducing immune-tolerance in nonhuman primate (NHP) and human kidney transplant recipients treated with depletional induction and belatacept/sirolimus maintenance. Fifteen NHPs received rhesus ATG induction and were divided into 3 groups: control (n = 6), pretransplant thymic irradiation (n = 4), and thymic irradiation with monthly donor-MSC infusion (n = 5). Sirolimus was discontinued at day-180, and belatacept at day-365 posttransplant. In humans, 6 patients enrolled in ITN062ST underwent transplantation with alemtuzumab induction; 4 received 12 monthly donor-MSC infusions followed by immunosuppression withdrawal (ISW) if eligible. Donor-MSC infusion was acutely well tolerated in humans and NHPs. Chimerism was not established, and tolerance was not induced in either study. Two of the 5 NHPs that received MSCs rejected while on belatacept monotherapy with detectable donor-specific antibodies. Two patients did not initiate ISW due to de novo donor-specific antibodies and borderline rejection, and 2 patients failed ISW due to reversible rejection. In conclusion, donor MSCs can be given to NHPs or humans repeatedly without acute consequences, but they neither lead to detectable chimerism nor induce tolerance. In a subset of recipients, infused MSCs can be sensitizing.
AB - We report the results of 2 independent, concurrently performed studies evaluating the safety and efficacy of donor-derived mesenchymal stromal cell (MSC) infusions in inducing immune-tolerance in nonhuman primate (NHP) and human kidney transplant recipients treated with depletional induction and belatacept/sirolimus maintenance. Fifteen NHPs received rhesus ATG induction and were divided into 3 groups: control (n = 6), pretransplant thymic irradiation (n = 4), and thymic irradiation with monthly donor-MSC infusion (n = 5). Sirolimus was discontinued at day-180, and belatacept at day-365 posttransplant. In humans, 6 patients enrolled in ITN062ST underwent transplantation with alemtuzumab induction; 4 received 12 monthly donor-MSC infusions followed by immunosuppression withdrawal (ISW) if eligible. Donor-MSC infusion was acutely well tolerated in humans and NHPs. Chimerism was not established, and tolerance was not induced in either study. Two of the 5 NHPs that received MSCs rejected while on belatacept monotherapy with detectable donor-specific antibodies. Two patients did not initiate ISW due to de novo donor-specific antibodies and borderline rejection, and 2 patients failed ISW due to reversible rejection. In conclusion, donor MSCs can be given to NHPs or humans repeatedly without acute consequences, but they neither lead to detectable chimerism nor induce tolerance. In a subset of recipients, infused MSCs can be sensitizing.
KW - T cell depletion
KW - costimulation blockade
KW - kidney transplantation
KW - mesenchymal stromal cells
UR - http://www.scopus.com/inward/record.url?scp=105006526654&partnerID=8YFLogxK
U2 - 10.1016/j.ajt.2025.05.008
DO - 10.1016/j.ajt.2025.05.008
M3 - Article
C2 - 40368061
AN - SCOPUS:105006526654
SN - 1600-6135
JO - American Journal of Transplantation
JF - American Journal of Transplantation
ER -