RT Journal Article
SR Electronic
T1 Exosome-mediated hematopoietic rejuvenation in a humanized mouse model indicate potential for cancer immunotherapy
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.02.233015
DO 10.1101/2020.08.02.233015
A1 Steven J. Greco
A1 Seda Ayer
A1 Khadidiatou Guiro
A1 Garima Sinha
A1 Robert J. Donnelly
A1 Markos El-Far
A1 Sri Harika Pamarthi
A1 Oleta A. Sandiford
A1 Marina Gergues
A1 Lauren S. Sherman
A1 Michael J. Schonning
A1 Jean-Pierre Etchegaray
A1 Nicholas M. Ponzio
A1 Narayanan Ramaswamy
A1 Pranela Rameshwar
YR 2020
UL http://biorxiv.org/content/early/2020/08/03/2020.08.02.233015.abstract
AB Aging is associated with increased morbidity and high economic costs due to a burdened healthcare system and decreased workforce. Parabiotic animal models indicated that secretome from young cells can restore aged tissue functions. We used a heterochronic co-culture system with young and aged mobilized peripheral blood (MPB) or umbilical cord blood (UCB) and showed hematopoietic restoration, independent of allogeneic difference. Bidirectional communication between the aged and young cells influenced the miRNA cargo of exosomes, resulting in partial reprograming of the aged cells. The restored cells enhanced hematopoiesis (e.g., increased lymphoid:myeloid ratio) in immunodeficient mice bearing autologous aged hematopoietic system. Four exosomal miRNAs targeting PAX and PPMIF were partly responsible for the hematopoietic rejuvenation. Notably, increased natural killer (NK) cells within the restored cells eliminated dormant breast cancer cells in vivo. The findings could be developed as preventive measure and treatment for sustained immune/hematopoietic competence with potential for immunotherapy.Competing Interest StatementThe authors have declared no competing interest.