The BMMSCs Derived From Juvenile Macaques Have the Ability to Promote Thymus Regeneration in Aged Macaques

Abstract

BackgroundThe thymus gland is an important central immune organ in the human body and plays an indispensable role in the immune system. Aging thymic atrophy is critical factors leading to immune function decline and senile debilitation in aged people. Immune function decline is one of the important mechanisms of aging. Some research reports indicated that Stem cell therapy have the ability to promote tissue regeneration，but reverse thymus atrophy or promote atrophy thymus regenerate by stem cells need to be confirmed further. MethodsThe elderly macaque models were systematic screened and the thymus structure and function were evaluated by imaging and histopathology methods. The juvenile BMMSCs were injected into macaque models body by intravenous infusion. The effects of thymus tissue structure and expression of related factors were investigated by using imaging, histopathology,cell and molecule observation and measurement techniques. To explore the mechanism of juvenile BMMSC on thymus atrophy in aging rhesus macaques, the gene transcription profile of thymus tissue were sequencing and analyzed by bioinformatic methods. .ResultsThrough PET-CT observation, the thymus tissue density gradually increased after treatment, CT value gradually increased, SUVmax >1;The percentage of CD3+T cells in peripheral blood increased first and then decreased, CD3+CD4+T cells increased slowly, and CD3+CD8+T cells increased first, then decreased and then increased. By detecting Tregs in peripheral blood, the percentage of Tregs in peripheral blood showed a trend of decreasing first and then increasing after treatment (P< 0.05).The levels of thymosin α and thymosin II in peripheral blood were analyzed by ELISA method. It was found that thymosin α was firstly increased and then decreased after BMSC infusion, and the levels of thymosin Ⅱ were firstly increased and then decreased.The area of thymus parenchyma increased, and the boundary between skin and medulla appeared. Some thymus tissues were regenerated and changed to normal structure.The cortical and medullary junction structure and dense thymus structure gradually appeared in the elderly treatment group.The degree of thymus tissue fibrosis was reduced, and the deposition of collagen fiber was reduced. Apoptosis cells decreased significantly in the elderly treatment group compared with the elderly group. BMMSCs inhibited the expression of genes related to aging and apoptosis.ConclusionTransplantation BMMSC derived from juvenile macaques can poromote thymus regeneration, reverse thymus atrophy by regulating gene transcription profiles in aged macaques.