Anti-aging Effect of Transplanted Amniotic Membrane Mesenchymal Stem Cells in a Premature Aging Model of Bmi-1 Deficiency.

To determine whether transplanted amniotic membrane mesenchymal stem cells (AMSCs) ameliorated the premature senescent phenotype of Bmi-1-deficient mice, postnatal 2-day-old Bmi-1−/− mice were injected intraperitoneally with the second-passage AMSCs from amniotic membranes of β-galactosidase (β-gal) transgenic mice or wild-type (WT) mice labeled with DiI. Three reinjections were given, once every seven days. Phenotypes of 5-week-old β-gal+ AMSC-transplanted or 6-week-old DiI+ AMSC-transplanted Bmi-1−/− mice were compared with vehicle-transplanted Bmi-1−/− and WT mice. Vehicle-transplanted Bmi-1−/− mice displayed growth retardation and premature aging with decreased cell proliferation and increased cell apoptosis; a decreased ratio and dysmaturity of lymphocytic series; premature osteoporosis with reduced osteogenesis and increased adipogenesis; redox imbalance and DNA damage in multiple organs. Transplanted AMSCs carried Bmi-1 migrated into multiple organs, proliferated and differentiated into multiple tissue cells, promoted growth and delayed senescence in Bmi-1−/− transplant recipients. The dysmaturity of lymphocytic series were ameliorated, premature osteoporosis were rescued by promoting osteogenesis and inhibiting adipogenesis, the oxidative stress and DNA damage in multiple organs were inhibited by the AMSC transplantation in Bmi-1−/− mice. These findings indicate that AMSC transplantation ameliorated the premature senescent phenotype of Bmi-1-deficient mice and could be a novel therapy to delay aging and prevent aging-associated degenerative diseases.

为了确定移植的羊膜间充质干细胞（AMSCs）是否改善了Bmi - 1基因缺陷小鼠的早衰表型，将出生2天的Bmi - 1−/−小鼠腹腔注射来自β - 半乳糖苷酶（β - gal）转基因小鼠或用DiI标记的野生型（WT）小鼠羊膜的第二代AMSCs。每7天注射一次，共注射3次。将5周龄接受β - gal + AMSC移植的或6周龄接受DiI + AMSC移植的Bmi - 1−/−小鼠的表型与注射载体的Bmi - 1−/−小鼠和野生型小鼠进行比较。注射载体的Bmi - 1−/−小鼠表现出生长迟缓及早衰，细胞增殖减少，细胞凋亡增加；淋巴细胞系比例降低且发育不成熟；出现早发性骨质疏松，成骨减少，脂肪生成增加；多个器官存在氧化还原失衡和DNA损伤。移植的携带Bmi - 1的AMSCs迁移到多个器官，增殖并分化为多种组织细胞，促进了Bmi - 1−/−移植受体的生长并延缓了衰老。淋巴细胞系发育不成熟得到改善，通过促进成骨和抑制脂肪生成挽救了早发性骨质疏松，AMSC移植抑制了Bmi - 1−/−小鼠多个器官的氧化应激和DNA损伤。这些发现表明，AMSC移植改善了Bmi - 1基因缺陷小鼠的早衰表型，可能是一种延缓衰老和预防衰老相关退行性疾病的新疗法。