Dual expression of hTERT and VEGF prolongs life span and enhances angiogenic ability of aged BMSCs.
Previous studies have confirmed the therapeutic effects of bone marrow stromal cells (BMSCs) transplantation on cerebral ischemia. However, the proliferative, differentiative, and homing capacity of BMSC from the elderly are significantly reduced, especially after several passages expansion in vitro. In this study, by introducing lentivirus-mediated hTERT and VEGF genes to modify human BMSCs from aged donors, we observed extended lifespan, promoted angiogenic capacity while less enhanced tumorigenicity of the genetically engineering BMSCs. These results therefore suggest that the modification of aged BMSCs by dual expression of hTERT and VEGF may be used for autologous cell replacement for ischemic cerebrovascular disease in elderly patients.
Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China; Department of Neurosurgery, Affiliated Bayi Brain Hospital, The Military General Hospital of Beijing PLA, Beijing, China.
Hao
H
Tang
Yongsheng
Y
Xiang
Xiaodan
X
Jiang
Yiquan
Y
Ke
Zongyu
Z
Xiao
Yang
Y
Guo
Qiujing
Q
Wang
Mouxuan
M
Du
Linsha
L
Qin
Yuxi
Y
Zou
Yingqian
Y
Cai
Zhenzhou
Z
Chen
Ruxiang
R
Xu
D000368:Aged; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D016026:Bone Marrow Transplantation; D060846:Cell Engineering; D016922:Cellular Senescence; D005818:Genetic Engineering; D006801:Humans; D018919:Neovascularization, Physiologic; D020521:Stroke / Q000628:therapy; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C509186:TERT protein, human; D019098:Telomerase
BCA; Bone marrow stromal cell; ELISA; FACS; Genetic engineering; IS; LP; MOI; MSC; PDL; TERC; TRAP; VEGF; bicinchoninic acid; enzyme-linked immunosorbent assay; fluorescence-activated cell sorting; hBMSC; hTERT; hTRET; human bone marrow stromal cell; human telomerase reverse transcriptase; internal standard; lentiviral particle; marrow stromal cell; multiplicity of infection; population doubling level; telomerase RNA component; telomeric repeat amplification protocol; vascular endothelial growth factor