Abstract 47: Age of Donor of Human Mesenchymal Stem Cells Drastically Affects Structural and Functional Recovery After Cell Therapy Following Ischemic Stroke

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Background and purpose: Cell transplantation therapy holds great potential to improve impairments after stroke. However, the importance of donor age on therapeutic efficacy is uncertain. We investigate regenerative capacity of transplanted cells focusing on donor age (young vs. old) for ischemic stroke.Methods: The value of platelet-derived growth factor (PDGF)-BB secreted from human mesenchymal stem cells (hMSC) was analyzed regarding in two age groups; young (20-30 years) and old (57-65 years) in vitro. Male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion, and received young or old hMSC trans-arterially at 24 h after stroke. Functional recovery was assessed with modified neurological severity score (mNSS). Structural recovery was assessed on neovascularization and endogenous cell migration as well as trophic factor secretion.Results: The value of PDGF-BB was significantly higher in young hMSC (40.47±4.29 pg/ml/104 cells) than that in old hMSC (25.35±3.16 pg/ml/104 cells; P=0.02) and negatively correlated with age (P=0.048, r=-0.79, Spearman). Rats treated with young hMSC (3.7±0.6) showed better behavior recovery in mNSS with prevention of brain atrophy than that with control (6.1±0.5) or old (5.2±0.7) at D21 (P<0.01). The number of RECA-1 and PDGFR-β double positive vessels in rat with young hMSC (113±48.6/mm2) was higher than that in control (61.5±35.9/mm2) or old (76.9±36.9/mm2) suggesting vessel maturation (P <0.01). Interestingly, migration of neural stem/progenitor cells expressing Musashi-1 positively correlated with astrocyte process alignment (P<0.01, r=0.27; Spearman), which was more pronounced in young hMSC (P <0.05).Conclusions: Aging of hMSC may be the critical factor which affects outcome of cell therapy, and transplantation of young hMSC could provide better functional recovery by vessel maturation and endogenous cell migration potentially due to dominance of trophic factor secretion.

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