Comparison between xenogeneic and allogeneic adipose mesenchymal stem cells in the treatment of acute cerebral infarct: proof of concept in rats

Journal of Translational Medicine

Exuperio Díez-Tejedor¹  Borja Enrique Sanz-Cuesta¹  María Teresa Vallejo-Cremades¹  Blanca Fuentes¹  Laura Otero-Ortega¹  Jaime Ramos-Cejudo¹  Berta Rodríguez-Frutos¹  María Gutiérrez-Fernández¹ 

[1] Department of Neurology and Stroke Centre, Neuroscience and Cerebrovascular Research Laboratory, La Paz University Hospital, Neuroscience Area of IdiPAZ (Health Research Institute), Autónoma University of Madrid, Paseo de la Castellana 261, Madrid, 28046, Spain

关键词: Stroke;    Safety;    Functional recovery;    Allogeneic and xenogeneic AD-MSCs;   

Others  :  1137651
DOI  :  10.1186/s12967-015-0406-3

 received in 2014-10-03, accepted in 2015-01-16,  发布年份 2015

【 摘 要 】

Background

Rat adipose tissue-derived-mesenchymal stem cells (rAD-MSCs) have proven to be safe in experimental animal models of stroke. However, in order to use human AD-MSCs (hAD-MSCs) as a treatment for stroke patients, a proof of concept is needed. We analyzed whether the xenogeneic hAD-MSCs were as safe and effective as allogeneic rAD-MSCs in permanent Middle Cerebral Artery Occlusion (pMCAO) in rats.

Methods

Sprague–Dawley rats were randomly divided into three groups, which were intravenously injected with xenogeneic hAD-MSCs (2 × 10⁶), allogeneic rAD-MSCs (2 × 10⁶) or saline (control) at 30 min after pMCAO. Behavior, cell implantation, lesion size and cell death were evaluated. Brain markers such as GFAP (glial fibrillary acid protein), VEGF (vascular endothelial growth factor) and SYP (synaptophysin) and tumor formation were analyzed.

Results

Compared to controls, recovery was significantly better at 24 h and continued to be so at 14 d after IV administration of either hAD-MSCs or rAD-MSCs. No reduction in lesion size or migration/implantation of cells in the damaged brain were observed in the treatment groups. Nevertheless, cell death was significantly reduced with respect to the control group in both treatment groups. VEGF and SYP levels were significantly higher, while those of GFAP were lower in the treated groups. At three months, there was no tumor formation.

Conclusions

hAD-MSCs and rAD-MSCs were safe and without side effects or tumor formation. Both treatment groups showed equal efficacy in terms of functional recovery and decreased ischemic brain damage (cell death and glial scarring) and resulted in higher angiogenesis and synaptogenesis marker levels.

【 授权许可】

   
2015 Gutiérrez-Fernández et al.; licensee BioMed Central.

【 图 表 】

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