Effect of human mesenchymal stem cell transplantation on cerebral ischemic volume-controlled photothrombotic mouse model

Biotechnol J. 2016 Nov;11(11):1397-1404. doi: 10.1002/biot.201600057. Epub 2016 Oct 11.

Abstract

Various animal models of stroke have been developed to simulate the human stroke with the development of the ischemic method facilitates preclinical stroke research. The photothrombotic ischemia model, based on the intravascular photochemical reaction, is widely used for in vivo studies. However, this study has limitations, which generated a relatively small-sized infarction model on superficial cortex compared to that of the MCAO stroke model. In this study, the photothorombosis mouse model is adapted and the optimum conditions for generation of cell death and deficits with high reproducibility is determined. The extent of damage within the cortex was assessed by infarct volume and cellular/behavioral analyses. In this model, the neural cell death and inflammatory responses is detected; moreover, the degree of behavioral impairment is correlated with the brain infarct volume. Further, to enhance the understanding of neural repair, the effect of neural differentiation by transplantation of human bone marrow-derived mesenchymal stem cells (BM-MSCs) is analyzed. The authors demonstrated that transplantation of BM-MSCs promoted the neural differentiation and behavioral performance in their photothrombosis model. Therefore, this research was meaningful to provide a stable animal model of stroke with low variability. Moreover, this model will facilitate development of novel MSC-based therapeutics for stroke.

Keywords: Cerebral ischemic stroke; Human bone marrow-derived mesenchymal stem cells (hBM-MSCs); Infarct volume; Neural differentiation; Photothrombotic mouse model.

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Brain Ischemia / genetics
  • Brain Ischemia / pathology
  • Brain Ischemia / therapy*
  • Cell Differentiation / genetics
  • Disease Models, Animal
  • Humans
  • Intracranial Thrombosis / genetics
  • Intracranial Thrombosis / pathology
  • Intracranial Thrombosis / therapy*
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells
  • Mice
  • Stroke / genetics
  • Stroke / physiopathology
  • Stroke / therapy*
  • Stroke Volume