Low intensity ultrasound targeted microbubble destruction assists MSCs delivery and improves neural function in brain ischaemic rats

Abstract

Background and purpose: The present study aimed to explore the feasibility and efficacy of the targeted non-invasive implantation of mesenchymal stromal cells (MSCs) by low-intensity ultrasound-targeted microbubble destruction (LI-UTMD) assisted blood–brain barrier (BBB) opening and its improvement on neurobehavioural outcomes in brain ischaemic rats.

Methods: A transcranial irradiation of low-intensity ultrasound by diagnostic devices was performed, and lipid microbubbles (MBs) and MSCs were simultaneously infused. Then, the MSC transmigration from brain vessels to parenchyma was demonstrated, and MSCs were statistically analysed on days 1, 4, 7 and 14. Behavioural function was statistically analysed.

Results: The extra-vascular leakage of lanthanum and EB was observed at the brain ischaemic area receiving ultrasound. MSCs were observed at the ultrasound irradiated brain hemisphere, and the number of MSCs in LI-UTMD assisted MSCs group was significantly higher than that in the MSCs group (p < .01). The attachment, traversing and trans-migration of MSCs across the BBB were recorded. Neuro-behavioural function was improved with this approach.

Conclusions: The transcranial irradiation of low intensity ultrasound targeted MBs destruction on brain ischaemic rats might be a safe and efficient BBB opening approach to prompt the successful delivery of MSCs into the targeted area of brain ischaemia, and ameliorate neurological function.

Keywords:

• MSCs implantation
• brain ischaemia
• neural function
• low intensity ultrasound targeted microbubbles destruction
• diagnostic devices

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

The present study was supported by the National Natural Science Foundation of China NSFC [81471795], the Army Cultivation Project in Medical Science and Technology [16QNP102] and the Chongqing Basic Research and Pilot Exploration Project [cstc2018jcyjAX0011].