Page 20 - ebook

[A. Biochemistry/Molecular Biology] A-10

Membrane-Free Stem Cell Extract Enhances Blood-Brain

Barrier Integrity by Suppressing NF-κB-mediated Activation

of NLRP3 Inflammasome in Mice with Ischemic Stroke

Ji Hyeon Ryu¹, Jisu Park¹, Ji Won Kim ¹, Min Jae Kim ², Hye Sook Park³, Young Sil Kim³, Hwa Kyoung

Shin², Yong-Il Shin¹,⁴*

¹Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan

Hospital, Yangsan 50612, Korea, ²Department of Korean Medical Science, School of Korean Medicine, Pusan
National University, Yangsan 50612, Korea, ³T-Stem Co., Ltd., Changwon 51573, Korea, ⁴Department of

Rehabilitation Medicine, Pusan National University School of Medicine, Yangsan 50612, Korea

Ischemic stroke is a major cause of death and disability worldwide, and the therapeutic agents are often inoperable
owing to the complex pathological processes and the impediment of the blood-brain barrier (BBB). This study was

performed to identify the role of membrane-free stem cell extract (MFSCE) derived from human adipose tissues in
photothrombotic stroke mice. Mice were treated with MFSCE once daily for 4 days and 1 h before ischemic damage.

Pretreatment with MFSCE reduced infarct volume and edema and improved neurological and motor functions. Both
Evans blue leakage and the water content of the brain tissue were reduced by pretreatment with MFSCE. MFSCE

increased the expression of the zonula occludens 1 (ZO-1) and claudin-5 tight junction proteins, and vascular
endothelial (VE)-cadherin, whereas decreased that of matrix metalloproteinase (MMP)-9. MFSCE decreased cell death

and the level of NLRP3 inflammasome, in accordance with the downregulation of the interleukin (IL)-1β and IL-18
pro-inflammatory cytokines in the ischemic brain. These effects might have occurred through the suppression of

the expression of toll-like receptor (TLR)-4 and activation of nuclear factor-κB (NF-κB). Cumulative results highlighted
the potential of MFSCE as a novel and preventive strategy for patients at high risk of ischemic stroke.