Page 21 - ebook

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 Kim¹, Min Jae Kim², Hye Sook Park³, Young Sil Kim³, Hwa Kyoung Shin², Yong-Il Shin¹,⁴*
1 Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan
2 Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan
3 T-Stem Co., Ltd., Changwon; 4 Department of Rehabilitation Medicine, Pusan National University School of Medicine, Yangsan
Abstract Membrane-free stem cell extract (MFSCE) derived from human adipose tissues has various biological activities.
However, the effects of MFSCE on blood–brain barrier dysfunction and brain damage are unknown. This study determined the role of MFSCE in
an ischemic stroke mouse model. Mice were treated with MFSCE once daily for 4 days and 1 h before ischemic damage. Experimental ischemia
was induced by photothrombosis. Pretreatment with MFSCE reduced infarct volume and edema and improved neurological as well as motor
functions. Evans blue leakage and brain-tissue water content of the brain tissue were reduced by the MFSCE pretreatment. MFSCE increased the
expression of the tight junction proteins zonula occludens 1 and claudin-5, as well as vascular endothelial-cadherin but decreased that of matrix
metalloproteinase 9. Notably, MFSCE treatment decreased cell death and the level of NOD-like receptor protein 3 inflammasome, in accordance
with the downregulation expression of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 in the ischemic brain. These effects might have
occurred through suppression of the expression of toll-like receptor 4 and activation of nuclear factor-κB. Cumulative results highlighted the
potential of MFSCE treatment as a novel and preventive strategy for patients at high risk of ischemic stroke.
Results
Fig.3. MFSCE
suppresses
neuron apoptosis
via the
suppression of
the
inflammasome in
ischemic brain
injury.

Fig.1. Pretreatment of membrane-free stem cell extract (MFSCE) reduced
brain damage and improved functional behavior after ischemic brain injury.

Fig.4. MFSCE exerts
anti-inflammatory effect
via the suppression of
the TLR-4/p65 pathway
in ischem-ic stroke.

Fig.5. The safety profile of MFSCE.

Fig.2. MFSCE increased tight junction proteins and reduced cerebral
edema.

Conclusion MFSCE, which is a stem cell component lacking the cell membrane, could successfully improve neural function after
ischemic damage by attenuating the disruption of BBB and brain edema.
This improvement might be achieved via the downregulation of NLRP3 in-flammasome-mediated neuronal death, in accordance with the
inhibition of pro-inflammatory cytokines in the ischemic cortex via the suppression of the TLR-4-mediated NF-κB pathway. Therefore,
pretreatment with MFSCE is a potential non-cell-and nontoxic-based stem cell therapeutic strategy for the prevention of cerebral
ischemic injury.