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According to statistics from The Lancet Neurology and Stroke and Vascular Neurology, stroke, also known as "stroke", is currently the second leading cause of death in the world
.
Source: KATERYNA KON/SCIENCE PHOTO LIBRARY/Getty Images In 2018, there were more than 1,114 strokes per 100,000 people in China, resulting in about 1.
57 million deaths, accounting for 22.
3% of the total deaths among Chinese residents
.
The disability rate of stroke has continued to rise in the past decade, and survivors suffer lifelong suffering from motor, sensory, speech, cognitive impairment and even paralysis
.
Therefore, scientists are working to find effective treatments for improving stroke outcomes
.
Ischemic stroke (cerebral infarction) is caused by blockage of blood vessels in the brain, resulting in insufficient blood supply to the brain and damage to brain tissue
.
Ischemic stroke is often accompanied by disruption of the blood-brain barrier
.
The blood-brain barrier is like the "firewall" of the nervous system, which can selectively prevent harmful substances from entering the brain from the blood.
Once damaged, it is likely to cause neuroinflammation and long-term neurological dysfunction
.
Among the various cells and extracellular matrix that constitute the blood-brain barrier, pericytes play an important role in the formation and maintenance of the integrity of the blood-brain barrier
.
Among other things, this group of cells is involved in regulating the chemical composition of the extracellular fluid surrounding brain cells and cerebral blood flow
.
After ischemic stroke, pericytes in the blood-brain barrier also die rapidly
.
Based on these phenomena, the joint research team of Professor Li Weiqiang and Xiang Peng from the Stem Cell and Tissue Engineering Research Center of Sun Yat-Sen University published a study in "Nature-Communications" and found that after transplantation of stem cell-derived pericytes into a mouse model of stroke, the Repairs broken blood-brain barrier and reduces neuronal death
.
The research team first induced human pluripotent stem cells to differentiate into pericyte-like cells through neural crest stem cells
.
Pericytes differentiated from stem cells express high levels of pericyte-specific markers CALD1, CSPG4 and PDGFRβ, but do not express smooth muscle cell marker αSMA
.
The study found that these pericytes were not only morphologically similar to primary cultured human cerebral vascular pericytes, but also exhibited powerful functions comparable to primary human cerebral vascular pericytes in terms of contractile properties, support of angiogenesis, and endothelial barrier reinforcement.
sex
.
The RNA sequencing results further confirmed this, proving that the two also share a very high similarity in gene expression profiles
.
An ischemic stroke (cerebral infarction) is caused by a blockage of a blood vessel in the brain
.
Credit: jamesbenet/Getty Images So do these pericytes have potential neurotherapeutics? To answer this question, the researchers infused the differentiated pericytes into stroke model (tMCAO) mice
.
The results showed that the implanted cells were rapidly recruited around the capillaries in the cerebral ischemic penumbra, which slowed down the brain injury, protected neurons from apoptosis, rapidly restored the neurological function of the brain-injured mice, and effectively improved the brain injury.
The locomotor ability of mice
.
Not only that, but pericyte transplantation also significantly restored the integrity of the blood-brain barrier after stroke
.
Compared with the control group, the pericyte-treated mice had significantly reduced brain edema, plasma protein deposition, and significantly reduced leakage of TRITC-dextran and Evans blue dyes, which are used to indicate the degree of barrier damage
.
It can be seen that pericyte transplantation can repair the blood-brain barrier in mice
.
To explore the mechanisms behind the therapeutic effects of pericyte transplantation, the researchers further analyzed RNA-sequencing data and found high levels of expression of the midkine gene MDK in these cells
.
Midkine enhances neurite outgrowth, neuronal cell survival, and plasminogen activator activity
.
Correspondingly, mouse neurological deficit scores confirmed that MDK knockdown significantly reduced the neuroprotective effects of pericytes
.
In the future, the research team will further explore the clinical translational significance of the research results in the treatment of ischemic stroke
.
Reference: 1.
Sun, J.
et al.
Transplantation of hPSC-derived pericyte-like cells promotes functional recovery in ischemic stroke mice.
Nat.
Commun.
2020 111 11, 1–20 (2020) © NatureNat Com | doi:10.
1038 /s41467-020-19042-y Chinese content is for reference only, all content is subject to the original English version.
.
Source: KATERYNA KON/SCIENCE PHOTO LIBRARY/Getty Images In 2018, there were more than 1,114 strokes per 100,000 people in China, resulting in about 1.
57 million deaths, accounting for 22.
3% of the total deaths among Chinese residents
.
The disability rate of stroke has continued to rise in the past decade, and survivors suffer lifelong suffering from motor, sensory, speech, cognitive impairment and even paralysis
.
Therefore, scientists are working to find effective treatments for improving stroke outcomes
.
Ischemic stroke (cerebral infarction) is caused by blockage of blood vessels in the brain, resulting in insufficient blood supply to the brain and damage to brain tissue
.
Ischemic stroke is often accompanied by disruption of the blood-brain barrier
.
The blood-brain barrier is like the "firewall" of the nervous system, which can selectively prevent harmful substances from entering the brain from the blood.
Once damaged, it is likely to cause neuroinflammation and long-term neurological dysfunction
.
Among the various cells and extracellular matrix that constitute the blood-brain barrier, pericytes play an important role in the formation and maintenance of the integrity of the blood-brain barrier
.
Among other things, this group of cells is involved in regulating the chemical composition of the extracellular fluid surrounding brain cells and cerebral blood flow
.
After ischemic stroke, pericytes in the blood-brain barrier also die rapidly
.
Based on these phenomena, the joint research team of Professor Li Weiqiang and Xiang Peng from the Stem Cell and Tissue Engineering Research Center of Sun Yat-Sen University published a study in "Nature-Communications" and found that after transplantation of stem cell-derived pericytes into a mouse model of stroke, the Repairs broken blood-brain barrier and reduces neuronal death
.
The research team first induced human pluripotent stem cells to differentiate into pericyte-like cells through neural crest stem cells
.
Pericytes differentiated from stem cells express high levels of pericyte-specific markers CALD1, CSPG4 and PDGFRβ, but do not express smooth muscle cell marker αSMA
.
The study found that these pericytes were not only morphologically similar to primary cultured human cerebral vascular pericytes, but also exhibited powerful functions comparable to primary human cerebral vascular pericytes in terms of contractile properties, support of angiogenesis, and endothelial barrier reinforcement.
sex
.
The RNA sequencing results further confirmed this, proving that the two also share a very high similarity in gene expression profiles
.
An ischemic stroke (cerebral infarction) is caused by a blockage of a blood vessel in the brain
.
Credit: jamesbenet/Getty Images So do these pericytes have potential neurotherapeutics? To answer this question, the researchers infused the differentiated pericytes into stroke model (tMCAO) mice
.
The results showed that the implanted cells were rapidly recruited around the capillaries in the cerebral ischemic penumbra, which slowed down the brain injury, protected neurons from apoptosis, rapidly restored the neurological function of the brain-injured mice, and effectively improved the brain injury.
The locomotor ability of mice
.
Not only that, but pericyte transplantation also significantly restored the integrity of the blood-brain barrier after stroke
.
Compared with the control group, the pericyte-treated mice had significantly reduced brain edema, plasma protein deposition, and significantly reduced leakage of TRITC-dextran and Evans blue dyes, which are used to indicate the degree of barrier damage
.
It can be seen that pericyte transplantation can repair the blood-brain barrier in mice
.
To explore the mechanisms behind the therapeutic effects of pericyte transplantation, the researchers further analyzed RNA-sequencing data and found high levels of expression of the midkine gene MDK in these cells
.
Midkine enhances neurite outgrowth, neuronal cell survival, and plasminogen activator activity
.
Correspondingly, mouse neurological deficit scores confirmed that MDK knockdown significantly reduced the neuroprotective effects of pericytes
.
In the future, the research team will further explore the clinical translational significance of the research results in the treatment of ischemic stroke
.
Reference: 1.
Sun, J.
et al.
Transplantation of hPSC-derived pericyte-like cells promotes functional recovery in ischemic stroke mice.
Nat.
Commun.
2020 111 11, 1–20 (2020) © NatureNat Com | doi:10.
1038 /s41467-020-19042-y Chinese content is for reference only, all content is subject to the original English version.
