CN-122005611-A - Exosomes derived from dental pulp stem cells promote recovery of nerve function after acute stroke

Abstract

The invention relates to the field of biotechnology, in particular to a medicament and application thereof. The medicine is exosome (DPSCs-Exos) derived from dental pulp stem cells. DPSCs-Exos can promote sensory-motor and cognitive function recovery after cerebral ischemia. DPSCs-Exos can improve ischemia for 45 min, and brain tissue injury and nerve function injury of animals after reperfusion for 28 days. DPSCs-Exos promotes the increase of protein arginine methyltransferase (PRMT 5) expression in Oligodendrocyte Precursor Cells (OPC), inhibits the expression of differentiation inhibitor 2 (ID 2), promotes proliferation and differentiation of OPCs into Oligodendrocytes (OL), and promotes repair of white matter integrity. In addition, DPSCs-Exos promote proliferation and migration of vascular endothelial cells and repair of blood brain barrier.

Inventors

• JIN XINCHUN
• GENG PANPAN
• WANG WEI
• DU WEIHONG

Assignees

• 首都医科大学

Dates

Publication Date

20260512

Application Date

20241112

Claims (10)

1. 1. A medicament, which is an exosome DPSCs-Exos derived from dental pulp stem cells.
2. 2. The medicament according to claim 1, characterized in that the effective dose of DPSCs-Exos is 2.5 x 10 9 particles/dose.
3. 3. Use of a medicament according to claim 1 for the preparation of a medicament for promoting elevated PRMT5 expression after acute ischemic stroke.
4. 4. Use of a medicament according to claim 1 for the preparation of a medicament for promoting the nuclear penetration of PRMT5 after acute ischemic stroke.
5. 5. Use of a medicament according to claim 1 for the preparation of a medicament for promoting reduced expression of ID2 after acute ischemic stroke.
6. 6. Use of a medicament according to claim 1 for the preparation of a medicament for promoting proliferation and differentiation of OPCs after acute ischemic stroke.
7. 7. Use of a medicament according to claim 1 for the preparation of a medicament for promoting the repair of white matter integrity after acute ischemic stroke.
8. 8. Use of a medicament according to claim 1 for the preparation of a medicament for promoting angiogenesis after acute ischemic stroke.
9. 9. Use of a medicament according to claim 1 for the preparation of a medicament for promoting the repair of blood brain barrier integrity after acute ischemic stroke.
10. 10. Use of a medicament according to claim 1 for the preparation of a neuroprotective medicament for the treatment of acute ischemic stroke.

Description

Exosomes derived from dental pulp stem cells promote recovery of nerve function after acute stroke Technical Field The invention relates to the field of biotechnology, in particular to a medicament and application thereof. Background Ischemic stroke refers to necrosis of brain tissue caused by stenosis or occlusion of blood supply arteries of the brain and insufficient blood supply to the brain. The high morbidity, disability rate, mortality rate and recurrence rate and the high treatment cost bring about a heavy burden to society and families. At present, the treatment means mainly focus on rapid reperfusion through intravenous thrombolysis and intravascular thrombectomy to achieve the treatment effect. However, these two approaches have time limitations and the probability of cerebral hemorrhage transformation after thrombolysis is high, and less than 5% of patients in developed countries can receive treatment, and less than 1% of China benefits. Most patients remain sequelae of hemiplegia, aphasia, cognitive dysfunction, etc. Research in recent years shows that cerebral white matter is more sensitive to ischemia and hypoxia injury, white matter injury accounts for about half of the infarct volume, is an important pathological basis of nerve function injury, and promotes white matter integrity repair to be a potential strategy for improving nerve dysfunction. White matter is composed mainly of myelinated axons and myelinated oligodendrocytes (oligodendrocytes, OLs). OLs are differentiated from oligodendrocyte precursor cells (oligodendrocyte progenitor cells, OPCs). Remodeling of brain white matter lesions is dependent on OPCs proliferation, migration, differentiation into mature OLs and encapsulation of axonal myelination. OPCs in adult brain tissue have a very limited capacity to differentiate and are not sufficient to support white matter repair in ischemic environments. Methods that increase the differentiation of OPCs to maturity OLs can be an effective strategy for promoting white matter integrity repair. Ischemic infarct zone neovascularization regulates cerebral blood flow, neuronal repair and regeneration, degree of functional recovery of patients and functional reconstruction of inter-nerve cell synaptic connections, but spontaneous neurovascular repair effects are very limited, while most blood vessels are nonfunctional vessels, post-stroke angiogenesis and functional angiogenesis are very important. Oligodendrocytes are closely related to the developing vasculature. Dental pulp stem cells (dental pulp STEM CELLS, DPSCs) are the first dental mesenchymal stem cells to be discovered and have more remarkable neural differentiation potential than other types. Exosomes are extracellular vesicles secreted by cells and capable of crossing the blood brain barrier (bloodbrain barrier, BBB), mainly responsible for intercellular substance transport and information transfer. Disclosure of Invention The invention aims at transplanting DPSCs-Exos to treat acute ischemic cerebral apoplexy, and observing the improvement effects of the treatment strategy on white matter integrity repair, angiogenesis and Blood Brain Barrier (BBB) integrity and sensory-motor and cognitive functions after acute cerebral apoplexy. In order to achieve the above object, the present invention provides the following technical solutions: In some embodiments of the invention, the effective dose of DPSCs-Exos is a particle number of 2.5X10 9 particles/serving. The invention provides application of the medicine in reducing the nerve function score after acute cerebral apoplexy reperfusion. The invention also provides application of the medicine in improving the sensory and motor of animals after acute cerebral apoplexy reperfusion. The invention also provides application of the medicine in improving the cognitive function of animals after acute cerebral apoplexy reperfusion. The invention also provides application of the medicine in promoting proliferation and differentiation of OPCs. The invention also provides application of the medicine in promoting angiogenesis. The invention also provides application of the medicine in promoting blood brain barrier integrity. The experimental results of the invention show that: (1) DPSCs-Exos can promote nerve function recovery after acute ischemic stroke. (2) DPSCs-Exos can promote the repair of white matter integrity after acute ischemic stroke. (3) DPSCs-Exos can promote proliferation and differentiation of OPCs into OLs after acute ischemic stroke. (4) DPSCs-Exos can promote blood brain barrier repair after acute ischemic cerebral apoplexy. (5) DPSCs-Exos can promote proliferation, migration and tube formation of endothelial cells after acute ischemic stroke. (6) DPSCs-Exos can promote protein arginine methyltransferase (PRMT 5) expression in OPC cells after acute ischemic stroke, and reduce differentiation inhibitor (ID 2) expression. (7) DPSCs-Exos can promote PRMT5 nuclear inhibition ID2 expre