Treatment of Moyamoya Disease With iPSC-derived Exosomes

Moyamoya disease is a cerebrovascular disease clinically characterized by chronic progressive stenosis or occlusion at the ends of bilateral internal carotid arteries and the origin of anterior cerebral arteries and middle cerebral arteries, followed by the formation of abnormal vascular networks at the base of the skull. Because this abnormal vascular network at the base of the skull looks like wisps of smoke on cerebral angiography, the Japanese Suzuki first named it "Moyamoya Disease" in the 1960s. Clinically, patients with Moyamoya disease mainly present with ischemic or hemorrhagic stroke, and there are two peaks of incidence in children aged 3-5 and middle-aged people aged 40-50. Epidemiological studies have found that Moyamoya disease is mainly distributed among the population in East Asia, including Japan, South Korea and China, and its incidence rate in China has shown a significant upward trend in recent years.Moreover, as the pathogenesis and treatment evaluation of Moyamoya disease are still in the research trough at present, new discoveries are prone to occur and thus attract a great deal of attention. It not only has a beneficial promoting effect on the treatment and diagnosis of patients, but also makes it easier for research topics to be reported in top journals.

In recent years, with the popularity of IPscs, the emerging therapeutic approach of extracellular vesicles derived from IPscs (iPSC-EVs) has gradually come into the public view. Extracellular vesicles derived from IPscs have specific bioactive substances related to iPSC functions. Their main advantages are manifested as follows: (1) They have a strong ability to promote regeneration and can promote vascular regeneration; (2) It has a powerful function of inhibiting inflammatory responses and can significantly inhibit the release of inflammatory factors by microglia, astrocytes and oligodendrocytes. (3) The homogeneity and stability of IPscs enable extracellular vesicles derived from IPscs to have high drugability; (4) IPscs have good potential for gene editing and can support the engineering of extracellular vesicles and drug delivery in extracellular vesicles. (5) The homing effect of IPSC-differentiated cells can endow the corresponding extracellular vesicles with better tissue-targeting characteristics.

This study intends to combine iPSC-EVs local skin transplantation with temporal muscle application to promote muscle angiogenesis and the establishment of extracranial and intracranial collateral circulation after temporal muscle application. The above-mentioned design features high efficiency, safety and convenience, and is an innovative exploration both at home and abroad. We hope to screen out safe, efficient and simple preparation methods and transplantation methods of iPSC-EVs through systematic experiments, establish an effective clinical evaluation system, and provide auxiliary means for intracranial and extracranial blood flow reconstruction surgery in the treatment of Moyamoya disease. Moreover, in terms of topic selection, iPSC is currently one of the most promising directions for innovative treatment worldwide.