Abstract
Objectives: Research on neurocognitive disorder, which is a significant barrier against a healthy life span, has been intensively conducted in this aging society. Problems, however, are not yet solved for treatments. The purpose of the present study is to evaluate safety and clinical efficacy on intranasal administration of stem cell secretome (stem cell supernatant/exosome) in patients with Alzheimer’s disease, the primary disease which causes cognitive disorders. Furthermore, this study explores future prospects of stem cell secretome therapy.
Methods: Research participants were patients with Alzheimer's disease who scored approximately 10–20 points of 30 (the full score) on the Hasegawa's dementia scale-Revised (HDS-R). Among 18 initial participants, 5 participants dropped out because of aggravation in pre-existing diseases and other factors. The number of final analysis participants was 13. Adipose-derived mesenchymal stem cell secretome was prescribed with intranasal administration at 3 vials/week for 8 weeks. (one vial included exosome: approximately 1×10 8, HGF, which is one of major hepatocyte growth factors: 1.2 × 10 5 pg, and multiple high-concentrated bioactive substances). Check list items were HDS-R, blood pressure, pulse, blood biochemistry tests, measurements of hormones, and MCI screening test (measurement tests of 9 types of proteins, which are related to Alzheimer’s disease). Evaluations were conducted before and after treatments to confirm safety of nasal drip therapy and to examine alternations in HDS-R scores, blood tests, and alternations of each protein in MCI screening test.
Results: Scores of HDS-R were significantly improved: mean values 15.6 ± 1.0 → 17.5 ± 1.4 (p = 0.030). More obvious significant differences were recognized in a subclass analysis of mild and moderate cases for patients who had around 15-20 scores in HDS-R: 17.2 ± 0.6 → 20.0 ± 0.8 (p = 0.006). Among blood tests, significant differences with a significant level of 1% or less than 1% were shown in platelet (decrease), albumin/globulin ratio (increase) and LDL cholesterol/HDL cholesterol ratio (decrease). MIC screening test provided, among 9 types of proteins, a significant increase in apolipoprotein A-1, which is related to amyloid β excretion: 131.6 ± 6.1 → 150.3 ± 7.0 (p = 0.010). No adverse events considered to be related to treatments were observed in 13 research participants during the treatments.
Conclusion: Intranasal administration of adipose-derived mesenchymal stem cell secretome for 8 weeks observed no safety problems and provided significant increases in scores of the Hasegawa's dementia scale-Revised (HDS-R). Therapy of intranasal administration of stem cell secretome (stem cell culture supernatant/exosome) is a safe and simple method, which can be performed at home. Judging from improvement effectiveness on cognitive functions, its possibility as a new treatment was suggested for Alzheimer’s cognitive disorder. Further studies are required to solve multiple problems and tasks, establish credible scientific evidence and organize environments for safety. It is our hope that stem cell secretome treatments will be implemented and widely introduced to clinical settings in an appropriate manner.
