Abstract
ObjectiveArteriosclerosis is an age-related disease and a leading cause of cardiovascular disease. In animal experiments, mesenchymal stem cells and its culture-conditioned medium have been shown to be promising tools for prevention or treatment of arteriosclerosis. On the basis of these evidences, we aimed to assess whether administration of autologous adipose-derived mesenchymal stem cells (Ad-MSC) is safe and effective for treatment of arteriosclerosis.MethodsWe retrospectively reviewed clinical records of patients with arteriosclerosis who had received autologous Ad-MSC administration at our clinic. Patients’ characteristics were recorded and data on lipid profile, intimal-media thickness (IMT), cardio-ankle vascular index (CAVI), and ankle-brachial index (ABI) before and after Ad-MSC administration were collected and compared.ResultsTreatment with Ad-MSC significantly improved HDL, LDL, and remnant-like particle (RLP) cholesterol levels. No adverse effect or toxicity was observed in relation to the treatment. Of the patients with abnormal HDL values before treatment, the vast majority showed improvement in the values. Overall, the measurements after treatment were significantly increased compared with those before treatment (p < 0.01). In addition, decreases in LDL cholesterol and RLP levels were observed after treatment in patients who had abnormal LDL cholesterol or RLP levels before treatment. The majority of patients with pre-treatment abnormal CAVI values had improved values after treatment. In patients with available IMT values, a significant decrease in the IMT values was found after therapy (p < 0.01). All patients with borderline arteriosclerosis disease had improved laboratory findings after treatment. In general, post-treatment values were significantly decreased as compared with pre-treatment values. Of the patients with normal ABI values before treatment at the same time as CAVI, the vast majority remained normal after treatment.ConclusionsThese findings suggest that Ad-MSC administration is safe and effective in patients developing arteriosclerosis, thereby providing an attractive tool for anti-aging application.
Highlights
Arteriosclerosis is an age-related disease and is considered a leading cause of death and disability in adults worldwide [1]
It inhibited expression of cytokines such as IL-1α, IL-1β, Interleukin 6 (IL-6), and Tumor necrosis factor-α (TNF-α) in the Cerebrospinal fluid (CSF) and periventricular brain region. It modulated immune function by impairing the differentiation of dendritic cells that are the main antigen-presenting cells in human immunity [20]. These results suggested the importance of immunomodulatory function of mesenchymal stem cells (MSC) which can be applicable to the effect of adipose-derived mesenchymal stem cells (Ad-MSC)
We excluded patients having any of the following infections using virus and bacterial tests: (1) Human immunodeficiency virus (HIV), (2) Hepatitis C virus (HCV) antibody (CLIA method), (3) Hepatitis B (HB) antigen (CLIA method), (4) HBs antigen (CLIA method), (5) Human T-lymphotropic virus (HTLV-I) antibody (CLEIA method), (6) syphilis (RPR method, Treponema pallidum particle agglutination assay (TPHA) method), (7) herpes simplex (CF method), (8) mycoplasma (PA method), and (9) parvovirus B19 (IgM antibody)
Summary
Study design and patients This retrospective study was performed following the ethical policies of the Sun Field Clinic in Tokyo, Japan, and were approved by its related Ethics Committee of the World Academy of Anti-Aging and Regenerative Medicine (approval No 4-001). A blood examination had been first performed including tests for infectious diseases such as hepatitis virus, rubella virus, herpes zoster virus, and HIV, which are generally performed before surgical procedures to determine if stem cell culture will be compromised. The Ad-MSC preparations had been checked for cell survival by trypan blue staining method, genetic stability by conventional karyotyping using G-banding method and microbiological, mycoplasma, and endotoxin contamination by nucleic acid testing-based assay and limulus amebocyte lysate kinetic turbidimetric assay. Data collection and processing Clinical records of patients who had received Ad-MSC treatment at our clinic were reviewed. The significance of differences between the two groups was tested by either paired t test or Fisher’s exact tests as appropriate, at the 0.05 significance level
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