ADIPOSE-DERIVED STEM CELL THERAPY ON NON-COMMUNICABLE DISEASE: A SYSTEMATIC REVIEW

The increasing number of non-communicable diseases demands practical therapy innovations, including adipose-derived stem cell application. This study aimed to analyze the effectiveness of adipose stem cell therapy on non-communicable disease patients. The method used in this study was a systematic review according to PRISMA 2020 guidelines. The database search was done on PubMed, Google Scholar, Proquest, and the EBSCO host database between 2016 and 2021. ROBINS-I tool and RoB-2 were used to assess the risk of bias in the clinical trial study. The first literature search identified a total of 2615 articles. After exclusion for some reason, 6 articles were included in this systematic review study. A total of five studies were included in this study. Based on the risk of bias assessment of the included studies, it was found that all studies had a low risk of bias in all domains. This study showed that the efficacy of adipose-derived


INTRODUCTION
Recently, the scientific world has been growing, especially medical sciences. The advancement of medical science has caused a shift in disease patterns, where noncommunicable diseases replaced the transmissible disease that was previously dominant. Even though there is a shift towards non-communicable diseases, some countries still face the double challenge of communicable and non-communicable diseases (Habib and Saha, 2010). The shifting pattern of the diseases was significantly influenced by the environmental changes, community behaviors, demographic transitions, technologies, economics, and sociocultural changes (Barouki et al., 2012). The increase in the non-communicable disease burden is in line with the elevation of its risk factors, such as obesity, high blood pressure, unhealthy eating patterns, diabetes mellitus, lack of physical activity, alcohol consumption, and smoking (Barouki et al., 2012;Habib and Saha, 2010;Nethan et al., 2017).
Non-communicable diseases (NCDs) are chronic diseases not transmitted from one patient to another in the environment. Generally, NCDs develop slowly over a long period (Habib and Saha, 2010 (Dans et al., 2011;Siegel et al., 2014).
The significant burden of morbidity and mortality due to NCD made it the primary concern in the development of the medical sciences. Currently, the management of NCD relies on drugs that are consumed routinely almost throughout life (Low et al., 2015).
Therefore, medical science developments focused on more specific and effective treatment.
And one of the prospective therapy in the future is the application of adipose-derived stem cells (AD-MSCs) (Mizuno et al., 2012;Patricia A Zuk, 2010).
Stem cells are undifferentiated cells that able to renewal, and are able to differentiate into various types of cells (Ullah et al., 2015) In addition, they have immunomodulating properties and paracrine effects in response to tissue injuries; therefore, they might be used to treat injury and diseases to replace damaged or missing cells (Mora and Rojas, 2013) Therefore, they are regarded as one of the solutions for NCDs therapy (Savitz et al., 2011).
Adipose tissue is a particularly enticing source for adult stem cells because the human body has large reserves that can be obtained in substantial quantities by minimally invasive methods (

METHODS
The selection process of articles was done according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guideline 2020 (Page et al., 2021).
Article searches were done using combination of keywords: "adipose-derived stem cells" AND "non-communicable diseases" OR "diabetic" OR "cancer" OR "stroke" OR "chronic obstructive pulmonary disease" OR "degenerative disease" in

Study selection process
The article selection process was

Data extraction
The article searching was performed from June 1, 2022, to June 30, 2022. The outcomes that we seek for this systematic review were the first's author name and year of publication, subjects, the country in which the study was conducted, the design of the study, the use of AD-MSCs for NCD, and potential adverse effects. Two researchers reviewed the articles.
Below is the diagram of the performed research process. The primary outcome assessed was the effectiveness of stem cells in inducing symptomatic and clinical improvements in NCD.
Another result that was also measured was the safety of the stem cell application.

Study quality and risk of bias
We

RESULTS
The results of the search process can be seen in Figure 1.   Most of the studies found that AD-MSCs didn't have serious side effects after being administered in human and animal subjects.

Assessment Risk of Bias
Based on the risk of bias assessment of the included studies, it was found that all studies had low risk of bias in all domains. No moderate or high risk was found in the included studies.

DISCUSSION
Of the five articles, four of the studies were performed on human subjects, and one study was Additionally, there was a decrease in FSH levels, however, this finding was inconsistent (Mashayekhi et al., 2021). Overall, the results of the reviewed studies claimed that adipose-derived stem cell therapy in humans was considered safe without significant side effects (Fraser et al., 2008). Furthermore, all studies about adipose-derived stem cell therapy showed an improvement in the patient's condition as expected. The abundance of adipose stem cells, their convenience in cell retrieval, their ability to differentiate into multiple lineages and release various cytokines, and their immunomodulatory effects suggest that adipose stem cells may have a significant role in regeneration (Ceccarelli et al., 2020;Zhang et al., 2020). Therefore, further studies in humans to develop a standardized method for cell isolation, culture conditions, proliferation, identification and characterization methodologies, as well as safety and efficacy guarantees are needed.