Application Of Stem Cells Research Articles

Avascular necrosis of the femoral head in patient with Lyme disease and Devic’s optic neuritis

Avascular necrosis of the femoral head is a condition that leads to the collapse of the femoral head, which eventually ends in osteonecrosis of the hip head and the need for a total hip replacement. It affects patients of both sexes between 20-55 years of age. The pathogenetic cause is a progressive reduction of blood circulation which leads to destruction of the femoral head. Most often the causes are corticosteroid therapy, alcoholism, smoking, trauma, etc. Decompression of the femoral head accompanied by application of mesenchymal stem cells to the necrotic zone is a promising regenerative method of treatment. We present a case of a 20-year-old patient who was diagnosed with avascular necrosis of the femoral head of the left hip, due to a high dosage of corticosteroid therapy, with Lyme disease and Devic’s optic neuritis. Corticosteroid- induced avascular necrosis of the femoral head most commonly affects the femoral head, but other skeletal parts are not excluded. Majority of patients complain of pain with an insidious onset, which exacerbates with physical activity, and tends to worse with time. Early diagnosis and treatment arecrucial. Despite some controversy regarding the treatment of avascular necrosis of the femoral head with stem cells, the general outcomes of using stem cells appear to be positive in terms of efficacy and safety.

Properties of scaffolds as carriers of mesenchymal stem cells for use in bone engineering.

Tissue engineering has become one of the most studied medical fields and appears to be promising for the regeneration of injured bone tissues. Even though the bone has self-remodeling properties, bone regeneration may be required in some cases. Current research concerns materials employed to develop biological scaffolds with improved features as well as complex preparation techniques. Several attempts have been made to achieve compatible and osteoconductive materials with good mechanical strength in order to provide structural support. The application of biomaterials and mesenchymal stem cells (MSCs) is a promising prospect for bone regeneration. Recently, various cells have been utilized alone or in combination with biomaterials to accelerate bone repair in vivo. However, the question of what cell source is the best for use in bone engineering remains open. This review focuses on studies that evaluated bone regeneration using biomaterials with MSCs. Different types of biomaterials for scaffold processing, ranging from natural and synthetic polymers to hybrid composites, are presented. These constructs demonstrated an enhanced ability to regenerate the bone in vivo using animal models. Additionally, future perspectives in tissue engineering, such as the MSC secretome, that is the conditioned medium (CM), and the extracellular vesicles (EVs), are also described in this review. This new approach has already shown promising results for bone tissue regeneration in experimental models.

Myocard Injury in COVID-19 Patients After Application Of Umbilical Cord Mesenchymal Stem Cell (UC-MSC) as Adjuvant Therapy in Persahabatan Hospital

Background: Myocardial injury was a frequent cardiovascular manifestation of COVID-19 and associated with high mortality. Cell-based approaches, primarily using mesenchymal stem cell (MSC) has demonstrated safety and possible efficacy as adjuvant therapy in COVID-19 patients. This study aims to evaluate myocardial injury in patients with moderate-severe and critically ill COVID-19 after the application of umbilical cord mesenchymal stem cell (UC-MSC) as adjuvant therapy in Persahabatan hospital. Method: This is a retrospective and prospective cohort study. A total of 28 subjects were allocated to 13 subjects in the control and 15 subjects in the experimental group. Subjects were given the standard treatment and UC-MSC or placebo. Myocardial injury is defined by an increase of troponin I >26 pg/ml. The biomarkers of troponin I, NT-proBNP and CRP was examined periodically. Cardiac pump evaluated by EF and TAPSE from echocardiography examination before and after UC-MSC application. The evaluation of myocardial injury, biomarkers, cardiac pump and 15-day mortality were observed between the two groups. Results: The incidence of myocardial injury was 28,6% of total subjects. Subjects with worsening myocardial injury were higher in the control group (6 subjects) than the experimental group (4 subjects) although not statistically significant. The difference in biomarkers (troponin I, NT- pro-BNP and CRP), cardiac pump function (EF and TAPSE) and 15-day mortality between two groups were not statistically significant. There was a trend of decreasing troponin I, NT-proBNP and CRP in the experimental group. Conclusion: UC-MSC application can be an option as adjuvant therapy in improving myocardial injury of moderate-severe and critically ill COVID-19 patients.

Active Ingredients and Natural Raw Materials Used in Foot Care in Diabetic Patients—A Literature Review

Diabetic foot syndrome is the leading cause of limb loss due to non-healing ulcers. Repeated injuries, abnormal foot loads, and ischemia lead to ulcers. Poor shoe selection and inadequate care worsen the situation. Lack of patient education contributes to bacterial infections, tissue necrosis, and amputation. Vigilant observation and regular care can reduce wound size and prevent new wounds. Cleansing, infection control, and pressure relief are crucial in diabetic foot treatment. In this review, the effect of selected active ingredients and natural raw materials used for topical application in the care of diabetic foot was analyzed. The main focus used was on ingredients of natural origin—research studies utilizing emollients, humectants, plant extracts, and animal-derived ingredients were discussed. In addition, research studies on the application of nanomaterials, ozone and stem cells are also discussed. The cosmetics industry and manufacturers of podiatric products play a vital role in diabetic care. They should prioritize proper formulation, optimal ingredient doses, and skin microbiome control. Educating diabetics and using cosmetic products with self-massage elements can reduce the risk of hard-to-heal ulcers.

Human Stem Cells for Cardiac Disease Modeling and Preclinical and Clinical Applications-Are We on the Road to Success?

Cardiovascular diseases (CVDs) are pointed out by the World Health Organization (WHO) as the leading cause of death, contributing to a significant and growing global health and economic burden. Despite advancements in clinical approaches, there is a critical need for innovative cardiovascular treatments to improve patient outcomes. Therapies based on adult stem cells (ASCs) and embryonic stem cells (ESCs) have emerged as promising strategies to regenerate damaged cardiac tissue and restore cardiac function. Moreover, the generation of human induced pluripotent stem cells (iPSCs) from somatic cells has opened new avenues for disease modeling, drug discovery, and regenerative medicine applications, with fewer ethical concerns than those associated with ESCs. Herein, we provide a state-of-the-art review on the application of human pluripotent stem cells in CVD research and clinics. We describe the types and sources of stem cells that have been tested in preclinical and clinical trials for the treatment of CVDs as well as the applications of pluripotent stem-cell-derived in vitro systems to mimic disease phenotypes. How human stem-cell-based in vitro systems can overcome the limitations of current toxicological studies is also discussed. Finally, the current state of clinical trials involving stem-cell-based approaches to treat CVDs are presented, and the strengths and weaknesses are critically discussed to assess whether researchers and clinicians are getting closer to success.

Advances in combined application of dental stem cells and small-molecule drugs in regenerative medicine.

Teeth are a kind of masticatory organs of special histological origin, unique to vertebrates, playing an important role in chewing, esthetics, and auxiliary pronunciation. In the past decades, with the development of tissue engineering and regenerative medicine, the studies of mesenchymal stem cells (MSCs) gradually attracted the interest of researchers. Accordingly, several types of MSCs have been successively isolated in teeth or teeth-related tissues, including dental pulp stem cells, periodontal ligament stem cells, stem cells from human exfoliated deciduous teeth, dental follicle stem cells, stem cells from apical papilla and gingival mesenchymal stem cells. These dental stem cells (DSCs) are easily accessible, possess excellent stem cell characteristics, such as high proliferation rates and profound immunomodulatory properties. Small-molecule drugs are widely used and show great advantages in clinical practice. As research progressed, small-molecule drugs are found to have various complex effects on the characteristics of DSCs, especially the enhancement of biological characteristics of DSCs, which has gradually become a hot issue in the field of DSCs research. This review summarizes the background, current status, existing problems, future research directions, and prospects of the combination of DSCs with three common small-molecule drugs: aspirin, metformin, and berberine.

Evaluation of safety and efficacy of the bone marrow mesenchymal stem cell and gelatin-nano-hydroxyapatite combination in canine femoral defect repair.

Femoral shaft fracture is a common bone trauma in dogs. The limitation of mesenchymal stem cells in bone defect applications is that the cell suspension cannot be fixed to the bone defect site. In the study, our objective was to substantiate the combined application of canine bone marrow mesenchymal stem cells (cBMSCs) and gelatin-nano-hydroxyapatite (Gel-nHAP) and evaluate its therapeutic effect on bone defect diseases in dogs. Experiments were performed to evaluate the following: (1) the porosity of Gel-nHAP; (2) the adhesion of cBMSCs to Gel-nHAP; and (3) the effect of Gel-nHAP on cBMSC proliferation. The efficacy and safety of the combination of cBMSC and Gel-nHAP in the repair of femoral shaft defects were evaluated in animal experiments. The results showed that Gel-nHAP supported the attachment of cBMSCs and exhibited good biocompatibility. In the animal bone defect repair experiment, significant cortical bone growth was observed in the Gel-nHAP group at week 8 (p < 0.05) and in the cBMSCs-Gel-nHAP group at week 4 (p < 0.01). We demonstrated that Gel-nHAP could promote the repair of bone defects, and the effect of cBMSC-Gel-nHAP on the repair of bone defects was profound.

Application of stem cells in regeneration medicine.

Regeneration is a complex process affected by many elements independent or combined, including inflammation, proliferation, and tissue remodeling. Stem cells is a class of primitive cells with the potentiality of differentiation, regenerate with self-replication, multidirectional differentiation, and immunomodulatory functions. Stem cells and their cytokines not only inextricably linked to the regeneration of ectodermal and skin tissues, but also can be used for the treatment of a variety of chronic wounds. Stem cells can produce exosomes in a paracrine manner. Stem cell exosomes play an important role in tissue regeneration, repair, and accelerated wound healing, the biological properties of which are similar with stem cells, while stem cell exosomes are safer and more effective. Skin and bone tissues are critical organs in the body, which are essential for sustaining life activities. The weak repairing ability leads a pronounced impact on the quality of life of patients, which could be alleviated by stem cell exosomes treatment. However, there are obstacles that stem cells and stem cells exosomes trough skin for improved bioavailability. This paper summarizes the applications and mechanisms of stem cells and stem cells exosomes for skin and bone healing. We also propose new ways of utilizing stem cells and their exosomes through different nanoformulations, liposomes and nanoliposomes, polymer micelles, microspheres, hydrogels, and scaffold microneedles, to improve their use in tissue healing and regeneration.

Bioactivity of human adult stem cells and functional relevance of stem cell-derived extracellular matrix in chondrogenesis

BackgroundAutologous chondrocyte implantation (ACI) has been used to treat articular cartilage defects for over two decades. Adult stem cells have been proposed as a solution to inadequate donor cell numbers often encountered in ACI. Multipotent stem/progenitor cells isolated from adipose, bone marrow, and cartilage are the most promising cell therapy candidates. However, different essential growth factors are required to induce these tissue-specific stem cells to initiate chondrogenic differentiation and subsequent deposition of extracellular matrix (ECM) to form cartilage-like tissue. Upon transplantation into cartilage defects in vivo, the levels of growth factors in the host tissue are likely to be inadequate to support chondrogenesis of these cells in situ. The contribution of stem/progenitor cells to cartilage repair and the quality of ECM produced by the implanted cells required for cartilage repair remain largely unknown. Here, we evaluated the bioactivity and chondrogenic induction ability of the ECM produced by different adult stem cells.MethodsAdult stem/progenitor cells were isolated from human adipose (hADSCs), bone marrow (hBMSCs), and articular cartilage (hCDPCs) and cultured for 14 days in monolayer in mesenchymal stromal cell (MSC)–ECM induction medium to allow matrix deposition and cell sheet formation. The cell sheets were then decellularized, and the protein composition of the decellularized ECM (dECM) was analyzed by BCA assay, SDS-PAGE, and immunoblotting for fibronectin (FN), collagen types I (COL1) and III (COL3). The chondrogenic induction ability of the dECM was examined by seeding undifferentiated hBMSCs onto the respective freeze-dried solid dECM followed by culturing in serum-free medium for 7 days. The expression levels of chondrogenic genes SOX9, COL2, AGN, and CD44 were analyzed by q-PCR.ResultshADSCs, hBMSCs, and hCDPCs generated different ECM protein profiles and exhibited significantly different chondrogenic effects. hADSCs produced 20–60% more proteins than hBMSCs and hCDPCs and showed a fibrillar-like ECM pattern (FNhigh, COL1high). hCDPCs produced more COL3 and deposited less FN and COL1 than the other cell types. The dECM derived from hBMSCs and hCDPCs induced spontaneous chondrogenic gene expression in hBMSCs.ConclusionsThese findings provide new insights on application of adult stem cells and stem cell-derived ECM to enhance cartilage regeneration.

Comparison of Biological Properties and Clinical Application of Mesenchymal Stem Cells from the Mesoderm and Ectoderm.

Since the discovery of mesenchymal stem cells (MSCs) in the 1970s, they have been widely used in the treatment of a variety of diseases because of their wide sources, strong differentiation potential, rapid expansion in vitro, low immunogenicity, and so on. At present, most of the related research is on mesoderm-derived MSCs (M-MSCs) such as bone marrow MSCs and adipose-derived MSCs. As a type of MSC, ectoderm-derived MSCs (E-MSCs) have a stronger potential for self-renewal, multidirectional differentiation, and immunomodulation and have more advantages than M-MSCs in some specific conditions. This paper analyzes the relevant research development of E-MSCs compared with that of M-MSCs; summarizes the extraction, discrimination and culture, biological characteristics, and clinical application of E-MSCs; and discusses the application prospects of E-MSCs. This summary provides a theoretical basis for the better application of MSCs from both ectoderm and mesoderm in the future.

Label-Free Evaluation of Maturation and Hepatotoxicity of Human iPSC-Derived Hepatocytes Using Hyperspectral Raman Imaging.

To promote the clinical application of human induced pluripotent stem cell (hiPSC)-derived hepatocytes, a method capable of monitoring regenerative processes and assessing differentiation efficiency without harming or modifying these cells is important. Raman microscopy provides a powerful tool for this as it enables label-free identification of intracellular biomolecules in live samples. Here, we used label-free Raman microscopy to assess hiPSC differentiation into hepatocyte lineage based on the intracellular chemical content. We contrasted these data with similar phenotypes from the HepaRG and from commercially available hiPSC-derived hepatocytes (iCell hepatocytes). We detected hepatic cytochromes, lipids, and glycogen in hiPSC-derived hepatocyte-like cells (HLCs) but not biliary-like cells (BLCs), indicating intrinsic differences in biomolecular content between these phenotypes. The data show significant glycogen and lipid accumulation as early as the definitive endoderm transition. Additionally, we explored the use of Raman imaging as a hepatotoxicity assay for the HepaRG and iCell hepatocytes, with data displaying a dose-dependent reduction of glycogen accumulation in response to acetaminophen. These findings show that the nondestructive and high-content nature of Raman imaging provides a promising tool for both quality control of hiPSC-derived hepatocytes and hepatotoxicity screening.

Application of Human Stem Cell Derived Retinal Organoids in the Exploration of the Mechanisms of Early Retinal Development.

The intricate neural circuit of retina extracts salient features of the natural world and forms bioelectric impulse as the origin of vision. The early development of retina is a highly complex and coordinated process in morphogenesis and neurogenesis. Increasing evidence indicates that stem cells derived human retinal organoids (hROs) in vitro faithfully recapitulates the embryonic developmental process of human retina no matter in the transcriptome, cellular biology and histomorphology. The emergence of hROs greatly deepens on the understanding of early development of human retina. Here, we reviewed the events of early retinal development both in animal embryos and hROs studies, which mainly comprises the formation of optic vesicle and optic cup shape, differentiation of retinal ganglion cells (RGCs), photoreceptor cells (PRs) and its supportive retinal pigment epithelium cells (RPE). We also discussed the classic and frontier molecular pathways up to date to decipher the underlying mechanisms of early development of human retina and hROs. Finally, we summarized the application prospect, challenges and cutting-edge techniques of hROs for uncovering the principles and mechanisms of retinal development and related developmental disorder. hROs is a priori selection for studying human retinal development and function and may be a fundamental tool for unlocking the unknown insight into retinal development and disease.

Managing Type 1 Diabetes from Gynecological Waste: Trash to Treasure.

Type 1 diabetes mellitus (T1DM), an autoimmune disease, involves the destruction of pancreatic β cells. β cells maintain glucose homeostasis by identifying blood glucose and accordingly releasing insulin to maintain normal physiologic glucose levels. Human umbilical cord blood (hUCB) cells pose a lesser risk of viral contamination due to low placental transmission during prenatal life. Additionally, they have advantages such as non-invasive harvest procedure gynecological waste, low immunogenicity, easy expansion in-vitro, and easy ethical access compared to deriving stem cells from other sources. According to the published preclinical data, the infusion of autologous cord blood cells is considered safe as they are non-antigenic. Depending on the degree of differentiation, the ability to regenerate themselves and the origin of many stem cell types can be differentiated. The application of stem cells (SCs) has great potential for managing T1DM due to their regenerative capabilities and promising immunological characteristics. Due to lesser ethical complications and easy procedures of isolation, hUCB has become a precious medical intervention.

Application of stem cells in guided bone regeneration

Modern medicine allows us to study and develop materials and methods of restorative treatment that would be based on the immunological mechanisms of bone repair. One of the promising directions in guided bone regeneration is the use of mesenchymal stem cells. Interest in MSCs is associated with their ability to regulate the inflammatory process, and directly participate in the formation of new bone structures, thereby providing a physiological repair process. The effector impact of MSCs on the inflammatory process due to their ability to form a specific microenvironment. Low expression of MHC-II and CD80/CD86, the production of PGE2 and NO determines their low immunoconflict, and the production of TGF-b1, IDO and IL-10 has an immunomodulating effect. The ability of MSCs to differentiate into an osteogenic phenotype is accompanied with the synthesis of ALP, BSP and, subsequently, Gla-protein and OPN determine the synthesis of the extracellular matrix and its subsequent mineralization. This process is provided by the action of Runx2, which activates the differentiation of MSCs along the osteogenic pathway. These effects of MSCs were taken as the basis for the development of a new method for the treatment of bone atrophy. To accomplish the task set, a model of bone tissue atrophy and a drug containing MSCs was developed, and an experimental study was conducted to evaluate the effectiveness of the developed methodology. As the main criteria, data from clinical and laboratory studies were taken. Visual changes in the studied area were taken into account, compared with a similar area in the developed model of atrophy, the parameters of the complete blood count (CBC) were evaluated. The performed study allows us to determine the developed treatment method as capable of fully recreating the conditions of bone repair processes, taking into account the optimization of the body’s immune reactions and repair processes, without additional external influence, to obtain predictable and controllable results.

Biogenesis, Composition and Potential Therapeutic Applications of Mesenchymal Stem Cells Derived Exosomes in Various Diseases.

Exosomes are nanovesicles with a wide range of chemical compositions used in many different applications. Mesenchymal stem cell-derived exosomes (MSCs-EXOs) are spherical vesicles that have been shown to mediate tissue regeneration in a variety of diseases, including neurological, autoimmune and inflammatory, cancer, ischemic heart disease, lung injury, and liver fibrosis. They can modulate the immune response by interacting with immune effector cells due to the presence of anti-inflammatory compounds and are involved in intercellular communication through various types of cargo. MSCs-EXOs exhibit cytokine storm-mitigating properties in response to COVID-19. This review discussed the potential function of MSCs-EXOs in a variety of diseases including neurological, notably epileptic encephalopathy and Parkinson's disease, cancer, angiogenesis, autoimmune and inflammatory diseases. We provided an overview of exosome biogenesis and factors that regulate exosome biogenesis. Additionally, we highlight the functions and potential use of MSCs-EXOs in the treatment of the inflammatory disease COVID-19. Finally, we covered a strategies and challenges of MSCs-EXOs. Finally, we discuss conclusion and future perspectives of MSCs-EXOs.

Innovations in cell therapy in pediatric diseases: a narrative review.

Stem cell therapy is a regenerative medicine modality that has the potential to decrease morbidity and mortality by promoting tissue regeneration or modulating the inflammatory response. An increase in the number of clinical trials investigating the efficacy and safety of stem cell therapy in pediatric diseases has led to advancements in this field. Currently, multiple sources and types of stem cells have been utilized in the treatment of pediatric diseases. This review aims to inform researchers and clinicians about preclinical and clinical stem cell therapy trials in pediatric patients. We discuss the different types of stem cells and the wide spectrum of stem cell therapy trials for pediatric diseases, with an emphasis on the outcomes and advancements in the field. PubMed and clinicaltrials.gov databases were searched on October 28, 2022 using the following Medical Subject Headings (MeSH) terms "stem cell" or "stem cell therapy" with an age filter <18 years. Our search was limited to publications published between 2000 and 2022. Diverse sources of stem cells have different properties and mechanisms of action, which allow tailored application of stem cells according to the pathophysiology of the disease. Advancements in stem cell therapies for pediatric diseases have led to improvements in clinical outcomes in some pediatric diseases or in quality of life, such therapies represent a potential alternative to the current treatment modalities. Stem cell therapy in pediatric diseases has shown promising results and outcomes. However, further studies focusing on the implementation and optimal treatment timeframe are needed. An increase in preclinical and clinical trials of stem cell therapy targeting pediatric patients is required to advance our therapeutic applications.

The Applications of Human Umbilical Cord Mesenchymal Stem Cells to Treat Spinal Cord Injuries

Due to the morbidity and resulting lifestyle changes of Spinal Cord Injuries (SCI), there has been an extensive need to evaluate potential treatments. Mesenchymal cells hold the capacity to address both the primary and secondary mechanisms of SCI. Human Umbilical Cord stem cells (hUC), in particular, show promise due to their rapid proliferation, immunological properties, and pluripotent capacity. These hUC-MSC can be isolated from the umbilical Cord Blood (hCB) and Wharton’s jelly, a viscous gel that maintains the umbilical cord’s integrity. While Wharton’s jelly-derived hUC-MSCs appear to have a greater capability for the treatment of SCI due to their increased proliferation, hCB-MSC additionally has long-term therapeutic potential in clinical trials.

Dissecting the Interrelationship between COVID-19 and Diabetes Mellitus.

COVID-19 disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to enormous morbidity and mortality worldwide. After gaining entry into the human host, the virus initially infects the upper and lower respiratory tract, subsequently invading multiple organs, including the pancreas. While on one hand, diabetes mellitus (DM) is a significant risk factor for severe COVID-19 infection and associated death, recent reports have shown the onset of DM in COVID-19-recovered patients. SARS-CoV-2 infiltrates the pancreatic islets and activates stress response and inflammatory signaling pathways, impairs glucose metabolism, and consequently leads to their death. Indeed, the pancreatic autopsy samples of COVID-19 patients reveal the presence of SARS-CoV-2 particles in β-cells. The current review describes how the virus enters the host cells and activates an immunological response. Further, it takes a closer look into the interrelationship between COVID-19 and DM with the aim to provide mechanistic insights into the process by which SARS-CoV-2 infects the pancreas and mediates dysfunction and death of endocrine islets. The effects of known anti-diabetic interventions for COVID-19 management are also discussed. The application of mesenchymal stem cells (MSCs) as a future therapy for pancreatic β-cells damage to reverse COVID-19-induced DM is also emphasized.

STEM CELL THERAPY IN STROKE

Stem cells are emerging as an attractive option because of their intrinsic ability as vectors for drug delivery to diseased tissues. The term stem cells or stem cells was first introduced by a Russian histologist, Alexander Maksimov (1874-1928). The purpose of this study is to describe the research and development of stem cell applications for stroke. This study is a literature study (review article) regarding stem cells (stem cells) in stroke which has been discussed in several scientific journals. From several articles that have been collected in giving stem cells to people with stroke, namely in bone marrow. MSC (Mesenchymal Stem Cell) is a multipotent stem cell from bone marrow and Adult SPM and because of its high applicability. Bone marrow is a rich source of hematopoietic stem cells so it can be applied to stroke patients.

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 stem cell therapy was inconsistent; however, the results were promising. In addition, the results showed that adipose-derived stem cell therapy was safe without significant side effects. Further study was needed to identify therapeutic strategies based on Evidence-based Medicine (EBM).