Adipose derived stem cell (ADSC) is the most popular mesenchymal stem cells (MSCs) used in the clinic in recent years. ADSC transplantation has some advantages compared to others from bone marrow, umbilical cord blood… ADSCs produced important growth factors for wound healing, modulate the immune system, decrease inflammation, and home in on injured tissues. Particularly, ADSC extraction from adipose tissue is a simple procedure with minimum invasion in the patients. Therefore, ADSCs were used in the treatment of many diseases and clinical trials since 2000s. To date, ADSC transplantation was approved in some countries to treat medical complications such graft versus host disease, osteoarthritis… This review is an overview of applications and future challenges of ADSC in clinic.

Adipose-derived stem cells; Stem cells; Stem cell transplantation; Cytotherapy; Regenerative medicine

Diabetes mellitus type 1 is an autoimmune disease with high incidence in adolescents and young adults. A seductive approach overcomes normally obstacles treatment is cell-replacement therapy to endogenous insulin production. The pancreatic duodenal homeobox 1 (Pdx1) is essential transcription factor pancreatic development, beta cell differentiation and other metabolic processes. This study aimed to orient umbilical cord blood-derived mesenchymal stem cell (UCB-MSCs) to pancreatic endocrine cells by Pdx1 electrotransfer. The results showed that the low voltage of electrotransfer significantly increased in the efficiency of electrotransfer and survival cells compared with other high voltages. Pdx-1 transfected UCB-MSCs over-expressed pancreatic related genes as Ngn3, Nkx6.1. These results suggested that Pdx1 transfected UCB-MSCs were successfully oriented pancreatic endocrine cells. Different to lentiviral vectors, electrotransfer is a safer method to transfer Pdx-1 to UCB-MSCs and a useful tool in translational research.

Diabetes; electrotransfer; endocrine pancreatic; mesenchymal stem cell; Pdx1; umbilical cord blood

Liver injury causes the formation of nodules and diffuses fibrosis or scar tissues termed liver fibrosis. Since efficient therapies to prevent fibrosis are not obtainable, it is necessary to build up a potential animal model of liver fibrosis to study. In this research, liver fibrosis micewere generated using Swiss mice and carbon tetrachloride – CCl4. CCl4 at doses of 0.8, 1.0 and 1.2 ml/kg was evaluated on mice to obtain an effective dose for liver fibrosis induction. This study aimed to build up a standardized hepatic fibrosis mouse model induced by carbon tetrachloride for further biomedical research. On Swiss mice, dose of CCL4 was considered and criterias of fibrosis were also evalutated such as serum markers, fibrosis marker-genes and histopathology. Mice were administrated with CCL4 in 8 consecutive weeks, 3 times/week. Body weight, survival rate and serum markers Aspartate aminotransferase/Alanine aminotransferase (AST/ALT), fibrosis markers (fibronectin, procollagen, nt5e, TGF-beta and integrin) and histopathology (Hematoxylin & Eosin staining) were measured to determine the suitable dose of CCL4. Results showed that CCL4 1.0 ml/kg is the efficient dose for liver fibrosis mouse model establishment. In a standardized liver fibrosis model, mice were treated with CCL4 1.0 ml/kg in 11 consecutive weeks, 3 times/week and evaluated serum markers level (AST, ALT, bilirubin, albumin), gene-expression of fibrosis markers using quantitative-RT PCR, histopathology (H&E staining) and connective tissue formation by Massive trichrome staining. The outcomes showed that serum markers and the level of fibrosis gene markers in standardized liver fibrosis mice had significantly increased. It is also recorded that there was a sharply increasing of fibronectin and procollagen expression (1222.40±4.20 and 241.35±1.18, respectively). We also recorded cirrhosis (fibrosis stage 3 – 5/6) in liver tissues of standardized liver fibrosis mice.

Liver fibrosis; liver cirrhosis; animal model of liver disease; liver fibrosis mouse model; hepatic fibrosis

Diabetic foot ulcer is a major complication of diabetes mellitus. It occurred in about 15% of all diabetic patients. To date, the outcome of management of diabetic foot ulcer is poor and low sufficient. Some new therapies were suggested to manage and treat this disease. In almost therapies, management of diabetic foot ulcer relates to debridement of the wound, revascularization, off-loading of the ulcer, antibacterial actions, stimulating granulation, epidermization and angiogenesis. This study aimed to evaluate the effects of activated platelet rich plasma (aPRP) on diabetic foot ulcer healing on volunteer patients. There were 6 patients enrolled in this study. All patients have non-healing foot ulcers. aPRP was isolated from peripheral blood and activated with calcium chloride. Patients were injected with aPRP two times with 14-day interval. All patients were monitored during 12 weeks. The results showed that 100% (6/6) ulcers completely closed after about 7 weeks. This result initially suggests that aPRP injection is efficient method to treat the non-healing foot ulcers. Level of evidence: IV.

Platelet rich plasma; Growth factors; Diabetic Ulcer; Wound healing; Chronic Ulcer

Cancer is an important reason causing death in almost countries. So cancer studies become as interesting research field. Many research groups approached cancer treatment with some different strategies. To date, there are four main strategies used in preclinical and clinical treatment included surgery, chemotherapy, radiation therapy, and biological therapy. In some indications, doctors combined them to make combinatorial therapies. In recent years, biological therapies become a promising therapy, especially in invasive cancer. Biological agents formed the targeting therapies that in principle only cancer cells effected by drugs. Biological therapies as monoclonal antibodies, immune cells based immunotherapies showed that the treatment efficiency in some cancers, in recent years. Biomedical Research and Therapy is developed basing on the progress in research and application of biology, biotechnology in disease treatment that included cancer. So that, in this year, Biomedical Research and Therapy will have a special issue with the theme “Biological therapy for cancer treatment”. We will invite some of the leaders in this field to critically review this issue. We expect that this issue will be of great interest for developing the novel approaches and innovations for cancer treatment.

Biological Research; Biological Therapy; Medicine; Biomedical

Osteoarthritis is one of the most common diseases, and it affects 12% of the population around the world. Although the disease is chronic, it significantly reduces the patient’s quality of life. At present, stem cell therapy is considered to be an efficient approach for treating this condition. Mesenchymal stem cells (MSCs) show the most potential for stem cell therapy of osteoarthritis. In fact, MSCs can differentiate into certain mesodermal tissues such as cartilage and bone. Therefore, in the present study, we applied adipose tissue-derived MSCs to osteoarthritis treatment. This study aimed to evaluate the clinical efficiency of autologous adipose tissue-derived MSC transplantation in patients with confirmed osteoarthritis at grade II and III. Adipose tissue was isolated from the belly, and used for extraction of the stromal vascular fraction (SVF). The SVF was mixed with activated platelet-rich plasma before injection. The clinical efficiencies were evaluated by the pain score (VAS), Lysholm score, and MRI findings. We performed the procedure in 21 cases from 2012 to 2013. All 21 patients showed improved joint function after 8.5 months. The pain score decreased from 7.6±0.5 before injection to 3.5±0.7 at 3 months and 1.5±0.5 at 6 months after injection. The Lysholm score increased from 61±11 before injection to 82±8.1 after injection. Significant improvements were noted in MRI findings, with increased thickness of the cartilage layer. Moreover, there were no side-effects or complications related to microorganism infection, graft rejection, or tumorigenesis. These results provide a new opportunity for osteoarthritis treatment. Level of evidence: IV.

Osteoarthritis; Adipose tissue-derived stem cell; Stromal vascular fraction; Platelet-rich plasma

Osteoarthritis is one of the most common diseases, and it affects 12% of the population around the world. Although the disease is chronic, it significantly reduces the patient’s quality of life. At present, stem cell therapy is considered to be an efficient approach for treating this condition. Mesenchymal stem cells (MSCs) show the most potential for stem cell therapy of osteoarthritis. In fact, MSCs can differentiate into certain mesodermal tissues such as cartilage and bone. Therefore, in the present study, we applied adipose tissue-derived MSCs to osteoarthritis treatment. This study aimed to evaluate the clinical efficiency of autologous adipose tissue-derived MSC transplantation in patients with confirmed osteoarthritis at grade II and III. Adipose tissue was isolated from the belly, and used for extraction of the stromal vascular fraction (SVF). The SVF was mixed with activated platelet-rich plasma before injection. The clinical efficiencies were evaluated by the pain score (VAS), Lysholm score, and MRI findings. We performed the procedure in 21 cases from 2012 to 2013. All 21 patients showed improved joint function after 8.5 months. The pain score decreased from 7.6±0.5 before injection to 3.5±0.7 at 3 months and 1.5±0.5 at 6 months after injection. The Lysholm score increased from 61±11 before injection to 82±8.1 after injection. Significant improvements were noted in MRI findings, with increased thickness of the cartilage layer. Moreover, there were no side-effects or complications related to microorganism infection, graft rejection, or tumorigenesis. These results provide a new opportunity for osteoarthritis treatment. Level of evidence: IV.

Osteoarthritis; Adipose tissue-derived stem cell; Stromal vascular fraction; Platelet-rich plasma

Introduction: Acute lower limb ischemia is a common peripheral artery disease whose treatment presents many difficulties. Stem cell transplantation is considered a novel and promising method of treating this disease. Umbilical cord blood (UCB) is rich in stem cells, including hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs). However, historically, banked umbilical cord blood has been used mainly to treat blood-related diseases. Therefore, this study compared the efficacy of umbilical cord blood-derived mononuclear cells (UCB-MNCs) with EPC transplantation for the treatment of acute hindlimb ischemia (ALI) in mouse models.

Methods: MNCs were isolated from UCB by Ficoll gradient centrifugation, after which the EPCs were sorted based on CD34+ and CD133+ markers and cultured according to a previously published protocol. To induce ALI, mice were immuno-suppressed using busulfan (BU) and cyclophosphamide (CY), after which the femoral arteries were burned. Induction of ALI in the immune suppressed mice was confirmed by the grade of tissue damage, pedal frequency in water, tissue edema, changes in histology, total white blood cell count, and white blood cell composition. Model mice were injected with a dose of MNCs or EPCs and un-treated control mice were injected with phosphate buffered saline. The efficiency of treatment was evaluated by comparing the grade of tissue damage between the three groups of mice.

Results: Mice aged 6–12 months were suitable for ALI, with 100% of mice exhibiting ischemia from grade I 10%, grade III 50%, grade IV 40%. For all ALI mice, a gradual increase in pedal frequency in water, increased tissue edema, necrosis of muscle tissue, and (Andaz, 1993 #6)loss of hindlimb function were observed after 20 days. Transplanted MNCs and EPCs significantly improved hindlimb ischemia compared with control treatment. Moreover, EPC transplantation significantly improved hindlimb ischemia compared with MNC transplantation. Following EPC and MNC transplantation, 44.44% and 33.33% of the mice recovered fully (grade 0), respectively. Specifically, all recovered mice exhibited hindlimb activities similar to those of normal mice

Hindlimb ischemia, Umbilical cord blood-derived stem cells, Mononuclear cells, Endothelial progenitor cells, Neovascularization.