Current Advances in Wound Healing and Regenerative Medicine.

Treating chronic wounds is a common and costly challenge worldwide. More advanced treatments are needed to improve wound healing and prevent severe complications such as infection and amputation. Like other medical fields, there have been advances in new technologies promoting wound healing potential. Regenerative medicine as a new method has aroused hope in treating chronic wounds. The technology improving wound healing includes using customizable matrices based on synthetic and natural polymers, different types of autologous and allogeneic cells at different differentiation phases, small molecules, peptides, and proteins as a growth factor, RNA interference, and gene therapy. In the last decade, various types of wound dressings have been designed. Emerging dressings include a variety of interactive/ bioactive dressings and tissue-engineering skin options. However, there is still no suitable and effective dressing to treat all chronic wounds. This article reviews different wounds and common treatments, advanced technologies and wound dressings, the advanced wound care market, and some interactive/bioactive wound dressings in the market.

Comparative immunogenicity and safety of SpikoGen®, a recombinant SARS-CoV-2 spike protein vaccine in children and young adults: An immuno-bridging clinical trial.

BACKGROUND: SpikoGen® is a recombinant subunit spike protein ectodomain vaccine manufactured in insect cells and formulated with the novel polysaccharide-based Advax-CpG55.2 adjuvant. This study aimed to compare the immunogenicity and safety of SpikoGen® vaccine in children, adolescents and young adults. METHODS: This was a non-randomized, three-arm, open-label, parallel-group, immuno-bridging, non-inferiority trial to compare the immunogenicity and safety of a primary course of two intramuscular doses of SpikoGen® vaccine in children aged 5 to < 12 years, adolescents aged 12 to < 18 years and young adults aged 18 to 40 years. Children 5-12 years received a half dose of 12.5 µg spike protein, whereas the other groups received the full vaccine dose. Vaccine immunogenicity was evaluated via assessment of serum anti-spike and neutralizing antibodies 14 days after the second dose. Solicited adverse events were recorded for 7 days after each vaccination. Safety assessments including serious adverse events were continued through six months after the second dose in children and adolescents. RESULTS: Two weeks after the second dose, seroconversion rates for neutralizing antibody levels were not significantly different for children (59.50 %), adolescents (52.06 %) and adults (56.01 %). The 95 % confidence interval of the difference in seroconversion rates between children and adults was within the prespecified non-inferiority margin of 10 % (-12 % to 5 %). SpikoGen® vaccine was well tolerated in all age groups with the most common solicited adverse events being injection site pain and fatigue which were generally transient and mild. CONCLUSION: SpikoGen® vaccine was shown to be safe, well tolerated and immunogenic in children as young as 5 years of age, with non-inferior responses to those seen in adults. The Iranian FDA authorisation of SpikoGen® vaccine is now extended down to 5 years of age.

Adipose-derived Stem Cells: Potentials, Availability and Market Size in Regenerative Medicine.

Adipose-derived stem cells (ADSCs) have been described as one of the most potent and accessible human adult stem cells which can be utilized in various therapeutic approaches. Due to the wide variety of cytokines and GFs secreted by them, ADSCs can be used for controlled drug release. These cells can be used for proliferation and differentiation of tissues regardless of survival conditions and immunologic problems. Because of their ability to differentiate into various lineages, ADSCs can be used in musculoskeletal problems, diabetes, heart diseases, obesity, neurologic and nephrogenic diseases, and wound healing, as well as applications in regenerative medicine such as osteogenic, cartilage, tendon, muscle, skin, CNS, cardiac and vascularization, as well as liver and even periodontal regeneration. To maintain the highest viability and efficiency, companies that provide ADSCs should offer the best product quality to gain market share and scientists need to acquire an understanding of sources where they can find the best products available. Therefore, in this article, we have reviewed the available products, companies and the market size currently available for ADSCs. Enormous effort has been made to list the most important trials, products and companies currently existent in the field. To achieve better outcomes in scientific research, there is the need to compare the products available and choose the best option according to desired goals. Thus, this paper provides a valuable reference for those interested in the field of ADSCs and their applications.

Circulating miRNAs can serve as potential diagnostic biomarkers in chronic myelogenous leukemia patients.

INTRODUCTION: Chronic Myelogenous Leukemia (CML) is a myeloproliferative disorder described as a malignant blood disorder by accounts for 15-20% of all adult leukemia. MicroRNAs (miRNAs) play an important role in post-transcriptional regulation of gene expressions. Expression level of tumor suppressor-miRNAs, described as miRNAs that target the oncogens, can contribute to diagnosis and prognosis of some malignant disorders including CML. We theorized that according to the excessive proliferation and alteration in miRNA expressions, there could be a change in the expression of miRNAs in plasma carried by exosomes. METHODS: We consequently decided to detect the differences between normal and aberrant miRNA expression in human plasma sample to find out the possibility of diagnosis by these alterations. The expression of candidate miRNAs were compared using RNA extracted from the plasma of 50 patients, as well as 30 healthy individuals. We analysed the plasma miR-16-1, miR-20, miR-106, miR-126, miR-155, miR-222, and miR-451 expression levels in CML patients by individual real-time quantitative RT-PCR. RESULTS: All selected miRNAs were found to be upregulated in newly diagnosed CML patients compared to the control, while upregulation of only three (miR-20, 106 and 222) were significant (17.4, 19 and 74.95 fold change, respectively; p<0.0001). IN CONCLUSION: microRNAs have a potential use in treatment of CML, as they can target the genes involved in cell cycle, MAPK, growth inhibition, TGF beta, and p53 signaling pathways. Therefore, these miRNA signatures provide the basis for their utilization as biomarkers in CML.

Generation of high yield insulin-producing cells (IPCs) from various sources of stem cells.

Type 1 diabetes mellitus occurs when beta cell mass is reduced to less than 20% of the normal level due to immune system destruction of beta cell resulting in an inability to secrete enough insulin. The prevalence of diabetes is expanding according to the American Diabetes Association and the World Health Organization (WHO), foretold to exceed 350 million by 2030. The current treatment does not cure many of the serious complications associated with the disease such as neuropathy, nephropathy, dyslipidemia, retinopathy and cardiovascular disease. Whole pancreas or isolated pancreatic islet transplantation as an alternative therapy can prevent or reduce some of the complications of diabetes. However, the shortage of matched organ or islets cells donor and alloimmune responses limit this therapeutic strategy. Recently, several reports have raised extremely promising results to use different sources of stem cells to differentiate insulin-producing cells and focus on the expansion of these alternative sources. Stem cells, due to their potential for multiple differentiation and self-renewal can differentiate into all cell types, including insulin-producing cells (IPCs). Generation of new beta cells can be achieved from various stem cell sources, including embryonic stem cells (ESCs), adult stem cells, such as mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs). Thus, this chapter discusses on the assistance of cellular reprogramming of various stem cells as candidates for the generation of IPCs using transcription factors/miRNA, cytokines/small molecules and tissue engineering.

Treatment of diabetic mice by microfluidic system-assisted transplantation of stem cells-derived insulin-producing cells transduced with miRNA.

AIMS: Cell-based therapy is a promising approach for the treatment of type-1 diabetes mellitus. Identifying stem cells with differentiation potential to Insulin-producing cells (IPCs) and their application is an emerging issue. Different strategies have been used to support cell survival and their specific functions to control hyperglycemia conditions. Novel technologies using appropriate materials/fibers can improve cell transplantation. MAIN METHODS: In the present study, IPCs were differentiated from adipose-derived stem cells transduced with miR-375 and anti-miR-7. The cells' survival rate was also improved using a microfluidic system before their in vivo transplantation. KEY FINDINGS: After adopting a stable, functional condition of the IPCs, the cells were used for in vivo grafting to diabetic mice, which resulted in a substantial drop in blood glucose during four weeks of grafting compared to the control group (p < 0.0001). The pattern of blood glucose levels in the mice receiving fiber entrapped IPCs, was similar to that of non-diabetic mice. Blood insulin was elevated in diabetic mice which received a transplant of fiber-entrapped-IPCs carrying miR-375 and anti-miR-7 after five weeks of transplantation compared to the diabetic mice (p < 0.014). SIGNIFICANCE: For the first time, this study showed that the two-component microfluidic system is useful for supporting the Collagen-Alginate fiber-entrapped IPCs and the miRNA-based cell therapy. Overall, our data show that the IPC encapsulation using a microfluidic system can support the cells in terms of morphology and biological function and their efficiency for controlling the hyperglycemia condition in diabetic mice.

The Predominant microRNAs in ß-cell Clusters for Insulin Regulation and Diabetic Control.

micro (mi)-RNAs are vital regulators of multiple processes including insulin signaling pathways and glucose metabolism. Pancreatic ß-cells function is dependent on some miRNAs and their target mRNA, which together form a complex regulative network. Several miRNAs are known to be directly involved in ß-cells functions such as insulin expression and secretion. These small RNAs may also play significant roles in the fate of ß-cells such as proliferation, differentiation, survival and apoptosis. Among the miRNAs, miR-7, miR-9, miR-375, miR-130 and miR-124 are of particular interest due to being highly expressed in these cells. Under diabetic conditions, although no specific miRNA profile has been noticed, the expression of some miRNAs and their target mRNAs are altered by posttranscriptional mechanisms, exerting diverse signs in the pathobiology of various diabetic complications. The aim of this review article is to discuss miRNAs involved in the process of stem cells differentiation into ß-cells, resulting in enhanced ß-cell functions with respect to diabetic disorders. This paper will also look into the impact of miRNA expression patterns on in vitro proliferation and differentiation of ß-cells. The efficacy of the computational genomics and biochemical analysis to link the changes in miRNA expression profiles of stem cell-derived ß-cells to therapeutically relevant outputs will be discussed as well.

Oxidized LDL: As a risk factor for cardiovascular disease in renal transplantation. / LDL oxidada: Como um fator de risco para doença cardiovascular no transplante renal.

OBJECTIVES: The mortality rate of chronic kidney disease (CKD) patients that have undergone renal replacement therapy is very high due to cardiovascular diseases (CVD). Some studies have indicated that cyclosporine A, a drug used to prevent transplant rejection, is associated with bone loss following transplantation. Furthermore, it has an oxidative effect on circulating lipids. Its prooxidant effect on cell membranes causes calcium release. This study aimed to examine whether or not renal transplantation result in improvement in oxidative stress and to assess the association between oxidized LDL (ox-LDL) and some variables in the prediction of CVD risk in Renal Transplantation (RT) patients that were compared with the control group. MATERIAL AND METHODS: A total number of 30 CKD patients were recruited to evaluate time dependent changes in biomarker of OS before and after RT. The ox-LDL, lipid metabolism parameters, CsA, creatinine, calcium and phosphate were assessed both before RT, 10 days and 6 months after RT in comparison with the control group (n = 30). RESULTS: Over 6 months, ox-LDL concentration changed from 79.7 ± 9.7 to 72 ± 7 mU/mL (p < 0.009). calcium phosphate level was positively correlated with the concentration of ox-LDL (R = 0.467, p = 0.011) and cyclosporine (R = 0.419, p = 0.024) 6 months after transplantation. CONCLUSION: The findings indicated that restoring renal function by transplantation, improves uremia induced oxidative stress. calcium phosphate product, as an independent risk factor for CVD, correlates with ox-LDL before RT and 6 months after RT. Calcium phosphate product correlates with cyclosporine in the RT group, too.

LDL oxidada: Como um fator de risco para doença cardiovascular no transplante renal / Oxidized LDL: As a risk factor for cardiovascular disease in renal transplantation

RESUMO Objetivos: A taxa de mortalidade de pacientes com doença renal crônica (DRC), que tenham sido submetidos à terapia de substituição renal, é muito elevada devido a doenças cardiovasculares (DCV). Alguns estudos indicaram que a ciclosporina A (CsA), um medicamento utilizado para prevenir a rejeição de transplante, está associada à perda óssea após o transplante. Além disso, ela tem um efeito oxidante sobre os lipídeos circulantes. Seu efeito pró-oxidante nas membranas celulares provoca a liberação de cálcio. Este estudo teve como objetivo analisar se o transplante renal pode ou não resultar em melhora no estresse oxidativo (EO); e avaliar a associação entre a LDL oxidada (LDL-ox) e algumas variáveis na predição do risco de DCV em pacientes transplantados renais (TR), comparados com o grupo controle. Materiais e Métodos: Um total de 30 pacientes com DRC foram recrutados para avaliação das alterações dependentes do tempo no biomarcador de EO antes e após TR. Foram avaliados: LDL-ox, parâmetros do metabolismo dos lipídeos, a CsA, creatinina, cálcio e fosfato tanto antes do TR, 10 dias e 6 meses após o TR, em comparação com o grupo controle (n = 30). Resultados: após 6 meses, a concentração de LDL-ox mudou de 79,7 ± 9,7-72 ± 7 mU/ml (p < 0,009). O nível de fosfato de cálcio foi positivamente correlacionado com a concentração de LDL-ox (R = 0,467, p = 0,011) e ciclosporina (r = 0,419, p = 0,024) 6 meses após o transplante. Conclusão: Os resultados indicaram que a restauração da função renal pelo transplante, melhora o estresse oxidativo induzido pela uremia. O produto de fosfato de cálcio, como um fator de risco independente para DCV, correlaciona-se com o LDL-ox antes do TR e 6 meses após o TR. O produto de fosfato de cálcio também se correlaciona com a ciclosporina no grupo TR.

ABSTRACT Objectives: The mortality rate of chronic kidney disease (CKD) patients that have undergone renal replacement therapy is very high due to cardiovascular diseases (CVD). Some studies have indicated that cyclosporine A, a drug used to prevent transplant rejection, is associated with bone loss following transplantation. Furthermore, it has an oxidative effect on circulating lipids. Its prooxidant effect on cell membranes causes calcium release. This study aimed to examine whether or not renal transplantation result in improvement in oxidative stress and to assess the association between oxidized LDL (ox-LDL) and some variables in the prediction of CVD risk in Renal Transplantation (RT) patients that were compared with the control group. Material and Methods: A total number of 30 CKD patients were recruited to evaluate time dependent changes in biomarker of OS before and after RT. The ox-LDL, lipid metabolism parameters, CsA, creatinine, calcium and phosphate were assessed both before RT, 10 days and 6 months after RT in comparison with the control group (n = 30). Results: Over 6 months, ox-LDL concentration changed from 79.7 ± 9.7 to 72 ± 7 mU/mL (p < 0.009). calcium phosphate level was positively correlated with the concentration of ox-LDL (R = 0.467, p = 0.011) and cyclosporine (R = 0.419, p = 0.024) 6 months after transplantation. Conclusion: The findings indicated that restoring renal function by transplantation, improves uremia induced oxidative stress. calcium phosphate product, as an independent risk factor for CVD, correlates with ox-LDL before RT and 6 months after RT. Calcium phosphate product correlates with cyclosporine in the RT group, too.

Evaluation of Serum Oxidized Low-Density Lipoprotein in Renal Transplant Recipients and Hemodialysis Patients and Relation With Involved Variables.

OBJECTIVES: Disturbances in metabolism of lipo-proteins and oxidative modification of low-density lipoprotein contribute to cardiovascular disease and development of oxidative stress in patients under renal replacement therapy (hemodialysis and renal transplant). This study was designed to compare oxidized low-density lipoprotein levels and lipid profiles in renal transplant recipients and hemo-dialysis patients. MATERIALS AND METHODS: We investigated the concentration of oxidized low-density lipoprotein in hemodialysis (n = 38) and renal transplant (n = 59) patients who had no active inflammatory disease, liver disease, or malignancy, and results were compared to a control group (n = 30). RESULTS: Renal transplant recipients had hypercholesterolemia, hypertriglyceridemia, and increased oxidized low-density lipoprotein levels (P = .019) compared with the control group. Hemodialysis patients had moderate hypertriglyceridemia (not significant), hypercholesterolemia, decrease in high-density lipoprotein, and increase in oxidized low-density lipoprotein levels (P < .0001) compared with the control group. In the renal transplant group, oxidized low-density lipoprotein level had a negative correlation with the duration after transplant (r = -0.407; P = .026), positive association with cyclosporine level (r = 0.288; P = .04), and negative correlation with high-density lipoprotein level (r = -.30; P = .05); oxidized low-density lipo-protein/high-density lipoprotein ratio also had a positive correlation with cyclosporine level (r = 0.309; P = .027) and negative correlation with high-density lipoprotein level (r = -0.72; P < .001) in the renal transplant group and high-density lipoprotein in the hemodialysis group (r = -0.87; P < .001). Multiple stepwise regression analyses showed that oxidized low-density lipoprotein only was associated with cyclosporine level (R2 = 0.155; ß=0.393; P = .024). CONCLUSIONS: History of cardiovascular disease is the most important factor associated with end-stage renal disease, and high oxidized low-density lipoprotein level, oxidized low-density lipo-protein/high-density lipoprotein ratio, and high-density lipoprotein level may affect cardiovascular disease.