Fibroblasts synthesize and secrete dermal collagen, matrix proteins, growth factors, and cytokines. These characteristics of fibroblasts provide a potential way for fibroblast therapy to treat skin ulcers more effectively than conventional therapies such as cytokine therapy and negative pressure wound therapy. However, the obstacle to the commercialization of fibroblast therapy is the limited supply of cells with consistent quality. In this study, we tested whether human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) could be differentiated into fibroblasts considering that they have characteristics of high differentiation rates, unlimited proliferation possibility from a single colony, and homogeneity. As a result, hESC-MSC-derived fibroblasts (hESC-MSC-Fbs) showed a significant increase in the expression of type I and III collagen, fibronectin, and fibroblast-specific protein-1 (FSP-1). Besides, vessel formation and wound healing were enhanced in hESC-MSC-Fb-treated skin tissues compared to PBS- or hESC-MSC-treated skin tissues, along with decreased IL-6 expression at 4 days after the formation of pressure ulcer wound in a mouse model. In view of the limited available cell sources for fibroblast therapy, hESC-MSC-Fbs show a promising potential as a commercial cell therapy source to treat skin ulcers.
Sepsis is a potentially life-threatening condition that occurs when the body’s response to infection leads to widespread inflammation and tissue damage. Negative cultures can make it difficult for clinicians to make a diagnosis and may raise questions about the validity of the definition of sepsis. In addition, the clinical distinctions between burn patients with blood culture-positive and -negative sepsis are also poorly understood. Therefore, this study aimed to examine the clinical differences between blood culture-positive and -negative sepsis in burn patients in order to improve the understanding of the pathophysiology and epidemiology of sepsis in this population. This study had a retrospective design, and the participants were adults aged ≥18 years. Patients diagnosed with sepsis were divided into two groups based on their blood culture results within 1 week of sepsis diagnosis. We enrolled 1643 patients admitted to our institution’s burn intensive care unit between January 2010 and December 2021. pH, platelet count, bicarbonate and haematocrit were significant in both the positive and negative groups. However, lymphocyte, red cell distribution width and blood urea nitrogen were significant only in the positive group, whereas lactate dehydrogenase was significant only in the negative group. Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumonia are common gram-negative bacterial species, and Staphylococcus aureus and Staphylococcus epidermidis are common gram-positive bacterial species seen in burn patients with positive blood cultures. Carbapenem resistance was found to be associated with an unfavourable prognosis in gram-negative bacteria, with the exception of P. aeruginosa. pH, platelet count, bicarbonate and haematocrit were routine biomarkers that demonstrated statistical significance in both groups. Lactate dehydrogenase was significant in the blood-negative group, while red cell distribution width, blood urea nitrogen and lymphocyte count were significant in the positive group. Furthermore, the most common causes of sepsis are gram-negative bacteria, including A. baumannii, K. pneumoniae and P. aeruginosa. Additionally, resistance to carbapenems is associated with unfavourable outcomes.
25 August 2023 in European Journal of Medical Research
Background: Sepsis is a grave medical disorder characterized by a systemic inflammatory response to infection. Furthermore, it is a leading cause of morbidity and mortality, especially in hospitalized patients. Acute kidney injury (AKI) is a common complication of sepsis and is associated with increased morbidity and mortality. Patients with burns are particularly vulnerable to developing sepsis and AKI due to the extensive tissue damage and immune suppression resulting from burn injury. In this study, unsupervised clustering algorithms were used to track longitudinal biomarkers in patients with burns and assess their impact on mortality. Methods: This retrospective study included adult patients with burns aged ≥ 18 years, who were admitted to the burn intensive care unit of Hallym University and Hangang Sacred Heart Hospital between July 2010 and December 2021. The patients were divided into two subgroups: those with sepsis (538 patients) and those without sepsis (826 patients). The longitudinal biomarkers were grouped into three clusters using the k-means clustering algorithm. Each cluster was assigned a letter from A to C according to its mortality rate. Results: The odds ratio (OR) of pH was 9.992 in the positive group and 31.745 in the negative group in cluster C. The OR for lactate dehydrogenase (LD) was 3.704 in the positive group and 6.631 in the negative group in cluster C. The OR for creatinine was 2.784 in the positive group and 8.796 in the negative group in cluster C. The OR for blood urea nitrogen (BUN) in the negative group was 0.348, indicating a negative predictor of mortality. Regarding the application of Continuous Renal Replacement Therapy (CRRT) and ventilation, ventilation was significant in both groups. In contrast, CRRT application was not significant in the sepsis-positive group. Furthermore, it was not selected as a variable in the negative group. Conclusions: The pH, LD, and creatinine were significant in both groups, while lactate and platelets were significant in the sepsis-positive group. In addition, albumin, glucose, and BUN were significant in the sepsis-negative group. Continuous renal replacement therapy was not significant in either group. However, the use of a ventilator was associated with poor prognosis.
Objective: Studies on development of an anal incontinence (AI) model targeting smooth muscle cells (SMCs) of the internal anal sphincter (IAS) have not been reported. The differentiation of implanted human adipose-derived stem cells (hADScs) into SMCs in an IAS-targeting AI model has also not been demonstrated. We aimed to develop an IAS-targeting AI animal model and to determine the differentiation of hADScs into SMCs in an established model. Materials and Methods: The IAS-targeting AI model was developed by inducing cryoinjury at the inner side of the muscular layer via posterior intersphincteric dissection in Sprague–Dawley rats. Dil-stained hADScs were implanted at the IAS injury site. Multiple markers for SMCs were used to confirm molecular changes before and after cell implantation. Analyses were performed using H&E, immunofluorescence, Masson’s trichrome staining, and quantitative RT–PCR. Results: Impaired smooth muscle layers accompanying other intact layers were identified in the cryoinjury group. Specific SMC markers, including SM22α, calponin, caldesmon, SMMHC, smoothelin, and SDF-1 were significantly decreased in the cryoinjured group compared with levels in the control group. However, CoL1A1 was increased significantly in the cryoinjured group. In the hADSc-treated group, higher levels of SMMHC, smoothelin, SM22α, and α-SMA were observed at two weeks after implantation than at one week after implantation. Cell tracking revealed that Dil-stained cells were located at the site of augmented SMCs. Conclusions: This study first demonstrated that implanted hADSc restored impaired SMCs at the injury site, showing stem cell fate corresponding to the established IAS-specific AI model.