Preclinical tumor mouse models for studying esophageal cancer.

Preclinical models are extensively employed in cancer research because they can be manipulated in terms of their environment, genome, molecular biology, organ systems, and physical activity to mimic human behavior and conditions. The progress made in in vivo cancer research has resulted in significant advancements, enabling the creation of spontaneous, metastatic, and humanized mouse models. Most recently, the remarkable and extensive developments in genetic engineering, particularly the utilization of CRISPR/Cas9, transposable elements, epigenome modifications, and liquid biopsies, have further facilitated the design and development of numerous mouse models for studying cancer. In this review, we have elucidated the production and usage of current mouse models, such as xenografts, chemical-induced models, and genetically engineered mouse models (GEMMs), for studying esophageal cancer. Additionally, we have briefly discussed various gene-editing tools that could potentially be employed in the future to create mouse models specifically for esophageal cancer research.

Adipose-derived human mesenchymal stem cells seeded on denuded or stromal sides of the amniotic membrane improve angiogenesis and collagen remodeling and accelerate healing of the full-thickness wound.

Several strategies have been proposed to enhance wound healing results. Along with other forms of wound dressing, the human amniotic membrane (HAM) has long been regarded as a biological wound dressing that decreases infection and enhances healing. This study investigates the feasibility and effectiveness of wound healing using decellularized HAM (dAM) and stromal HAM (sAM) in combination with adipose-derived human mesenchymal stem cells (AdMSCs). The dAM and sAM sides of HAM were employed as wound dressing scaffolds, and AdMSCs were seeded on top of either dAM or sAM. Sixty healthy Wistar rats were randomly divided into three groups: untreated wound, dAM/AdMSCs group, and sAM/AdMSCs group. The gene expression of VEGF and COL-I was measured in vitro. Wound healing was examined after wounding on days 3, 7, 14, and 21. The expression level of VEGF was significantly higher in sAM/AdMSCs than dAM/AdMSCs (P ≤ 0.05), but there was no significant difference in COL-I expression (P ≥ 0.05). In vivo research revealed that on day 14, wounds treated with sAM/AdMSCs had more vascularization than wounds treated with dAM/AdMSCs (P ≤ 0.01) and untreated wound groups on days 7 (P ≤ 0.05) and 14 (P ≤ 0.0001), respectively. On days 14 (P < 0.05 for sAM/AdMSCs, P < 0.01 for dAM/AdMSCs), and 21 (P < 0.05 for sAM/AdMSCs, P < 0.01 for dAM/AdMSCs), the collagen deposition in the wound bed was significantly thicker in the sAM/AdMSCs and dAM/AdMSCs groups compared to untreated wounds. The study demonstrated that the combination of sAM and AdMSCs promotes wound healing by enhancing angiogenesis and collagen remodeling.

Scaphoid Bone Nonunions: Clinical and Functional Outcomes of Collagen/PGA Scaffolds and Cell-Based Therapy.

In this study, the procedure for treating the nonunion complication of scaphoid fractures using collagen/poly glycolic acid (CPGA) scaffolds with bone marrow mesenchymal stem cell (BM-MSC) therapy was adopted and compared with the commonly employed autologous bone tissue graft. With conducting a two-armed clinical trial, 10 patients with scaphoid nonunions were enrolled in this investigation. Patients were randomly assigned to two groups treated with (1) CPGA + cell therapy and (2) autologous iliac crest bone graft standard therapy. Treatment outcomes were evaluated three months after surgery, measuring the grip and pinch strengths and wrist range of motion, with two questionnaires: Patient-Rated Wrist Evaluation (PRWE) and Quick form of Disabilities of the Arm, Shoulder, and Hand (QDASH). We have also assessed the union rate using clinical and radiologic healing criteria one and three months post-operatively. Restorative effects of CPGA + cell therapy were similar to those of the autologous bone graft standard therapy, except for the grip strength (P = 0.048) and QDASH score (P = 0.044) changes, which were higher in the CPGA + cell therapy group. Three months following the surgery, radiographic images and computed tomography (CT) scans also demonstrated that the scaphoid union rate in the test group was comparable to that of scaphoids treated with the standard autograft method. Our findings demonstrate that the CPGA + cell therapy is a potential alternative for bone grafting in the treatment of bone nonunions.

Comparing the Effects of Two Cryoprotectant Protocols, Dimethyl-Sulfoxide (DMSO) and Glycerol, on the Recovery Rate of Cultured Keratinocytes on Amniotic Membrane.

Background: Off-the-shelf supply of viable engineered tissue is critical for effective and fast treatment of life-threatening injuries such as deep burns. An expanded keratinocyte sheet on the human amniotic membrane (KC sheet-HAM) is a beneficial tissue-engineering product for wound healing. To access an on-hand supply for the widespread application and overcome the time-consuming process, it is necessary to develop a cryopreservation protocol that guarantees the higher recovery of viable keratinocyte sheets after freeze-thawing. This research aimed to compare the recovery rate of KC sheet-HAM after cryopreservation by dimethyl-sulfoxide (DMSO) and glycerol. Methods: Amniotic membrane was decellularized with trypsin, and keratinocytes were cultured on it to form a multilayer, flexible, easy-to-handle KC sheet-HAM. The effects of 2 different cryoprotectants were investigated by histological analysis, live-dead staining, and proliferative capacity assessments before and after cryopreservation. Results: KCs well adhered and proliferated on the decellularized amniotic membrane and successfully represented 3 to 4 stratified layers of epithelialization after 2 to 3 weeks culture period; making it easy to cut, transfer, and cryopreserve. However, viability and proliferation assay indicated that both DMSO and glycerol cryosolutions have detrimental effects on KCs, and KCs-sheet HAM could not recover to the control level after 8 days of culture post-cryo. The KC sheet lost its stratified multilayer nature on AM, and sheet layers were reduced in both cryo-groups compared to the control. Conclusion: Expanding keratinocytes on the decellularized amniotic membrane as a multilayer sheet made a viable easy-to-handle sheet, nonetheless cryopreservation reduced viability and affected histological structure after thawing. Although some viable cells were detectable, our research highlighted the need for a better cryoprotectant protocol other than DMSO and glycerol, specific for the successful banking of viable tissue constructs.