methylcellulose and Ischemia

Stem cells therapy is an effective treatment for critical limb ischemia diseases (CLI), but is limited to low cells retention and poor target release in severe ischemia tissues. Due to the notable feature of CLI, namely, the temperature of ischemia tissues decreases with the severity of the lesions, a thermoresponsive and reversible hydrogel based on methylcellulose-salt system encapsulating stem cells is facilely prepared and successfully achieved the goal of releasing stem cells in lower temperature areas. The investigations show that the thermogel presents notable biocompatibility, thermoresponsiveness, and cytoprotection. Furthermore, the combined transplantation of hydrogel and stem cells system effectively inhibits the fibrosis and muscular atrophy of lower limb ischemia, accelerates the recovery of lower limb blood flow, and promotes angiogenesis, indicating that the reversible thermogel can promote vascular repair by controlling the release of loaded stem cells in the treatment of CLI.

Topics: Animals; Atrophy; Biopolymers; Extremities; Female; Fibrosis; HEK293 Cells; Humans; Hydrogels; Ischemia; Male; Methylcellulose; Mice; Mice, Inbred C57BL; Mice, Nude; Neovascularization, Pathologic; Neovascularization, Physiologic; Perfusion; Pregnancy; Pregnancy, Animal; Rheology; Stem Cell Transplantation; Stem Cells; Stress, Mechanical; Temperature

The proximity of cells in three-dimensional (3D) organization maximizes the cell-cell communication and signaling that are critical for cell function. In this study, 3D cell aggregates composed of human umbilical vein endothelial cells (HUVECs) and cord-blood mesenchymal stem cells (cbMSCs) were used for therapeutic neovascularization to rescue tissues from critical limb ischemia. Within the cell aggregates, homogeneously mixed HUVECs and cbMSCs had direct cell-cell contact with expressions of endogenous extracellular matrices and adhesion molecules. Although dissociated HUVECs/cbMSCs initially formed tubular structures on Matrigel, the grown tubular network substantially regressed over time. Conversely, 3D HUVEC/cbMSC aggregates seeded on Matrigel exhibited an extensive tubular network that continued to expand without regression. Immunostaining experiments show that, by differentiating into smooth muscle cell (SMC) lineages, the cbMSCs stabilize the HUVEC-derived tubular network. The real-time PCR analysis results suggest that, through myocardin, TGF-β signaling regulates the differentiation of cbMSCs into SMCs. Transplantation of 3D HUVEC/cbMSC aggregates recovered blood perfusion in a mouse model of hindlimb ischemia more effectively compared to their dissociated counterparts. The experimental results confirm that the transplanted 3D HUVEC/cbMSC aggregates enhanced functional vessel formation within the ischemic limb and protected it from degeneration. The 3D HUVEC/cbMSC aggregates can therefore facilitate the cell-based therapeutic strategies for modulating postnatal neovascularization.

Topics: Animals; Cell Aggregation; Collagen; Disease Models, Animal; Drug Combinations; Fetal Blood; Fluorescent Antibody Technique; Gene Expression Regulation; Hindlimb; Human Umbilical Vein Endothelial Cells; Humans; Ischemia; Laminin; Limb Salvage; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Methylcellulose; Mice; Mice, Inbred BALB C; Neovascularization, Physiologic; Perfusion; Proteoglycans

Topics: Anesthetics, Local; Animals; Blood Flow Velocity; Capillary Fragility; Capillary Permeability; Cells; Cheek; Contrast Media; Cricetinae; Dextrans; Gels; Hemolysis; Humans; Ischemia; Lidocaine; Male; Mepivacaine; Methods; Methylcellulose; Microcirculation; Radiography; Regional Blood Flow; Solutions; Staining and Labeling; Time Factors; Urethra

Topics: Animals; Blood Pressure Determination; Desoxycorticosterone; Eosinophils; Female; Hypertension, Renal; Ischemia; Juxtaglomerular Apparatus; Kidney Glomerulus; Methylcellulose; Microscopy, Electron; Rats; Renal Artery Obstruction