Human iPSC-Derived Vascular Smooth Muscle Cells in a Fibronectin Functionalized Collagen Hydrogel Augment Endothelial Cell Morphogenesis

Tissue-engineered constructs have immense potential as autologous grafts for wound healing. Despite the rapid advancement in fabrication technology, the major limitation is controlling angiogenesis within these constructs to form a vascular network. Here, we aimed to develop a 3D hydrogel that can regulate angiogenesis. We tested the effect of fibronectin and vascular smooth muscle cells derived from human induced pluripotent stem cells (hiPSC-VSMC) on the morphogenesis of endothelial cells. The results demonstrate that fibronectin increases the number of EC networks. However, hiPSC-VSMC in the hydrogel further substantiated the number and size of EC networks by vascular endothelial growth factor and basic fibroblast growth factor secretion. A mechanistic study shows that blocking αvβ3 integrin signaling between hiPSC-VSMC and fibronectin impacts the EC network formation via reduced cell viability and proangiogenic growth factor secretion. Collectively, this study set forth initial design criteria in developing an improved pre-vascularized construct.

Morus alba Root Extract Induces the Anagen Phase in the Human Hair Follicle Dermal Papilla Cells

Restoring hair follicles by inducing the anagen phase is a promising approach to prevent hair loss. Hair follicle dermal papilla cells (HFDPCs) play a major role in hair growth via the telogen-to-anagen transition. The therapeutic effect of Morus alba activates β-catenin in HFDPCs, thereby inducing the anagen phase. The HFDPCs were treated with M. alba root extract (MARE) to promote hair growth. It contains chlorogenic acid and umbelliferone and is not cytotoxic to HFDPCs at a concentration of 20%. It was demonstrated that a small amount of MARE enhances growth factor secretion (related to the telogen-to-anagen transition). Activation of β-catenin was observed in MARE-treated HFDPCs, which is crucial for inducing the anagen phase. The effect of conditioned medium derived from MARE-treated HFDPCs on keratinocytes and endothelial cells was also investigated. The findings of this study demonstrate the potency of MARE in eliciting the telogen-to-anagen transition.

Cultivation of 3D Dermal Tissue by Application of Autologous Matrix

The most common reasons for major skin loss are thermal trauma — burns and scalds that can result in rapid, extensive, deep wounds as well as chronic non-healing wounds. Treatment using common techniques is poor and depending on the trauma level can result in death. There is a substantial need for skin integrity restoration. The main goal of this study was to develop an autologous 3D skin model that could eventually be translated into clinical applications. The study examined a variety of factors — extracellular matrix components, cell count, culture medium modification and role of structurally and functionally high-quality 3D skin dermis layer tissue culture production. The results of this study are an essential prerequisite to standardise the use of both clinical, as well as in vitro test systems. Dermal cell lines applied in the study were isolated form patient biopsies obtained at Pauls Stradiņš Clinical University Hospital. Blood plasma type AB was used for fibrin matrix formation. As catalysts, CaCl2 or calcium gluconate, and tranexamic acid were applied. 3D tissue functionality was assessed by evaluation of gene expression and changes in growth factor secretion. Fibrin matrix formulations with 1% and 1.5% CaCl2 and 5 mg, 7 mg and 10 mg tranexamic acid concentration were tested. Better matrix properties were observed with higher concentration of CaCl2 and tranexamic acid. Differences in levels of collagen gene expression and growth factor secretion were observed. Changes in levels of fibroblast growth factor and gene expression were observed in fibrin matrix samples and the surface-cultivated cell culture monolayer, but structural protein synthesis was not detected.

The influence of an electromagnetic field on adipose-derived stem/stromal cells’ growth factor secretion: Modulation of FGF-2 production by in vitro exposure

Adipose-derived stem/stromal cells (ASCs) have tremendous potential for use in regenerative medicine; their secretome is especially important for regenerative processes. We hypothesized that exposure of ASCs to an electromagnetic field (EMF) can influence the proregenerative potential of cells by influencing the secretion of growth factors (GFs) responsible for regenerative properties. We showed that the exposure of ASCs to an EMF (50 Hz; 1.5mT) affected the secretion of GFs as well as the cell cycle process. The most important observation was a statistically significant, 3-fold increase in FGF-2 concentration at 48 h, and a 2-fold decrease at 72 h when compared to the control group. This finding is very important for regenerative medicine, because with precisely adjusted parameters, an EMF can be used to stimulate the production of GFs, mainly of FGF-2, by ASCs, thereby increasing proregenerative properties. The ASC secretome after EMF treatment could be a method for easy, simple and cost-effective stem cell differentiation and therapy facilitation.

Advances in electrical and magnetic stimulation on nerve regeneration

Central and peripheral nerve injuries pose a great threat to people. Complications such as inflammation, muscle atrophy, traumatic neuromas and delayed reinnervation can bring huge challenges to clinical practices and barriers to complete nerve regrowth. Physical interventions such as electrical and magnetic stimulation show satisfactory results with varying parameters for acute and chronic nerve damages. The biological basis of electrical and magnetic stimulation mainly relies on protein synthesis, ion channel regulation and growth factor secretion. This review focuses on the various paradigms used in different models of electrical and magnetic stimulation and their regenerative potentials and underlying mechanisms in nerve injuries. The combination of physical stimulation and conductive biomaterial scaffolds displays an infinite potentiality in translational application in nerve regeneration.