Passage-dependent relationship between mesenchymal stem cell mobilization and chondrogenic potential. Tan A R,Alegre-Aguarón E,O'Connell G D,VandenBerg C D,Aaron R K,Vunjak-Novakovic G,Chloe Bulinski J,Ateshian G A,Hung C T Osteoarthritis and cartilage OBJECTIVE:Galvanotaxis, the migratory response of cells in response to electrical stimulation, has been implicated in development and wound healing. The use of mesenchymal stem cells (MSCs) from the synovium (synovium-derived stem cells, SDSCs) has been investigated for repair strategies. Expansion of SDSCs is necessary to achieve clinically relevant cell numbers; however, the effects of culture passage on their subsequent cartilaginous extracellular matrix production are not well understood. METHODS:Over four passages of SDSCs, we measured the expression of cell surface markers (CD31, CD34, CD49c, CD73) and assessed their migratory potential in response to applied direct current (DC) electric field. Cells from each passage were also used to form micropellets to assess the degree of cartilage-like tissue formation. RESULTS:Expression of CD31, CD34, and CD49c remained constant throughout cell expansion; CD73 showed a transient increase through the first two passages. Correspondingly, we observed that early passage SDSCs exhibit anodal migration when subjected to applied DC electric field strength of 6 V/cm. By passage 3, CD73 expression significantly decreased; these cells exhibited cell migration toward the cathode, as previously observed for terminally differentiated chondrocytes. Only late passage cells (P4) were capable of developing cartilage-like tissue in micropellet culture. CONCLUSIONS:Our results show cell priming protocols carried out for four passages selectively differentiate stem cells to behave like chondrocytes, both in their motility response to applied electric field and their production of cartilaginous tissue. 10.1016/j.joca.2014.10.001

Percutaneous direct current stimulation - a new electroceutical solution for severe neurological pain and soft tissue injuries. Molsberger Albrecht,McCaig Colin D Medical devices (Auckland, N.Z.) There is a high medical need to improve the effectiveness of the treatment of pain and traumatic soft tissue injuries. In this context, electrostimulating devices have been used with only sporadic success. There is also much evidence of endogenous electrical signals that play key roles in regulating the development and regeneration of many tissues. Transepithelial potential gradients are one source of the direct current (DC) electrical signals that stimulate and guide the migration of inflammatory cells, epithelial cells, fibroblasts and mesenchymal stem cells to achieve effective wound healing. Up to now, this electrophysiological knowledge has not been adequately translated into a clinical treatment. Here, we present a mobile, handheld electroceutical smart device based on a microcontroller, an analog front end and a battery, which generates DC electric fields (EFs), mimicking and modulating the patient's own physiological electrical signals. The electrical stimulation is applied to percutaneous metal probes, which are located close to the inflamed or injured tissue of the patient. The treatment can be used in an ambulatory or stationary environment. It shows unexpectedly, highly effective treatment for certain severe neurological pain conditions, as well as traumatic soft tissue injuries (muscle/ligament ruptures, joint sprains). Without EF intervention, these conditions, respectively, are either virtually incurable or take several months to heal. We present three cases - severe chronic cluster headache, acute massive muscle rupture of the rectus femoris and an acute ankle sprain with a ruptured anterior talofibular ligament - to demonstrate clinical effectiveness and discuss the fundamental differences between mimicking DC simulation and conventional transcutaneous electric nerve stimulation (TENS) or TENS-like implanted devices as used for peripheral nerve cord, spinal cord or dorsal root stimulation. 10.2147/MDER.S163368

Direct coupled electrical stimulation towards improved osteogenic differentiation of human mesenchymal stem/stromal cells: a comparative study of different protocols. Scientific reports Electrical stimulation (ES) has been described as a promising tool for bone tissue engineering, being known to promote vital cellular processes such as cell proliferation, migration, and differentiation. Despite the high variability of applied protocol parameters, direct coupled electric fields have been successfully applied to promote osteogenic and osteoinductive processes in vitro and in vivo. Our work aims to study the viability, proliferation, and osteogenic differentiation of human bone marrow-derived mesenchymal stem/stromal cells when subjected to five different ES protocols. The protocols were specifically selected to understand the biological effects of different parts of the generated waveform for typical direct-coupled stimuli. In vitro culture studies evidenced variations in cell responses with different electric field magnitudes (numerically predicted) and exposure protocols, mainly regarding tissue mineralization (calcium contents) and osteogenic marker gene expression while maintaining high cell viability and regular morphology. Overall, our results highlight the importance of numerical guided experiments to optimize ES parameters towards improved in vitro osteogenesis protocols. 10.1038/s41598-024-55234-y

In vitro effects of direct current electric fields on adipose-derived stromal cells. Hammerick Kyle E,Longaker Michael T,Prinz Fritz B Biochemical and biophysical research communications Endogenous electric fields play an important role in embryogenesis, regeneration, and wound repair and previous studies have shown that many populations of cells, leukocytes, fibroblasts, epithelial cells, and endothelial cells, exhibit directed migration in response to electric fields. As regenerative therapies continue to explore ways to control mesenchymal progenitor cells to recreate desirable tissues, it is increasingly necessary to characterize the vast nature of biological responses imposed by physical phenomena. Murine adipose-derived stromal cells (mASCs) migrated toward the cathode in direct current (DC) fields of physiologic strength and show a dose dependence of migration rate to stronger fields. Electric fields also caused mASCs to orient perpendicularly to the field vector and elicited a transient increase in cytosolic calcium. Additionally, their galvanotactic response appears to share classic chemotactic signaling pathways that are involved in the migration of other cell types. Galvanotaxis is one predominant result of electric fields on mASCs and it may be exploited to engineer adult stem cell concentrations and locations within implanted grafts or toward sites of wound repair. 10.1016/j.bbrc.2010.05.003

Alignment and elongation of human adipose-derived stem cells in response to direct-current electrical stimulation. Tandon Nina,Goh Brian,Marsano Anna,Chao Pen-Hsiu Grace,Montouri-Sorrentino Chrystina,Gimble Jeffrey,Vunjak-Novakovic Gordana Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference In vivo, direct current electric fields are present during embryonic development and wound healing. In vitro, direct current (DC) electric fields induce directional cell migration and elongation. For the first time, we demonstrate that cultured human adipose tissue-derived stem cells (hASCs) respond to the presence of direct-current electric fields. Cells were stimulated for 2-4 hours with DC electric fields of 6 V/cm that were similar to those encountered in vivo post-injury. Upon stimulation, hASCs were observed to elongate and align perpendicularly to the applied electric field, disassemble gap junctions, and upregulate the expression of genes for connexin-43, thrombomodulin, vascular endothelial growth factor, and fibroblast growth factor. In separate related studies, human epicardial fat-derived stem cells (heASCs) were also observed to align and elongate. It is interesting that the morphological and phenotypic characteristics of mesenchymal stem cells derived both from liposuction aspirates and from cardiac fat can be modulated by direct current electric fields. In further studies, we will quantify the effects of the electrical fields in the context of wound healing. 10.1109/IEMBS.2009.5333142