The effect of an external magnetic force on cell adhesion and proliferation of magnetically labeled mesenchymal stem cells

<p>Abstract</p> <p>Background</p> <p>As the strategy for tissue regeneration using mesenchymal stem cells (MSCs) for transplantation, it is necessary that MSCs be accumulated and kept in the target area. To accumulate MSCs effectively, we developed a novel technique for a magnetic targeting system with magnetically labeled MSCs and an external magnetic force. In this study, we examined the effect of an external magnetic force on magnetically labeled MSCs in terms of cell adhesion and proliferation.</p> <p>Methods</p> <p>Magnetically labeled MSCs were plated at the bottom of an insert under the influence of an external magnetic force for 1 hour. Then the inserts were turned upside down for between 1 and 24 hours, and the number of MSCs which had fallen from the membrane was counted. The gene expression of MSCs affected magnetic force was analyzed with microarray. In the control group, the same procedure was done without the external magnetic force.</p> <p>Results</p> <p>At 1 hour after the inserts were turned upside down, the average number of fallen MSCs in the magnetic group was significantly smaller than that in the control group, indicating enhanced cell adhesion. At 24 hours, the average number of fallen MSCs in the magnetic group was also significantly smaller than that in control group. In the magnetic group, integrin alpha2, alpha6, beta3 BP, intercellular adhesion molecule-2 (ICAM-2), platelet/endothelial cell adhesion molecule-1 (PECAM-1) were upregulated. At 1, 2 and 3 weeks after incubation, there was no statistical significant difference in the numbers of MSCs in the magnetic group and control group.</p> <p>Conclusions</p> <p>The results indicate that an external magnetic force for 1 hour enhances cell adhesion of MSCs. Moreover, there is no difference in cell proliferation after using an external magnetic force on magnetically labeled MSCs.</p

Tissue engineering of functional articular cartilage: the current status

Osteoarthritis is a degenerative joint disease characterized by pain and disability. It involves all ages and 70% of people aged >65 have some degree of osteoarthritis. Natural cartilage repair is limited because chondrocyte density and metabolism are low and cartilage has no blood supply. The results of joint-preserving treatment protocols such as debridement, mosaicplasty, perichondrium transplantation and autologous chondrocyte implantation vary largely and the average long-term result is unsatisfactory. One reason for limited clinical success is that most treatments require new cartilage to be formed at the site of a defect. However, the mechanical conditions at such sites are unfavorable for repair of the original damaged cartilage. Therefore, it is unlikely that healthy cartilage would form at these locations. The most promising method to circumvent this problem is to engineer mechanically stable cartilage ex vivo and to implant that into the damaged tissue area. This review outlines the issues related to the composition and functionality of tissue-engineered cartilage. In particular, the focus will be on the parameters cell source, signaling molecules, scaffolds and mechanical stimulation. In addition, the current status of tissue engineering of cartilage will be discussed, with the focus on extracellular matrix content, structure and its functionality

Traditional transcutaneous approaches in head and neck surgery

The treatment of laryngeal and hypopharyngeal malignancies remains a challenging task for the head and neck surgeon as the chosen treatment modality often has to bridge the gap between oncologically sound radicality and preservation of function. Due to the increase in transoral laser surgery in early tumor stages and chemoradiation in advanced stages, the usage of traditional transcutaneous approaches has decreased over the recent past. In addition, the need for a function-sparing surgical approach as well as highest possible quality of life has become evident. In view of these facts, rationale and importance of traditional transcutaneous approaches to the treatment of laryngeal and hypopharyngeal malignancies are discussed in a contemporary background. The transcutaneous open partial laryngectomies remain a valuable tool in the surgeon's armamentarium for the treatment of early and advanced laryngeal carcinomas, especially in cases of impossible laryngeal overview using the rigid laryngoscope. Open partial laryngetomies offer superior overview and oncologic safety at the anterior commissure, especially in recurrencies. In select advanced cases and salvage settings, the supracricoid laryngectomy offers a valuable tool for function-preserving but oncologically safe surgical therapy at the cost of high postoperative morbidity and a very demanding rehabilitation of swallowing.In hypopharyngeal malignancies, the increasing use of transoral laser surgery has led to a decline in transcutaneous resections via partial pharyngectomy with partial laryngectomy in early tumor stages. In advanced stages of tumors of the piriform sinus and the postcricoid area with involvement of the larynx, total laryngectomy with partial pharyngectomy is an oncologically safe approach. The radical surgical approach using circumferent laryngopharyngectomy with/without esophagectomy is indicated in salvage cases with advanced recurrences or as a primary surgical approach in patients where chemoradiation does not offer sufficient oncologic control or preservation of function. In cases with impending reconstruction, fasciocutaneous free flaps (anterolateral thigh flap, radial forearm flap) seem to offer superior results to enteric flaps in cases where the cervical esophagus is not involved leading to better voice rehabilitation with fewer complications and postoperative morbidity. In salvage situations, the Gastroomental Free Flap has proven to be a valuable tool.In conclusion, the choice of a surgical treatment modality is influenced by the patient's anatomy, tumor size and location as well as the surgeon's personal expertise

Tailored integrin-extracellular matrix interactions to direct human mesenchymal stem cell differentiation

Integrins provide the primary link between mesenchymal stem cells (MSCs) and their surrounding extracellular matrix (ECM), with different integrin pairs having specificity for different ECM molecules or peptide sequences contained within them. It is widely acknowledged that the type of ECM present can influence MSC differentiation; however, it is yet to be determined how specific integrin–ECM interactions may alter this or how they change during differentiation. We determined that human bone marrow–derived mesenchymal stem cells (hMSCs) express a broad range of integrins in their undifferentiated state and show a dramatic, but transient, increase in the level of α5 integrin on day 7 of osteogenesis and an increase in α6 integrin expression throughout adipogenesis. We used a nonfouling polystyrene-block-poly(ethylene oxide)-copolymer (PS-PEO) surface to present short peptides with defined integrin-binding capabilities (RGD, IKVAV, YIGSR, and RETTAWA) to hMSCs and investigate the effects of such specific integrin–ECM contacts on differentiation. hMSCs cultured on these peptides displayed different morphologies and had varying abilities to differentiate along the osteogenic and adipogenic lineages. The peptide sequences most conducive to differentiation (IKVAV for osteogenesis and RETTAWA and IKVAV for adipogenesis) were not necessarily those that were bound by those integrin subunits seen to increase during differentiation. Additionally, we also determined that presentation of RGD, which is bound by multiple integrins, was required to support long-term viability of hMSCs. Overall we confirm that integrin–ECM contacts change throughout hMSC differentiation and show that surfaces presenting defined peptide sequences can be used to target specific integrins and ultimately influence hMSC differentiation. This platform also provides information for the development of biomaterials capable of directing hMSC differentiation for use in tissue engineering therapies