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In the present study, we evaluated the differentiation potential of human dental pulp stem cells (hDPSCs) toward Schwann cells, together with their functional capacity with regard to myelination and support of neurite outgrowth in vitro. Successful Schwann cell differentiation was confirmed at the morphological and ultrastructural level by transmission electron microscopy. Furthermore, compared to undifferentiated hDPSCs, immunocytochemistry and ELISA tests revealed increased glial marker expression and neurotrophic factor secretion of differentiated hDPSCs (d-hDPSCs), which promoted survival and neurite outgrowth in 2-dimensional dorsal root ganglia cultures. In addition, neurites were myelinated by d-hDPSCs in a 3-dimensional collagen type I hydrogel neural tissue construct. This engineered construct contained aligned columns of d-hDPSCs that supported and guided neurite outgrowth. Taken together, these findings provide the first evidence that hDPSCs are able to undergo Schwann cell differentiation and support neural outgrowth in vitro, proposing them to be good candidates for cell-based therapies as treatment for peripheral nerve injury.—Martens, W., Sanen, K., Georgiou, M., Struys, T., Bronckaers, A., Ameloot, M., Phillips, J., Lambrichts, I. Human dental pulp stem cells can differentiate into Schwann cells and promote and guide neurite outgrowth in an aligned tissue-engineered collagen construct in vitro.

Stroke is the second most common cause of death and is a major cause of permanent disability. Given the current demographic trend of an ageing population and associated increased risk, the prevalence of and socioeconomic burden caused by stroke will continue to rise. Current therapies are unable to sufficiently ameliorate the disease outcome and are not applicable to all patients. Therefore, strategies such as cell-based therapies with mesenchymal stem cell (MSC) or induced pluripotent stem cell (iPSC) pave the way for new treatment options for stroke. These cells showed great preclinical promise despite the fact that the precise mechanism of action and the optimal administration route are unknown. To gain dynamic insights into the underlying repair processes after stem cell engraftment, noninvasive imaging modalities were developed to provide detailed spatial and functional information on the donor cell fate and host microenvironment. This review will focus on MSCs and iPSCs as types of widely used stem cell sources in current (bio)medical research and compare their efficacy and potential to ameliorate the disease outcome in animal stroke models. In addition, novel noninvasive imaging strategies allowing temporospatial in vivo tracking of transplanted cells and coinciding evaluation of neuronal repair following stroke will be discussed. Esther Wolfs, Jessica Ratajczak, Tim Vangansewinkel, Petra Hilkens, and Annelies Bronckaers are funded by Fonds Wetenschappelijk Onderzoek by grants G0A7514N, G089213N, G029112N, 12D8516N, and 1508015N, respectively. Yorg Dillen is funded by Bijzonder On- ¨ derzoeksfonds by grant BOF15DOC04.

Enkele minder bekende morfologische eigenschappen en detail-structuren van het Proximale Interphalangeale (PIP-) gewricht van de normale vinger worden besproken, die een rol zouden kunnen spelen bij de pathogenese van reumatoïde artritis. Naast het verloop van de capillairen in het gewrichtskapsel, en het gekruiste, laagsgewijze verloop van de vezelbundels in het proprius collateraal ligament (PCL) van het PIP-gewricht, spreken vooral de intra-articulaire plicae synoviales (synovial folds), en de in het PCL aanwezige gelamelleerde proprioceptieve lichaampjes tot de verbeelding. Ideeën worden geopperd omtrent mogelijke microtraumata van deze structuren. Recente literatuurgegevens suggereren namelijk het pathogenetisch belang van zulke microtraumata, die ook aanleiding kunnen zijn tot chronische gewrichtsontstekingen zoals reumatoïde artritis waarvan de (vroege) symptomen immers vaak de hand betreffen, met name de PIP-gewrichten.

Objective: Current available therapies are unable to adequately promote functional recovery in patients suffering from neurological disorders such as stroke, which are a major cause of death and permanent disability. As an alternative treatment, cell-based therapies are now emerging. Human neural stem cells are the most promising candidates to induce neuronal repair, but due to ethical and practical considerations, alternative sources of progenitor cells with neuronal differentiation potential are needed. The aim of the present study was to differentiate stem cells that were isolated from the human dental pulp (hDPSCs) towards functionally active neuronal cells in vitro. Methods: hDPSCs were subjected to a two-step protocol. First, neurosphere-formation was used to acquire neuronal induction. Secondly, neuronal maturation was induced, based on cAMP and NT-3 signaling. The ultrastructural characteristics of intra-neurospheral hDPSCs and their microenvironment were determined by means of transmission electron microscopy (TEM). Neurogenic maturated hDPSCs (d-hDPSCs) were subjected to immunocytochemical, PCR, ultrastructural and electrophysiological analysis. An Enzyme-Linked Immunosorbent Assay (ELISA) was performed for VEGF, NGF, BDNF and GDNF in order to evaluate the secretome of hDPSCs before and after neurogenic differentiation. Results: Based on the ultrastructural analysis it was shown that within the neurospheres, intercellular communication was promoted. Moreover, hDPSCs grew out of the neurospheres in vitro and established a neurogenic differentiated hDPSC culture (d-hDPSCs) which was characterized by the increased expression of the neuronal markers NeuN, MAP-2 and NCAM compared to the nondifferentiated counterpart. Moreover, the secretion of BDNF, VEGF and NGF differed between dhDPSCs and hDPSCSs. Ultrastructurally, d-hDPSCs acquired neuronal features including multiple intercommunicating cytoplasmic extensions and increased vesicular transport. Finally, patch clamp analysis demonstrated the functional activity of d-hDPSCs by the presence of TTX-sensitive voltagegated sodium and TEA-sensitive potassium channels. A subset of d-hDPSCs was able to fire a single action potential. Conclusions: Although promising results were achieved, establishing a completely functional dhDPSC culture remains a challenge. The results in this study demonstrate that hDPSCs are capable of neuronal commitment with distinct features of neuronal cells.

INTRODUCTION: Auto-transplantation of third molars is frequently undertaken in order to restore a perfect occlusion and to improve mastication following a substantial loss of molars. However, little is known about the precise role of the periodontal membrane during this procedure. Therefore, we investigated if the epithelial rests of Malassez persist in the periodontal ligament of auto-transplanted teeth and, if so, whether these may show signs of a neuro-epithelial relationship. CASE PRESENTATION: We report a case of a 21-year-old Caucasian woman who underwent an auto-transplantation of two third molars. After two years, renewed progressive caries of the auto-transplanted teeth led to the removal of the auto-transplanted elements. The periodontal ligament was removed and studied with a light and transmission electron microscope. CONCLUSION: In this report we examined the ultrastructure of the periodontal ligament after auto-transplantation in order to see if the periodontal ligament recovers completely from this intervention. We observed fully developed blood vessels and a re-innervation of the epithelial rests of Malassez which were proliferating following auto-transplantation. This proliferation might be critical in the remodelling of the alveolar socket in order to provide a perfect fit for the transplanted tooth. In order to minimalise the damage to the epithelial rests of Malassez, the extraction of the tooth should be as atraumatic as possible in order to provide an optimal conservation of the periodontal ligament which will be beneficial to the healing-process.

ispartof: The Chinese Journal of Dental Research vol:10 issue:2 pages:7-13 status: published

The use of multimodal contrast agents can potentially overcome the intrinsic limitations of individual imaging methods. We have validated synthetic antiferromagnetic nanoparticles (SAF-NPs) as bimodal contrast agents for in vitro cell labeling and in vivo cell tracking using magnetic resonance imaging (MRI) and computed tomography (CT). SAF-NP-labeled cells showed high contrast in MRI phantom studies (r(2)* = 712 s(-1) mM(-1)), while pelleted cells showed clear contrast enhancement in CT. After intravenous SAF-NP injection, nanoparticles accumulated in the liver and spleen, as visualized in vivo by significant MRI contrast enhancement. Intravenous injection of SAF-NP-labeled cells resulted in cell accumulation in the lungs, which was clearly detectable by using CT but not by using MRI. SAF-NPs proved to be very efficient cell labeling agents for complementary MRI- and CT-based cell tracking. Bimodal monitoring of SAF-NP labeled cells is in particular of interest for applications where the applied imaging methods are not able to visualize the particles and/or cells in all organs. agency for Innovation by Science and Technology IWT 080017 IWT 140061 European Commission European Commission Joint Research Centre H2020_FET-OPEN-766456 H2020-NMP-2015-686009 FP7-NMP-2008-228933

Funding: This research was funded by the Flemish foundation for Innovation, Science and Technology for the IWT SBO ‘Imagine’ (080017) and IWT SBO ‘NanoCoMIT’ (140061), the European Commission under the ‘PANA’ project, Call H2020-NMP-2015-two-stage (grant 686009), and by the University of Leuven for program financing PF IMIR (10/017). Acknowledgments: We are grateful for technical assistance by Jesse Trekker (IMEC, KULeuven) for particle characterization, Marc Jans (Lab of Histology, UHasselt) for ex vivo TEM measurement, Tom Dresselaers (Biomedical MRI, KULeuven) for help with MRI experiments and Joris Deconinck (IMEC) for ICP-OES experiments is highly appreciated. We would also like to thank Visualsonics for their guidance and help with photoacoustic imaging experimentation. This research was funded by the Flemish foundation for Innovation, Science and Technology for the IWT SBO 'Imagine' (080017) and IWT SBO 'NanoCoMIT' (140061), the European Commission under the 'PANA' project, Call H2020-NMP-2015-two-stage (grant 686009), and by the University of Leuven for program financing PF IMIR (10/017). Himmelreich, U (corresponding author), Katholieke Univ Leuven, Fac Med, Dept Imaging & Pathol, Biomed MRI, Herestr 49, B-3000 Leuven, Belgium ; Katholieke Univ Leuven, Mol Small Anim Imaging Ctr MoSAIC, Herestr 49, B-3000 Leuven, Belgium. antoinedhollander@hotmail.com; greetje.vandevelde@kuleuven.be; Hilde.Jans@imec.be; brmvanspauwen@gmail.com; elien.vermeersch@kuleuven.be; jithin.jose@fujifilm.com; tom.struys@sprofit.com; Tim.Stakenborg@imec.be; liesbet.lagae@imec.be; uwe.himmelreich@kuleuven.be