Petra Wilder-Smith

Human Gingiva-Derived Mesenchymal Stem Cells Elicit Polarization of M2 Macrophages and Enhance Cutaneous Wound Healing

Increasing evidence has supported the important role of mesenchymal stem cells (MSCs) in wound healing, however, the underlying mechanism remains unclear. Recently, we have isolated a unique population of MSCs from human gingiva (GMSCs) with similar stem cell‐like properties, immunosuppressive, and anti‐inflammatory functions as human bone marrow‐derived MSCs (BMSCs). We describe here the interplay between GMSCs and macrophages and the potential relevance in skin wound healing. When cocultured with GMSCs, macrophages acquired an anti‐inflammatory M2 phenotype characterized by an increased expression of mannose receptor (MR; CD206) and secretory cytokines interleukin (IL)‐10 and IL‐6, a suppressed production of tumor necrosis factor (TNF)‐α, and decreased ability to induce Th‐17 cell expansion. In vivo, we demonstrated that systemically infused GMSCs could home to the wound site in a tight spatial interaction with host macrophages, promoted them toward M2 polarization, and significantly enhanced wound repair. Mechanistically, GMSC treatment mitigated local inflammation mediated by a suppressed infiltration of inflammatory cells and production of IL‐6 and TNF‐α, and an increased expression of IL‐10. The GMSC‐induced suppression of TNF‐α secretion by macrophages appears to correlate with impaired activation of NFκB p50. These findings provide first evidence that GMSCs are capable to elicit M2 polarization of macrophages, which might contribute to a marked acceleration of wound healing. STEM CELLS 2010;28:1856–1868

Enhanced detection of early-stage oral cancer in vivo by optical coherence tomography using multimodal delivery of gold nanoparticles

Contrast in optical coherence tomography (OCT) images can be enhanced by utilizing surface plasmon resonant gold nanoparticles. To improve the poor in vivo transport of gold nanoparticles through biological barriers, an efficient delivery strategy is needed. In this study, the improved penetration and distribution of gold nanoparticles were achieved by microneedle and ultrasound, respectively, and it was demonstrated that this multimodal delivery of antibody-conjugated PEGylated gold nanoparticles enhanced the contrast in in vivo OCT images of oral dysplasia in a hamster model.

Effects on oral soft tissue produced by a diode laser in vitro

This investigation determined incision characteristics and soft‐tissue damage resulting from standardized incisions using a wide range of laser modes and parameters of a diode laser at 810 nm.

In vivo diagnosis of oral dysplasia and malignancy using optical coherence tomography: Preliminary studies in 50 patients

In vivo, non‐invasive optical coherence tomography (OCT) permits high‐resolution imaging of tissue surfaces and subsurfaces, with the potential capability for detection and mapping of epithelial pathologies.

Effects of ultrasonic root-end cavity preparation on the root apex

This study determined the effect of bur and ultrasonic preparation on the root apex. After cleaning, shaping, and obturation of root canals of 47 single-rooted teeth and resection of their apexes were done, 24 root-end cavities were prepared with a bur, and the rest were prepared with ultrasonic tips attached to two different ultrasonic units. After photographs of the prepared root ends were taken, their resin replicas were prepared and examined with a scanning electron microscope. Photographs and scanning electron microscope photomicrographs were examined for the presence or absence of cracks. The results showed a significantly higher incidence of crack formation in the walls of root-end cavities prepared by ultrasonic tips compared with those made by the bur.

Pilot study of laser effects on oral mucositis in patients receiving chemotherapy.

PURPOSEThe purpose of this study was to examine the effectiveness of laser therapy in the prevention and/or healing of chemotherapy-induced oral mucositis lesions. This study also evaluated the ease and feasibility of the laser therapy and the impact of the treatment on improving the patients quality of life. PATIENTS AND METHODSFifteen patients with an episode of prior chemotherapy-induced grade 3 or 4 mucositis with 5-fluorouracil continuous infusion consented to participate in this study. All patients were provided with standardized mouth care instructions at the initiation of chemotherapy treatments. Enrolled patients received laser therapy treatments 24 hours before the chemotherapy and then recommenced weekly with evenly distributed exposure to the standardized designated areas by one operator during the entire cycle of chemotherapy at the same doses until the mucositis resolved or the chemotherapy cycle was completed. Intraoral perfusion was measured by laser Doppler technology. Patients were assessed for response to laser therapy according to standardized mucositis grading criteria by evaluating development of lesions, extent and duration of lesions, and time to healing. The effect of laser therapy on ability to continue planned chemotherapy, the reduction in dose, delays, and ability to maintain planned dose intensity were assessed. The impact of laser therapy on pain control was evaluated using the visual analogue score. A quality-of-life survey was completed by each patient at the initiation of chemotherapy and then weekly throughout the chemotherapy. RESULTSEleven of 15 patients experienced grade 0 mucositis, three patients experienced grade 1 to 2 mucositis, and one patient experienced grade 3 to 4 mucositis. Fourteen patients completed the laser therapy as planned, and none of the patients withdrew from the laser therapy treatments because of noncompliance. One patient continued to experience grade 4 mucositis that necessitated an interruption in the planned chemotherapy regimen and, consequently, the laser treatment. Patients tolerated the laser therapy very well and did not report any increased discomfort. No significant changes in perfusion were observed as a result of laser therapy. DISCUSSIONIn this pilot study, laser therapy significantly reduced the incidence and the severity of mucositis in chemotherapy patients. The laser therapy does not appear to promote wound healing by affecting the intraoral perfusion, as assessed by Doppler measurements. The mechanisms involved in the mediating of the observed effects remain unknown at this time. Continued research is warranted to determine the optimal laser wavelength and parameters.

Three-Dimensional Spheroid Culture of Human Gingiva-Derived Mesenchymal Stem Cells Enhances Mitigation of Chemotherapy-Induced Oral Mucositis

Mesenchymal stem cells (MSCs) are capable of regenerative and immunomodulatory functions in cell-based therapies in a variety of human diseases and injuries; however, their therapeutic efficacy and potential side effects remain major obstacles in clinical applications. We report here a 3D spheroid culture approach to optimize stem cell properties and therapeutic effects of human gingiva-derived mesenchymal stem cells (GMSCs) in mitigation of experimental oral mucositis. Under growth condition of ultra-low attachment, GMSCs spontaneously aggregated into 3D spheroids and exhibited distinct early stem cell phenotype characterized by elevated expression Stro-1 and CXC chemokine receptor 4 (CXCR-4) as well as OCT-4 and Nanog, 2 important transcriptional factors relevant to stem cell properties, and decreased expression of MSC-associated markers, including CD29, CD90, and CD105. Functionally, spheroid GMSCs are capable of enhanced multipotency and augmented secretion of several chemokines and cytokines relevant to cell migration, survival, and angiogenesis. More importantly, spheroid GMSCs expressed increased levels of reactive oxygen species, hypoxia-inducible factor (HIF)-1 and -2α, and manganese superoxide dismutase, which correlated with improved resistance to oxidative stress-induced apoptosis. Using an in vivo murine model of chemotherapy-induced oral mucositis, we demonstrated that spheroid-derived GMSCs possessed better therapeutic efficacy than their adherent cells in reversing body weight loss and promoting the regeneration of disrupted epithelial lining of the mucositic tongues. These findings suggest that 3D spheroid culture allows early stemness preservation and potentially precondition GMSCs for enhanced mitigation of oral mucositis.

The soft laser: Therapeutic tool or popular placebo?

Because of the alleged effectiveness of soft laser therapy in the treatment of a wide range of medical and dental conditions, it is becoming increasingly popular with both patients and practitioners. It was the purpose of this study to assess soft laser treatment of hypersensitive dentin, gingivitis, pulp-capped teeth, herpes labialis, and nausea. Clinical trails demonstrated no advantage in augmenting or replacing conventional treatment of these conditions with soft laser therapy, despite its positive effect on patient attitude toward treatment.

Ability Of Optical Coherence Tomography To Detect Caries Beneath Commonly Used Dental Sealants

The onset and progression of early tooth decay is often preventable with dental sealants. However, occasionally decay progresses underneath the sealant. Current technology does not permit monitoring of potential lesion progression or arrest. Dental sealants themselves mask the visual cues that identify early tooth decay, and radiographs are not sufficiently sensitive. Therefore, clinicians can be reluctant to use dental sealant. The objective of this ex vivo study was to evaluate the ability of dentists to detect decay beneath commonly used dental sealants using optical coherence tomography (OCT) imaging.

Optical coherence tomography of malignancy in hamster cheek pouches

Optical coherence tomography (OCT)/optical Doppler tomography (ODT) provides real-time in vivo high-resolution (10-microm) imaging of tissues and real-time spatially resolved blood flow in microvasculature. Hamster cheek pouches with induced dysplasia and malignancies were imaged with OCT/ODT to assess the potential for application to airway malignancy. In 22 Golden Syrian hamsters, 0.5% 9,10-dimethyl-1,2-benzanthracene induces carcinogenesis over 10 weeks in right side cheek pouches; the left side three served as controls. The cheek pouches are imaged in vivo prior to sacrifice, and in vitro after excision, using a prototype 1310-nm broadband superluminescent diode based OCT/ODT device. Images are compared to standard histopathology. OCT imaging offers good resolution of the hamster cheek pouches to depths of 1 to 3 mm and paralleled histologic images. The feasibility of high-resolution functional imaging is demonstrated in this hamster cheek pouch tumor model. ODT accurately detects vascular change associated with carcinogenesis.