Clinical characteristics and salivary biomarkers of burning mouth syndrome.

OBJECTIVES: To investigate the clinical characteristics and salivary biomarkers in each type of burning mouth syndrome (BMS) patients. MATERIALS AND METHODS: Ninety-eight postmenopausal female patients with BMS were included. Fifty and 21 patients were assigned to the primary and secondary groups, respectively. Twenty-seven patients with both primary and secondary characteristics were assigned to the intermediate group. Comprehensive clinical characteristics and salivary biomarkers were analyzed. RESULTS: Significant differences in age, proportion of hyposalivator patients based on unstimulated whole saliva (UWS), symptom distribution, severties of burning sensation and effect of oral complaints in daily life (Eff-life), and positive symptom distress index (PSDI) were observed among the three groups. The primary group had significant higher UWS flow rate, fewer UWS hyposalivator proportions, and lesser severity of Eff-life than the secondary group. The intermediate group had significantly greater intensities of burning sensation and Eff-life and higher PSDI score than did the primary group. The primary group had significantly higher cortisol and dehydroepiandrosterone (DHEA) levels in stimulated whole saliva than did the secondary group. CONCLUSIONS: This study's findings show that clinical characteristics differentiate each BMS type. Cortisol and DHEA levels are potential salivary biomarkers for discriminating between the primary and secondary types of BMS.

Advancements in Human Embryonic Stem Cell Research: Clinical Applications and Ethical Issues.

BACKGROUND: The development and use of human embryonic stem cells (hESCs) in regenerative medicine have been revolutionary, offering significant advancements in treating various diseases. These pluripotent cells, derived from early human embryos, are central to modern biomedical research. However, their application is mired in ethical and regulatory complexities related to the use of human embryos. METHOD: This review utilized key databases such as ClinicalTrials.gov, EU Clinical Trials Register, PubMed, and Google Scholar to gather recent clinical trials and studies involving hESCs. The focus was on their clinical application in regenerative medicine, emphasizing clinical trials and research directly involving hESCs. RESULTS: Preclinical studies and clinical trials in various areas like ophthalmology, neurology, endocrinology, and reproductive medicine have demonstrated the versatility of hESCs in regenerative medicine. These studies underscore the potential of hESCs in treating a wide array of conditions. However, the field faces ethical and regulatory challenges, with significant variations in policies and perspectives across different countries. CONCLUSION: The potential of hESCs in regenerative medicine is immense, offering new avenues for treating previously incurable diseases. However, navigating the ethical, legal, and regulatory landscapes is crucial for the continued advancement and responsible application of hESC research in the medical field. Considering both scientific potential and ethical implications, a balanced approach is essential for successfully integrating hESCs into clinical practice.

Perfect circular polarization of elastic waves in solid media.

Elastic waves involving mechanical particle motions of solid media can couple volumetric and shear deformations, making their manipulation more difficult than electromagnetic waves. Thereby, circularly polarized waves in the elastic regime have been little explored, unlike their counterparts in the electromagnetic regime, where their practical usage has been evidenced in various applications. Here, we explore generating perfect circular polarization of elastic waves in an isotropic solid medium. We devise a novel strategy for converting a linearly polarized wave into a circularly polarized wave by employing an anisotropic medium, which induces a so-far-unexplored coupled resonance phenomenon; it describes the simultaneous occurrence of the Fabry-Pérot resonance in one diagonal plane and the quarter-wave resonance in another diagonal plane orthogonal to the former with an exact 90° out-of-phase relation. We establish a theory explaining the involved physics and validate it numerically and experimentally. As a potential application of elastic circular polarization, we present simulation results demonstrating that a circularly polarized elastic wave can detect an arbitrarily oriented crack undetectable by a linearly polarized elastic wave.

Effects of Zinc Compounds on the Enzymatic Activities of Lysozyme and Peroxidase and Their Antifungal Activities.

This study aimed to investigate the effects of zinc compounds on the enzymatic activities of lysozyme, peroxidase, and the glucose oxidase-mediated peroxidase (GO-PO) system and their antifungal activities. Four different zinc compounds (zinc chloride, gluconate, lactate, and sulfate) were incubated with hen egg-white lysozyme (HEWL), bovine lactoperoxidase (bLPO), the GO-PO system, and human unstimulated whole saliva in solution and on a hydroxyapatite surface. Enzymatic activities of lysozyme, peroxidase, and the GO-PO system were measured through the hydrolysis of Micrococcus lysodeikticus, oxidation of fluorogenic 2',7'-dichlorofluorescin, and glucose assay, respectively. Interactions between zinc and enzymes were analyzed by surface plasmon resonance (SPR). The minimum inhibitory concentration (MIC) and candidacidal activities of zinc compounds were examined against three Candida albicans strains. Zinc gluconate and sulfate significantly increased the enzymatic activities of salivary lysozyme in the solution assay and of HEWL and salivary lysozyme on the hydroxyapatite surface. However, all examined zinc compounds significantly decreased the enzymatic activities of bLPO and salivary peroxidase in solution and on the surface. SPR analyses revealed binding of zinc to lysozyme and peroxidase, with affinity differing according to the zinc compounds. The MIC of zinc compounds against C. albicans was 1.0-2.4 mM. Candidacidal activities were 17.7-38.8% and 23.7-47.0% at 1.0 and 10 mM concentrations, respectively. In conclusion, zinc compounds enhanced lysozyme activity but inhibited peroxidase activity. Zinc compounds exhibited concentration-dependent candidacidal activity against C. albicans. Zinc compounds are potential therapeutic agents for oral health, especially for geriatric patients.

Transcriptomic Profiling of Reproductive Age Marmoset Monkey Ovaries.

The decline in ovarian reserve and the aging of the ovaries is a significant concern for women, particularly in the context of delayed reproduction. However, there are ethical limitations and challenges associated with conducting long-term studies to understand and manipulate the mechanisms that regulate ovarian aging in human. The marmoset monkey offers several advantages as a reproductive model, including a shorter gestation period and similar reproductive physiology to that of human. Additionally, they have a relatively long lifespan compared to other mammals, making them suitable for long-term studies. In this study, we focused on analyzing the structural characteristics of the marmoset ovary and studying the mRNA expression of 244 genes associated with ovarian aging. We obtained ovaries from marmosets at three different reproductive stages: pre-pubertal (1.5 months), reproductive (82 months), and menopausal (106 months) ovaries. The structural analyses revealed the presence of numerous mitochondria and lipid droplets in the marmoset ovaries. Many of the genes expressed in the ovaries were involved in multicellular organism development and transcriptional regulation. Additionally, we identified the expression of protein-binding genes. Within the expressed genes, VEGFA and MMP9 were found to be critical for regulating ovarian reserve. An intriguing finding of the study was the strong correlation between genes associated with female infertility and genes related to fibrosis and wound healing. The authors suggest that this correlation might be a result of the repeated rupture and subsequent healing processes occurring in the ovary due to the menstrual cycle, potentially leading to the indirect onset of fibrosis. The expression profile of ovarian aging-related gene set in the marmoset monkey ovaries highlight the need for further studies to explore the relationship between fibrosis, wound healing, and ovarian aging.

Effects of Cetrorelix on Ovary and Endometrium Prior to Anti-PD-L1 Antibody in Murine Model.

BACKGROUND: Recent anti-cancer agents, immune checkpoint inhibitors (ICIs), have emerged as effective agents targeting the programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway. While the administration of gonadotropin-releasing hormone (GnRH) analogs before cytotoxic agents is known to preserve female reproductive organ function, the potential effects of ICIs and the protective impact of GnRH analogs on female reproductive organs, especially concerning ovarian reserve and endometrial receptivity, remain unknown. In this study, we attempted to elucidate the protective or regenerative effect on the female reproductive organ of cetrorelix prior to anti-PD-L1 antibody administration. METHOD: Using a murine model, we examined the effects of Anti-PD-L1 antibody treatment on ovarian and uterine morphology, compared them with controls, and further assessed any potential protective effect of cetrorelix, a GnRH analog. Histological examinations and quantitative reverse transcription polymerase chain reaction were employed to study the morphological changes and associated gene expression patterns. RESULTS: Anti-PD-L1 treatment led to a significant depletion of primordial/primary ovarian follicles and impaired decidualization in uterine stromal cells. However, while pretreatment with cetrorelix could restore normal decidualization patterns in the uterus, it did not significantly ameliorate ovarian follicular reductions. Gene expression analysis reflected these observations, particularly with marked changes in the expression of key genes like Prl and Igfbp1, pivotal in uterine decidualization. CONCLUSION: Our study underscores the potential reproductive implications of cetrorelix treatment prior to Anti-PD-L1 therapy, shedding light on its short-term protective effects on the uterus. Further studies are necessary to understand long-term and clinical implications.

Sprr1 and miR-130b contribute to the senescence-like phenotype in aging.

Aging is an inevitable process with senescence being one of its hallmarks. Recent advances have indicated that the elimination of senescent cells can reduce the signs of aging and increase healthy life span. Here, we identify a negative modulator of aging, Sprr1a, and in turn a negative modulator of Sprr1a, miR-130b. We show that reductions in Sprr1a levels, including via miR-130b expression, promotes cell senescence-like phenotype. We find that mediators of senescence, such as inflammatory cytokines and cell cycle regulators, are modulated by the miR-130b and Sprr1a-related pathway. For example, the levels of p16, p53 and p21 become decreased or increased upon the respective expression of Sprr1a versus miR-130b. Further, as shown in relation to p16 levels and ß-galactosidase levels, cells expressing Sprr1a exhibit significant protection from senescence-inducing factors such as radiation or Doxorubicin, suggesting that Sprr1a might contribute to protection against age-related pathologies. Taken together, we introduce two modulators of properties associated with senescence-like phenotype.

Ultrasonic barrier-through imaging by Fabry-Perot resonance-tailoring panel.

Imaging technologies that provide detailed information on intricate shapes and states of an object play critical roles in nanoscale dynamics, bio-organ and cell studies, medical diagnostics, and underwater detection. However, ultrasonic imaging of an object hidden by a nearly impenetrable metal barrier remains intractable. Here, we present the experimental results of ultrasonic imaging of an object in water behind a metal barrier of a high impedance mismatch. In comparison to direct ultrasonic images, our method yields sufficient object information on the shapes and locations with minimal errors. While our imaging principle is based on the Fabry-Perot (FP) resonance, our strategy for reducing attenuation in our experiments focuses on customising the resonance at any desired frequency. To tailor the resonance frequency, we placed an elaborately engineered panel of a specific material and thickness, called the FP resonance-tailoring panel (RTP), and installed the panel in front of a barrier at a controlled distance. Since our RTP-based imaging technique is readily compatible with conventional ultrasound devices, it can realise underwater barrier-through imaging and communication and enhance skull-through ultrasonic brain imaging.

Identification of Stem Cell-Like Cells in the Ovary.

Understanding the function of stem cells and cellular microenvironments in in vitro oogenesis, including ovarian folliculogenesis, is crucial for reproductive biology. Because mammalian females cannot generate oocytes after birth, the number of oocyte decreases with the progression of reproductive age. Meanwhile, there is an emerging need for the neogenesis of female germ cells to treat the increasing infertility-related issues in cancer survivors. The concept of oocytes neogenesis came from the promising results of stem cells in reproductive medicine. The stem cells that generate oocytes are defined as stem cell-like cells in the ovary (OSCs). Several recent studies have focused on the origin, isolation, and characteristic of OSCs and the differentiation of OSCs into oocytes, ovarian follicles and granulosa cells. Hence, in this review, we focus on the experimental trends in OSC research and discuss the methods of OSC isolation. We further summarized the characteristics of OSCs and discuss the markers used to identify OSCs differentiated from various cell sources. We believe that this review will be beneficial for advancing the research and clinical applications of OSCs.

Synergistic Promoting Effects of X-Linked Inhibitor of Apoptosis Protein and Matrix on the In Vitro Follicular Maturation of Marmoset Follicles.

BACKGROUND: In vitro follicular maturation (IVFM) of ovarian follicles is an emerging option for fertility preservation. Many paracrine factors and two-dimensional or three-dimensional (3D) environments have been used for optimization. However, since most studies were conducted using the murine model, the physiological differences between mice and humans limit the interpretation and adaptation of the results. Marmoset monkey is a non-human primate (NHPs) with more similar reproductive physiology to humans. In this study, we attempted to establish a 3D matrix (Matrtigel)-based IVFM condition for marmoset ovarian follicles in combination with anti-apoptotic factor, X-linked inhibitor of apoptosis protein (XIAP). METHODS: Marmoset follicles were isolated as individual follicles and cultured in a single drop with the addition of 0, 10, and 100 µg/mL of XIAP molecules. Matured oocytes and granulosa cells from mature follicles were collected and analyzed. The average number of isolated follicles was less than 100, and primordial and antral follicles were abundant in the ovaries. RESULTS: IVFM of marmoset follicles in 3D matrix conditions with XIAP increased the rates of survival and in vitro follicle development. Furthermore, oocytes from the 3D cultures were successfully fertilized and developed in vitro. The addition of XIAP increased the secretion of estradiol and aromatase. Furthermore, expression of granulosa-specific genes, such as bone morphogenetic protein 15, Oct4, and follicle-stimulating hormone receptor were upregulated in the in vitro-matured follicles than in normal, well-grown, and atretic follicles. Apoptosis-related B-cell lymphoma-2 was highly expressed in the atretic follicles than in the XIAP-treated follicles, and higher caspase-3 was localized in the XIAP-treated follicles. CONCLUSION: In this study, we attempted to establish a 3D-matrix-based marmoset IVFM condition and demonstrated the synergistic effects of XIAP. The use of a 3D matrix may be applied as an optimal culture condition for marmoset ovarian follicles.

Non-invasive ultrasonic inspection of sludge accumulation in a pipe.

Sludge accumulated inside a fluid-flowing pipe used in a chemical or semiconductor processing factory should be periodically removed to avoid flow blockage that increases undesirable pressure inside the pipe. Accordingly, it is common practice to periodically dismantle a pipe system, clean up the accumulate sludge, and reassemble. Therefore, an accurate estimation of sludge accumulation in the pipe is important to minimize the halting time of a chemical process using the system. Considering the lack of a practically efficient, non-invasive method to estimate the severity of sludge accumulation without interrupting the on-going chemical process, we propose an ultrasonic, non-invasive, real-time inspection method using a pair of ultrasonic wedge transducers installed circumferentially on the outer wall of a pipe at the same axial coordinate. To detect lowly accumulated sludge, an ultrasonic wave path from a transmitting transducer via a test pipe with accumulated sludge to a receiving transducer is carefully designed. The severity of sludge accumulation can then be determined by the amplitude of the longitudinal wave picked up by another transducer installed on the other side of the wall. We performed a series of experiments with steel and PVC pipes that are partially filled with water and sludge of different heights. The experimental results confirmed the effectiveness and practical viability of the proposed inspection method.

Transcriptome Analyses Identify Potential Key microRNAs and Their Target Genes Contributing to Ovarian Reserve.

Female endocrinological symptoms, such as premature ovarian inefficiency (POI) are caused by diminished ovarian reserve and chemotherapy. The etiology of POI remains unknown, but this can lead to infertility. This has accelerated the search for master regulator genes or other molecules that contribute as enhancers or silencers. The impact of regulatory microRNAs (miRNAs) on POI has gained attention; however, their regulatory function in this condition is not well known. RNA sequencing was performed at four stages, 2-(2 W), 6-(6 W), 15-(15 W), and 20-(20 W) weeks, on ovarian tissue samples and 5058 differentially expressed genes (DEGs) were identified. Gene expression and enrichment were analyzed based on the gene ontology and KEGG databases, and their association with other proteins was assessed using the STRING database. Gene set enrichment analysis was performed to identify the key target genes. The DEGs were most highly enriched in 6 W and 15 W groups. Figla, GDF9, Nobox, and Pou51 were significantly in-creased at 2 W compared with levels at 6 W and 20 W, whereas the expression of Foxo1, Inha, and Taf4b was significantly de-creased at 20 W. Ccnd2 and Igf1 expression was maintained at similar levels in each stage. In total, 27 genes were upregulated and 26 genes interacted with miRNAs; moreover, stage-specific upregulated and downregulated interactions were demonstrated. Increased and decreased miRNAs were identified at each stage in the ovaries. The constitutively expressed genes, Ccnd2 and Igf1, were identified as the major targets of many miRNAs (p < 0.05), and Fshr and Foxo3 interacted with miRNAs, namely mmu-miR-670-3p and mmu-miR-153-3p. miR-26a-5p interacted with Piwil2, and its target genes were downregulated in the 20 W mouse ovary. In this study, we aimed to identify key miRNAs and their target genes encompassing the reproductive span of mouse ovaries using mRNA and miRNA sequencing. These results indicated that gene sets are regulated in the reproductive stage-specific manner via interaction with miRNAs. Furthermore, consistent expression of Ccnd2 and Igf1 is considered crucial for the ovarian reserve and is regulated by many interactive miRNAs.

Transcriptomic analysis of rat kidney reveals a potential mechanism of sex differences in susceptibility to cisplatin-induced nephrotoxicity.

Although cisplatin is an effective platinum-based anticancer drug against solid cancer, its availability is limited owing to its adverse side effects. Our study aimed to identify the potential relationship within cisplatin-induced multi-organ physiological changes and genetic factors associated with sex differences in nephrotoxicity susceptibility. To investigate this, mice received a single intraperitoneal injection of cisplatin. Cisplatin administration resulted in renal dysfunction, as evidenced by the elevation in serum biomarkers of renal damage (blood urea nitrogen and creatinine) and the degree of histopathological alterations. In particular, along with testicular damage and low testosterone levels, we also observed a decrease in male-specific (CYP3A2) or male-dominant (CYP2B1 and CYP3A1) CYP isoforms in the livers of rats with hepatotoxicity following cisplatin treatment, which may be associated with an imbalance in male hormone regulation caused by renal and testicular injury. Notably, we found that male rats were more susceptible to cisplatin-induced nephrotoxicity, as characterized by histopathological and biochemical analyses. Therefore, RNA sequencing was performed at baseline (pre-treatment) and at 48 h following cisplatin administration (post-treatment) to identify the genes associated with sex differences in nephrotoxicity susceptibility. Gap junctions, which play a role in replenishing damaged cells to maintain tissue homeostasis, and mismatch repair associated with a pathological apoptotic mechanism against cisplatin nephrotoxicity were significantly enriched only in males following cisplatin treatment. Moreover, among the 322 DEGs showing different basal expression patterns between males and females before cisplatin treatment, the male expressed high levels of genes, which are responsible for transmembrane transport and regulation of apoptotic process, pre-cisplatin treatment; additionally, genes involved in the PI3K-Akt signaling pathway and the oxidation-reduction process were significantly lower in males before cisplatin treatment. Collectively, our comprehensive findings provided valuable insight into the potential mechanisms of sex differences in cisplatin-induced nephrotoxicity susceptibility.

ASSOCIATIONS WITH RECURRENCE OF MACULAR EDEMA IN BRANCH RETINAL VEIN OCCLUSION AFTER THE DISCONTINUATION OF ANTI VASCULAR ENDOTHELIAL GROWTH FACTOR.

PURPOSE: To identify factors predicting the recurrence of macular edema after the discontinuation of intravitreal antivascular endothelial growth factor injection in patients with branch retinal vein occlusion. METHODS: This retrospective study included only subjects who had discontinued injections at 3 months after the final bevacizumab injection due to fully resolved macular edema. Fifty-two eyes meeting the criteria were included in the study and divided into two groups (recurrence and no recurrence). Clinical features and measurements of retinal thickness at the time of the diagnosis and when the decision to stop injections was made (stopping point) were analyzed. RESULTS: At the stopping point, the no recurrence group showed a thinner parafoveal inner retina, better best-corrected visual acuity, and lower incidence of ellipsoid zone disruption in multivariate logistic regression analysis (all P < 0.05). Similarly, parafoveal inner retinal thinning of more than 30 µm, when compared with the corresponding region of the fellow eye or the unaffected region of the affected eye, was significantly related to less recurrence of macular edema. CONCLUSION: Thinning of the parafoveal inner retina as well as better vision and intact outer retinal layers are associated with a lack of recurrence of macular edema. These findings suggest that inner retinal atrophy after branch retinal vein occlusion may result in a reduction in oxygen demand in the affected retinal tissue and less production of vascular endothelial growth factor.

Epigenetic Regulation of Cardiomyocyte Differentiation from Embryonic and Induced Pluripotent Stem Cells.

With the intent to achieve the best modalities for myocardial cell therapy, different cell types are being evaluated as potent sources for differentiation into cardiomyocytes. Embryonic stem cells and induced pluripotent stem cells have great potential for future progress in the treatment of myocardial diseases. We reviewed aspects of epigenetic mechanisms that play a role in the differentiation of these cells into cardiomyocytes. Cardiomyocytes proliferate during fetal life, and after birth, they undergo permanent terminal differentiation. Upregulation of cardiac-specific genes in adults induces hypertrophy due to terminal differentiation. The repression or expression of these genes is controlled by chromatin structural and epigenetic changes. However, few studies have reviewed and analyzed the epigenetic aspects of the differentiation of embryonic stem cells and induced pluripotent stem cells into cardiac lineage cells. In this review, we focus on the current knowledge of epigenetic regulation of cardiomyocyte proliferation and differentiation from embryonic and induced pluripotent stem cells through histone modification and microRNAs, the maintenance of pluripotency, and its alteration during cardiac lineage differentiation.

Recent Advancements in Engineered Biomaterials for the Regeneration of Female Reproductive Organs.

Various gynecologic diseases and chemoradiation or surgery for the management of gynecologic malignancies may damage the uterus and ovaries, leading to clinical problems such as infertility or early menopause. Embryo or oocyte cryopreservation-the standard method for fertility preservation-is not a feasible option for patients who require urgent treatment because the procedure requires ovarian stimulation for at least several days. Hormone replacement therapy (HRT) for patients diagnosed with premature menopause is contraindicated for patients with estrogen-dependent tumors or a history of thrombosis. Furthermore, these methods cannot restore the function of the uterus and ovaries. Although autologous transplantation of cryopreserved ovarian tissue is being attempted, it may re-introduce malignant cells after cancer treatment. With the recent development in regenerative medicine, research on engineered biomaterials for the restoration of female reproductive organs is being actively conducted. The use of engineered biomaterials is a promising option in the field of reproductive medicine because it can overcome the limitations of current therapies. Here, we review the ideal properties of biomaterials for reproductive tissue engineering and the recent advancements in engineered biomaterials for the regeneration of female reproductive organs.

Consecutive Low Doses of Streptozotocin Induce Polycystic Ovary Syndrome Features in Mice.

Polycystic ovarian syndrome (PCOS) is a common reproductive endocrine disorder in reproductive-age women. Due to its various pathophysiological properties and clinical heterophenotypes, the mechanism of PCOS pathogenesis is still unclear. Several animal models have been used to study PCOS and allow the exploration of the specific mechanism underlying PCOS. We focused on streptozotocin (STZ) to develop a non-steroidal and non-diabetic PCOS model. We administered multiple STZ injections to female C57BL/6 mice (3-4 weeks old) at different concentrations: STZ-15 (15 mg/kg), STZ-30 (30 mg/kg), and STZ-60 (60 mg/kg) treatments. During the experimental period, we analyzed body weight, blood glucose levels, and estrous cycle pattern. Furthermore, five weeks after STZ administration, we examined hormone levels and the morphology of ovarian tissues. Mice in the STZ-15 group did not show differences in body weights, blood glucose level, insulin level, and insulin tolerance compared to wild-type and control groups whereas those in the STZ-60 group presented a typical diabetes phenotype. In the case of the STZ-30 group, only increased blood glucose level was observed. Total testosterone levels were significantly elevated in STZ-15 and STZ-30 groups. Luteinizing hormone (LH) and estradiol levels were not significantly changed in the STZ-treated groups. The number of ovarian antral follicles and atretic follicles significantly increased in the ovary of mice in the STZ-15 and STZ-30 groups. All STZ-treated groups manifested irregular estrus cycles. However, the patterns of estrous cycles were different between mice treated with different STZ concentrations. We found that PI3K-AKT and IRS-1 signaling in the ovary was enhanced by low doses of STZ treatment. Taken together, our finding indicates that multiple injections of STZ at low doses induce PCOS features in mice without induction of diabetes features.

Comparison of Genetically Engineered Immunodeficient Animal Models for Nonclinical Testing of Stem Cell Therapies.

For the recovery or replacement of dysfunctional cells and tissue-the goal of stem cell research-successful engraftment of transplanted cells and tissues are essential events. The event is largely dependent on the immune rejection of the recipient; therefore, the immunogenic evaluation of candidate cells or tissues in immunodeficient animals is important. Understanding the immunodeficient system can provide insights into the generation and use of immunodeficient animal models, presenting a unique system to explore the capabilities of the innate immune system. In this review, we summarize various immunodeficient animal model systems with different target genes as valuable tools for biomedical research. There have been numerous immunodeficient models developed by different gene defects, resulting in many different features in phenotype. More important, mice, rats, and other large animals exhibit very different immunological and physiological features in tissue and organs, including genetic background and a representation of human disease conditions. Therefore, the findings from this review may guide researchers to select the most appropriate immunodeficient strain, target gene, and animal species based on the research type, mutant gene effects, and similarity to human immunological features for stem cell research.

In Vivo Study for Clinical Application of Dental Stem Cell Therapy Incorporated with Dental Titanium Implants.

The aim of this study was to investigate the behavior of dental-derived human mesenchymal stem cells (d-hMSCs) in response to differently surface-treated implants and to evaluate the effect of d-hMSCs on local osteogenesis around an implant in vivo. d-hMSCs derived from alveolar bone were established and cultured on machined, sandblasted and acid-etched (SLA)-treated titanium discs with and without osteogenic induction medium. Their morphological and osteogenic potential was assessed by scanning electron microscopy (SEM) and real-time polymerase chain reaction (RT-PCR) via mixing of 5 × 106 of d-hMSCs with 1 mL of Metrigel and 20 µL of gel-cell mixture, which was dispensed into the defect followed by the placement of customized mini-implants (machined, SLA-treated implants) in New Zealand white rabbits. Following healing periods of 2 weeks and 12 weeks, the obtained samples in each group were analyzed radiographically, histomorphometrically and immunohistochemically. The quantitative change in osteogenic differentiation of d-hMSCs was identified according to the type of surface treatment. Radiographic analysis revealed that an increase in new bone formation was statistically significant in the d-hMSCs group. Histomorphometric analysis was in accordance with radiographic analysis, showing the significantly increased new bone formation in the d-hMSCs group regardless of time of sacrifice. Human nuclei A was identified near the area where d-hMSCs were implanted but the level of expression was found to be decreased as time passed. Within the limitations of the present study, in this animal model, the transplantation of d-hMSCs enhanced the new bone formation around an implant and the survival and function of the stem cells was experimentally proven up to 12 weeks post-sacrifice.