Data@TAMU

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Browsing Data@TAMU by Funding Agency "DHHS-NIH-National Institute of Dental and Craniofacial Research"

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    Research Project
    Regulating Niche of Periodontium Mesenchymal Stem Cells under the Physiological Condition
    Biomedical Sciences; TAMHSC; https://hdl.handle.net/20.500.14641/366; DHHS-NIH-National Institute of Dental and Craniofacial Research
    Regulating niche of periodontium mesenchymal stem cells under the physiological condition The periodontium is composed of cementum, alveolar bone and periodontal ligament (PDL) in between. Their physiological turnover was known to be supported by stem cell populations1, 2. Based on mostly in vitro approaches, the periodontal stem cells (PDLSC) were isolated from human molar PDL3. Despite of that, in vivo location and identification of the periodontium stem cells remain largely unknown. Periodontium regeneration during or after periodontitis is a most challenging issue despite of various treatment strategies being designed. The regeneration capability difference strongly suggests that periodontium stem cells behave differentially under physiological or pathological conditions. Activity of stem cells was known to be regulated by the niche they are residing in. Various niche signals interplay which each other and keep stem cells in a dynamic balance4, 5. Despite of tremendous progress of the niche studies for other stem cell populations, the in vivo niche of periodontium stem cells has never been studied. To address above challenges, it is therefore imperative to find out the in vivo identity of the periodontium mesenchymal stem cells (MSCs) and to learn their niche organization. Based on our preliminary experiments, Gli1+ cells are identified as the MSCs for adult periodontium tissue. The Gli1+ cells are exclusively surrounding the neurovascular bundle and are more enriched in the apical region of the PDL space. These Gli1+ cells are negative for lineage differentiation or classical MSC markers. They give rise to the PDL, cementum, alveolar bone and apical root pulp during physiological turnover. Blockage of canonical Wnt signaling leads to failure of Gli1+ stem cells activation and severe periodontal tissue loss. With these preliminary findings, comprehensive investigation is proposed for investigating the in vivo properties and regulating niche of Gli1+ periodontium MSCs under physiological condition. The hypothesis is that Gli1+ MSCs are the dominant stem cell population within the periodontium and are regulated by a negative feedback loop within the periodontium. Canonical Wnt signaling pathway activates and maintains periodontium MSCs. Sclerostin ligand secreted from the cementum and alveolar bone negatively regulates the Gli1+ stem cell activities. Interplays between the two opposing signals keep the periodontium MSCs in a dynamic balance.
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    Research Project
    Therapeutic Effects of MSC-Derived Extracellular Vesicles on Sjögrens Syndrome
    Molecular And Cellular Medicine; TAMHSC; https://hdl.handle.net/20.500.14641/319; DHHS-NIH-National Institute of Dental and Craniofacial Research
    Abstract: Sjögren's syndrome is a chronic inflammatory autoimmune disease affecting mainly salivary glands and lacrimal glands with an incidence of about 1% in the general population and up to 3% in people above the age of 50, with women accounting for more than 90% of diagnosed cases. Hypofunction of salivary glands or dry mouth is a major symptom of Sjögren's syndrome and severely impairs the quality of life of patients. No effective treatment of Sjögren's syndrome is available now. Mesenchymal stem/stromal cells (MSCs) are conventionally isolated from tissues such as bone marrow, are capable of inhibiting immune responses and inflammation, and have shown therapeutic efficacies in Sjögren's syndrome. However, there are many limitations of using tissue-derived MSCs directly for therapies including their limited expandability, considerable donor variations and variations caused by different expansion methods, and the lack of standard assays for testing therapeutic efficacy of the To overcome these limitations, we have derived MSCs efficiently from human induced pluripotent stem cells (iPSCs) with almost unlimited expandability using a modified protocol that can be easily scaled up to produce very large amounts of standardized MSCs. Our iPSC-derived MSCs showed anti-inflammatory and immunosuppressive effects comparable to tissue-derived MSCs. Nevertheless, there are still many difficulties in clinical application of MSCs such as the need for frozen storage and shipping and to thaw frozen cells, the high cost, and the dynamic changes of live cells. Extracellular vesicles (EVs) are nano- sized particles released from cells spontaneously. EVs carry bioactive molecules similar to their originating cells, and are much safer and more feasible for clinical application compared to their originating cells. MSC EVs showed immunosuppressive activities similar to MSCs in vitro. Our preliminary study indicated that systemically injected iPSC-MSCs or their EVs inhibited the inflammation of salivary gland in a mouse model of Sjögren's syndrome. This proposal aims to determine the potentials and mechanisms of iPSC-MSC EVs in preventing the progression of Sjögren's syndrome using a more faithful mouse model. First, we will determine effects of systemic infusion of iPSC-MSC EVs on preventing progression of Sjögren's syndrome and related changes in immune cells and salivary gland cells. Second, we will determine components of iPSC-MSC EVs essential for preventing progression of Sjögren's syndrome. The success of the proposed research will provide the proof-of-concept for a novel and clinically feasible therapy for Sjögren's syndrome, and will also encourage further research on MSC EVs for improving treatment of a broad range of disorders that have low therapeutic alternatives but share similar inflammatory and/or immune backgrounds including rheumatoid arthritis, inflammatory bowel diseases, graft versus host disease, and rejections of transplants.