Use of autologous adipose-derived mesenchymal stem cells for creation of laryngeal cartilage

OBJECTIVES/HYPOTHESIS: Adipose-derived mesenchymal stem cells (ASCs) are an exciting potential cell source for tissue engineering because cells can be derived from the simple excision of autologous fat. This study introduces a novel approach for tissue-engineering cartilage from ASCs and a customized collagen oligomer solution, and demonstrates that the resultant cartilage can be used for laryngeal cartilage reconstruction in an animal model. STUDY DESIGN: Basic science experimental design. METHODS: ASCs were isolated from F344 rats, seeded in a customized collagen matrix, and cultured in chondrogenic differentiation medium for 1, 2, and 4 weeks until demonstrating cartilage-like characteristics in vitro. Large laryngeal cartilage defects were created in the F344 rat model, with the engineered cartilage used to replace the cartilage defects, and the rats followed for 1 to 3 months. Staining examined cellular morphology and cartilage-specific features. RESULTS: In vitro histological staining revealed rounded chondrocyte-appearing cells evenly residing throughout the customized collagen scaffold, with positive staining for cartilage-specific markers. The cartilage was used to successfully repair large cartilaginous defects in the rat model, with excellent functional results. CONCLUSIONS: This study is the first study to demonstrate, in an animal model, that ASCs cultured in a unique form of collagen oligomer can create functional cartilage-like grafts that can be successfully used for partial laryngeal cartilage replacement

Cartilage Engineering: Optimization of Media for Chondrogenic Differentiation In Vitro

Lower back pain from intervertebral disc injury affects around 84% of the population at some point in their life, which at its worst may cause total immobilization. This pain can only be temporarily relieved by spinal fusion or intervertebral disc replacement; however, both of these cause loss of natural motion in patients by removing damaged fibrocartilage discs. While these techniques help mitigate pain briefly, no permanent solution exists currently to both relieve pain and preserve natural motion. My work may be a solution by eventually providing patient-specific implants that resemble native tissue in the regeneration process that could be absorbed and remodeled by the body. The purpose of this study is to use tunable type I oligomeric collagen matrices for culturing of patient-derived stem cells to optimize chondrogenic media. Human adipose stem cells (hASCs) were passaged and used in conjunction with oligomer collagen, which was polymerized as cell/oligomer mixtures and plastically compressed to a density of 24.5mg/mL, with 4.5x105 cells per sample. These cell-matrix constructs were cultured with different media and supplements (namely TGF-β (3) and L-ascorbic-acid-2-phosphate) for 1 week. Safranin-o staining was used to detect sulfated glycosaminoglycans, a direct measure of chondrogenesis. Preliminary results show that supplemented DMEM media has the most chondrogenic potential, but further study is required. These results will be used to further improve the process of chondrogenesis in vitro in order to develop fibrocartilage constructs for use in vivo, eventually allowing for implantable constructs that both preserve natural disc height and relieve pain more permanently

Spectral Perspective on the Stability of Discrete-Time Markov Jump Systems with Multiplicative Noise

We apply the spectrum analysis approach to address the stability of discrete-time Markov jump systems with state-multiplicative noise. In terms of the spectral distribution of a generalized Lyapunov operator, spectral criteria are presented to testify three different kinds of stochastic stabilities: asymptotic mean square stability, critical stability, and essential instability

Stem cell-derived tissue-engineered constructs for hemilaryngeal reconstruction

OBJECTIVES: As an initial step toward our goal of developing a completely tissue-engineered larynx, the aim of this study was to describe and compare three strategies of creating tissue-engineered muscle-polymer constructs for hemilaryngeal reconstruction. METHODS: Cartilage-mimicking polymer was developed from electrospun poly(D,L-lactide-co-ε-caprolactone) (PCL). Primary muscle progenitor cell cultures were derived from syngeneic F344 rat skeletal muscle biopsies. Twenty F344 rats underwent resection of the outer hemilaryngeal cartilage with the underlying laryngeal adductor muscle. The defects were repaired with muscle stem cell-derived muscle-PCL constructs (5 animals), myotube-derived muscle-PCL constructs (5 animals), motor end plate-expressing muscle-PCL constructs (5 animals), or PCL alone (controls; 5 animals). The outcome measures at 1 month included animal survival, muscle thickness, and innervation status as determined by electromyography and immunohistochemistry. RESULTS: All of the animals survived the 1-month implant period and had appropriate weight gain. The group that received motor end plate-expressing muscle-PCL constructs demonstrated the greatest muscle thickness and the strongest innervation, according to electromyographic activity and the percentage of motor end plates that had nerve contact. CONCLUSIONS: Although all of the tissue-engineered constructs provided effective reconstruction, those that expressed motor end plates before implantation yielded muscle that was more strongly innervated and viable. This finding suggests that this novel approach may be useful in the development of a tissue-engineered laryngeal replacement

Associations between Benign Cutaneous Nevi and Risk of Type 2 Diabetes Mellitus in Men and Women: Results from Two Prospective Cohort Studies

poster abstractABSTRACT Objective: Previous studies suggest that the number of cutaneous nevi and type 2 diabetes mellitus (T2DM) are both associated with endogenous sex hormone levels. However, no prospective studies have specifically examined the relationship between the number of benign cutaneous nevi and T2DM. Research Design and Methods: We prospectively examined the associations between the number of nevi and risk of T2DM among 23,748 men (1986-2010) from the Health Professionals Follow-up Study (HPFS) and 67,050 women (1989-2010) from the Nurses' Health Study (NHS). Information on the numbers of melanocytic nevi on arms and the incidence of T2DM was collected by validated questionnaires. Results: During 1,831,118 person-years of follow-up, we documented 8748 incident cases of T2DM. After adjustment for age, BMI, and other diabetes risk factors, the number of nevi was significantly associated with increased risk of T2DM. Multivariable-adjusted HRs (95% CIs) for <1, 1-5, 6-14, and ≥15 nevi were 1.00 (reference), 1.02 (0.92, 1.14), 1.10 (0.87, 1.38), and 1.70 (1.22, 2.36), respectively, for men (P trend = 0.03) and 1.00 (reference), 1.15 (1.09, 1.21), 1.25 (1.11, 1.40), and 1.70 (1.38, 2.09), respectively, for women (P trend = 0.019). This positive association remained consistent across subgroups of participants. Conclusions: Mole count may represent a novel marker for development of T2DM in men and women, indicating a unique nevus development-related mechanism, possibly due to altered levels or functions of endogenous steroid sex hormones, in the pathogenesis of T2DM. Further studies are warranted to clarify the relationship of nevogenesis and T2DM and underlying mechanisms

Deep Learning for Physical-Layer 5G Wireless Techniques: Opportunities, Challenges and Solutions

The new demands for high-reliability and ultra-high capacity wireless communication have led to extensive research into 5G communications. However, the current communication systems, which were designed on the basis of conventional communication theories, signficantly restrict further performance improvements and lead to severe limitations. Recently, the emerging deep learning techniques have been recognized as a promising tool for handling the complicated communication systems, and their potential for optimizing wireless communications has been demonstrated. In this article, we first review the development of deep learning solutions for 5G communication, and then propose efficient schemes for deep learning-based 5G scenarios. Specifically, the key ideas for several important deep learningbased communication methods are presented along with the research opportunities and challenges. In particular, novel communication frameworks of non-orthogonal multiple access (NOMA), massive multiple-input multiple-output (MIMO), and millimeter wave (mmWave) are investigated, and their superior performances are demonstrated. We vision that the appealing deep learning-based wireless physical layer frameworks will bring a new direction in communication theories and that this work will move us forward along this road.Comment: Submitted a possible publication to IEEE Wireless Communications Magazin

Mesenchymal stem cells protect against obstruction-induced renal fibrosis by decreasing STAT3 activation and STAT3-dependent MMP-9 production

STAT3 is a transcription factor implicated in renal fibrotic injury, but the role of STAT3 in mesenchymal stem cell (MSC)-induced renoprotection during renal fibrosis remains unknown. We hypothesized that MSCs protect against obstruction-induced renal fibrosis by downregulating STAT3 activation and STAT3-induced matrix metalloproteinase-9 (MMP-9) expression. Male Sprague-Dawley rats underwent renal arterial injection of vehicle or MSCs (1 × 106/rat) immediately before sham operation or induction of unilateral ureteral obstruction (UUO). The kidneys were harvested after 4 wk and analyzed for collagen I and III gene expression, collagen deposition (Masson's trichrome), fibronectin, α-smooth muscle actin, active STAT3 (p-STAT3), MMP-9, and tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) expression. In a separate arm, the STAT3 inhibitor S3I-201 (10 mg/kg) vs. vehicle was administered to rats intraperitoneally just after induction of UUO and daily for 14 days thereafter. The kidneys were harvested after 2 wk and analyzed for p-STAT3 and MMP-9 expression, and collagen and fibronectin deposition. Renal obstruction induced a significant increase in collagen, fibronectin, α-SMA, p-STAT3, MMP-9, and TIMP-1 expression while exogenously administered MSCs significantly reduced these indicators of obstruction-induced renal fibrosis. STAT3 inhibition with S3I-201 significantly reduced obstruction-induced MMP-9 expression and tubulointerstitial fibrosis. These results demonstrate that MSCs protect against obstruction-induced renal fibrosis, in part, by decreasing STAT3 activation and STAT3-dependent MMP-9 production