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[Display omitted] • CFS were manufactured using recycled CF with TPU lamination for in vitro research. • CFS heating device has stable thermal performance compared to conventional CP. • FIR-CFS did not exhibit cytotoxicity under most of the tested conditions. • FIR-CFS induces the osteogenesis of TMSCs, independent of its thermal effects. • FIR-CFS has the potential to alleviate symptoms of osteoporosis. Far-infrared (FIR) therapy has been extensively studied because of its numerous benefits in improving human health. A planar heating element device was designed to assess the in vitro efficacy of FIR therapy by using a flexible carbon fiber composite sheet (CFS) with versatile designs and shapes. The physical properties were optimized for in vitro assays, and low hygroscopicity and stable thermal performance were obtained through thermoplastic polyurethane (TPU) lamination. The CFS evenly released FIR at temperatures ranging from 25 to 80 °C. There was no significant effect on cell viability under most conditions. However, the FIR emitted from the CFS at 70 and 80 °C for 2 h increased apoptotic cell death. The FIR irradiation between 60 and 80 °C for 1 h or less effectively induced osteogenesis of the tonsil-derived mesenchymal stem cells (TMSCs) without inducing cytotoxicity. The most significant osteogenic induction occurred at 60 and 70 °C, as evidenced by increased calcium mineralization and osteogenic markers. This study demonstrated that CFS efficiently generates the FIR, which induces the osteogenicity of TMSCs at a non-cytotoxic level, suggesting the potential applicability of the CFS device for treating bone diseases such as osteoporosis. [ABSTRACT FROM AUTHOR]

Abstract Background and aims Osteoporosis, which is a disease characterized by weakening of the bone, affects a large portion of the senior population. The current therapeutic options for osteoporosis have side effects, and there is no effective treatment for severe osteoporosis. Thus, we urgently need new treatment strategies, such as topical therapies and/or safe and effective stem cell therapies. Methods We investigated the therapeutic potential of directly injecting human tonsil-derived mesenchymal stem cells (TMSC) into the right proximal tibias of ovariectomized postmenopausal osteoporosis model mice. Injections were given once (1×) or twice (2×) during the 3-month experimental period. At the end of the experiment, micro-computed tomographic images revealed some improvement in the proximal tibias and more significant improvement in the femoral heads of treated mice. Results Osteogenic effect was qualitatively and quantitatively more pronounced in TMSC/2×-treated mice. Furthermore, TMSC/2× mice exhibited significant recovery of the serum osteocalcin level, which is pathologically elevated in osteoporosis, and increased serum alkaline phosphatase, which indicates bone formation. TMSC therapy was generally well tolerated and caused no apparent toxicity in the experimental mice. Moreover, TMSC therapy reduced visceral fat. Conclusion Our results demonstrate that double injection of TMSC directly into the proximal tibia triggers recovery of osteoporosis, and thus could be a potential therapeutic approach for severe bone loss. [ABSTRACT FROM AUTHOR]

To restore damaged parathyroid function, parathyroid tissue engineering is the best option. Previously, we reported that differentiated tonsil-derived mesenchymal stem cells (dTMSC) restore in vivo parathyroid function, but only if they are embedded in a scaffold. Because of the limited biocompatibility of Matrigel, however, here we developed a more clinically applicable, scaffold-free parathyroid regeneration system. Scaffold-free dTMSC spheroids were engineered in concave microwell plates made of polydimethylsiloxane in control culture medium for the first 7 days and differentiation medium (containing activin A and sonic hedgehog) for next 7 days. The size of dTMSC spheroids showed a gradual and significant decrease up to day 5, whereafter it decreased much less. Cells in dTMSC spheroids were highly viable (>80%). They expressed high levels of intact parathyroid hormone (iPTH), the parathyroid secretory protein 1, and cell adhesion molecule, N-cadherin. Furthermore, dTMSC spheroids-implanted parathyroidectomized (PTX) rats revealed higher survival rates (50%) over a 3-month period with physiological levels of both serum iPTH (57.7–128.2 pg/mL) and ionized calcium (0.70–1.15 mmol/L), compared with PTX rats treated with either vehicle or undifferentiated TMSC spheroids. This is the first report of a scaffold-free, human stem cell-based parathyroid tissue engineering and represents a more clinically feasible strategy for hypoparathyroidism treatment than those requiring scaffolds. Statement of Significance Herein, we have for the first time developed a scaffold-free parathyroid tissue spheroids using differentiated tonsil-derived mesenchymal stem cells (dTMSC) to restore in vivo parathyroid cell functions. This new strategy is effective, even for long periods (3 months), and is thus likely to be more feasible in clinic for hypoparathyroidism treatment. Development of TMSC spheroids may also provide a convenient and efficient scaffold-free platform for researchers investigating conditions involving abnormal calcium homeostasis, such as osteoporosis. [ABSTRACT FROM AUTHOR]

Controlling the senescence of mesenchymal stem cells (MSCs) is essential for improving the efficacy of MSC-based therapies. Here, a model of MSC senescence was established by replicative subculture in tonsil-derived MSCs (TMSCs) using senescence-associated β-galactosidase, telomere-length related genes, stemness, and mitochondrial metabolism. Using transcriptomic and proteomic analyses, we identified glucose-regulated protein 78 (GRP78) as a unique MSC senescence marker. With increasing cell passage number, GRP78 gradually translocated from the cell surface and cytosol to the (peri)nuclear region of TMSCs. A gelatin-based hydrogel releasing a sustained, low level of reactive oxygen species (ROS-hydrogel) was used to improve TMSC quiescence and self-renewal. TMSCs expressing cell surface-specific GRP78 (csGRP78+), collected by magnetic sorting, showed better stem cell function and higher mitochondrial metabolism than unsorted cells. Implantation of csGRP78+ cells embedded in ROS-hydrogel in rats with calvarial defects resulted in increased bone regeneration. Thus, csGRP78 is a promising biomarker of senescent TMSCs, and the combined use of csGRP78+ cells and ROS-hydrogel improved the regenerative capacity of TMSCs by regulating GRP78 translocation. [ABSTRACT FROM AUTHOR]