Bone defects caused by trauma, severe infection, tumor resection and skeletal abnormalities are common osteoporotic conditions and major challenges in orthopedic surgery, and there is still no effective solution to this problem. Consequently, new treatments are needed to develop regeneration procedures without side effects. Exosomes secreted by mesenchymal stem cells (MSCs) derived from human induced pluripotent stem cells (hiPSCs, hiPSC-MSC-Exos) incorporate the advantages of both MSCs and iPSCs with no immunogenicity. However, there are no reports on the application of hiPSC-MSC-Exos to enhance angiogenesis and osteogenesis under osteoporotic conditions. HiPSC-MSC-Exos were isolated and identified before use. The effect of hiPSC-MSC-Exos on the proliferation and osteogenic differentiation of bone marrow MSCs derived from ovariectomized (OVX) rats (rBMSCs-OVX) in vitro were investigated. In vivo, hiPSC-MSC-Exos were implanted into critical size bone defects in ovariectomized rats, and bone regeneration and angiogenesis were examined by microcomputed tomography (micro-CT), sequential fluorescent labeling analysis, microfil perfusion and histological and immunohistochemical analysis. The results in vitro showed that hiPSC-MSC-Exos enhanced cell proliferation and alkaline phosphatase (ALP) activity, and up-regulated mRNA and protein expression of osteoblast-related genes in rBMSCs-OVX. In vivo experiments revealed that hiPSC-MSC-Exos dramatically stimulated bone regeneration and angiogenesis in critical-sized calvarial defects in ovariectomized rats. The effect of hiPSC-MSC-Exos increased with increasing concentration. In this study, we showed that hiPSC-MSC-Exos effectively stimulate the proliferation and osteogenic differentiation of rBMSCs-OVX, with the effect increasing with increasing exosome concentration. Further analysis demonstrated that the application of hiPSC-MSC-Exos+β-TCP scaffolds promoted bone regeneration in critical-sized calvarial defects by enhancing angiogenesis and osteogenesis in an ovariectomized rat model.

We discuss a general scheme for creating atomic spin-orbit coupling (SOC) such as the Rashba or Dresselhaus types using magnetic-field-gradient pulses. In contrast to conventional schemes based on adiabatic center-of-mass motion with atomic internal states restricted to a dressed-state subspace, our scheme works for the complete subspace of a hyperfine-spin manifold by utilizing the coupling between the atomic magnetic moment and external magnetic fields. A spatially dependent pulsed magnetic field acts as an internal-state-dependent impulse, thereby coupling the atomic internal spin with its orbital center-of-mass motion, as in the Einstein-de Haas effect. This effective coupling can be dynamically manipulated to synthesize SOC of any type (Rashba, Dresselhaus, or any linear combination thereof). Our scheme can be realized with most experimental setups of ultracold atoms and is especially suited for atoms with zero nuclear spins.

Squeezed spin states possess unique quantum correlation or entanglement that are of significant promises for advancing quantum information processing and quantum metrology. In recent back to back publications [C. Gross et al, Nature 464, 1165 and Max F. Riedel et al, Nature 464, 1170Nature 464, (2010], reduced spin fluctuations are observed leading to spin squeezing at −8.2dB and −2.5dB respectively in two-component atomic condensates exhibiting one-axis-twisting interactions (OAT). The noise reduction limit for the OAT interaction scales as ∝ 1/N 2/3 , which for a condensate with N ∼ 10 3 atoms, is about 100 times below standard quantum limit. We present a scheme using repeated Rabi pulses capable of transforming the OAT spin squeezing into the two-axis-twisting type, leading to Heisenberg limited noise reduction ∝ 1/N , or an extra 10-fold improvement for N ∼ 10 3 .PACS numbers: 42.50.-p, 03.75.GgSqueezed spin states (SSS) [2,3] are entangled quantum states of a collection of spins in which the correlations among individual spins reduce quantum uncertainty of a particular spin component below the classical limit for uncorrelated particles [2]. Research in SSS is a topical area due to its significant applications in high-precision measurements [3][4][5][6][7][8][9][10] and in quantum information science [11][12][13][14][15]. Squeezed spin states were first introduced by Kitagawa and Ueda, who considered two ways to produce them. The simplest to implement uses a "one-axis twisting" (OAT) Hamiltonian, but the state it produces does not have ideal squeezing properties. A more complex approach uses a "two-axis twisting" (TAT) Hamiltonian and produces an improved state. Other mechanisms for producing SSS have also been investigated, especially those based on atom-photon interactions [16,17] and quantum non-demolition measurements [18][19][20][21].Atomic Bose-Einstein condensates are promising systems for observing spin squeezing. Assuming fixed spatial modes, condensed atoms are described by a collection of pseudo-spin 1/2 atoms, with spin up (|↑ ) and down (|↓ ) denoting the two internal states or spatial modes [12,[22][23][24][25]. The two recent experiments [4, 5] raise significant hope for reaching the theoretical limit of spin squeezing ∝ 1/N 2/3 with N the total number of atoms for the OAT model [2]. Both experiments utilize two internal hyperfine states of condensed atoms, with the OAT interaction cleverly constructed from binary atomic collisions, possibly accompanied by systematic and fundamental imperfections not confined to the two state/mode approximation. They can be further degraded by atomic decoherence and dissipation [4,5]. This Letter describes a readily implementable idea for improved spin squeezing in the two experiments. Given the reported OAT model parameters [4,5], we propose a coherent control scheme capable of transforming the OAT into the effective TAT spin squeezing, leading to a Heisenberg limited noise reduction ∝ 1/N , or a further 10 fold improvement for a condensate with ∼ 10 3 at...

Inflammatory cytokines play a major role in cartilage destruction in diseases such as osteoarthritis and rheumatoid arthritis. Because physical therapies such as continuous passive motion yield beneficial effects on inflamed joints, we examined the intracellular mechanisms of mechanical strain-mediated actions in chondrocytes. By simulating the effects of continuous passive motion with cyclic tensile strain (CTS) on chondrocytes in vitro, we show that CTS is a potent antagonist of IL-1β actions and acts as both an anti-inflammatory and a reparative signal. Low magnitude CTS suppresses IL-1β-induced mRNA expression of multiple proteins involved in catabolic responses, such as inducible NO synthase, cyclo-oxygenase II, and collagenase. CTS also counteracts cartilage degradation by augmenting mRNA expression for tissue inhibitor of metalloproteases and collagen type II that are inhibited by IL-1β. Additionally, CTS augments the reparative process via hyperinduction of aggrecan mRNA expression and abrogation of IL-1β-induced suppression of proteoglycan synthesis. Nonetheless, the presence of an inflammatory signal is a prerequisite for the observed CTS actions, as exposure of chondrocytes to CTS alone has little effect on these parameters. Functional analysis suggests that CTS-mediated anti-inflammatory actions are not mediated by IL-1R down-regulation. Moreover, as an effective antagonist of IL-1β, the actions of CTS may involve disruption/regulation of signal transduction cascade of IL-1β upstream of mRNA transcription. These observations are the first to show that CTS directly acts as an anti-inflammatory signal on chondrocytes and provide a molecular basis for its actions.