Mesenchymal stem cells (MSCs) are usually cultured in a normoxic atmosphere (21%) in vitro, while the oxygen concentrations in human tissues and organs are 1% to 10% when the cells are transplanted in vivo. However, the impact of hypoxia on MSCs has not been deeply studied, especially its translational application. In the present study, we investigated the characterizations of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in hypoxic (1%) and normoxic (21%) atmospheres with a long-term culture from primary to 30 generations, respectively. The comparison between both atmospheres systematically analyzed the biological functions of MSCs, mainly including stemness maintenance, immune regulation, and resistance to chondrocyte apoptosis, and studied their joint function and anti-inflammatory effects in osteoarthritis (OA) rats constructed by collagenase II.Aims
Methods
Cervical spinal arthrodesis is the standard of care for the treatment of spinal diseases induced neck pain. However, adjacent segment disease (ASD) is the primary postoperative complication, which draws great concerns. At present, controversy still exists for the etiology of ASD. Knowledge of cervical spinal loading pattern after cervical spinal arthrodesis is proposed to be the key to answer these questions. Musculoskeletal (MSK) multi-body dynamics (MBD) models have an opportunity to obtain spinal loading that is very difficult to directly measure in vivo. In present study, a previously validated cervical spine MSK MBD model was developed for simulating cervical spine after single-level anterior arthrodesis at C5-C6 disc level. In this cervical spine model, postoperative sagittal alignment and spine rhythms of each disc level, different from normal healthy subject, were both taken into account. Moreover, the biomechanical properties of facet joints of adjacent levels after anterior arthrodesis were modified according to the experimental results. Dynamic full range of motion (ROM) flexion/extension simulation was performed, where the motion data after arthrodesis was derived from published in-vivo kinematic observations. Meanwhile, the full ROM flexion/extension of normal subject was also simulated by the generic cervical spine model for comparative purpose. The intervertebral compressive and shear forces and loading-sharing distribution (the proportions of intervertebral compressive and shear force and facet joint force) at adjacent levels (C3-C4, C4-C5 and C6-C7 disc levels) were then predicted. By comparison, arthrodesis led to a significant increase of adjacent intervertebral compressive force during the head extension movement. Postoperative intervertebral compressive forces at adjacent levels increased by approximate 20% at the later stage of the head extension movement. However, there was no obvious alteration in adjacent intervertebral compressive force, during the head flexion movement. For the intervertebral shear forces in the anterior-posterior direction, no significant differences were found between the arthrodesis subject and normal subject, during the head flexion/extension movement. Meanwhile, cervical spinal loading-sharing distribution after anterior arthrodesis was altered compared with the normal subject's distribution, during the head extension movement. In the postoperative loading-sharing distribution, the percentage of intervertebral disc forces was further increased as the motion angle increased, compared with normal subject. In conclusion, cervical spinal loading after anterior arthrodesis was significantly increased at adjacent levels, during the head extension movement. Cervical spine musculoskeletal MBD model provides an attempt to comprehend postoperative ASD after anterior arthrodesis from a biomechanical perspective.