Recent studies have shown that mesenchymal stem cell (MSC)-based therapy might be an effective approach for the treatment of intervertebral disc degeneration (IDD). However, many unanswered questions remain before clinical translation, such as the most effective stem cell type, a reliable transplantation method, including the carrier choice, and the fate of stem cells after misdirected delivery, among others. The objective of the study was to evaluate the fate and effect of allogenic bone marrow MSCs after transplantation into an IDD model. The L2-3, L3-4 and L4-5 intervertebral discs (IVDs) of four rabbits were stabbed to create IDD. Rabbit MSCs were expanded in vitro and in part transduced with retrovirus/eGFP. After 3 weeks, 1 × 10(5) MSCs were injected into the IVDs. The rabbits were followed by X-ray and MRI 3 and 9 weeks after injection. Then the animals were sacrificed and the spines analysed histologically. MRI showed no signs of regeneration. X-ray and gross anatomy inspection demonstrated large anterolateral osteophytes. Histological analysis showed that the osteophytes were composed of mineralized tissue surrounded by chondrocytes, with the labelled MSCs among the osteophyte-forming cells. The labelled MSCs were not found in the nucleus. Inflammatory cells were not observed in any injected IVDs. These results raise concern that MSCs can migrate out of the nucleus and undesirable bone formation may occur. While cause cannot be inferred from this study, the presence of MSCs in the osteophytes suggests a potential side-effect with this approach. IVD regeneration strategies need to focus on cell carrier systems and annulus-sealing technologies to avoid pitfalls.

Despite previous studies on the restoration of tactile sensation on the fingers and the hand, there are no examples of use of the routed sensory information to finely control the prosthesis hand in complex grasp and manipulation tasks. Here it is shown that force and slippage sensations can be elicited in an amputee subject by means of biologically-inspired slippage detection and encoding algorithms, supported by a stick-slip model of the performed grasp. A combination of cuff and intraneural electrodes was implanted for eleven weeks in a young woman with hand amputation, and was shown to provide close-to-natural force and slippage sensations, paramount for significantly improving the subject’s manipulative skills with the prosthesis. Evidence is provided about the improvement of the subject’s grasping and manipulation capabilities over time, thanks to neural feedback. The elicited tactile sensations enabled the successful fulfillment of fine grasp and manipulation tasks with increasing complexity. Grasp performance was quantitatively assessed by means of instrumented objects and a purposely developed metrics. Closed-loop control capabilities enabled by the neural feedback were compared to those achieved without feedback. Further, the work investigates whether the described amelioration of motor performance in dexterous tasks had as central neurophysiological correlates changes in motor cortex plasticity and whether such changes were of purely motor origin, or else the effect of a strong and persistent drive of the sensory feedback.

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This study clarifies the mechanism of MSCs and NPCs interaction in a 3-dimensional environment, excluding cell fusion. These data support the use of undifferentiated MSC for stem cell therapy for IDD treatment.