Chronic low back pain (LBP) remains a challenging condition to treat, and especially to cure. If conservative treatment approaches fail, the current “gold standard” for intervertebral disc degeneration (IDD)-provoked back pain is spinal fusion. However, due to its invasive and destructive nature, the focus of orthopedic research related to the intervertebral disc (IVD) has shifted more towards cell-based therapeutic approaches. They aim to reduce or even reverse the degenerative cascade by mimicking the human body’s physiological healing system. The implementation of progenitor and/or stem cells and, in particular, the delivery of mesenchymal stromal cells (MSCs) has revealed significant potential to cure the degenerated/injured IVD. Over the past decade, many research groups have invested efforts to find ways to utilize these cells as efficiently and sustainably as possible. This narrative literature review presents a summary of achievements made with the application of MSCs for the regeneration of the IVD in recent years, including their preclinical and clinical applications. Moreover, this review presents state-of-the-art strategies on how the homing capabilities of MSCs can be utilized to repair damaged or degenerated IVDs, as well as their current limitations and future perspectives.

Introduction: Cell transplantation shows promising results for intervertebral disc (IVD) repair, however, contemporary strategies present concerns regarding needle puncture damage, cell retention, and straining the limited nutrient availability. Mesenchymal stromal cell (MSC) homing is a natural mechanism of long‐distance cellular migration to sites of damage and regeneration. Previous ex vivo studies have confirmed the potential of MSC to migrate over the endplate and enhance IVD‐matrix production. In this study, we aimed to exploit this mechanism to engender IVD repair in a rat disc degeneration model.Methods: Female Sprague Dawley rats were subjected to coccygeal disc degeneration through nucleus pulposus (NP) aspiration. In part 1; MSC or saline was transplanted into the vertebrae neighboring healthy or degenerative IVD subjected to irradiation or left untouched, and the ability to maintain the IVD integrity for 2 and 4 weeks was assessed by disc height index (DHI) and histology. For part 2, ubiquitously GFP expressing MSC were transplanted either intradiscally or vertebrally, and regenerative outcomes were compared at days 1, 5, and 14 post‐transplantation. Moreover, the homing potential from vertebrae to IVD of the GFP⁺ MSC was assessed through cryosection mediated immunohistochemistry.Results: Part 1 of the study revealed significantly improved maintenance of DHI for IVD vertebrally receiving MSC. Moreover, histological observations revealed a trend of IVD integrity maintenance. Part 2 of the study highlighted the enhanced DHI and matrix integrity for discs receiving MSC vertebrally compared with intradiscal injection. Moreover, GFP rates highlighted MSC migration and integration in the IVD at similar rates as the intradiscally treated cohort.Conclusion: Vertebrally transplanted MSC had a beneficial effect on the degenerative cascade in their neighboring IVD, and thus potentially present an alternative administration strategy. Further investigation will be needed to determine the long‐term effects, elucidate the role of cellular homing versus paracrine signaling, and validate our observations on a large animal model.

Purpose: This study aims to analyze the effect of pro-inflammatory cytokine-stimulated human annulus fibrosus cells (hAFCs) on the sensitization of dorsal root ganglion (DRG) cells. We further hypothesized that celecoxib (cxb) could inhibit hAFCs-induced DRG sensitization. Methods: hAFCs from spinal trauma patients were stimulated with TNF-α or IL-1β. Cxb was added on day 2. On day 4, the expression of pro-inflammatory and neurotrophic genes was evaluated using RT-qPCR. Levels of prostaglandin E2 (PGE-2), IL-8, and IL-6 were measured in the conditioned medium (CM) using ELISA. hAFCs CM was then applied to stimulate the DRG cell line (ND7/23) for 6 days. Then, calcium imaging (Fluo4) was performed to evaluate DRG cell sensitization. Both spontaneous and bradykinin-stimulated (0.5 μM) calcium responses were analyzed. The effects on primary bovine DRG cell culture were performed in parallel to the DRG cell line model. Results: IL-1ß stimulation significantly enhanced the release of PGE-2 in hAFCs CM, while this increase was completely suppressed by 10 µM cxb. hAFCs revealed elevated IL-6 and IL-8 release following TNF-α and IL-1β treatment, though cxb did not alter this. The effect of hAFCs CM on DRG cell sensitization was influenced by adding cxb to hAFCs; both the DRG cell line and primary bovine DRG nociceptors showed a lower sensitivity to bradykinin stimulation. Conclusion: Cxb can inhibit PGE-2 production in hAFCs in an IL-1β-induced pro-inflammatory in vitro environment. The cxb applied to the hAFCs also reduces the sensitization of DRG nociceptors that are stimulated by the hAFCs CM.

Introduction: Patients and physicians often underestimate cat bite injuries. The deep and narrow wound seals quickly and provides an environment for the inoculated saliva and bacteria. Interestingly, the literature reports no bacterial growth in the microbiological workup of wound swaps in up to 43%. The time between bite injury and the first clinical presentation, the start of antibiotic treatment and surgical debridement might affect these findings. Therefore, the current project examines if (1) these factors impact the outcome of microbiological results following cat bite injuries and (2) the detection of bacterial growth leads to higher complication rates, longer hospital stays, longer total treatment time, or higher total treatment costs. Materials and methods: This single-center retrospective study analyzed data from 102 adult patients. All patients received antibiotic and surgical treatment following a cat bite injury. Microbiological samples were collected during surgery in all cases. The time from the bite incident to the first presentation, beginning of antibiotic administration, and surgical debridement was calculated. Demographic data, complication rate, length of hospital stay, total treatment time, and total treatment costs were recorded. (1) A generalized linear model was fitted using the microbiological outcome as the dependent variable. (2) Two groups (negative or positive microbiological results) were formed and statistically compared. Results: The median age was 50 (SD 16), and 72% were female. (1) The time from the bite incident to the first clinical presentation, antibiotic administration, or surgical treatment was not associated with the outcome of the microbiological result. (2) No significant differences were observed between the two groups. Conclusions: Our data do not suggest that early antibiotic administration or delayed surgical treatment affects the outcome of the microbiological workup following cat bite injuries to the hand and forearm. The microbiological outcome did not affect the complication rate, treatment time, and total treatment costs.

Isolated fractures of the greater tuberosity represent up to 20% of all proximal humeral fractures. Conservative and surgical treatment strategies are reported. Fracture displacement on radiographs is a key factor in treatment decisions, but the accuracy of measurement methods can limit this process. This study aimed to (Aim I) assess the inter- and intraobserver reliability of established radiographic measurements of fracture displacement and (Aims II/III) determine if these measurements can predict superior, posterior, or combined superior + posterior fracture displacement quantified on CT scans in a patient cohort. Forty-nine cases of isolated greater tuberosity fractures with complete radiographs and CT scans were analyzed. (Aim I) Displacement was measured on radiographs in millimeters as superior ('sup') and lateral ('lat') displacement, along with Mutch's superior ratio ('sGT'), anterior/posterior ratio ('apGT'), and Nyffeler's impingement index ('I-Ind'). Reliability was assessed by three independent observers. (Aim II) A humerus saw-bone model with predefined superior, posterior, and combined fracture displacements was used to validate a CT-based measurement technique. (Aim III) This CT-based method was applied to patient CT scans, and linear regression was used to test if radiographic measurements predicted the CT-measured displacements. (Aim I) Inter- and intraobserver reliability was excellent for 'I-Ind' (inter 0.98/intra 0.94), good-excellent for 'lat' (0.82/0.76) and 'sGT' (0.75/0.94), and moderate for 'sup' (0.73/0.66) and 'apGT' (0.64/0.49). (Aim II) The CT-based technique accurately measured superior (R²=0.99), posterior (R²=0.99), and combined (R²=0.99) displacement. (Aim III) Patient CT scans showed mean displacement of 3.3±2.5 mm superior, 8.4±5.6 mm posterior, and 11.6±7 mm combined. Superior displacement correlated with 'sup' (p<0.001), posterior with 'lat' (p<0.001), 'apGT' (p=0.004), 'I-Ind' (p=0.048), and combined displacement with 'lat' (p<0.001) and 'apGT' (p=0.006). In fractures displaced ≥5mm, 'sup' (p=0.002) correlated with superior, 'lat' (p=0.003) and 'I-Ind' (p=0.049) with posterior, and 'lat' (p<0.001) with combined displacement. The CT-based technique accurately measured fragment displacement in the saw-bone model. For fractures with ≥5mm displacement, 'lat' was the best predictor of combined displacement (interobserver reliability: 0.82-0.94). However, in the reported cohort, 'lat' underestimated the "true" fragment displacement. Therefore, in 'lat' measurements ≥ 3mm, a CT scan for quantification of fragment displacement should be considered. However, these findings must be confirmed in bigger patient populations before clinical translation.