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Traumatic spinal cord injuries (SCIs) affect millions of people worldwide; the majority of whom are in the chronic phase of their injury. Unfortunately, most current treatments target the acute/subacute injury phase as the microenvironment of chronically injured cord consists of a well-established glial scar with inhibitory chondroitin sulfate proteoglycans (CSPGs) which acts as a potent barrier to regeneration. It has been shown that CSPGs can be degraded in vivo by intrathecal Chondroitinase ABC (ChABC) to produce a more permissive environment for regeneration by endogenous cells or transplanted neural stem cells (NSCs) in the subacute phase of injury. Using a translationally-relevant clip-contusion model of cervical spinal cord injury in mice we sought to determine if ChABC pretreatment could modify the harsh chronic microenvironment to enhance subsequent regeneration by induced pluripotent stem cell-derived NSCs (iPS-NSC). Seven weeks after injury—during the chronic phase—we delivered ChABC by intrathecal osmotic pump for one week followed by intraparenchymal iPS-NSC transplant rostral and caudal to the injury epicenter. ChABC administration reduced chronic-injury scar and resulted in significantly improved iPSC-NSC survival with clear differentiation into all three neuroglial lineages. Neurons derived from transplanted cells also formed functional synapses with host circuits on patch clamp analysis. Furthermore, the combined treatment led to recovery in key functional muscle groups including forelimb grip strength and measures of forelimb/hindlimb locomotion assessed by Catwalk. This represents important proof-of-concept data that the chronically injured spinal cord can be ‘unlocked’ by ChABC pretreatment to produce a microenvironment conducive to regenerative iPS-NSC therapy. [ABSTRACT FROM AUTHOR]

Study Design: An ambispective analysis.Objective: The aim of this study was to report the global prevalence of specific degenerative cervical pathologies in patients with degenerative cervical myelopathy (DCM) through detailed review of magnetic resonance imaging (MRIs).Summary Of Background Data: DCM encompasses a spectrum of age-related conditions that result in progressive spinal cord injury.Methods: MRIs of 458 patients (age 56.4 ± 11.8, 285 male, 173 female) were reviewed for specific degenerative features, directionality of cord compression, levels of spinal cord compression, and signal changes on sagittal T2-weighted imaging (T2WI) and sagittal T1-weighted imaging (T1WI). Data were analyzed for differences between sex using Chi-square tests and geographic variations using Kruskal-Wallis tests.Results: Spondylosis was frequently present (89.7%) and was commonly accompanied by enlargement of the ligamentum flavum (LF) (59.9%). Single-level disc pathology, ossification of posterior longitudinal ligament (OPLL), and spondylolisthesis had a prevalence of ∼10% each. OPLL was accompanied by spondylosis in 91.7%. Klippel-Feil syndrome was observed in 2.0%. The Asia-Pacific region had more OPLL (29%, P = 3 × 10) and less spondylolisthesis (1.9%, P = 0.002). Females presented more commonly with single-level disc pathology (13.9% vs. 6.7%; P = 0.013), and males with spondylosis (92.3% vs. 85.6%; P = 0.02) and enlargement of LF (61.4% vs. 49.1%; P = 0.01). C5 to C6 was the most frequent maximum compressed site (39.5%) and region for T2WI hyperintensity (38.9%). T2WI hyperintensity more commonly presented in males (82.4% vs. 66.7%; P < 0.001).Conclusion: This is the largest report on the prevalence and spectrum of pathology in patients with DCM. Herein, it has been demonstrated that degenerative features are highly interrelated, that females presented with milder MRI evidence of DCM, and that variations exist in the prevalence of pathologies between geographical regions.Level Of Evidence: 2. [ABSTRACT FROM AUTHOR]

Background: Although dysphagia is a common complication after anterior cervical decompression and fusion, important risk factors have not been rigorously evaluated. Furthermore, the impact of dysphagia on neurological and quality-of-life outcomes is not fully understood. The aim of this study was to determine the prevalence of and risk factors for dysphagia, and the impact of this complication on short and long-term clinical outcomes, in patients treated with anterior cervical decompression and fusion.Methods: Four hundred and seventy patients undergoing a 1-stage anterior or 2-stage anteroposterior cervical decompression and fusion were enrolled in the prospective AOSpine CSM (Cervical Spondylotic Myelopathy) North America or International study at 26 global sites. Logistic regression analyses were conducted to determine important clinical and surgical predictors of perioperative dysphagia. Preoperatively and at each follow-up visit, patients were evaluated using the modified Japanese Orthopaedic Association scale (mJOA), Nurick score, Neck Disability Index (NDI), and Short Form-36 Health Survey (SF-36). A 2-way repeated-measures analysis of covariance was used to evaluate differences in outcomes at 6 and 24 months between patients with and those without dysphagia, while controlling for relevant baseline characteristics and surgical factors.Results: The overall prevalence of dysphagia was 6.2%. Bivariate analysis showed the major risk factors for perioperative dysphagia to be a higher comorbidity score, older age, a cardiovascular or endocrine disorder, a lower SF-36 Physical Component Summary score, 2-stage surgery, and a greater number of decompressed levels. Multivariable analysis showed patients to be at an increased risk of perioperative dysphagia if they had an endocrine disorder, a greater number of decompressed segments, or 2-stage surgery. Both short and long-term improvements in functional, disability, and quality-of-life scores were comparable between patients with and those without dysphagia.Conclusions: The most important predictors of dysphagia are an endocrine disorder, a greater number of decompressed levels, and 2-stage surgery. At the time of both short and long-term follow-up, patients with perioperative dysphagia exhibited improvements in functional, disability, and quality-of life scores that were similar to those of patients without dysphagia.Level Of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Study Design: Analysis of a combined prospective dataset.Objective: To compare clinical outcomes in patients with and without preexisting depression or bipolar disorder undergoing surgery for degenerative cervical myelopathy (DCM).Summary Of Background Data: Psychiatric comorbidities, including depression, have been associated with worse clinical outcomes after lumbar spine surgery; however, it is unclear whether these psychiatric disorders are also predictive of outcomes in patients undergoing surgery for the treatment of DCM.Methods: Four hundred and one patients with symptomatic DCM were enrolled in the prospective AOSpine International or North America study at twelve North American sites. Patients were evaluated preoperatively and at 6, 12, and 24 months using the modified Japanese Orthopedic Association scale (mJOA), Nurick score, Neck Disability Index (NDI), and Short- Form 36v2 (SF-36v2) Health Survey. A mixed model analytic approach was used to evaluate differences in outcomes at 24 months among patients with and without psychiatric disorders, while controlling for relevant baseline characteristics and surgical factors.Results: Ninety-seven patients (24.19%) were diagnosed with preexisting depression or bipolar disorder. There were more females (65.98%) with these psychiatric disorders than males (34.02%) (P < 0.0001). Patients with psychiatric comorbidities were more likely to have cardiovascular (P = 0.0177), respiratory (P < 0.0001), gastrointestinal (P < 0.0001), rheumatologic (P = 0.0109), and neurologic (P = 0.0309) disorders. At 24 months after surgery, patients in both groups demonstrated significant improvements on the mJOA, Nurick, NDI, and SF-36v2 Physical Component Score (PCS). Patients with depression or bipolar disorder, however, did not exhibit a significant or clinically important change on the SF-36v2 Mental Component Score (MCS). There were no differences in mJOA and Nurick scores at 24 months among patients in each group. Improvement in NDI, SF-36v2 PCS, and MCS, however, were smaller in patients with depression or bipolar disorder than those without.Conclusion: Patients with depression or bipolar disorder have smaller functional and quality of life improvements after surgery compared to patients without psychiatric comorbidities.Level Of Evidence: 2. [ABSTRACT FROM AUTHOR]

Extramedullary hematopoiesis (EMH) occasionally occurs in patients exhibiting hematological disorders with decreased hematopoietic efficacy. EMH is rarely observed in the spinal epidural space and patients are usually asymptomatic. In particular, in the patients with polycythemia vera, spinal cord compression due to EMH is extremely rare. We report a case of polycythemia vera, in which operative therapy proved to be an effective treatment for myelopathy caused by spinal EMH. [ABSTRACT FROM AUTHOR]

Study Design: A prospective multicenter cohort study.Objective: The aim of this study was to compare outcomes of surgery for the treatment for degenerative cervical myelopathy (DCM) between Caucasians and East Asians.Summary Of Background Data: Numerous studies have indicated that race can influence both disease prevalence and clinical prognosis in a variety of medical conditions; however, none have evaluated the impact of race on surgical outcomes in patients with DCM.Methods: Four hundred and seventy-nine patients with symptomatic DCM were enrolled in the prospective AOSpine CSM-International study at 16 global sites. Preoperatively, and at each follow-up, patients were evaluated using the modified Japanese Orthopedic Association scale (mJOA), the Nurick score, the Neck Disability Index (NDI), and the Short- Form 36 (SF-36) Health Survey. A mixed-model analytic approach was used to evaluate differences in outcomes between races at 24 months postoperatively, while controlling for relevant baseline characteristics and surgical factors.Results: Three hundred and twenty-four (67.64%) patients were Caucasian and 106 (22.13%) were East Asian. There was no difference in the incidence of ossification of the posterior longitudinal ligament (OPLL) between the two races; however a greater percentage of Caucasians in India (46.15%) and Turkey (41.38%) displayed evidence of OPLL than Caucasians in other regions (P < 0.001). The frequency of spondylosis was significantly higher in Caucasians (P < 0.001). Caucasians had a longer duration of symptoms (27.33 ± 34.47 months) than East Asians (23.11 ± 35.68 months) (P < 0.001), and a lower preoperative score on the SF-36 Physical Component Score (33.85 ± 9.04) than East Asians (37.47 ± 8.67) (P < 0.001). At 24 months after surgery, there were no differences in functional status or QOL between East Asians and Caucasians, after adjusting for baseline characteristics, surgical preferences, and disease causation. Rates of perioperative complications were not significantly different between the races (P = 0.261).Conclusion: Decompressive surgery for DCM results in comparable functional gains and is equally safe in Caucasians and East Asians.Level Of Evidence: 2. [ABSTRACT FROM AUTHOR]

Favorable clinical outcomes have been described for elective spine surgery in patients with LSS. However, the way preoperative motor weakness (MW) affects the patient's health-related quality of life (HRQoL) after surgery is not well understood. This study sought to determine how baseline MW affects elective spine surgery in patients with degenerative lumbar spinal stenosis (LSS). Single center retrospective case series. This study included 305 surgically treated patients with LSS who had 2-year follow-up (age 71±9 years, male 62%). Demographic, radiographic, and clinical outcomes were analyzed. The Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) was used to assess the HRQoLs at baseline and at 1-year, 2-year, and 3-year postoperation. The HRQoLs were compared between those with or without preop MW. Adjusted multivariate logistic regression analyses (MRAs) were performed to determine whether MW affected HRQoLs. A total of 116 patients (38%) were categorized as MW+. The patient background including age, sex, presence of degenerative spondylolisthesis, type of surgery, and presence of neurological claudication were similar between the 2 groups. However, the 1-, 2-, and 3-year postoperative VAS of back pain, leg pain, leg numbness, JOABPEQ lumbar function, social life, mental health, and walking ability were all inferior in the MW+ group, whereas a similar percentage of patients achieved a minimum clinically important difference in all subdomains at 3 years. The adjusted MRA showed that having ≥2 muscles with MW, and severity of MW (MMT grade) were independent risk factors for both difficulty climbing stairs and walking >15 minutes (muscles with MW≥2; stair climbing: OR 6.4[2.3-17.4], walking: OR 3.2[1.4-7.3], severity of MW; stair climbing: OR 2.5[1.4-4.4], walking:OR 2.2[1.3-3.7]). The patients with baseline MW had inferior HRQoL for up to 3 years compared to that of those without MW; however, the amount of improvement in HRQoL was comparable. Timely follow-up is important to determine the deterioration of motor function. This abstract does not discuss or include any applicable devices or drugs. [ABSTRACT FROM AUTHOR]

Postoperative neck pain has been reported as an unsolved postoperative complication of surgery for cervical ossification of the posterior longitudinal ligament (OPLL). The aim of the present study was to elucidate factors having a significant association with postoperative deterioration of neck pain in cervical OPLL patients. We studied a cohort of patients in a prospective registry of 478 patients who had undergone cervical spine surgery for cervical OPLL. We excluded those without evaluation of preoperative neck pain. Therefore, 438 patients were included in the present study. Neck pain was evaluated with the visual analogue scale (VAS, 0–100 mm). Postoperative neck pain deterioration was defined as a ≥20 mm increase of VAS neck pain. Patient factors, neurological status, imaging factors and surgical factors were assessed. Univariate analyses followed by multivariate analysis using stepwise logistic regression was performed. Six months after surgery, 50 (11.6%) patients showed postoperative neck pain deterioration and 76 (17.4%) patients showed postoperative neck pain deterioration 2 years after surgery. Six months after surgery, the rate of neck pain deterioration was significantly higher in patients who had undergone posterior surgery. Two years after surgery, the number of levels fused was significantly correlated with neck pain deterioration. [ABSTRACT FROM AUTHOR]

Rehabilitative treatment, including treadmill training, is considered an important strategy for restoring motor function after spinal cord injury (SCI). However, many unexplained problems persist regarding the appropriate rehabilitative method and the mechanism underlying the beneficial effects of rehabilitation. Moreover, only a few preclinical studies have been performed on rehabilitative interventions for chronic SCI, although most patients have chronic injuries. In fact, several preclinical studies reported that rehabilitative training was less effective when applied during the chronic phase than when applied sooner. While numerous studies have examined the effects of treadmill training during the subacute phase, the training conditions vary considerably among preclinical reports. Therefore, establishing a standard training protocol is essential for achieving beneficial rehabilitation effects at the chronic stage. Since the difficulty of applying an appropriate training load hinders training at constant speeds, it is important to adjust the training intensity in accordance with the exercise tolerance of an individual animal to provide further functional recovery benefits. Here, we created a novel quadrupedal treadmill training protocol based on the overload principle for mice with incomplete thoracic SCI. We subjected SCI model mice to rehabilitative training according to the protocol for two consecutive weeks starting at 42 days after injury. We examined the treadmill speeds at which the mice were able to run based on the severity of paresis and investigated the impact of the protocol on functional recovery. Assessment of running speed changes during the treadmill training period revealed faster treadmill speeds for mice with mild paresis than for those with severe paresis. The training parameters, including the speed and distance traveled, were positively correlated with the changes in motor function. These results suggest that the most suitable running speed during treadmill training differs according to the level of motor dysfunction and that running longer distances has a positive impact on motor functional recovery. Based on this established protocol, we compared functional and histological results between the chronic SCI groups with and without rehabilitation. The gait analyses showed significantly better functional improvement in the rehabilitation group than in the nonrehabilitation group. Histological analyses revealed that the BDNF- and VGLUT1-positive areas of lumbar enlargement were significantly increased in the rehabilitation group. These findings implied that rehabilitation promoted not only motor performance but also motor control, including forelimb-hindlimb coordination, even in chronic SCI, resulting in functional improvement by treadmill training alone. Therefore, rehabilitative training based on the overload principle appears to be one of the appropriate treatment options for incomplete thoracic SCI, and evidence of its efficacy exists in actual clinical settings. • We developed a novel treadmill training protocol based on the overload principle for mice with incomplete thoracic SCI. • Spinal cord-injured mice with milder paresis could adapt to a faster treadmill speed than those with more severe paresis. • Motor functional recovery correlated with the distance traveled. • Treadmill training based on the overload principle had a positive impact on motor function and histological results. [ABSTRACT FROM AUTHOR]

In chronic kidney disease, fibroblast dysfunction causes renal fibrosis and renal anemia. Renal fibrosis is mediated by the accumulation of myofibroblasts, whereas renal anemia is mediated by the reduced production of fibroblast-derived erythropoietin, a hormone that stimulates erythropoiesis. Despite their importance in chronic kidney disease, the origin and regulatory mechanism of fibroblasts remain unclear. Here, we have demonstrated that the majority of erythropoietin-producing fibroblasts in the healthy kidney originate from myelin protein zero-Cre (P0-Cre) lineage-labeled extrarenal cells, which enter the embryonic kidney at E13.5. In the diseased kidney, P0-Cre lineage-labeled fibroblasts, but not fibroblasts derived from injured tubular epithelial cells through epithelial-mesenchymal transition, transdifferentiated into myofibroblasts and predominantly contributed to fibrosis, with concomitant loss of erythropoietin production. We further demonstrated that attenuated erythropoietin production in transdifferentiated myofibroblasts was restored by the administration of neuroprotective agents, such as dexamethasone and neurotrophins. Moreover, the in vivo administration of tamoxifen, a selective estrogen receptor modulator, restored attenuated erythropoietin production as well as fibrosis in a mouse model of kidney fibrosis. These findings reveal the pathophysiological roles of P0-Cre lineage-labeled fibroblasts in the kidney and clarify the link between renal fibrosis and renal anemia. [ABSTRACT FROM AUTHOR]

Multipotent somatic stem cells have been identified in various adult tissues. However, the stem/progenitor cells of the peripheral nerves have been isolated only from fetal tissues. Here, we isolated Schwann-cell precursors/immature Schwann cells from the injured peripheral nerves of adult mice using a floating culture technique that we call "Schwann-spheres." The Schwann-spheres were derived from de-differentiated mature Schwann cells harvested 24 hours to 6 weeks after peripheral nerve injury. They had extensive self-renewal and differentiation capabilities. They strongly expressed the immature- Schwann-cell marker p75, and differentiated only into the Schwann-cell lineage. The spheres showed enhanced myelin formation and neurite growth compared to mature Schwann cells in vitro. Mature Schwann cells have been considered a promising candidate for cell-transplantation therapies to repair the damaged nervous system, whereas these "Schwannspheres" would provide a more potential autologous cell source for such transplantation. [ABSTRACT FROM AUTHOR]

Various types of induced pluripotent stem (iPS) cells have been established by different methods, and each type exhibits different biological properties. Before iPS cell-based clinical applications can be initiated, detailed evaluations of the cells, including their differentiation potentials and tumorigenic activities in different contexts, should be investigated to establish their safety and effectiveness for cell transplantation therapies. Here we show the directed neural differentiation of murine iPS cells and examine their therapeutic potential in a mouse spinal cord injury (SCI) model. "Safe" iPS-derived neurospheres, which had been pre-evaluated as nontumorigenic by their transplantation into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse brain, produced electrophysiologically functional neurons, astrocytes, and oligodendrocytes in vitro. Furthermore, when the safe iPS-derived neurospheres were transplanted into the spinal cord 9 d after contusive injury, they differentiated into all three neural lineages without forming teratomas or other tumors. They also participated in remyelination and induced the axonal regrowth of host 5HT+ serotonergic fibers, promoting locomotor function recovery. However, the transplantation of iPS-derived neurospheres pre-evaluated as "unsafe" showed robust teratoma formation and sudden locomotor functional loss after functional recovery in the SCI model. These findings suggest that pre-evaluated safe iPS clone-derived neural stem/progenitor cells may be a promising cell source for transplantation therapy for SCI. [ABSTRACT FROM AUTHOR]

Background: While several mouse strains have recently been developed for tracing neural crest or oligodendrocyte lineages, each strain has inherent limitations. The connection between human SOX10 mutations and neural crest cell pathogenesis led us to focus on the Sox10 gene, which is critical for neural crest development. We generated Sox10-Venus BAC transgenic mice to monitor Sox10 expression in both normal development and in pathological processes. Results: Tissue fluorescence distinguished neural crest progeny cells and oligodendrocytes in the Sox10-Venus mouse embryo. Immunohistochemical analysis confirmed that Venus expression was restricted to cells expressing endogenous Sox10. Time-lapse imaging of various tissues in Sox10-Venus mice demonstrated that Venus expression could be visualized at the single-cell level in vivo due to the intense, focused Venus fluorescence. In the adult Sox10-Venus mouse, several types of mature and immature oligodendrocytes along with Schwann cells were clearly labeled with Venus, both before and after spinal cord injury. Conclusions: In the newly-developed Sox10-Venus transgenic mouse, Venus fluorescence faithfully mirrors endogenous Sox10 expression and allows for in vivo imaging of live cells at the single-cell level. This Sox10-Venus mouse will thus be a useful tool for studying neural crest cells or oligodendrocytes, both in development and in pathological processes. [ABSTRACT FROM AUTHOR]

Abstract: Mesenchymal stem cells (MSCs) are a heterogeneous subset of stromal stem cells isolated from many adult tissues. Previous studies reported that MSCs can differentiate to both mesodermal and neural lineages by a phenomenon referred to as ‘‘dedifferentiation’’ or ‘‘transdifferentiation’’. However, since MSCs have only been defined in vitro, much of their development in vivo is still unknown. Here, we prospectively identified MSCs in the bone marrow from adult transgenic mice encoding neural crest-specific P0-Cre/Floxed-EGFP and Wnt1-Cre/Floxed-EGFP. EGFP-positive MSCs formed spheres that expressed neural crest stem cell genes and differentiated into neurons, glial cells, and myofibroblasts. Interestingly, we observed MSCs both in the GFP+ and GFP− fraction and found that there were no significant differences in the in vitro characteristics between these two populations. Our results suggest that MSCs in adult bone marrow have at least two developmental origins, one of which is the neural crest. [Copyright &y& Elsevier]

Background: This study investigated how diffuse idiopathic skeletal hyperostosis (DISH) influences clinical characteristics in patients with cervical ossification of the posterior longitudinal ligament (OPLL). Although DISH is considered unlikely to promote neurologic dysfunction, this relationship remains unclear. Methods: Patient data were prospectively collected from 16 Japanese institutions. In total, 239 patients with cervical OPLL were enrolled who had whole-spine computed tomography images available. The primary outcomes were visual analog scale pain scores and the results of other self-reported clinical questionnaires. Correlations were sought between clinical symptoms and DISH using the following grading system: 1, DISH at T3-T10; 2, DISH at both T3–10 and C6–T2 and/or T11–L2; and 3, DISH beyond the C5 and/or L3 levels. Results: DISH was absent in 132 cases, grade 1 in 23, grade 2 in 65, and grade 3 in 19. There were no significant correlations between DISH grade and clinical scores. However, there was a significant difference in the prevalence of neck pain (but not in back pain or low back pain) among the three grades. Interestingly, DISH localized in the thoracic spine (grade 1) may create overload at the cervical spine and lead to neck pain in patients with cervical OPLL. Conclusion: This study is the first prospective multicenter cross-sectional comparison of subjective outcomes in patients with cervical OPLL according to the presence or absence of DISH. The severity of DISH was partially associated with the prevalence of neck pain. [ABSTRACT FROM AUTHOR]

Ossification of the posterior longitudinal ligament (OPLL) is commonly associated with diabetes mellitus (DM); however, the impact of DM on cervical spine surgery for OPLL remains unclear. This study was performed to evaluate the influence of diabetes DM on the outcomes following cervical spine surgery for OPLL. In total, 478 patients with cervical OPLL who underwent surgical treatment were prospectively recruited from April 2015 to July 2017. Functional measurements were conducted at baseline and at 6 months, 1 year, and 2 years after surgery using JOA and JOACMEQ scores. The incidence of postoperative complications was categorized into early (≤30 days) and late (>30 days), depending on the time from surgery. From the initial group of 478 patients, 402 completed the 2-year follow-up and were included in the analysis. Of the 402 patients, 127 (32%) had DM as a comorbid disease. The overall incidence of postoperative complications was significantly higher in patients with DM than in patients without DM in both the early and late postoperative periods. The patients with DM had a significantly lower JOA score and JOACMEQ scores in the domains of lower extremity function and quality of life than those without DM at the 2-year follow-up. [ABSTRACT FROM AUTHOR]

This study aimed to clarify whether ossification predisposition influences clinical symptoms including pain, restriction of activities of daily living, and quality of life in patients with cervical ossification of the posterior longitudinal ligament (OPLL). Cervical ossification predisposition potentially causes neurologic dysfunction, but the relationship between clinical symptoms and radiologic severity of OPLL has not yet been investigated. Data were prospectively collected from 16 institutions across Japan. We enrolled 239 patients with cervical OPLL. The primary outcomes were patient-reported outcomes, including visual analog scale (VAS) pain scores and other questionnaires. Whole-spine computed tomography images were obtained, and correlations were investigated between clinical symptoms and radiologic findings, including the distribution of OPLL, the sum of the levels where OPLL was present (OP-index), and the canal narrowing ratio (CNR) grade. The cervical OP-index was Grade 1 in 113 patients, Grade 2 in 90, and Grade 3 in 36. No significant correlations were found between radiologic outcomes and VAS pain scores. The cervical OP-index was associated with lower extremity function, social dysfunction, and locomotive function. The CNR grade was not correlated with clinical symptoms, but Grade 4 was associated with lower extremity dysfunction. Thickness and extension of ossified lesions may be associated with lower extremity dysfunction in cervical OPLL. [ABSTRACT FROM AUTHOR]

The transplantation of neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs) has beneficial effects on spinal cord injury (SCI). However, while there are many subtypes of NPCs with different regional identities, the subtype of iPSC-derived NPCs that is most appropriate for cell therapy for SCI has not been identified. Here, we generated forebrain- and spinal cord-type NPCs from human iPSCs and grafted them onto the injured spinal cord in mice. These two types of NPCs retained their regional identities after transplantation and exhibited different graft-host interconnection properties. NPCs with spinal cord regional identity but not those with forebrain identity resulted in functional improvement in SCI mice, especially in those with mild-to-moderate lesions. This study highlights the importance of the regional identity of human iPSC-derived NPCs used in cell therapy for SCI. [ABSTRACT FROM AUTHOR]