Subarachnoid transplantation of human umbilical cord mesenchymal stem cell in rodent model with subacute incomplete spinal cord injury: Preclinical safety and efficacy study.

Functional multipotency renders human umbilical cord mesenchymal stem cell (hUC-MSC) a promising candidate for the treatment of spinal cord injury (SCI). However, its safety and efficacy have not been fully understood for clinical translation. In this study, we performed cellular, kinematic, physiological, and anatomical analyses, either in vitro or in vivo, to comprehensively evaluate the safety and efficacy associated with subarachnoid transplantation of hUC-MSCs in rats with subacute incomplete SCI. Concerning safety, hUC-MSCs were shown to have normal morphology, excellent viability, steady proliferation, typical biomarkers, stable karyotype in vitro, and no tumorigenicity both in vitro and in vivo. Following subarachnoid transplantation of hUC-MSCs in the subject rodents, the biodistribution of hUC-MSCs was restricted to the spinal cord, and no toxicity to immune system or organ function was observed. Body weight, organ weight, and the ratio of the latter upon the former between stem cell-transplanted rats and placebo-injected rats revealed no statistical differences. Regarding efficacy, hUC-MSCs could differentiate into osteoblasts, chondrocytes, adipocytes and neural progenitor cells in vitro. While in vivo studies revealed that subarachnoid transplantation of stem cells resulted in significant improvement in locomotion, earlier automatic micturition recovery and reduced lesion size, which correlated with increased regeneration of tracking fiber and reduced parenchymal inflammation. In vivo luminescence imaging showed that a few of the transplanted luciferase-labeled hUC-MSCs tended to migrate towards the lesion epicenter. Shortened latency and enhanced amplitude were also observed in both motor and sensory evoked potentials, indicating improved signal conduction in the damaged site. Immunofluorescent staining confirmed that a few of the administrated hUC-MSCs integrated into the spinal cord parenchyma and differentiated into astrocytes and oligodendrocytes, but not neurons. Moreover, decreased astrogliosis, increased remyelination, and neuron regeneration could be observed. To the best of our knowledge, this preclinical study provides detailed safety and efficacy evidence regarding intrathecal transplantation of hUC-MSCs in treating SCI for the first time and thus, supports its initiation in the following clinical trial.

Dose optimization of intrathecal administration of human umbilical cord mesenchymal stem cells for the treatment of subacute incomplete spinal cord injury.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising candidate for spinal cord injury (SCI) repair owing to their advantages of low immunogenicity and easy accessibility over other MSC sources. However, modest clinical efficacy hampered the progression of these cells to clinical translation. This discrepancy may be due to many variables, such as cell source, timing of implantation, route of administration, and relevant efficacious cell dose, which are critical factors that affect the efficacy of treatment of patients with SCI. Previously, we have evaluated the safety and efficacy of 4 × 106 hUC-MSCs/kg in the treatment of subacute SCI by intrathecal implantation in rat models. To search for a more accurate dose range for clinical translation, we compared the effects of three different doses of hUC-MSCs - low (0.25 × 106 cells/kg), medium (1 × 106 cells/kg) and high (4 × 106 cells/kg) - on subacute SCI repair through an elaborate combination of behavioral analyses, anatomical analyses, magnetic resonance imaging-diffusion tensor imaging (MRI-DTI), biotinylated dextran amine (BDA) tracing, electrophysiology, and quantification of mRNA levels of ion channels and neurotransmitter receptors. Our study demonstrated that the medium dose, but not the low dose, is as efficient as the high dose in producing the desired therapeutic outcomes. Furthermore, partial restoration of the γ-aminobutyric acid type A (GABAA) receptor expression by the effective doses indicates that GABAA receptors are possible candidates for therapeutic targeting of dormant relay pathways in injured spinal cord. Overall, this study revealed that intrathecal implantation of 1 × 106 hUC-MSCs/kg is an alternative approach for treating subacute SCI.

Quantification of lumbar vertebral fat deposition: Correlation with menopausal status, non-alcoholic fatty liver disease and subcutaneous adipose tissue.

Purpose: To assess abdominal fat deposition and lumbar vertebra with iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL-IQ) and investigate their correlation with menopausal status. Materials and Methods: Two hundred forty women who underwent routine abdominal MRI and IDEAL-IQ between January 2016 and April 2021 were divided into two cohorts (first cohort: 120 pre- or postmenopausal women with severe fatty livers or without fatty livers; second cohort: 120 pre- or postmenopausal women who were obese or normal weight). The fat fraction (FF) values of the liver (FFliver) and lumbar vertebra (FFlumbar) in the first group and the FF values of subcutaneous adipose tissue (SAT) (FFSAT) and FFlumbar in the second group were measured and compared using IDEAL-IQ. Results: Two hundred forty women were evaluated. FFlumbar was significantly higher in both pre- and postmenopausal women with severe fatty liver than in patients without fatty livers (premenopausal women: p < 0.001, postmenopausal women: p < 0.001). No significant difference in the FFlumbar was observed between obese patients and normal-weight patients among pre- and postmenopausal women (premenopausal women: p = 0.113, postmenopausal women: p = 0.092). Significantly greater lumbar fat deposition was observed in postmenopausal women than in premenopausal women with or without fatty liver and obesity (p < 0.001 for each group). A high correlation was detected between FFliver and FFlumbar in women with severe fatty liver (premenopausal women: r=0.76, p<0.01; postmenopausal women: r=0.82, p<0.01). Conclusion: Fat deposition in the vertebral marrow was significantly associated with liver fat deposition in postmenopausal women.

Short-Term Effect of Lumbar Traction on Intervertebral Discs in Patients with Low Back Pain: Correlation between the T2 Value and ODI/VAS Score.

OBJECTIVE: The effect of lumbar traction on low back pain (LBP) patients is controversial. Our study aims to assess changes in the intervertebral disc water content after lumbar traction using T2 mapping and explore the correlation between changes in the T2 value and Oswestry Disability Index (ODI)/visual analogue scale (VAS) score. DESIGN: Lumbar spine magnetic resonance imaging was performed, and the ODI/VAS scores were recorded in all 48 patients. Midsagittal T2-weighted imaging and T2 mapping were performed to determine the Pfirrmann grade and T2 value. Then, the T2 values were compared between pre- and posttraction, and the correlation between changes in the T2 value and ODI/VAS scores were examined. RESULTS: In the traction group, the changes in the nucleus pulposus (NP) T2 values for Pfirrmann grades II-IV and the annulus fibrosus (AF) T2 values for Pfirrmann grade II were statistically significant after traction (P < 0.05). Changes in the mean NP T2 value of 5 discs in each patient and in the ODI/VAS score showed a strong correlation (r = 0.822, r = 0.793). CONCLUSION: T2 mapping can be used to evaluate changes in the intervertebral disc water content. Ten sessions of traction resulted in a significant increase in quantitative T2 measurements of the NP in discs for Pfirrmann grade II-IV degeneration and remission of the patients' clinical symptoms in the following 6 months. Changes in the mean NP T2 value of 5 discs in each patient were strongly correlated with changes in the ODI/VAS score.

Quantification of penile fat infiltration using the mDIXON Quant sequence: a pilot study on the correlation with penis hardness and erectile dysfunction.

OBJECTIVE: The purpose of this study was to determine fat/water signal ratios using the mDIXON Quant sequence, quantitatively assess fat infiltration in the penis, and explore its possible relationship with penile hardness and erectile dysfunction. METHODS: Routine pelvic MRI with the mDIXON Quant sequence was performed in 62 subjects, including 22 people in the normal group, 20 people in the normal erectile hardness group, and 20 people in the erectile dysfunction (ED) group. The fat/water signal ratio in the penis was measured using the mDIXON Quant sequence. Shear wave elastography was used to evaluate the hardness of the corpus cavernosa of the penis. RESULTS: The fat/water signal ratio of the corpus spongiosum was significantly lower than that of the corpus cavernosa in the normal group (p = 0.03) and ED group (p < 0.01). There was no significant difference in the fat/water signal ratios between the normal group and the normal erectile hardness group. Fat infiltration was significantly lower, and erectile hardness was significantly higher in the normal erectile hardness group than in the ED group, and the fat infiltration in the left and right corpus cavernosa was inversely proportional to the erectile hardness of the penis. CONCLUSION: This study suggests that mDIXON Quant can be used as a non-invasive, quantitative, and objective method for evaluating penile fat infiltration. This method could help diagnose penile fat infiltration in patients with erectile dysfunction and varying body mass indexes. Our results could also allow for a more accurate diagnosis and monitoring of erectile hardness function by quantitatively measuring penile fat infiltration. ADVANCES IN KNOWLEDGE: (1) The proton density fat fraction technology is a new tool for the objective, quantitative and non-invasive evaluation of penile fat infiltration. (2) The quantitative measurement of fat infiltration in the corpora cavernosa might help diagnose and monitor penile erection hardness and its function more accurately.

Quantification of fat deposition in the testis and epididymis using mDIXON Quant sequence: correlation with age and ejaculation.

PURPOSE: The objective of this study was to quantitatively assess fat deposition in the testis and epididymis by measuring the fat/water signal ratios with mDIXON Quant and to investigate its correlation with age and ejaculation. MATERIALS AND METHODS: Routine pelvic magnetic resonance imaging and mDIXON Quant were performed on 120 subjects. The fat/water signal ratios of the testis and epididymis were measured based on the fat/water signal intensity on mDIXON Quant. RESULTS: The fat/water signal ratio values of the testis and epididymis in the early adulthood group (0.952-3.550%, p < 0.05, and 5.182-12.725%, p < 0.05, respectively) were significantly higher than those in the late childhood group (0.611-2.198% and 1.310-4.520%) and in the youth group (0.659-2.360% and 1.568-4.469%), and they were lower than those in the middle adulthood group (1.538-4.249%, p < 0.05, and 5.830-19.002%, p < 0.05). The fat deposition decreased in the testis of the youth group, who ejaculated more than ten times per month (0.750-2.022%, p < 0.05), and the fat/water signal ratios of the epididymis decreased in one subject in the early adulthood group who had three ejaculations within 12 h. CONCLUSION: The findings of this study suggest that mDIXON Quant may be useful as a noninvasive, quantitative, and objective method for evaluating the fat deposition of the testis and epididymis. This method can provide guidance for fat deposition in the testis and epididymis in different age groups with varying ejaculation experiences. Additionally, our findings may facilitate more accurate diagnosis and monitoring of the reproductive function of the testis and epididymis by quantitatively measuring their fat deposition with age.