Expression of neurotrophic factors in injured spinal cord after transplantation of human-umbilical cord blood stem cells in rats.

We induced percutaneous spinal cord injuries (SCI) using a balloon catheter in 45 rats and transplanted human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) at the injury site. Locomotor function was significantly improved in hUCB-MSCs transplanted groups. Quantitative ELISA of extract from entire injured spinal cord showed increased expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3). Our results show that treatment of SCI with hUCB-MSCs can improve locomotor functions, and suggest that increased levels of BDNF, NGF and NT-3 in the injured spinal cord were the main therapeutic effect.

Improved rat spinal cord injury model using spinal cord compression by percutaneous method.

Here, percutaneous spinal cord injury (SCI) methods using a balloon catheter in adult rats are described. A balloon catheter was inserted into the epidural space through the lumbosacral junction and then inflated between T9-T10 for 10 min under fluoroscopic guidance. Animals were divided into three groups with respect to inflation volume: 20 µL (n = 18), 50 µL (n = 18) and control (Fogarty catheter inserted but not inflated; n = 10). Neurological assessments were then made based on BBB score, magnetic resonance imaging and histopathology. Both inflation volumes produced complete paralysis. Gradual recovery of motor function occurred when 20 µL was used, but not after 50 µL was applied. In the 50 µL group, all gray and white matter was lost from the center of the lesion. In addition, supramaximal damage was noted, which likely prevented spontaneous recovery. This percutaneous spinal cord compression injury model is simple, rapid with high reproducibility and the potential to serve as a useful tool for investigation of pathophysiology and possible protective treatments of SCI in vivo.

Percutaneous transplantation of human umbilical cord-derived mesenchymal stem cells in a dog suspected to have fibrocartilaginous embolic myelopathy.

The use of human umbilical cord blood-derived mesenchymal stem cells for cell transplantation therapy holds great promise for repairing spinal cord injury. Here we report the first clinical trial transplantation of human umbilical cord (hUCB)-derived mesenchymal stem cells (MSCs) into the spinal cord of a dog suspected to have fibrocartilaginous embolic myelopathy (FCEM) and that experienced a loss of deep pain sensation. Locomotor functions improved following transplantation in a dog. Based on our findings, we suggest that transplantation of hUCB-derived MSCs will have beneficial therapeutic effects on FCEM patients lacking deep pain sensation.

Schwann cell-like remyelination following transplantation of human umbilical cord blood (hUCB)-derived mesenchymal stem cells in dogs with acute spinal cord injury.

Human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) have significant therapeutic potential in cell-based therapies following spinal cord injury (SCI). To evaluate this potential, we conducted our preliminary investigations on the remyelination of injured spinal cords with hUCB-MSC transplantations and we observed its long term effects on dogs with SCI. Of the ten injured dogs, seven were transplanted with hUCB-MSCs 1 week after SCI, whereas the remaining three dogs were not transplanted. Two transplanted dogs died over the first month after transplantation because of urinary tract infection, bedsores and sepsis. The SCI dogs showed no improvement in motor and sensory functions and their urinary dysfunction persisted until they were euthanized (from 3 months to 1 year) while hind-limb recovery in 4 dogs among the five transplanted dogs was significantly improved. In the recovered dogs, functional recovery was sustained for three years following transplantation. Histological results from five transplanted dogs showed that many axons were remyelinated by P0-positive myelin sheaths after transplantation. Our results suggest that transplantation of hUCB-derived MSCs may have beneficial therapeutic effects. Furthermore, histological results provided the first in vivo evidence that hUCB-MSCs are able to enhance the remyelination of peripheral-type myelin sheaths following SCI.

Anterior segment parameters using Pentacam and prediction of corneal endothelial cell loss after cataract surgery.

PURPOSE: We evaluated various preoperative anterior segment parameters measured with a Pentacam rotating Scheimpflug camera and compared them with those of conventional methods. We also evaluated the effect of different parameters on corneal endothelial cells after cataract surgery. METHODS: Pentacam examination was performed in 88 eyes from 88 patients to evaluate central anterior chamber depth (ACD(pentacam)), nuclear density (Densitometry(pentacam)), anterior chamber volume (ACV), and lens thickness (LT(pentacam)). We compared values of ACD(pentacam) with those of ultrasound (ACD(sono)) and also compared Densitometry(pentacam) values with those of Lens Opacities Classification System (LOCS III) classification. We evaluated the effect of the following preoperative values measured with Pentacam on postoperative endothelial cell loss: pupil size measured both preoperatively and before capsulorrhexsis (Pupil(CCC)), amount of viscoelastics, and LT measured by ultrasound (LT(sono)). RESULTS: A SIGNIFICANT CONCORDANCE WAS FOUND BETWEEN THE TWO GRADING METHODS OF NUCLEAR OPACITY: Densitometry(pentacam) and LOCS III classification (τ(b) = 0.414, p = 0.000). We also found a positive correlation between ACD(pentacam) and ACD(sono) (r = 0.823, p = 0.000) and between ACD(pentacam) and ACV (r = 0.650, p = 0.000). There were significant differences between the results of LT(pentacam) and LT(sono). The final regression model identified Densitometry(pentacam), viscoelastics and Pupil(CCC) as independent predictors of decreased postoperative corneal endothelial cell density (CD) at postoperative day 3, and Densitometry(pentacam), viscoelastics, and ACV as independent predictors of decreased CD two months postoperatively (p<0.05). CONCLUSIONS: Good agreement was found between all results obtained with the Pentacam and conventional methods except LT. Analyzing anterior chamber parameters preoperatively using Pentacam could be helpful to predict postoperative endothelial cell loss.

Risk factors for endothelial cell loss after phacoemulsification: comparison in different anterior chamber depth groups.

PURPOSE: To assess the risk factors for endothelial cell loss after phacoemulsification with implantation of intraocular lens according to anterior chamber depth (ACD). METHODS: This prospective study included 94 eyes of 94 patients undergoing phacoemulsification cataract surgery. To assess the risk factors for corneal endothelial cell loss, we examined seven variables at 1 day, 1 week, 6 weeks, and 12 weeks postoperatively in each ACD-stratified group. RESULTS: Multiple linear regression analysis showed that the only variable influencing the percentage decrease in corneal endothelial cell density throughout the postoperative follow-up period in the long ACD group (ACD III) was nucleosclerosis. The variables influencing the percentage decrease in corneal endothelial cell density in the short ACD group (ACD I) at one day and one week postoperatively were corneal incisional tunnel length and nucleosclerosis. CONCLUSIONS: Risk factors for endothelial cell loss after phaoemulsification were different according to ACD. Long corneal tunnel length can be one of the risk factors for endothelial cell loss in short ACD eyes.

Percutaneous transplantation of human umbilical cord blood-derived multipotent stem cells in a canine model of spinal cord injury.

OBJECT: The authors describe a method for percutaneous transplantation of human umbilical cord blood (hUCB)-derived multipotent stem cells (MSCs) under fluoroscopic guidance. The investigators then tested whether percutaneous transplantation of hUCB-derived MSCs improved neurological functional recovery after acute spinal cord injury (SCI). METHODS: The authors induced SCI in 10 dogs by percutaneous balloon compression. The 10 injured dogs were assigned randomly to the following groups (2 dogs each): Group 1, evaluated 2 weeks after sham transplantation; Group 2, evaluated 2 weeks after transplantation; Group 3, evaluated 4 weeks after sham transplantation; Group 4, evaluated 4 weeks after transplantation; and Group 5, evaluated 4 weeks after multispot transplantations. The dogs with sham transplantation (Groups 1 and 3) received the same volume of saline, as a control. A spinal needle was advanced into the spinal canal, and the investigators confirmed that the end of the spinal needle was located in the ventral part of spinal cord parenchyma by using contrast medium under fluoroscopic guidance. The hUCB-derived MSCs were transplanted into the cranial end of the injured segment in 6 injured dogs at 7 days after SCI. RESULTS: Two dogs in Group 2 showed no improvement until 2 weeks after transplantation. Three of 4 dogs (Groups 4 and 5) that received cellular transplants exhibited gradual improvement in hindlimb locomotion from 3 weeks after cell transplantation. The CM-DiI-labeled hUCB-derived MSCs were observed in the spinal cord lesions at 4 weeks posttransplantation and exerted a significant beneficial effect by reducing cyst and injury size. The transplanted cells were positive for NeuN, glial fibrillary acidic protein, and von Willebrand factor. CONCLUSIONS: The percutaneous transplantation technique described here can be easily performed, and it differs from previous techniques by avoiding surgical exposure and allowing cells to be more precisely transplanted into the spinal cord. This technique has many potential applications in the treatment of human SCI by cell transplantation. The results also suggest that transplantation of hUCB-derived MSCs may have therapeutic effects that decrease cavitation for acute SCI.

Development of an improved canine model of percutaneous spinal cord compression injury by balloon catheter.

We developed a minimally invasive canine model of spinal cord injury (SCI). A balloon catheter was inserted into the epidural space via the lumbosacral space, and inflated between L2 and L3 for 30 or 60 min under fluoroscopic guidance. Motor function after SCI was assessed using modified Tarlov scale. All seven dogs showed complete paraplegia after the procedure, neurological problems were evident and the modified Tarlov scores remained at zero after the SCI procedure; no improvement in clinical signs was observed. The dogs underwent 3T MR imaging at 3 days and 1 year after SCI. Histopathologic examinations were conducted at 2 weeks, 12 weeks and 1 year after SCI. In the present study, we described an animal model of minimally invasive spinal cord injury using a balloon catheter without laminectomy under fluoroscopic guidance. And, this percutaneous spinal cord compression injury model has many potential applications. The described percutaneous spinal cord compression injury model offers a new means of administering SCI and has many potential applications.

Infiltrative lipoma in cervical bones in a dog.

A 4-year-old, neutered male Maltese presented with a 2-month history of right hemiparesis. The radiographic findings revealed bone lysis, and sclerotic changes in the right section of the fifth and sixth cervical bones with a mild radiolucent mass around the lesion. The magnetic resonance imaging revealed a hyperintense mass located in the region extending from the muscles to the bones and compressing the spinal cord. The mass was removed via a hemilaminectomy in the cervical area using the ventral and dorsal approach, and a histological examination confirmed that it was adipose tissue. An infiltrative lipoma was diagnosed based on these findings. The dog has ambulated normally for 24 months since undergoing surgery.