Intrathecal injection of human placental mesenchymal stem cells derived exosomes significantly improves functional recovery in spinal cord injured rats.

BACKGROUND: Spinal cord injury (SCI) due to lack of restoration of damaged neuronal cells is associated with sensorimotor impairment. This study was focused on using the human placental mesenchymal stem cells- exosome (HPMSCs- Exosomes) in an animal model of severe SCI under myelogram procedure. METHODS AND RESULTS: Intrathecal injection of exosomes was performed in the acute phase of SCI in female rats. The improved functional recovery of the animals was followed for 6 weeks in control (saline, n = 6) and HPMSCs- EXO (HPMSCs-Exosomes, n = 6) groups. Pathological changes and glial scar size were evaluated. The Immunohistochemistry (IHC) of GFAP and NF200 factors as well as the apoptosis assay was investigated in the tissue samples from the injury site. The results demonstrated that HPMSCs-exosomes can improve motor function by attenuating apoptosis of neurons at the injury site, decreasing GFAP expression and increasing NF200 in the HPMSCs-EXO group. Also, HPMSCs-exosomes by preventing the formation of cavities causes preservation of tissue in SCI rats. CONCLUSIONS: These findings demonstrate the effectiveness of HPMSC-Exosomes as a therapeutic method to improve functional recovery, reduce pathological changes associated with injury, and prevent chronicity after SCI. The neuroprotective and anti-apoptotic potential of HPMSCs- Exosomes may be a promising therapeutic approach for SCI. Another result was the importance of intrathecal injection of exosomes in the acute phase, which accelerated the healing process. Furthermore, the myelogram can be a feasible and suitable method to confirm the accuracy of intrathecal injection and examine the subarachnoid space in the laboratory animals.

Occurrence of myxoma in a bearded dragon (Pogona vitticeps): Surgical and histopathological studies.

Myxoma is a benign mesenchymal tumor of skin and soft connective tissues considered to be of fibroblastic origin. A female bearded dragon (Pogona vitticeps) with a raised mass on the left side of the body was referred to the Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran. The mass had become evident and grew more extensive within the previous 11-month period. The dragon was anesthetized with 5.00% isoflurane, and the mass was removed surgically. Tissue samples of the mass were fixed in 10.00% neutral buffered formalin, sectioned and stained with Hematoxylin and Eosin (H&E), Alcian blue (pH: 2.50), and periodic acid Schiff (PAS) staining techniques. The patient was administered meloxicam, lincomycin, and marbofloxacin. Histopathologically, the capsulated mass was composed of myxoid structure. Stellate-to-reticular cells distributed in a mucinous stroma containing few tiny blood vessels were seen. Myxoid cells displayed a PAS-positive cytoplasm. The myxomatous matrix was alcianophilic at the pH of 2.50. To our knowledge, this is the first report of surgery, treatment, and histopathological study of myxoma in a bearded dragon (P. vitticeps). The sutures were also removed 12 days after the operation. No new growth of the mass was observed three months following the surgical procedures.

Prevention of Peritendinous Adhesion Formation After the Flexor Tendon Surgery in Rabbits: A Comparative Study Between Use of Local Interferon-α, Interferon-ß, and 5-Fluorouracil.

BACKGROUND: Peritendinous adhesion is the most common complication after tendon surgery, particularly in zone II of the hand. Prevention of inflammation around the tendon, which develops after trauma and surgery, can decrease the tendon adhesion formation. This study compares the effect of some anti-inflammatory cytokines with 5-fluorouracil (5-FU) on the tensile strength and in prevention of peritendinous adhesion formation. METHODS: Sixteen rabbits were allocated equally into 4 groups. Tendons of the index and ring fingers in zone II of the right hind paw were cut in all animals and then repaired. Interferon (IFN)-α in group 1, 5-FU in group 2, normal saline in group 3, and IFN-ß in group 4 were locally applied to the repaired sites. Three weeks later, tensometric and histopathologic evaluations were performed. RESULTS: The force required for removing the tendon from the sheath was not different between the groups (P = 0.130), but the time required for removal was significantly shorter in 5-FU group (P = 0.049). The strength of repair was not different between the groups in terms of force and time needed for rupture (P = 0.11 and 0.67, respectively). In histopathologic examination, normal architecture of the tendon and peritendon environment was less disturbed in the IFN groups, especially in IFN-ß specimens. CONCLUSIONS: Local application of 5-FU significantly reduced peritendinous adhesion. Local IFN-α and IFN-ß had no significant effect on the prevention of peritendinous adhesion formation. The strength of the repair was not affected by these cytokines and 5-FU.

Transected sciatic nerve repair by diode laser protein soldering.

BACKGROUND AND OBJECTIVE: Despite advances in microsurgical techniques, repair of peripheral nerve injuries (PNI) is still a major challenge in regenerative medicine. The standard treatment for PNI includes suturing and anasthomosis of the transected nerve. The objective of this study was to compare neurorraphy (nerve repair) using standard suturingto diode laser protein soldering on the functional recovery of transected sciatic nerves. STUDY DESIGN/MATERIALS AND METHODS: Thirty adult male Fischer-344 Wistar rats were randomly assigned to 3 groups: 1. The control group, no repair, 2. the standard of care suture group, and 3. The laser/protein solder group. For all three groups, the sciatic nerve was transected and the repair was done immediately. For the suture repair group, 10.0 prolene suture was used and for the laser/protein solder group a diode laser (500mW output power) in combination with bovine serum albumen and indocyanine green dye was used. Behavioral assessment by sciatic functional index was done on all rats biweekly. At 12weeks post-surgery, EMG recordings were done on all the rats and the rats were euthanized for histological evaluation of the sciatic nerves. The one-way ANOVA test was used for statistical analysis. RESULTS: The average time required to perform the surgery was significantly shorter for the laser-assisted nerve repair group compared to the suture group. The EMG evaluation revealed no difference between the two groups. Based on the sciatic function index the laser group was significantly better than the suture group after 12weeks (p<0.05). Histopathologic evaluation indicated that the epineurium recovery was better in the laser group (p<0.05). There was no difference in the inflammation between the suture and laser groups. CONCLUSION: Based on this evidence, laser/protein nerve soldering is a more efficient and efficacious method for repair of nerve injury compared to neurorraphy using standard suturing methods.

Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells with Platelet-Rich Plasma Accelerate Distraction Osteogenesis in A Canine Model.

OBJECTIVE: Distraction osteogenesis (DO) is a surgical procedure used to generate large volumes of new bone for limb lengthening. MATERIALS AND METHODS: In this animal experimental study, a 30% lengthening of the left tibia (mean distraction distance: 60.8 mm) was performed in ten adult male dogs by callus distraction after osteotomy and application of an Ilizarov fixator. Distraction was started on postoperative day seven with a distraction rate of 0.5 mm twice per day and carried out at a rate of 1.5 mm per day until the end of the study. Autologous bone marrow mesenchymal stem cells (BM-MSCs) and platelet-rich plasma (PRP) as the treatment group (n=5) or PRP alone (control group, n=5) were injected into the distracted callus at the middle and end of the distraction period. At the end of the consolidation period, the dogs were sacrificed after which computerized tomography (CT) and histomorphometric evaluations were performed. RESULTS: Radiographic evaluationsrevealed that the amount and quality of callus formations were significantly higher in the treatment group (P<0.05). As measured by CT scan, the healing parametersin dogs of the treatment group were significantly greater (P<0.05). New bone formation in the treatment group was significantly higher (P<0.05). CONCLUSION: The present study showed that the transplantation of BM-MSCs positively affects early bony consolidation in DO. The use of MSCs might allow a shortened period of consolidation and therefore permit earlier device removal.

Diced ear cartilage with perichondrial attachment in rhinoplasty: a new concept.

BACKGROUND: Diced cartilage is a valuable material that has recently been added to the graft options in rhinoplasty. Shaping, fixation, and resorption are the main concerns with this material. Perichondrially attached diced conchal cartilage may be a new possibility to solve some of these problems. OBJECTIVES: The authors evaluate the outcome of perichondrially attached diced cartilage in a rabbit model and compare the results with injectable cartilage grafting. METHODS: Ear cartilage was removed from 1 auricle in each of the 16 rabbits included in this study; samples were divided in 2 pieces. After precise weighing, both segments were diced. The perichondrium was left attached to 1 of the pieces. Both segments were inserted in 2 separate pockets in the dorsum of the animal. After a 3-month period, both samples were removed and measured for growth/resorption. RESULTS: At the beginning of this study, the difference in weight between groups was statistically insignificant (P = .213), but 3 months after insertion, significant growth was observed in the perichondrial group (P = .019). CONCLUSIONS: The vascularization and significant growth in weight of the perichondrially attached diced cartilage samples are evidence of the viability of this material. The structural integrity and solid framework afforded by this option suggest that the material should be used more frequently in nasoskeletal augmentation.

A comparison between neurally induced bone marrow derived mesenchymal stem cells and olfactory ensheathing glial cells to repair spinal cord injuries in rat.

Cell therapy has proven to be a highly promising method in clinical applications, raising so much hope for the treatment of injured tissues with low, if any, self regeneration potential such as central and peripheral nervous system. Neurally induced bone marrow derived mesenchymal stem cells (NIMSCs) as well as olfactory ensheathing cells (OECs) were transplanted in a rat model of sub-acute spinal cord injury and the behavioral and histological analyses were conducted. A balloon-compression technique was used to produce an injury at T8-T9 level of spinal cord. After a week post injury, rats were injected with either NIMSCs or OECs at the center of developing lesion cavity, 3mm cranial and 3mm caudal to the cavity. Weekly behavioral assessment using BBB score was done over five-week period post transplantation and finally histological assessment was performed to locate labeled cells in the tissue in order to evaluate the reduction of cavity formation and axonal regeneration. Evaluation of locomotor performance showed significant behavioral improvement in NIMSC group over OEC and control groups. The histological analyses revealed the presence of transplanted cells in the spinal cord parenchyma. Volume of injured area that was occupied with syrinx cavity in NIMSC group was significantly less than control group. In addition, meanwhile neurofilament-positive axons significantly showed higher expression in rats receiving NIMSC compared to the other two groups. In conclusion NIMSC caused both behavioral and histological improvement that potentially makes them a promising candidate for cell therapy approaches of spinal cord injuries.

Survival of block and fascial-wrapped diced cartilage grafts: an experimental study in rabbits.

INTRODUCTION: Cartilage grafts have become an integral part in plastic surgery. Classic autogenous cartilage harvesting techniques are associated with significant donor- and recipient-site morbidity. The use of cartilage micrografts wrapped in a sleeve was first developed to decrease the complication rates of block cartilage grafts. The aim of this study was to compare the resorption rate of solid block cartilage graft and diced cartilage wrapped in fascia graft in rabbits. MATERIALS AND METHODS: In 12 rabbits, 1 solid block cartilage and 1 diced graft wrapped in fascia were implanted in subcutaneous pockets. By the end of the fourth month, the cartilage implants were dissected free and photographed and weighed exactly. Then specimens were stained with hematoxylin and eosin to determine their architectural characteristics. RESULTS: In the solid block cartilage graft group, the means ± standard deviation preimplant weight values were 5.34 ± 1.68. The weight was changed to 7.74 ± 3.26. The change was not statistically significant. In diced cartilage grafts wrapped in fascia, the means ± standard deviation preimplanted weight values were 8.13 ± 1.83. These values were changed to 2.79 ± 1.97, meaning statistically significant resorption of diced cartilage grafts wrapped in fascia (P < 0.001). In histologic examination, block cartilage grafts showed viable cartilage but diced cartilage grafts wrapped in fascia yielded fibrosis and inflammatory cell infiltration. CONCLUSION: The amplitude of resorption of the diced cartilage wrapped in fascia is considerable compared with one-piece block grafts. It may be anticipated that the enthusiasm for this technique will decline once the long-term results of pertaining clinical studies are available.