Safety and efficiency of Wharton's Jelly-derived mesenchymal stem cell administration in patients with traumatic brain injury: First results of a phase I study.

BACKGROUND: Traumatic brain injury (TBI) is characterized by a disruption in the normal function of the brain due to an injury following a trauma, which can potentially cause severe physical, cognitive, and emotional impairment. Stem cell transplantation has evolved as a novel treatment modality in the management of TBI, as it has the potential to arrest the degeneration and promote regeneration of new cells in the brain. Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) have recently shown beneficial effects in the functional recovery of neurological deficits. AIM: To evaluate the safety and efficiency of MSC therapy in TBI. METHODS: We present 6 patients, 4 male and 2 female aged between 21 and 27 years who suffered a TBI. These 6 patients underwent 6 doses of intrathecal, intramuscular (i.m.) and intravenous transplantation of WJ-MSCs at a target dose of 1 × 106/kg for each application route. Spasticity was assessed using the Modified Ashworth scale (MAS), motor function according to the Medical Research Council Muscle Strength Scale, quality of life was assessed by the Functional Independence Measure (FIM) scale and Karnofsky Performance Status scale. RESULTS: Our patients showed only early, transient complications, such as subfebrile fever, mild headache, and muscle pain due to i.m. injection, which resolved within 24 h. During the one year follow-up, no other safety issues or adverse events were reported. These 6 patients showed improvements in their cognitive abilities, muscle spasticity, muscle strength, performance scores and fine motor skills when compared before and after the intervention. MAS values, which we used to assess spasticity, were observed to statistically significantly decrease for both left and right sides (P < 0.001). The FIM scale includes both motor scores (P < 0.05) and cognitive scores (P < 0.001) and showed a significant increase in pretest posttest analyses. The difference observed in the participants' Karnofsky Performance Scale values pre and post the intervention was statistically significant (P < 0.001). CONCLUSION: This study showed that cell transplantation has a safe, effective and promising future in the management of TBI.

Phase I study on the safety and preliminary efficacy of allogeneic mesenchymal stem cells in hypoxic-ischemic encephalopathy.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is a leading cause of morbidity and mortality in the adult as well as in the neonate, with limited options for treatment and significant dysfunctionality. AIM: To investigate the safety and preliminary efficacy of allogeneic mesenchymal stem cells (MSCs) in HIE patients. METHODS: Patients who had HIE for at least 6 mo along with significant dysfunction and disability were included. All patients were given Wharton's jelly-derived MSCs at 1 × 106/kg intrathecally, intravenously, and intramuscularly twice a month for two months. The therapeutic effects and prognostic implications of MSCs were evaluated by multiple follow-ups. Functional independence measure (FIM), modified Ashworth, and Karnofsky scales were used to assess any side effects, neurological and cognitive functions, and overall outcomes. RESULTS: The 8 subjects included in the study had a mean age of 33.25 ± 10.18 years. Mean HIE exposure and mean post-HIE durations were 45.63 ± 10.18 and 19.67 ± 29.04 mo, respectively. Mean FIM score was 18.38 ± 1.06, mean modified Ashworth score was 43.5 ± 4.63, and mean Karnofsky score was 20. For the first 24 h, 5 of the patients experienced a subfebrile state, accompanied by mild headaches due to intrathecally administration and muscle pain because of intramuscularly administration. Neurological and functional examinations, laboratory tests, electroencephalography, and magnetic resonance imaging were performed to assess safety of treatment. Mean FIM score increased by 20.88 ± 3.31 in the first month (P = 0.027) and by 31.38 ± 14.69 in 12 mo (P = 0.012). The rate of patients with an FIM score of 126 increased from 14.58% to 16.57% in the first month and 24.90% in 12 mo. CONCLUSION: Multiple triple-route Wharton's jelly-derived MSC administrations were found to be safe for HIE patients, indicating neurological and functional improvement. Based on the findings obtained here, further randomized and placebo research could be performed.

Functional Recovery After Wharton's Jelly-Derived Mesenchymal Stem Cell Administration in a Patient with Traumatic Brain Injury: A Pilot Study.

AIM: To introduce a traumatic brain injury (TBI) patient who underwent stem cell transplantation (SCT) in order to minimize the remaining injury deficiencies. MATERIAL AND METHODS: This study included a 29 years old male who had TBI resulting from a vehicle accident which took place one and a half years ago. The participant received six doses of intrathecal, intramuscular, and intravenous transplantation of Wharton?s jellv-derived mesenchymal stem cells (WJ-MSCs) at a goal dose of 1xl0 < sup > 6 < /sup > / kg respectively for each route of administration for six months. RESULTS: No important negative effects were reported. The patients? speech, cognitive, memory and fine motor skills were improved. The efficacy of treatment with SCT was assessed with cranial magnetic resonance imaging (MRI), computed tomography (CT) screening, and electroencephalography (EEG). CONCLUSION: SCT can have a promising future as a medical approach in recurrent TBI.

Kyphoplasty in the Early Oncologic Diagnosis and Treatment of Vertebral Fractures: A Clinical Study.

AIM: To elucidate the characteristics of kyphoplasty in correlation with spinal metastasis. MATERIAL AND METHODS: Data of patients treated by kyphoplasty between January 2017 and December 2019 were reviewed retrospectively. Preoperative prophylactic antibiotics and low-molecular-weight heparin injections were performed. Postoperative follow-up was conducted at least 24 hours after the procedure. All patients were treated under sedoanalgesia. Bone biopsies were collected from all patients. RESULTS: One hundred ninety-nine vertebra fractures were treated in 130 patients. The mean age of the patients was 65.27 ± 8.79 years (18?90 years) and 66 patients were male (50.7%). Forty-five patients had osteoporosis, six patients showed malignancy, and osteomyelitis was found in three patients, while the others? presentations were secondary to trauma. Most commonly, the L1 (n=59), Th12 (n=45), and L2 (n=34) levels were found to develop vertebral fractures. Forty patients had multiple levels of vertebral fracture, with a higher rate of osteoporosis (n=24; 60%). Three patients showed undiagnosed oncologic disease with an initial diagnosis of acute fracture following minor trauma, while the primary oncologic diagnosis was established by bone biopsy taken during the routine procedure in each procedure (e.g., plasmacytoma, lymphoma, adenocarcinoma of the lung). None of the patients developed an infection due to kyphoplasty, permanent neuromotor deficit, or mortality. The mean postoperative hospital length of stay was 1.6 days. CONCLUSION: Bone biopsy should be performed to diagnose early spinal metastases. Although an accurate bone biopsy may not be obtained from some patients, particularly from those with osteoporosis, performing bone biopsy during the procedure does not cause time loss or any other complications, and protects the surgeon from possible medicolegal problems.