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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.
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BACKGROUND: Cerebral palsy (CP) describes a group of disorders affecting movement, balance, and posture. Disturbances in motor functions constitute the main body of CP symptoms. These symptoms surface in early childhood and patients are affected for the rest of their lives. Currently, treatment involves various pharmacotherapies for different types of CP, including antiepileptics for epilepsy and Botox A for focal spasticity. However, none of these methods can provide full symptom relief. This has prompted researchers to look for new treatment modalities, one of which is mesenchymal stem cell therapy (MSCT). Despite being a promising tool and offering a wide array of possibilities, mesenchymal stem cells (MSCs) still need to be investigated for their efficacy and safety. AIM: To analyze the efficacy and safety of MSCT in CP patients. METHODS: Our sample consists of four CP patients who cannot stand or walk without external support. All of these cases received allogeneic MSCT six times as 1 × 106/kg intrathecally, intravenously, and intramuscularly using umbilical cord-derived MSCs (UC-MSC). We monitored and assessed the patients pre- and post-treatment using the Wee Functional Independence Measure (WeeFIM), Gross Motor Function Classification System (GMFCS), and Manual Ability Classification Scale (MACS) instruments. We utilized the Modified Ashworth Scale (MAS) to measure spasticity. RESULTS: We found significant improvements in MAS scores after the intervention on both sides. Two months: Right χ2 = 4000, P = 0.046, left χ2 = 4000, P = 0.046; four months: Right χ2 = 4000, P = 0.046, left χ2 = 4000, P = 0.046; 12 months: Right χ2 = 4000, P = 0.046, left χ2 = 4000, P = 0.046. However, there was no significant difference in motor functions based on WeeFIM results (P > 0.05). GMFCS and MACS scores differed significantly at 12 months after the intervention (P = 0.046, P = 0.046). Finally, there was no significant change in cognitive functions (P > 0.05). CONCLUSION: In light of our findings, we believe that UC-MSC therapy has a positive effect on spasticity, and it partially improves motor functions.
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BACKGROUND: Peripheral nerve injury can result in significant clinical complications that have uncertain prognoses. Currently, there is a lack of effective pharmacological interventions for nerve damage, despite the existence of several small compounds, peptides, hormones, and growth factors that have been suggested as potential enhancers of neuron regeneration. Despite the objective of achieving full functional restoration by surgical intervention, the persistent challenge of inadequate functional recovery remains a significant concern in the context of peripheral nerve injuries. AIM: To examine the impact of exosomes on the process of functional recovery following a complete radial nerve damage. METHODS: A male individual, aged 24, who is right-hand dominant and an immigrant, arrived with an injury caused by a knife assault. The cut is located on the left arm, specifically below the elbow. The neurological examination and electrodiagnostic testing reveal evidence of left radial nerve damage. The sural autograft was utilized for repair, followed by the application of 1 mL of mesenchymal stem cell-derived exosome, comprising 5 billion microvesicles. This exosome was split into four equal volumes of 0.25 mL each and delivered microsurgically to both the proximal and distal stumps using the subepineural pathway. The patient was subjected to a period of 180 d during which they had neurological examination and electrodiagnostic testing. RESULTS: The duration of the patient's follow-up period was 180 d. An increasing Tinel's sign and sensory-motor recovery were detected even at the 10th wk following nerve grafting. Upon the conclusion of the 6-mo post-treatment period, an evaluation was conducted to measure the extent of improvement in motor and sensory functions of the nerve. This assessment was based on the British Medical Research Council scale and the Mackinnon-Dellon scale. The results indicated that the level of improvement in motor function was classified as M5, denoting an excellent outcome. Additionally, the level of improvement in sensory function was classified as S3+, indicating a good outcome. It is noteworthy that these assessments were conducted in the absence of physical therapy. At the 10th wk post-injury, despite the persistence of substantial axonal damage, the nerve exhibited indications of nerve re-innervation as evidenced by control electromyography (EMG). In contrast to the preceding. EMG analysis revealed a significant electrophysiological enhancement in the EMG conducted at the 6th-mo follow-up, indicating ongoing regeneration. CONCLUSION: Enhanced comprehension of the neurobiological ramifications associated with peripheral nerve damage, as well as the experimental and therapy approaches delineated in this investigation, holds the potential to catalyze future clinical progress.
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BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of death and long-term neurological impairment in the pediatric population. Despite a limited number of treatments to cure HIE, stem cell therapies appear to be a potential treatment option for brain injury resulting from HIE. AIM: To investigate the efficacy and safety of stem cell-based therapies in pediatric patients with HIE. METHODS: The study inclusion criteria were determined as the presence of substantial deficit and disability caused by HIE. Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) were intrathecally (IT), intramuscularly (IM), and intravenously administered to participants at a dose of 1 × 106/kg for each administration route twice monthly for 2 mo. In different follow-up durations, the effect of WJ-MSCs administration on HIE, the quality of life, prognosis of patients, and side effects were investigated, and patients were evaluated for neurological, cognitive functions, and spasticity using the Wee Functional Independence Measure (Wee FIM) Scale and Modified Ashworth (MA) Scale. RESULTS: For all participants (n = 6), the mean duration of exposure to hypoxia was 39.17 + 18.82 min, the mean time interval after HIE was 21.83 ± 26.60 mo, the mean baseline Wee FIM scale score was 13.5 ± 0.55, and the mean baseline MA scale score was 35 ± 9.08. Three patients developed only early complications such as low-grade fever, mild headache associated with IT injection, and muscle pain associated with IM injection, all of which were transient and disappeared within 24 h. The treatment was evaluated to be safe and effective as demonstrated by magnetic resonance imaging examinations, electroencephalographies, laboratory tests, and neurological and functional scores of patients. Patients exhibited significant improvements in all neurological functions through a 12-mo follow-up. The mean Wee FIM scale score of participants increased from 13.5 ± 0.55 to 15.17 ± 1.6 points (mean ± SD) at 1 mo (z = - 1.826, P = 0.068) and to 23.5 ± 3.39 points at 12 mo (z = -2.207, P = 0.027) post-treatment. The percentage of patients who achieved an excellent functional improvement (Wee FIM scale total score = 126) increased from 10.71% (at baseline) to 12.03% at 1 mo and to 18.65% at 12 mo post-treatment. CONCLUSION: Both the triple-route and multiple WJ-MSC implantations were safe and effective in pediatric patients with HIE with significant neurological and functional improvements. The results of this study support conducting further randomized, placebo-controlled studies on this treatment in the pediatric population.
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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.
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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.
Subject(s)
Brain Injuries, Traumatic/surgery , Mesenchymal Stem Cell Transplantation/methods , Recovery of Function , Wharton Jelly/transplantation , Adult , Humans , Male , Pilot ProjectsABSTRACT
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.