Effects of exosomes from mesenchymal stem cells on functional recovery of a patient with total radial nerve injury: A pilot study

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,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.

Feasibility of allogeneic mesenchymal stem cells in pediatric hypoxic-ischemic encephalopathy: Phase I study

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 1×10^(6)/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 posttreatment.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.

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.