Abnormal Development of the Corpus Callosum in Autism Spectrum Disorder: An MRI Study.

BACKGROUND: Altered size in the corpus callosum (CC) has been reported in individuals with autism spectrum disorder (ASD), but few studies have investigated younger children. Moreover, knowledge about the age-related changes in CC size in individuals with ASD is limited. OBJECTIVES: Our objective was to investigate the age-related size of the CC and compare them with age-matched healthy controls between the ages of 2 and 18 years. METHODS: Structural-weighted images were acquired in 97 male patients diagnosed with ASD; published data were used for the control group. The CC was segmented into 7 distinct subregions (rostrum, genu, rostral body, anterior midbody, posterior midbody, isthmus, and splenium) as per Witelson's technique using ITK-SNAP software. We calculated both the total length and volume of the CC as well as the length and height of its 7 subregions. The length of the CC measures was studied as both continuous and categorical forms. For the continuous form, Pearson's correlation was used, while categorical forms were based on age ranges reflecting brain expansion during early postnatal years. Differences in CC measures between adjacent age groups in individuals with ASD were assessed using a Student t-test. Mean and standard deviation scores were compared between ASD and control groups using the Welch t-test. RESULTS: Age showed a moderate positive association with the total length of the CC (r = 0.43; Padj = 0.003) among individuals with ASD. Among the subregions, a positive association was observed only in the anterior midbody of the CC (r = 0.41; Padj = 0.01). No association was found between the age and the height of individual subregions or with the total volume of the CC. In comparison with healthy controls, individuals with ASD exhibited shorter lengths and heights of the genu and splenium of the CC across wide age ranges. CONCLUSION: Overall, our results highlight a distinct abnormal developmental trajectory of CC in ASD, particularly in the genu and splenium structures, potentially reflecting underlying pathophysiological mechanisms that warrant further investigation.

Severity of muscle impairment and its progression assessed using musculoskeletal magnetic resonance imaging and diffusion tension imaging in 78 boys with Duchenne muscular dystrophy: a retrospective study.

Purpose: Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy. Current diagnostic tests like genetic testing, needle electromyography, and muscle biopsy are either not easily available or invasive, and they are impractical for assessing disease progression and treatment outcomes. Therefore, there is a need for a non-invasive and accurate investigative modality for DMD. In recent years, musculoskeletal magnetic resonance imaging (MRI-MSK) along with fractional anisotropy (FA) and diffusion tensor imaging (DTI) have become major non-invasive tools. Material and methods: T1-weighted MRI-MSK and FA measures of DTI of 78 DMD patients were retrospectively studied to identify the distinct pattern of muscle involvement and fatty infiltration as age and/or disease progresses. Correlation analysis was performed between MRI-MSK grade score vs. age, muscle strength, and Vignos scale. Spearman's rank correlation coefficient was used. Results: As age increased, the MRI grade score and Vignos score increased. There was a statistically significant high positive correlation between MRI-MSK grade score and age, and low positive correlation with Vignos scores. With increasing age, the muscle strength on manual muscle testing (MMT) and FA value decreased. There was high negative correlation with muscle strength on MMT and low positive correlation between FA values and MMT score. Conclusions: On T1-weighted MRI, a distinct pattern, extent, and distribution of lower limb muscle involvement can be seen. MRI-MSK grade score worsens with progressing age, reducing strength, and increasing functional impairment. FA alone may not be an accurate marker in assessing progression of DMD. MRI-MSK and other DTI measures should be further explored as diagnostic and prognostic tools for DMD.

Phase 1 clinical trial for intravenous administration of mesenchymal stem cells derived from umbilical cord and placenta in patients with moderate COVID-19 virus pneumonia: results of stage 1 of the study.

OBJECTIVE: Mesenchymal stem cells can serve as a therapeutic option for COVID-19. Their immunomodulatory and anti-inflammatory properties can regulate the exaggerated inflammatory response and promote recovery of lung damage. METHOD: Phase-1, single-centre open-label, prospective clinical trial was conducted to evaluate the safety and efficacy of intravenous administration of mesenchymal stem cells derived from umbilical cord and placenta in moderate COVID-19. The study was done in 2 stages with total 20 patients. Herein, the results of stage 1 including first 10 patients receiving 100 million cells on day 1 and 4 with a follow up of 6 months have been discussed. RESULTS: No adverse events were recorded immediately after the administration of MSCs or on follow up. There was no deterioration observed in clinical, laboratory and radiological parameters. All symptoms of the study group resolved within 10 days. Levels of inflammatory biomarkers such as NLR, CRP, IL6, ferritin and D-dimer improved in all patients after intervention along with improved oxygenation demonstrated by improvement in the SpO2/FiO2 ratio and PaO2/FiO2 ratio. None of the patients progressed to severe stage. 9 out of 10 patients were discharged within 9 days of their admission. Improvements were noted in chest x-ray and chest CT scan scores at day 7 in most patients. No post-covid fibrosis was observed on chest CT 28 days after intervention and Chest X ray after 6 months of the intervention. CONCLUSION: Administration of 100 million mesenchymal stem cells in combination with standard treatment was found to be safe and resulted in prevention of the cytokine storm, halting of the disease progression and acceleration of recovery in moderate COVID-19. This clinical trial has been registered with the Clinical Trial Registry- India (CTRI) as CTRI/2020/08/027043. http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=43175.

A pilot study for treatment of COVID-19 patients in moderate stage using intravenous administration of ozonized saline as an adjuvant treatment-registered clinical trial.

OBJECTIVE: Ozone therapy has tremendous therapeutic potential owing to its antiviral, anti-inflammatory and antioxidant properties, and potential to improve oxygenation. A pilot clinical trial was conducted to evaluate the safety and efficacy ofintravenous ozonised saline treatment in patients with moderate COVID-19 pneumonia. PATIENTS AND METHODS: 10 patients were administered 200 ml freshly prepared ozonised saline intravenously over 1 h once a day for 8 days along with standard medical treatment. Clinical symptoms were monitored everyday and laboratory biomarkers, radiological findings at 1,3,6,10 days. Telephonic follow up was done for all after discharge till Day 14. 7 out of 10 patients required oxygen supplementation at recruitment. RESULTS: There was severe adverse event recorded in the study group.All patients improved from moderate to mild category in average 8 days and were discharged in average 9.7 days. None deteriorated to severe stage. All clinical symptoms resolved within 6 days and oxygen supplementation requirement reduced to none within 4.1 days. There wasstatistically significant reduction inCRP (p = 0.003), D-Dimer (p = 0.049), IL6 (p = 0.002)and statistically significant improvement (p = 0.001) in SpO2/FiO2 ratio. Change in LDH was borderline statistically not significant (p = 0.058).All patients showed significant resolution of bilateral interstitial infiltrates at the end of 10 days. CONCLUSION: Resolved clinical symptoms, improved oxygenation, clearance of infiltrates on Chest X-ray and improvement in biomarkers in a short period with non-progression of the disease showed that IV ozonised saline therapy was safe and effective to prevent disease progression in COVID-19, making it an effective novel therapeutic tool.

Multiple doses of cell therapy and neurorehabilitation in amyotrophic lateral sclerosis: A case report.

Cell therapy, along with intensive rehabilitation has been shown to significantly improve outcomes in amyotrophic lateral sclerosis (ALS), in addition to standard therapy. We present a 40-years-old male ALS patient, suffering for the past four years, who underwent multiple doses of cell therapy at our institution. Along with riluzole treatment and lithium co-administration, his treatment involved multiple intrathecal transplants of autologous bone marrow-derived mononuclear cells, followed by multidisciplinary neurorehabilitation. The outcome measures of ALSFunctional Rating Scale Revised score remained stable, and importantly, Six Minute Walk Test distance improved from 475.2 m to 580.8 m, over a span of 16 months. Improved outcomes are indicative of slowing down of disease progression. Multiple doses of intrathecal autologous cell therapy along with rehabilitation and lithium, in addition to standard riluzole treatment is a novel approach for decelerating disease progression and qualitatively improving living conditions for ALS patients and their caregivers.

Autologous bone marrow mononuclear cell transplantation in patients with chronic traumatic brain injury- a clinical study.

BACKGROUND: Chronic Traumatic Brain Injury (TBI) is one of the common causes of longterm disability worldwide. Cell transplantation has gained attention as a prospective therapeutic option for neurotraumatic disorders like TBI. The postulated mechanism of cell transplantation which includes angiogenesis, axonal regeneration, neurogenesis and synaptic remodeling, may tackle the pathology of chronic TBI and improve overall functioning. METHODS: To study the effects of cell transplantation, 50 patients with chronic TBI were enrolled in an open label non-randomized study. The intervention included intrathecal transplantation of autologous bone marrow mononuclear cells and neurorehabilitation. Mean follow up duration was 22 months. Fifteen patients underwent second dose of cell transplantation, 6 months after their first intervention. Percentage analysis was performed to analyze the symptomatic improvements in the patients. Functional independence measure (FIM) was used as an outcome measure to evaluate the functional changes in the patients. Statistical tests were applied on the pre-intervention and post-intervention scores for determining the significance. Comparative Positron Emission Tomography- computed tomography (PET CT) scans were performed in 10 patients to monitor the effect of intervention on brain function. Factors such as age, multiple doses, time since injury and severity of injury were also analyzed to determine their effect on the outcome of cell transplantation. Adverse events were monitored throughout the follow up period. RESULTS: Overall 92% patients showed improvements in symptoms such as sitting and standing balance, voluntary control, memory, oromotor skills lower limb activities, ambulation, trunk & upper limb activity, speech, posture, communication, psychological status, cognition, attention and concentration, muscle tone, coordination, activities of daily living. A statistically significant (at p ≤ 0.05 with p-value 0) improvement was observed in the scores of FIM after intervention on the Wilcoxon signed rank test. Better outcome of the intervention was found in patients with mild TBI, age less than 18 years and time since injury less than 5 years. Ten patients who underwent a repeat PET CT scan brain showed improved brain metabolism in areas which correlated to the symptomatic changes. Two patients had an episode of seizures which was managed with medication. They both had an abnormal EEG before the intervention and 1 of them had previous history and was on antiepileptics. No other major adverse events were recorded. CONCLUSION: This study demonstrates the safety and efficacy of cell transplantation in chronic TBI on long term follow up. Early intervention in younger age group of patients with mild TBI showed the best outcome in this study. In combination with neurorehabilitation, cell transplantation can enhance functional recovery and improve quality of life of patients with chronic TBI. PET CT scan brain should be explored as a monitoring tool to study the efficacy of intervention.

Intrathecal transplantation of autologous bone marrow mononuclear cells in patients with sub-acute and chronic spinal cord injury: An open-label study.

OBJECTIVE: The objective of the study was to analyze the effect of intrathecal transplantation of autologous bone marrow-derived mononuclear cells (BMMNCs) in functional recovery of spinal cord injury (SCI) patients along with neurorehabilitation and to evaluate various factors influencing the outcome of cellular therapy. METHODS: We conducted an open-label study including 180 sub-acute and chronic SCI patients. All patients received intrathecal autologous BMMNCs along with neurorehabilitation. 80-100 mL of bone marrow was aspirated and BMMNCs were obtained using density gradient separation. An average of 1.06 × 108 cells with 97% viability was administered through lumbar puncture immediately. After transplantation, all patients underwent neurorehabilitation. Patients were followed up after an average of 9 ± 7 months. They were assessed for functional symptomatic changes and the outcome measures used were functional independence measure (FIM) and walking index for SCI (WISCI). RESULTS: Patients showed symptomatic improvement in sitting/standing balance, bed mobility, trunk stability, upper limb function, mobility, sensation, bowel/bladder functions, and activities of daily living with no serious adverse events. Scores on FIM and WISCI showed statistically significant improvement. On subgroup analysis, it was found that early intervention and more than one dose of BMMNCs demonstrate a better functional outcome. Younger patients demonstrated better improvements in functional independence. Both cervical and dorsolumbar levels of injury show significant improvements in motor and sensory deficits. CONCLUSIONS: Autologous BMMNC transplantation with neurorehabilitation is safe, effective, enhances functional recovery, and improves the quality of life of SCI patients in sub-acute and chronic stage.

Multiple Cellular Therapies Along with Neurorehabilitation in Spastic Diplegic Cerebral Palsy: A Case Report.

Cerebral palsy (CP) is a chronic childhood disorder that is characterized by a group of motor and cognitive impairments, resulting in abnormal movement patterns, loss of motor control, incoordination, and unbalanced posture. It can also have an impact on fine motor skills, gross motor skills, and oral motor functioning. Currently, the treatment of CP is palliative and does not cure the disease pathology. Hence, there is a need for an intervention that might be able to alter the core pathology. Autologous bone marrow mononuclear cells (BMMNC) transplantation is one of the novel treatment strategies in recent years. In this study, we presented the case of a 4-year-old male child with spastic diplegic CP who underwent two intrathecal transplantations at interval of seven months with autologous BMMNC along with neurorehabilitation program. During an overall 16-month follow-up, significant improvements were observed in motor control, coordination, balance, sitting tolerance, and memory. The abnormal 'W' sitting posture and scissoring gait pattern of the patient resolved. Started sitting with good head, trunk, and pelvic alignment and attained regular gait pattern; the patient started to walk independently without support as well. On objective scale, Gross Motor Functional Measure score improved from 60.67 to 81.78. The patient's Gross Motor Functional Classification System grade improved from Level 3 to Level 2, and Functional Independent Measure score improved from 97 to 99. A comparative positron emission tomography-computed tomography (PET CT) brain scan was performed before and seven months after the first intervention, which revealed improvement in the metabolism of the anterior cingulate lobe, parietal cortex, medial temporal cortex, thalamus, basal ganglia, and cerebellum. No adverse events were recorded throughout the study. Thus, multiple cellular therapies, along with neurorehabilitation, might be a novel safe, feasible option to enhance recovery in CP.

Cell transplantation as a novel therapeutic strategy for autism spectrum disorders: a clinical study.

BACKGROUND: Autism spectrum disorders [ASD] is a lifelong disability mainly affecting the development, communication, social interaction and behavior of an individual. Cell transplantation is emerging as a potential therapeutic strategy for ASD. Our previously published proof of concept study showed beneficial effects of cell transplantation in ASD. This study shows effect of cell transplantation in a larger sample size of ASD patients. METHODS: 254 patients diagnosed with ASD on DSM V criteria were enrolled in this open label non-randomized study. The intervention included intrathecal transplantation of autologous bone marrow mononuclear cells and neurorehabilitation. On mean follow up of 7.50 months, percentage analysis was performed on all symptomatic changes. Changes in outcome measures, Indian Scale for Assessment of Autism [ISAA] and Childhood Autism Rating Scale [CARS], were analyzed statistically using Wilcoxon Signed-Rank Test. Comparative analysis of Positron Emission Tomography [PET CT] scan brain, performed before and 6 months after intervention, was done in 86 patients to monitor the outcome at cellular level. Change in the standardized uptake values was statistically evaluated using T-Test [P≤0.05]. RESULTS: Improvements were observed in eye contact, attention and concentration, hyperactivity, sitting tolerance, social interaction, stereotypical behavior, aggressiveness, communication, speech, command following and self-stimulatory behavior. Statistically significant improvement was observed in scores of ISAA and CARS after intervention. A significantly better outcome of the intervention was found in patients at younger age and with shorter duration of disease [<5 years from time of diagnosis]. 86 patients who underwent a repeat PET CT scan showed improved brain metabolism after intervention in areas which correlated to the symptomatic changes. No major procedure related adverse events were recorded. However, 5 patients, with history of seizure and abnormal EEG, had an episode of seizure which was managed using medications. Outcome of intervention in these patients was not affected by seizures as improvements were observed in them. CONCLUSION: The results of this study indicate that autologous bone marrow mononuclear cells in combination with neurorehabilitation are a safe and effective treatment modality for ASD. It improves the quality of life of patients and helps them to integrate in mainstream lifestyle.

The Baseline Pattern and Age-related Developmental Metabolic Changes in the Brain of Children with Autism as Measured on Positron Emission Tomography/Computed Tomography Scan.

[18F] 2-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography scan was performed on 45 children with autism to study the baseline pattern and age-related developmental changes in the brain metabolism. Median standardized uptake values (SUVs) were compared with published healthy control data. Results showed that, in contrary to control data, the median SUVs in children with autism decrease linearly with increase in age. As compared to controls, autism children below 5 years showed greater metabolism and older children showed lower metabolism. In autism group, comparison of absolute SUVs within different regions of the brain revealed relatively lower metabolism in amygdala, hippocampus, parahippocampal gyrus, caudate nucleus, cerebellum, mesial temporal lobe, thalamus, superior and middle temporal pole, and higher metabolic uptake in calcarine fissure and Heschl's gyrus. These results help in understanding the baseline metabolism and developmental changes of brain among different age groups in autism.

Cellular Therapy for Chronic Traumatic Brachial Plexus Injury.

Cellular therapy is being actively pursued as a therapeutic modality in many of the neurological diseases. A variety of stem cells from diverse sources have been studied in detail and have been shown to exhibit angiogenetic and immunomodulatory properties in addition to other neuroprotective effects. Published clinical data have shown bone marrow mononuclear cell (BMMNC) injection in neurological disorders is safe and possesses regenerative potential. We illustrate a case of 27-year-old male with traumatic brachial plexus injury, administered with autologous BMMNCs intrathecally and intramuscularly, followed by multidisciplinary rehabilitation. At the follow-up assessment of 3 and 7 months after first cell transplantation, improvements were recorded in muscle strength and movements. Electromyography (EMG) performed after the intervention showed a response in biceps and deltoid muscles suggesting the process of reinnervation at the site of injury. In view of the improvements observed after the treatment, the patient underwent second cell transplantation 8 months after the first transplantation. Muscle wasting had completely stopped with an increase in the muscle girth. No adverse effects were noted. Improvements were maintained for 4 years. A comprehensive randomized study for this type of injury is needed to establish the therapeutic benefits of cellular therapy.

An open-label proof-of-concept study of intrathecal autologous bone marrow mononuclear cell transplantation in intellectual disability.

BACKGROUND: The underlying pathophysiology in intellectual disability (ID) involves abnormalities in dendritic branching and connectivity of the neuronal network. This limits the ability of the brain to process information. Conceptually, cellular therapy through its neurorestorative and neuroregenerative properties can counteract these pathogenetic mechanisms and improve neuronal connectivity. This improved networking should exhibit as clinical efficacy in patients with ID. METHODS: To assess the safety and efficacy of cellular therapy in patients with ID, we conducted an open-label proof-of-concept study from October 2011 to December 2015. Patients were divided into two groups: intervention group (n = 29) and rehabilitation group (n = 29). The intervention group underwent cellular transplantation consisting of intrathecal administration of autologous bone marrow mononuclear cells and standard neurorehabilitation. The rehabilitation group underwent only standard neurorehabilitation. The results of the symptomatic outcomes were compared between the two groups. In the intervention group analysis, the outcome measures used were the intelligence quotient (IQ) and the Wee Functional Independence Measure (Wee-FIM). To compare the pre-intervention and post-intervention results, statistical analysis was done using Wilcoxon's matched-pairs test for Wee-FIM scores and McNemar's test for symptomatic improvements and IQ. The effect of age and severity of the disorder were assessed for their impact on the outcome of intervention. Positron emission tomography-computed tomography (PET-CT) brain scan was used as a monitoring tool to study effects of the intervention. Adverse events were monitored for the safety of cellular therapy. RESULTS: On symptomatic analysis, greater improvements were seen in the intervention group as compared to the rehabilitation group. In the intervention group, the symptomatic improvements, IQ and Wee-FIM were statistically significant. A significantly better outcome of the intervention was found in the paediatric age group (<18 years) and patients with milder severity of ID. Repeat PET-CT scan in three patients of the intervention group showed improved metabolism in the frontal, parietal cortex, thalamus, mesial temporal structures and cerebellum. No major adverse events were witnessed. CONCLUSIONS: Cellular transplantation with neurorehabilitation is safe and effective for the treatment of underlying brain deficits in ID. TRIAL REGISTRATION: ClinicalTrials.gov NCT02245724. Registered 12 September 2014.

Improved Quality of Life in A Case of Cerebral Palsy after Bone Marrow Mononuclear Cell Transplantation.

Cerebral palsy (CP) is a non progressive, demyelinating disorder that affects a child's development and posture and may be associated with sensation, cognition, communication and perception abnormalities. In CP, cerebral white matter is injured resulting in the loss of oligodendrocytes. This causes damage to the myelin and disruption of nerve conduction. Cell therapy is being explored as an alternate therapeutic strategy as there is no treatment currently available for CP. To study the benefits of this treatment we have administered autologous bone marrow mononuclear cells (BMMNCs) to a 12-year-old CP case. He was clinically re-evaluated after six months and found to demonstrate positive clinical and functional outcomes. His trunk strength, upper limb control, hand functions, walking stability, balance, posture and coordination improved. His ability to perform activities of daily living improved. On repeating the Functional Independence Measure (FIM), the score increased from 90 to 113. A repeat positron emission tomography-computed tomography (PET-CT) scan of the brain six months after intervention showed progression of the mean standard deviation values towards normalization which correlated to the functional changes. At one year, all clinical improvements have remained. This indicated that cell transplantation may improve quality of life and have a potential for treatment of CP.

The effect of autologous bone marrow mononuclear cell transplantation on the survival duration in Amyotrophic Lateral Sclerosis - a retrospective controlled study.

Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive neurodegenerative disorder with fatal prognosis. Cellular therapy has been studied for ALS in various animal models and these advances have highlighted its potential to be a treatment modality. This is a retrospective controlled cohort study of total 57 patients. Out of these, 37 patients underwent autologous bone marrow mononuclear cell transplantation in addition to standard rehabilitation and Riluzole. Control group consisted of 20 patients who did not receive cell transplantation. The survival duration since the onset of the disease for both the groups was computed using a Kaplan-Meier Survival analysis and compared using log-rank test. Effect of age at onset, type of onset and lithium on survival duration in the intervention group was analyzed. Mean survival duration of patients in intervention group was 87.76 months which was higher than the control group mean survival duration of 57.38 months. Survival duration was significantly (p = 0.039) higher in people with the onset of the disease below 50 years of age. Limb onset and lithium also showed positive influence on the survival duration. Mean survival duration of the intervention group was also higher than the survival duration of ALS patients in previous epidemiological studies. In addition to the standard treatment with Riluzole, early intervention with combination of BMMNCs transplantation and Lithium may have a positive effect on the survival duration in ALS. Prospective randomized controlled studies with a larger sample size and rigorous methodology are required for conclusive findings.

A clinical study of autologous bone marrow mononuclear cells for cerebral palsy patients: a new frontier.

Cerebral palsy is a nonprogressive heterogeneous group of neurological disorders with a growing rate of prevalence. Recently, cellular therapy is emerging as a potential novel treatment strategy for cerebral palsy. The various mechanisms by which cellular therapy works include neuroprotection, immunomodulation, neurorestoration, and neurogenesis. We conducted an open label, nonrandomized study on 40 cases of cerebral palsy with an aim of evaluating the benefit of cellular therapy in combination with rehabilitation. These cases were administered autologous bone marrow mononuclear cells intrathecally. The follow-up was carried out at 1 week, 3 months, and 6 months after the intervention. Adverse events of the treatment were also monitored in this duration. Overall, at six months, 95% of patients showed improvements. The study population was further divided into diplegic, quadriplegic, and miscellaneous group of cerebral palsy. On statistical analysis, a significant association was established between the symptomatic improvements and cell therapy in diplegic and quadriplegic cerebral palsy. PET-CT scan done in 6 patients showed metabolic improvements in areas of the brain correlating to clinical improvements. The results of this study demonstrate that cellular therapy may accelerate the development, reduce disability, and improve the quality of life of patients with cerebral palsy.

Cell therapy attempted as a novel approach for chronic traumatic brain injury - a pilot study.

Traumatic brain injury is an injury to the brain parenchyma resulting from external factors such as vehicular accidents, falls, or sports injuries. Its outcome involves primary insult followed by a cascade of secondary insult, resulting in diffuse axonal injury further causing white matter damage. Surgical intervention targets the primary damage, whereas only few treatment alternatives are available to treat the secondary damage. Cellular therapy could be one of the prospective therapeutic options, as it has the potential to arrest the degeneration and promote regeneration of new cells in the brain. We conducted a pilot study on 14 cases who were administered with autologous bone marrow mononuclear cells, intrathecally. The follow up was done at 1 week, 3 months and 6 months after the intervention. The Functional Independence Measure scale, the SF-8 Health Survey Scoring and the disability rating scale were used as outcome measures. These scales showed a positive shift in scores at the end of 6 months. Improvements were observed in various symptoms, along with activities of daily living. Improvement in PET CT scan performed before and 6 months after the intervention in 3 patients corresponded to the clinical and functional improvements observed in these patients. The results of this study suggest that cell therapy may promote functional recovery leading to an improved quality of life in chronic TBI. Although the results are positive, the improvements after cell therapy are not optimal. Hence, additional multicenter, controlled studies are required to establish cell therapy as a standard therapeutic approach.

The role of cell transplantation in modifying the course of limb girdle muscular dystrophy: a longitudinal 5-year study.

Limb girdle muscular dystrophy (LGMD), a group of progressive degenerative disorders, causes functional limitation affecting the quality of life. Cell therapy is being widely explored and preliminary studies have shown beneficial effects. Cell therapy induces trophic-factors release, angiogenesis, anti-inflammation, and protein synthesis, which helps in the reparative process at the microcellular level. In this 5-year longitudinal study, the effect of autologous bone marrow mononuclear cells is studied on the natural course of 65 patients with LGMD. Functional Independence Measure and manual muscle testing showed statistically significant improvement, post-cell transplantation. The key finding of this study was demonstration of a plateau phase in the disease progression of the patients. No adverse events were noted. Autologous bone marrow mononuclear cells may be a novel, safe, and effective treatment approach to control the rate of progression of LGMD, thus improving the functional outcomes. Further randomized controlled trials are required.

Autologous bone marrow mononuclear cells intrathecal transplantation in chronic stroke.

Cell therapy is being widely explored in the management of stroke and has demonstrated great potential. It has been shown to assist in the remodeling of the central nervous system by inducing neurorestorative effect through the process of angiogenesis, neurogenesis, and reduction of glial scar formation. In this study, the effect of intrathecal administration of autologous bone marrow mononuclear cells (BMMNCs) is analyzed on the recovery process of patients with chronic stroke. 24 patients diagnosed with chronic stroke were administered cell therapy, followed by multidisciplinary neurorehabilitation. They were assessed on functional independence measure (FIM) objectively, along with assessment of standing and walking balance, ambulation, and hand functions. Out of 24 patients, 12 improved in ambulation, 10 in hand functions, 6 in standing balance, and 9 in walking balance. Further factor analysis was done. Patients of the younger groups showed higher percentage of improvement in all the areas. Patients who underwent cell therapy within 2 years after the stroke showed better changes. Ischemic type of stroke had better recovery than the hemorrhagic stroke. This study demonstrates the potential of autologous BMMNCs intrathecal transplantation in improving the prognosis of functional recovery in chronic stage of stroke. Further clinical trials are recommended. This trial is registered with NCT02065778.

Functional recovery in chronic stage of spinal cord injury by neurorestorative approach: a case report.

Spinal cord injury (SCI) at an early age can be debilitating for the child's growth. Current treatments show a level of stagnancy, after which the recovery is minimal. Cellular therapy is an emerging area of research and has been found to possess many benefits in the previous studies. Transplantation of autologous bone marrow mononuclear cells (BMMNCs) has demonstrated therapeutic potential for many neurological conditions, including spinal cord injury. Here we report a case of 6-year-old girl with traumatic SCI at the level of C7-D1 4 years back, who underwent 2 doses of cell transplantation with autologous BMMNCs with an interval of 6 months along with standard rehabilitation. The patient did not have any major or minor side effects. The patient showed clinical improvements throughout the 6 months after transplantation, which was assessed using Functional Independence Measure (before: 82, after: 101 out of 126). There were patchy areas of sensory gain in bilateral feet recorded, with improvements in the bladder sensation and control. Improved gait was seen as a result of better strength in abdominals and back extensors. The fact that there was functional improvement in the chronic plateau phase indicates the potential of cell therapy in chronic SCI. Further clinical studies are warranted.