Degeneration and regeneration of the nervous system

Computational and Mathematical Methods in Medicine

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American Heart Association Council on cardiovascular nursing.

Turning blood into brain: Cells bearing neuronal antigens generated in vivo from bone marrow

Spinal cord injury often results into severe neurological deficits. Currently, there is no treatment available which can reverse the damage. Cell transplantation is a novel treatment strategy which has shown promising results in animal models of spinal cord injury. We administered fifty six chronic cervical spinal cord injury patients with autologous bone marrow mononuclear cells, intrathecally. As a part of the protocol, all the patients also underwent rehabilitation along with cell transplantation. On a mean follow up of 2 years ± 1 month, symptoms such as trunk stability, sitting balance, trunk muscle strength, upper limb strength, standing balance, deep touch sensation, bladder sensation, spasticity and walking balance demonstrated improvements. On performing McNemars test, a significant association was found between the improvements in these symptoms and the intervention. The improvement in Functional Independence Measure (FIM) scores was statistically significant using Wilcoxon Signed Rank test. A detailed analysis of factors such as age, cause of injury, chronicity of injury and rehabilitation before the intervention was performed. Here, we also compare this chronic cervical SCI group with chronic thoracolumbar SCI patients of our previous study. Though functional improvements were observed at greater extent in chronic thoracolumbar SCI group, the results in chronic cervical SCI group were also significant. Cell transplantation may promote neurofunctional recovery and improve the quality of life of the patients with chronic cervical spinal cord injury.

/pdf/role-of-autologous-bone-marrow-mononuclear-cells-in-chronic-1edlxnkcoq.pdf

Role of Autologous Bone Marrow Mononuclear Cells in Chronic Cervical Spinal Cord Injury-A Longterm Follow Up Study

Cellular therapy has been viewed as a novel therapeutic modality for many neurological disorders. Autologous Bone Marrow Mononuclear Cells (BMMNCs) used in many studies, have a safe and ethical profile. These cells have been studied in great depth and have shown angiogenetic and immunomodulatory properties in addition to other neuroprotective effects. These peculiar mechanisms may serve to be beneficial in autism. Recently, hypoperfusion and immune alteration are identified as major underlying pathogenetic mechanisms in autism. We present a case of autism with comorbid mental retardation; treated with intrathecal administration of autologous BMMNCs. Results were documented objectively on Indian Scale for Assessment of Autism (ISAA) and Positron Emission Tomography Computed Tomography (PET CT) scan. On regular follow up assessment of the patient over 18 months, there was significant clinical improvement in social relationship, communication and behavior. On outcome measure, ISAA score improved from 111 (Moderate autism) to 73 (Mild Autism). PET CT scans comparison of pre and post therapy showed balancing effect on brain metabolism. This case provides a great insight into the clinical effects of autologous BMMNCs in autism. Though a case study, the improvements guide us to plan future studies to explore different options of cellular therapy in autism.

/pdf/autologous-bone-marrow-mononuclear-cells-may-be-explored-as-2de4w1nagk.pdf

Autologous Bone Marrow Mononuclear Cells may be Explored as a NovelPotential Therapeutic Option for Autism

Becker's Muscular Dystrophy (BMD) is a dystrophinopathy manifested as progressive muscle degeneration. Autologous Bone Marrow Mononuclear Cells (BMMNCs) have shown some myogenic potential. The paracrine effects of the BMMNCs reduce the inflammation and are thought to reduce muscle degeneration. We treated a 39 year old dental surgeon suffering from BMD. Muscle strength was reduced when measured using modified Medical Research Council's Manual Muscle Testing (mMRC-MMT). Static sitting balance was poor. He was wheelchair dependent for ambulation and moderately independent in Activities of Daily Living (ADL). Functional Independence Measure (FIM) score was 93. Musculoskeletal Magnetic Resonance Imaging (MRI-MSK) showed moderate fatty infiltration in the muscles. Three cellular transplantations were carried out. Clinical assessment and the investigations were repeated. Progressive increase in the muscle strength was noted. Ambulation was independent using push-knee splints and minimal assistance when weary. Static and dynamic balance in sitting and standing improved. FIM score increased from 93 to 105. There was no increase in the degree of fatty infiltration, as seen on the MRI-MSK. The case study provides evidence for the putative benefits of cellular therapy in altering the disease progression in BMD. It also suggests augmented clinical benefits of combination of cellular therapy and rehabilitation.

/pdf/cellular-transplantation-alters-the-disease-progression-in-23y64gpz4h.pdf

Cellular Transplantation Alters the Disease Progression in Becker's Muscular Dystrophy.

Cerebral palsy is defined as motor impairment that limits activity, and is caused by non-progressive disruption during cerebral development in fetus or infant. The standard treatment is focused on rehabilitation and symptomatic management, which does not address the underlying brain damage. Recently cellular therapy has been seen as promising strategy to improve function of damaged areas of brain. Many mechanisms of action are postulated including cytokine release, angiogenesis, activation of satellite cells, decrease inflammation decrease neuronal apoptosis; and neuronal regeneration. We present a case of a two year old girl with spastic cerebral palsy, who was administered autologous bone marrow derived mononuclear cells intrathecally. Six months after the therapy she showed significant functional improvements along with correlating dramatic changes in Positron Emission Tomography-Computed Tomography scan. These changes provide objective evidence of functional restoration of affected areas of brain by cellular therapy.

/pdf/positron-emission-tomography-computed-tomography-scan-59zqhg3uqz.pdf

Positron Emission Tomography-Computed Tomography Scan Captures the Effects of Cellular Therapy in a Case of Cerebral Palsy

Autism is a complex neurodevelopmental disorder with a worldwide prevalence of 1 in 88. With greater understanding of mechanism of action of cellular therapy it is now possible to address the pathogenesis of autism. Recent findings of cellular therapy offering immunomodulatory, angigogenetic and paracrine effects make it a lucrative option for treatment of autism. We administered a 33 year old adult patient of autism intrathecally, with autologous bone marrow mononuclear cells (BMMNCs), twice with an interval of six months. On follow up at 3, 6 and 9 months post first intervention, he was re-evaluated clinically and no major or minor side effects were observed. At 6 and 9 months objective outcome measures of Indian Scale for Assessment of Autism (ISAA) and Clinical Global Impression (CGI) were used and they showed significant improvement. At the end of 9 months, on ISAA, the score improved from 94 to 64. The CGI showed improvement by change in severity of illness from 3 (Mildly ill) to 1 (Borderline mentally ill). Global improvement on CGI was scored 2 (much improved) with an efficacy index of 5 (moderate therapeutic effect). PET CT scan was repeated at 6 months which showed a balancing effect in the metabolism of affected areas. The changes observed on the PET CT scan correlated with clinical improvements. MRI remained same at 6 months thereby, indicating that PET CT scan may serve as a better monitoring tool for effects of cellular therapy. In this case study, we hypothesize that cellular therapy has repaired the neural connections and achieved balance in the excitatory and inhibitory neuronal cells by various mechanisms of neuroprotection, neuromodulation and neurorestoration. Cell therapy holds great potential and randomized controlled trials may be conducted to study their long term effects in treating autism.

https://www.longdom.org/open-access/intrathecal-autologous-bone-marrow-mononuclear-cell-transplantation-in-a-case-of-adult-autism-2165-7890.1000113.pdf

Hemangi Sane

Papers

Role of Autologous Bone Marrow Mononuclear Cells in Chronic Cervical Spinal Cord Injury-A Longterm Follow Up Study

Autologous Bone Marrow Mononuclear Cells may be Explored as a NovelPotential Therapeutic Option for Autism

Cellular Transplantation Alters the Disease Progression in Becker's Muscular Dystrophy.

Positron Emission Tomography-Computed Tomography Scan Captures the Effects of Cellular Therapy in a Case of Cerebral Palsy

Intrathecal Autologous Bone Marrow Mononuclear Cell Transplantation in a Case of Adult Autism