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Intrathecal Autologous Bone Marrow Derived Mesenchymal Stem Cells for Ischemic Stroke: Short Term Safety and Efficacy Study
Abo Elkheir W,
Reda M. A.,
Montaser I. A.,
Salem A. E.,
Sakr M. A.
Issue:
Volume 3, Issue 4-1, July 2015
Pages:
1-6
Received:
1 April 2015
Accepted:
2 April 2015
Published:
6 May 2015
Abstract: Background: Preclinical and animal studies provide considerable hope for stem cell therapy in cerebrovascular stroke. This study was designed as a pilot study to explore this provisional data. Autologous bone marrow derived mesenchymal stem cells were chosen due to their proven angiogenic, paracrine and neuroregenerative functions. Subjects and Methods: The present study included 32 patients with ischemic stroke fulfilling the following criteria: Inclusion Criteria: 1. Patients with established stroke in the distribution of the middle cerebral artery territory. 2. Six months at least after the onset of acute ischemic stroke. 3. CT brain at the onset denoting acute ischemic stroke. Exclusion Criteria: 1. Hemorrhagic stroke. 2. Conditions which mimick stroke,e.g., multiple sclerosis, vasculitis, arteriovenous malformations, trauma, tumours. Patients were randomly divided into control group (11 patients) and study group (21 patients) which was further divided according to the time between the onset of the stroke and the beginning of the study into: Group I : onset of the stroke and the beginning of the study :6-12 months( 12 patients: 6 males and 6 females). Group II: onset of stroke and the beginning of the study :13-36 months (9 patients: 5 males and 4 females). Control Group: 11 stroke patients : 6 males and 5 females. Time from onset of stroke to beginning of the study ranged from 6-30 months. Both study and control group were subjected to thorough clinical and laboratory assessment , CT brain, National institutes of Health Stroke Scale (NIHSS) and th Barthel active daily life (ADL) scale at the start of therapy, and at 1,3,6 and 12 months after the start of therapy. Stem Cell Injection: 10 million autologous bone marrow-derived MSCs were injected via lumbar puncture in the study group. Results and Conclusions: Changes in Follow-up Parameters: 1. Changes in NIHSS score: Control group showed non-significant decrease in NIHSS score starting from the 3rd month. On the other hand, study group showed highly significant decrease in NIHSS score starting from 6th month, more in group I. 2. Changes in ADL score: ADL score showed non-significant increase starting from 3rd month in the control group, while it showed a highly significant increase in the study group starting from 6th month, more pronounced in group I. Intrathecal administration of MSCs is safe and enhances regeneration in ischemic stroke patients.
Abstract: Background: Preclinical and animal studies provide considerable hope for stem cell therapy in cerebrovascular stroke. This study was designed as a pilot study to explore this provisional data. Autologous bone marrow derived mesenchymal stem cells were chosen due to their proven angiogenic, paracrine and neuroregenerative functions. Subjects and Met...
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Two-Step Induction of Dopaminergic Neurone Differentiation of Leukapharesis-Derived Mesenchymal Stem Cells
Zeinab M. Ismail,
Menna M. Abdel-Dayem,
Nagla M. Salama,
Hala Gabr,
Dalia I. Ismail,
Ahmed S. Abdelhafiz,
Shaimaa I. El-Jaafary
Issue:
Volume 3, Issue 4-1, July 2015
Pages:
7-17
Received:
9 April 2015
Accepted:
9 April 2015
Published:
6 May 2015
Abstract: Background: Neurodegenerative diseases represent a great medical challenge with marked consequences on quality of life of the patients and their families. Parkinson's disease (PD) constitutes a relatively common neurodegenerative disorder characterized by defect in dopaminergic neurons. The regenerative effect of mesenchymal stem cells (MSCs) stimulated research into their effect in treatment of PD. Subjects and Methods: Leukapharesis-derived MSC were isolated from 10 leukapharesis products using plastic adherence. Isolated MSCs were passaged, and passage III cells were induced to dopaminergic neurones using two-step protocol applying sequentially nerve growth factor and addition of ascorbic acid. Neuronal induction was evaluated by immunostaining against neurofilament protein, while dopaminergic neurons induction was evaluated using immunostaining against tyrosine hydroxylase. Results and Conclusions: MSCs were isolated in a rate of 0.12%-0.15% of leukapharesis cells, with viability ranging from 70-96%. NF positivity was 15.38±3.84, while the percentage of cells stained for TH was 5.94±0.65.MSCs could be successfully induced to dopaminergic neuron-like cells in vitro.
Abstract: Background: Neurodegenerative diseases represent a great medical challenge with marked consequences on quality of life of the patients and their families. Parkinson's disease (PD) constitutes a relatively common neurodegenerative disorder characterized by defect in dopaminergic neurons. The regenerative effect of mesenchymal stem cells (MSCs) stimu...
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The Role of Adipose Derived Mesenchymal Stem Cells in Enhancement of Peripheral Nerve Injuries Repair
Ayad H.,
Zahra M.,
Gabr H.,
Ismaeil A.,
Abo Elkheir Y.
Issue:
Volume 3, Issue 4-1, July 2015
Pages:
18-23
Received:
29 May 2015
Accepted:
1 June 2015
Published:
30 June 2015
Abstract: Background: About 50% of peripheral nerve injuries leave permenant disability. Trials to enhance nerve repair using stem cells are undergoing. Adipose derived mesenchymal stem cells (ADSCs) are good candidates for cellular-induced regeneration. Aim of the Work: The aim of the present work is to evaluate the effect of ADSCs on enhancing repair of peripheral nerve injuries. Subjects and Methods: This study was conducted on 18 patients with recent trauma involving nerve injuries at the wrist region. Patients were divided into: Group I: underwent surgical end-to-end closure GroupII: underwent surgical end-to-end closure and injection of ADSCs into the nerve sheath and surrounding tissue. Both groups were followed up using clinical assessment using Sensory Recovery Grading and Muscle Strength Grading systems in addition to electrophysiological nerve conduction tests. Results and Conclusions: This study collected a range of 1 to 2 x106 ADSCs from an average of 100-150 ml fat. After 1 year, stem cell group showed significantly higher motor and sensory improvement in ulnar nerve injury; while in the median nerve injury, stem cell group showed higher motor recovery with no difference in sensory recovery.
Abstract: Background: About 50% of peripheral nerve injuries leave permenant disability. Trials to enhance nerve repair using stem cells are undergoing. Adipose derived mesenchymal stem cells (ADSCs) are good candidates for cellular-induced regeneration. Aim of the Work: The aim of the present work is to evaluate the effect of ADSCs on enhancing repair of pe...
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Intrathecal Autologous Bone Marrow Derived MSC Therapy in Cerebral Palsy: Safety and Short Term Efficacy
Hala Gabr,
Wael Abou El-Kheir,
Osama Ghannam,
Mohamed Esewy El-Fiki,
Yehia Salah
Issue:
Volume 3, Issue 4-1, July 2015
Pages:
24-29
Received:
29 May 2015
Accepted:
1 June 2015
Published:
30 June 2015
Abstract: Objectives: Cerebral palsy (CP) is a disorder caused by injury or abnormal development of the brain at or immediately after birth. Current management of CP may improve the symptoms, such as muscle tone and gait, but is not directed to the original damage. Cellular therapy is evolving as a regenerative tool in many diseases with neural damage. Mesenchymal stem cells (MSCs) have been proven to transdifferentiate into neural lineage and improve neurodegeneration in animal models and in few clinical trials. This study was designed to evaluate the safety and efficacy of autologous MSC therapy in cases of CP. Subjects and Methods: this study is a randomized controlled trial enrolling 100 CP patients aged 1-7 years. Patients were assigned into two groups: Study group (44 patients after drop out cases) and control group (50 patients). All patients were subjected to history taking and clinical assessment. The study groups underwent bone marrow aspiration and MSC separation. MSCs were injected intrathecally. Follow-up was done using Child Health Questionnaire, Gross Motor Function classification System and Pediatric evaluation of disability inventory. Results: Overall assessment revealed improvement in motor, cognitive, or social parameters in 8 patients (18.18%). Study group showed improvement in Child Health Questionnaire, Gross Motor Function Classification, but not Pediatric Evaluation of Disablity Inventory. No correlation was found between improvement and age or gender. Complications observed were transient related to injection, no neurological or radiological complications were observed. Conclusions: Autologous MSC injection in CP patients showed short-term safety, with variable efficacy in improving motor and cognitive defects.
Abstract: Objectives: Cerebral palsy (CP) is a disorder caused by injury or abnormal development of the brain at or immediately after birth. Current management of CP may improve the symptoms, such as muscle tone and gait, but is not directed to the original damage. Cellular therapy is evolving as a regenerative tool in many diseases with neural damage. Mesen...
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Allogenic Mesenchymal Stromal Cell Therapy for Type III Spinal Muscular Atrophy: Case Report
Abo Elkheir W.,
Gabr H.,
Salah Y.
Issue:
Volume 3, Issue 4-1, July 2015
Pages:
30-33
Received:
9 June 2015
Accepted:
10 June 2015
Published:
30 June 2015
Abstract: Rationale : Spinal Muscular Atrophy (SMA) is the most common genetic disorder and presents the most common cause of infant mortality. To date, patient management is symptomatic and focuses on improvement of independence and treatment of complications. Stem cell therapy represents a novel therapeutic option for many neurological diseases. Presenting concerns of the patient: This patient with type III SMA presented with generalized hypotonia and muscle weakness with inability to raise hands and legs, support back or neck, in addition to respiratory distress. Diagnosis: Clinical examination showed hypotonia and loss of reflexes. Creatine kinase levelxxx, electrophysiologyxx. Interventions: Allogenic mesenchymal stem cells (MSCs) were injected in a dose of xxx intrathecally and a dose of xxx injected systemically. Outcomes: The patient showed improvement of GFM score and upgrading of the GFMC grade from Grade V to Grade III in 3 months. Improved quality of life was reflected in improvement of the PEDI scores. Improvement was noticed in respiration. No complications were encountered. Improvement was maintained until date. Conclusions: Allogenic MSC therapy may present a new therapeutic strategy for SMA patients. Controlled clinical trials are recommended to document the safety and efficacy of the procedure.
Abstract: Rationale : Spinal Muscular Atrophy (SMA) is the most common genetic disorder and presents the most common cause of infant mortality. To date, patient management is symptomatic and focuses on improvement of independence and treatment of complications. Stem cell therapy represents a novel therapeutic option for many neurological diseases. Presenting...
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Stem Cell Transplantation for Traumatic Spinal Cord Injury: What Have We Learned from Previous Experience
Elhawary S.,
Wagih A.,
Essam B.,
Tarek I.,
Aamer M.,
Ellessy R. M.
Issue:
Volume 3, Issue 4-1, July 2015
Pages:
34-42
Received:
20 June 2015
Accepted:
22 June 2015
Published:
6 July 2015
Abstract: Spinal cord injuries represent one of the most devastating illnesses that can affect the human body. Before the advent of the regenerative medicine era, it was regarded as an untreatable condition. Stem cell plasticity and translational medicine research open a new window of hope for this category of patients. Clinical trials of stem cell therapy for spinal cord injuries are now more than a decade old. However, the diversity of clinical trial design, cell type, dose and route of injection, make it extremely difficult to draw decisions from these previous experience. This review tries to collect as much evidence as we can from previous studies in order to suggest paths for future research in this setting.
Abstract: Spinal cord injuries represent one of the most devastating illnesses that can affect the human body. Before the advent of the regenerative medicine era, it was regarded as an untreatable condition. Stem cell plasticity and translational medicine research open a new window of hope for this category of patients. Clinical trials of stem cell therapy f...
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Neurogenic Differentiation of Bone Marrow-derived Mesenchymal Stem Cells Using Neural Induction Medium: A Morphological and Histochemical Study
Ahmedy E.,
Kandel S.,
Gabr H.,
Rizk S.,
Khalifa . K,
Kamal S.
Issue:
Volume 3, Issue 4-1, July 2015
Pages:
43-50
Received:
26 June 2015
Accepted:
27 June 2015
Published:
6 July 2015
Abstract: Background: Mesenchymal stem cells (MSCs) are multipotent adult stem cells present in all tissues. They are present in bone marrow, and can differentiate in vitro into neurons, glial cells and myofibroblasts . MSCs have been proposed as sources of stem cells for regeneration of the CNS. Thus, one of the goals of regenerative medicine is to regenerate damaged brain tissue and spinal cord by harnessing the power of stem cells to initiate neurogenesis in damaged areas of the brain. Objective: The aim of this work is to study in-vitro induced neurogenesis using MSCs as model of stem cells. Methodology : Bone marrow-MSCs were isolated, expanded and passaged. MSCs were identified using morphology and flowcytometric analysis. Co-expression of Oct ¾ was done. MSCs were induced to neural lineage using Neural Induction Media (NIM) : a cocktail of retinoic acid dissolved in DEMSO, recombinant human Fibroblast Growth Factor (FGF) basic, recombinant human Epidermal Growth Factor (EGF) and Insulin-like Growth Factor I (IGF-I) . Neural induction was verified morphologically, and immunologically using GFAP positivity and nestin expression. Results: BM-MSCs express CD44 and OCT ¾ which decrease with age. MSCs induced with NIM show morphological changes consistent with neurogenesis, positive GFAP and nestin expression as compared to the uninduced cells. Conclusion: MSCs isolated from bone marrow aspirate and can be differentiated into GFAP positive neural cells.
Abstract: Background: Mesenchymal stem cells (MSCs) are multipotent adult stem cells present in all tissues. They are present in bone marrow, and can differentiate in vitro into neurons, glial cells and myofibroblasts . MSCs have been proposed as sources of stem cells for regeneration of the CNS. Thus, one of the goals of regenerative medicine is to regenera...
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In Vitro Differentiation of Human Bone Marrow Stem Cells into Retinal Pigment Epithelium
Nehal Draz,
Makram F. Attalah,
Hany M. Shaheen,
Wael Abo Elkeir
Issue:
Volume 3, Issue 4-1, July 2015
Pages:
51-55
Received:
26 June 2015
Accepted:
27 June 2015
Published:
6 July 2015
Abstract: Introduction: Dysfunction, degeneration, and loss of retinal pigment epithelial (RPE) cells are prominent features of subtypes of retinitis pigmentosa (RP) which is a cause of visual disability. In this condition, there is progressive visual loss that often leads to blindness. A variety of therapeutic approaches to delay the degenerative process are under development, the most promising of which is the stem cell regenerative therapy. Stem cells are self-renewing cells capable of transdifferentiation into a number of cell lineages. Mesenchymal stem cells (MSCs) represent a type of stem cell with remarkable proliferative, regenerative and transdifferentiation ability. Aim of the Work: The aim of this work was to evaluate the ability of bone marrow derived MSCs to differentiate into retinal pigmented epithelial cells in vitro as a step towards regeneration of degenerated retinal cells as in cases of retinitis pigmentosa. Patients and Methods: The present study was carried out on 20 bone marrow samples obtained from donors undergoing bone marrow aspirations, at EL-Maadi Military Hospital. 3 ml bone marrow were aspirated, mesenchymal stem cells were separated and induced to RPE lineage through culture in the presence of nicotinamide NIC and factors from the TGF-b superfamily (Activin A). The BMSC- derived pigmented-like cells were evaluated for the morphology, function, and marker expression of authentic RPE using RT-PCR for RPE65 mRNA. Results: Bone marrow derived mesenchymal stem cells in all samples demonstrated the morphologic characteristics as well as molecular markers of RPE cells after 8 weeks of culture with activin A and nicotinamide. Conclusion: In the present study, compelling evidences support the possibility of differentiation of bone marrow stem cells into retinal pigmented epithelial cells (RPE) which have the morphology, function, and marker expression of authentic RPE.
Abstract: Introduction: Dysfunction, degeneration, and loss of retinal pigment epithelial (RPE) cells are prominent features of subtypes of retinitis pigmentosa (RP) which is a cause of visual disability. In this condition, there is progressive visual loss that often leads to blindness. A variety of therapeutic approaches to delay the degenerative process ar...
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Stem Cells for Neuro-regeneration: State of the Art
Wagih A.,
Elhawary S.,
Ellessy R. M.,
Esam B.,
Tarek I.,
Aamer M.
Issue:
Volume 3, Issue 4-1, July 2015
Pages:
56-70
Received:
9 June 2015
Accepted:
17 June 2015
Published:
9 July 2015
Abstract: Neuroregeneration (NR) is a long-sought medical dream which has intrigued vast research in the past decades. A traditional physiologic dogma that central nervous system does not regenerate has been strongly challenged in the recent years since the advent of the stem cell era. Stem cell research in the regenerative field passes through three main stages. The first stage is the in-vitro experiments which studies the exact molecular and cellular mechanisms underlying stem cell-mediated NR. The second stage is the application of these data in experimental animal settings to provide "proof of concept" of stem cell therapy in animal models. The final step is the translation of these data in pilot clinical trials. In this review, we will try to gather the different data of stem cell-mediated NR from various experimental and clinical researches.
Abstract: Neuroregeneration (NR) is a long-sought medical dream which has intrigued vast research in the past decades. A traditional physiologic dogma that central nervous system does not regenerate has been strongly challenged in the recent years since the advent of the stem cell era. Stem cell research in the regenerative field passes through three main st...
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