Delayed post-treatment with bone marrow-derived mesenchymal stem cells is neurorestorative of striatal medium-spiny projection neurons and improves motor function after neonatal rat hypoxia–ischemia

Cameron, Stella H.; Alwakeel, Amr J.; Goddard, Liping; Hobbs, Catherine; Gowing, Emma K.; Barnett, Elizabeth; Kohe, Sarah; Sizemore, Rachel J.; Oorschot, Dorothy E.

doi:10.1016/j.mcn.2015.03.019

Cited by 34 publications

(34 citation statements)

References 77 publications

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“…A previous study has shown that the collection, preparation, and infusion of fresh autologous UCB cells for use in infants with HIE is feasible [78]. In addition to stem cell transplantation, there is ongoing research in the field of stem cell factors (e.g., G-CSF) [79,80,81,82]. …”

Section: Clinical Strategies Of Antioxidants In Hiementioning

confidence: 99%

Oxidative Stress in Hypoxic-Ischemic Encephalopathy: Molecular Mechanisms and Therapeutic Strategies

Zhao

Zhu

Fujino

et al. 2016

IJMS

152

108

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Hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of morbidity and mortality in neonates. Because of high concentrations of sensitive immature cells, metal-catalyzed free radicals, non-saturated fatty acids, and low concentrations of antioxidant enzymes, the brain requires high levels of oxygen supply and is, thus, extremely sensitive to hypoxia. Strong evidence indicates that oxidative stress plays an important role in pathogenesis and progression. Following hypoxia and ischemia, reactive oxygen species (ROS) production rapidly increases and overwhelms antioxidant defenses. A large excess of ROS will directly modify or degenerate cellular macromolecules, such as membranes, proteins, lipids, and DNA, and lead to a cascading inflammatory response, and protease secretion. These derivatives are involved in a complex interplay of multiple pathways (e.g., inflammation, apoptosis, autophagy, and necrosis) which finally lead to brain injury. In this review, we highlight the molecular mechanism for oxidative stress in HIE, summarize current research on therapeutic strategies utilized in combating oxidative stress, and try to explore novel potential clinical approaches.

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Section: Clinical Strategies Of Antioxidants In Hiementioning

confidence: 99%

Oxidative Stress in Hypoxic-Ischemic Encephalopathy: Molecular Mechanisms and Therapeutic Strategies

Zhao

Zhu

Fujino

et al. 2016

IJMS

152

108

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“…Mesenchymal stem cells have proven safety and effectiveness in neurorestorative therapy in a number of settings (24). Bone marrow is the best source of MSCs (25).…”

Section: Discussionmentioning

confidence: 99%

Intrathecal Autologous Bone Marrow Derived MSC Therapy in Cerebral Palsy: Safety and Short Term Efficacy

Gabr¹,

El-Kheir²,

Ghannam³

et al. 2015

BIO

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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.

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“…Las células madre contribuyen a regular la homeostasis y a reparar los tejidos aportando nuevas células diferenciadas [129]. El empleo de esta terapia en modelos de daño cerebral agudo pretende restaurar el tejido dañado a través de la formación de nuevas neuronas, vasos sanguíneos (angiogénesis) y mediante el fomento de la sinaptogénesis [130]. Las células madre mesenquimales (CMM) son células multipotentes, con capacidad de diferenciarse hacia células de origen mesodérmico como osteocitos, condrocitos y adipocitos, y también hacia neuronas y astrocitos [131,132].…”

Section: Células Madre Mesenquimalesunclassified

“…Se han realizado diversos estudios valorando la eficacia de la administración intranasal de CMM, describiéndose su efecto beneficioso tras el daño HI, disminuyendo el tamaño de la lesión y mejorando el comportamiento cognitivo y motor [133][134][135][136][137]. Esta terapia ha demostrado además ser capaz de restaurar la pérdida de proyecciones del cuerpo estriado tras la EHI, efecto realizado de forma independiente de su dosis, mientras que dosis altas son capaces incluso de mejorar la función motora [130].…”

Section: Células Madre Mesenquimalesunclassified

Hipoxia-isquemia neonatal: bases celulares y moleculares del daño cerebral y modulación terapéutica de la neurogénesis

et al. 2019

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Delayed post-treatment with bone marrow-derived mesenchymal stem cells is neurorestorative of striatal medium-spiny projection neurons and improves motor function after neonatal rat hypoxia–ischemia

Cited by 34 publications

References 77 publications

Oxidative Stress in Hypoxic-Ischemic Encephalopathy: Molecular Mechanisms and Therapeutic Strategies

Oxidative Stress in Hypoxic-Ischemic Encephalopathy: Molecular Mechanisms and Therapeutic Strategies

Intrathecal Autologous Bone Marrow Derived MSC Therapy in Cerebral Palsy: Safety and Short Term Efficacy

Hipoxia-isquemia neonatal: bases celulares y moleculares del daño cerebral y modulación terapéutica de la neurogénesis

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