Mesenchymal stem cells promote proliferation of endogenous neural stem cells and survival of newborn cells in a rat stroke model

Yoo, Seung‐Wan; Kim, Sung‐Soo; Lee, Soo-Yeol; Lee, Hey-Sun; Kim, Hyunsoo; Lee, Young‐Don; Suh‐Kim, Haeyoung

doi:10.3858/emm.2008.40.4.387

Cited by 148 publications

(97 citation statements)

References 53 publications

(56 reference statements)

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“…Similar observations outside the hippocampus in stroke and even in spinal injury have shown that MSCs mediate neurogenesis mainly by influencing endogenous neuroprogenitors. 9,49 These observations imply that Quantitative real-time PCR was performed on complementary DNA (cDNA) samples prepared from these RNA sample for the detection of the following genes: glial fibrillary acidic protein (GFAP), microtubule-associated protein 2 (MAP2), proliferating cell nuclear antigen (PCNA), brainderived neurotrophic factor (BDNF), fibroblast growth factor-2 (FGF-2), CXCR4, stromal cell-derived factor 1 (SDF-1) and doublecortin (DCX). Results are presented as mean±s.e.…”

Section: Discussionmentioning

confidence: 99%

“…7 Moreover, transplantation of MSCs in the central nervous systems prevents apoptosis and promotes neurogenesis (proliferation and differentiation) of 'host' neural cells and stem cells in the engrafted site. [7][8][9] MSCs were therefore suggested as candidates for treating a variety of neurodegenerative diseases, in particular Parkinson's disease, multiple sclerosis, cerebral hemorrhage and brain cancer. [10][11][12][13] Neurogenesis is a continuous process of the formation of new neurons, which occurs in the dentate gyrus in the hippocampus throughout life.…”

Section: Introductionmentioning

confidence: 99%

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Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior

et al. 2009

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Adult bone marrow-derived mesenchymal stem cells (MSCs) are regarded as potential candidates for treatment of neurodegenerative disorders, because of their ability to promote neurogenesis. MSCs promote neurogenesis by differentiating into neural lineages as well as by expressing neurotrophic factors that enhance the survival and differentiation of neural progenitor cells. Depression has been associated with impaired neurogenesis in the hippocampus and dentate gyrus. Therefore, the aim of this study was to analyze the therapeutic potential of MSCs in the Flinders sensitive line (FSL), a rat animal model for depression. Rats received an intracerebroventricular injection of culture-expanded and 1,1 0 -dioctadecyl-3,3,3 0 ,3 0 -tetramethylindocarbocyanine perchlorate (DiI)-labeled bone marrow-derived MSCs (10 5 cells). MSC-transplanted FSL rats showed significant improvement in their behavioral performance, as measured by the forced swim test and the dominant-submissive relationship (DSR) paradigm. After transplantation, MSCs migrated mainly to the ipsilateral dentate gyrus, CA1 and CA3 regions of the hippocampus, and to a lesser extent to the thalamus, hypothalamus, cortex and contralateral hippocampus. Neurogenesis was increased in the ipsilateral dentate gyrus and hippocampus of engrafted rats (granular cell layer) and was correlated with MSC engraftment and behavioral performance. We therefore postulate that MSCs may serve as a novel modality for treating depressive disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior

et al. 2009

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“…11 One might suppose that cerebral damage would lead to a molecular and cellular imbalance in the neurovascular niche favoring negative regulators and thus impair endogenous neurogenesis. However, studies in rodents provide accumulating evidence that the neurogenic capacity is preserved or even increases after injurious events such as seizures, 12 stroke, 13 or hypoxia-ischemia (HI). 14 This intriguing discovery prompted a wave of studies addressing not only the more fundamental aspects of neurogenesis, but also its possible role in the development and treatment of several neurologic disorders, such as epilepsy, 12 Parkinson's disease, 15 and Alzheimer's disease.…”

Section: Introductionmentioning

confidence: 99%

The Endogenous Regenerative Capacity of the Damaged Newborn Brain: Boosting Neurogenesis with Mesenchymal Stem Cell Treatment

Donega

Velthoven

Nijboer

et al. 2013

J Cereb Blood Flow Metab

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Neurogenesis continues throughout adulthood. The neurogenic capacity of the brain increases after injury by, e.g., hypoxiaischemia. However, it is well known that in many cases brain damage does not resolve spontaneously, indicating that the endogenous regenerative capacity of the brain is insufficient. Neonatal encephalopathy leads to high mortality rates and long-term neurologic deficits in babies worldwide. Therefore, there is an urgent need to develop more efficient therapeutic strategies. The latest findings indicate that stem cells represent a novel therapeutic possibility to improve outcome in models of neonatal encephalopathy. Transplanted stem cells secrete factors that stimulate and maintain neurogenesis, thereby increasing cell proliferation, neuronal differentiation, and functional integration. Understanding the molecular and cellular mechanisms underlying neurogenesis after an insult is crucial for developing tools to enhance the neurogenic capacity of the brain. The aim of this review is to discuss the endogenous capacity of the neonatal brain to regenerate after a cerebral ischemic insult. We present an overview of the molecular and cellular mechanisms underlying endogenous regenerative processes during development as well as after a cerebral ischemic insult. Furthermore, we will consider the potential to use stem cell transplantation as a means to boost endogenous neurogenesis and restore brain function.

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“…8,9 Furthermore, several studies have reported that transplanted BMSCs accelerate neuroplasticity and facilitate neuronal regeneration, as well as functional recovery. [10][11][12][13][14] Therefore, BMSC therapy may be a novel method to repair brain lesions and promote patients with functional disorders after severe TBI. Here, we report our experiences with autologous BMSC transplant that we have used in a clinical trial for patients with TBI complications.…”

Section: Introductionmentioning

confidence: 99%

Autologous Bone Marrow Mesenchymal Stem Cell Therapy in the Subacute Stage of Traumatic Brain Injury by Lumbar Puncture

Tian

Wang²,

Wang³

et al. 2013

Exp Clin Transplant

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Objectives: To explore the clinical therapeutic effects and safety of autologous bone marrow mesenchymal stem cell therapy for traumatic brain injury by lumbar puncture. Materials and Methods: A total of 97 patients (24 with persistent vegetative state and 73 with disturbance motor activity) who developed a complex cerebral lesion after traumatic brain injury received autologous bone marrow mesenchymal stem cell therapy voluntarily. The stem cells were isolated from the bone marrow of the patients and transplanted into the subarachnoid space by lumbar puncture. Results: Fourteen days after cell therapy, no serious complications or adverse events were reported. To a certain extent, 38 of 97 patients (39.2%) improved in the function of brain after transplant (P = .007). Eleven of 24 patients (45.8%) with persistent vegetative state showed posttherapeutic improvements in consciousness (P = .024). Twentyseven of 73 patients (37.0%) with a motor disorder began to show improvements in motor functions (P = .025). The age of patients and the time elapsed between injury and therapy had effects on the outcomes of the cellular therapy (P < .05). No correlation was found between the number of cell injections and improvements (P > .05). Conclusions:This study suggests that the bone marrow stem cell therapy is safe and effective on patients with traumatic brain injury complications, such as persistent vegetative state and motor disorder, through lumbar puncture. Young patients improve more easily than older ones. The earlier the cellular therapy begins in the subacute stage of traumatic brain injury, the better the results.

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Mesenchymal stem cells promote proliferation of endogenous neural stem cells and survival of newborn cells in a rat stroke model

Abstract: Mesenchymal stem cells (MSCs) secrete bioactive factors that exert diverse responses in vivo. In the present study, we explored mechanism how MSCs may lead to higher functional recovery in the animal stroke model.

Cited by 148 publications

References 53 publications

Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior

Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior

The Endogenous Regenerative Capacity of the Damaged Newborn Brain: Boosting Neurogenesis with Mesenchymal Stem Cell Treatment

Autologous Bone Marrow Mesenchymal Stem Cell Therapy in the Subacute Stage of Traumatic Brain Injury by Lumbar Puncture

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