Comparisons of the therapeutic effects of three different routes of bone marrow mesenchymal stem cell transplantation in cerebral ischemic rats

Zhang, Honglian; Xie, Xing; Xiong, Ying-qiong; Liu, Shimin; Hu, Guozhu; Cao, Weijun; Wu, Xiao‐Mu

doi:10.1016/j.brainres.2017.12.017

Cited by 40 publications

(33 citation statements)

References 70 publications

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“…A similar conclusion was drawn by Park et al (2018), who argued in favor of local delivery of stem cells as delivery in the direct microenvironment of the lesion enhanced the paracrine potential of stem cells. In contrast, a study by Zhang et al (2018) comparing intracerebral, intravenous and intra-arterial rat BM-MSC therapy in an adult rat model of ischemic stroke reported superior functional recovery, synaptogenesis, neurogenesis and axonal remodeling following intra-arterial MSC delivery compared to the other two administration methods. However, when considering the most optimal route of administration of stem cells for a specific neurological condition, it is vital to take both the pathophysiology of the injury and the clinical condition of the patients into account.…”

Section: Strategies To Optimize Msc Therapy In Preterm Wmimentioning

confidence: 84%

“…Moreover, entrapment of MSCs in the spleen or liver has been reported to suppress T-cell activation and to contribute to the inactivation of destructive peripheral immune responses (Kurtz, 2008; Jellema et al, 2013). While intra-arterial MSC injection leads to a higher number of cells in the brain than intravenous application, it can lead to harmful microvascular occlusions (van Velthoven et al, 2010b; Park et al, 2018; Sarmah et al, 2018; Zhang et al, 2018). Interestingly, although this review provides a large body of evidence reporting a beneficial effect of intravenous MSC therapy, a recent meta-analysis including 64 studies regarding adult ischemic stroke found that the effect size and thus therapeutic potential of the invasive intracerebral route was superior compared to other routes of administration (Sarmah et al, 2018).…”

Section: Strategies To Optimize Msc Therapy In Preterm Wmimentioning

confidence: 99%

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The Potential of Stem Cell Therapy to Repair White Matter Injury in Preterm Infants: Lessons Learned From Experimental Models

et al. 2019

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Diffuse white matter injury (dWMI) is a major cause of morbidity in the extremely preterm born infant leading to life-long neurological impairments, including deficits in cognitive, motor, sensory, psychological, and behavioral functioning. At present, no treatment options are clinically available to combat dWMI and therefore exploration of novel strategies is urgently needed. In recent years, the pathophysiology underlying dWMI has slowly started to be unraveled, pointing towards the disturbed maturation of oligodendrocytes (OLs) as a key mechanism. Immature OL precursor cells in the developing brain are believed to be highly sensitive to perinatal inflammation and cerebral oxygen fluctuations, leading to impaired OL differentiation and eventually myelination failure. OL lineage development under normal and pathological circumstances and the process of (re)myelination have been studied extensively over the years, often in the context of other adult and pediatric white matter pathologies such as stroke and multiple sclerosis (MS). Various studies have proposed stem cell-based therapeutic strategies to boost white matter regeneration as a potential strategy against a wide range of neurological diseases. In this review we will discuss experimental studies focusing on mesenchymal stem cell (MSC) therapy to reduce white matter injury (WMI) in multiple adult and neonatal neurological diseases. What lessons have been learned from these previous studies and how can we translate this knowledge to application of MSCs for the injured white matter in the preterm infant? A perspective on the current state of stem cell therapy will be given and we will discuss different important considerations of MSCs including cellular sources, timing of treatment and administration routes. Furthermore, we reflect on optimization strategies that could potentially reinforce stem cell therapy, including preconditioning and genetic engineering of stem cells or using cell-free stem cell products, to optimize cell-based strategy for vulnerable preterm infants in the near future.

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Section: Strategies To Optimize Msc Therapy In Preterm Wmimentioning

confidence: 84%

Section: Strategies To Optimize Msc Therapy In Preterm Wmimentioning

confidence: 99%

The Potential of Stem Cell Therapy to Repair White Matter Injury in Preterm Infants: Lessons Learned From Experimental Models

et al. 2019

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“…For these reasons, MSCs are the first stem cells to have been tested in clinical studies for the treatment of stroke. Preclinical studies demonstrated that administration of MSCs via intracerebral (10,11), intravenous (12)(13)(14), intra-arterial (15,16), and intraventricular/intrathecal routes (17) showed therapeutic benefits of MSCs in animal models of acute stroke (18). Although intravenous administration of autologous MSCs from bone marrow was found to be safe and well tolerated in ischemic stroke patients (19)(20)(21)(22), no significant improvement was observed in neurological outcomes following intravenous administration of allogeneic MSCs (23).…”

Section: Introductionmentioning

confidence: 99%

Neurogenin-1 Overexpression Increases the Therapeutic Effects of Mesenchymal Stem Cells through Enhanced Engraftment in an Ischemic Rat Brain

Kim

Marasini

Yoon

et al. 2020

IJSC

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Background and Objectives: Stem cell therapy is a promising strategy for treating neurological diseases but its effectiveness is influenced by the route of administration and the characteristics of the stem cells. We determined whether neural induction of mesenchymal stem cells (MSCs) was beneficial when the cells were delivered intra-arterially through the carotid artery. Methods and Results: MSCs were neurally induced using a retroviral vector expressing the neurogenic transcription factor neurogenin-1 (Ngn1). The LacZ gene encoding bacterial β-galactosidase was used as a control. Ischemic stroke was induced by transluminal occlusion of the middle cerebral artery and 3 days later the MSCs were delivered intra-arterially through the internal carotid artery. Magnetic resonance imaging analysis indicated that compared to MSCs expressing LacZ (MSCs/LacZ), MSCs expressing Ngn1 (MSCs/Ngn1) exhibited increased recruitment to the ischemic region and populated this area for a longer duration. Immunohistochemical analysis indicated that compared to MSCs/LacZ, MSCs/Ngn1 more effectively alleviated neurological dysfunction by blocking secondary damage associated with neuronal cell death and brain inflammation. Microarray and real-time PCR analysis indicated that MSCs/Ngn1 exhibited increased expression of chemotactic cytokine receptors, adherence to endothelial cells, and migration ability. Conclusions: Neural induction with Ngn1 increases the homing ability of MSCs, enhancing their engraftment efficiency in the ischemic rat brain. Intra-arterial delivery of neurally induced MSCs/Ngn1 3 days after ischemic injury blocks neuronal cell death and inflammation, and improves functional recovery. Thus, intra-arterial administration of stem cells with neural properties may be a novel therapy for the treatment of ischemic stroke.

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“…These mechanisms include, among others, the reduction of autophagy, which is one of the side effects during I/R injury and the anatomical restoration of cortical interhemispheric connections . In fact, it has been demonstrated that there is no difference among the intracerebral, intravenous, and intra‐arterial delivery of these cells concerning the functional recovery of the ischemic brain . However, intra‐arterial delivery may provide more evident results.…”

Section: Cell‐based Approachesmentioning

confidence: 99%

Advanced Functional Materials and Cell‐Based Therapies for the Treatment of Ischemic Stroke and Postischemic Stroke Effects

Tapeinos

Larrañaga

Tomatis

et al. 2019

Adv Funct Materials

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Ischemic stroke is considered one of the most threatening neurological disorders with high percentages of mortality and morbidity worldwide. Although in recent years, several nanotechnological advances have improved the survival rates, severe untreated poststroke side‐effects continue to significantly influence the way of life of many. Tissue plasminogen activator and mechanical thrombectomy are considered the gold standards for the treatment of acute cerebral ischemia. These, however, fail to improve postischemic disorders. Herein, after a brief description of the pathophysiology of ischemic stroke and the following biochemical cascade, the most recent biomaterial and cell‐based strategies are reviewed for its treatment. Other therapeutics that have been proposed not only for the treatment of cerebral ischemia but also for the regeneration of the infarcted brain that is responsible for a variety of disorders, including cognitive, motor, and speech problems are also presented. Finally, a few reported studies on diagnostic and theranostic nanostructures are also provided.

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Comparisons of the therapeutic effects of three different routes of bone marrow mesenchymal stem cell transplantation in cerebral ischemic rats

Cited by 40 publications

References 70 publications

The Potential of Stem Cell Therapy to Repair White Matter Injury in Preterm Infants: Lessons Learned From Experimental Models

The Potential of Stem Cell Therapy to Repair White Matter Injury in Preterm Infants: Lessons Learned From Experimental Models

Neurogenin-1 Overexpression Increases the Therapeutic Effects of Mesenchymal Stem Cells through Enhanced Engraftment in an Ischemic Rat Brain

Advanced Functional Materials and Cell‐Based Therapies for the Treatment of Ischemic Stroke and Postischemic Stroke Effects

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