Intranasal delivery of central nervous system‐retargeted human mesenchymal stromal cells prolongs treatment efficacy of experimental autoimmune encephalomyelitis

Fransson, Moa; Piras, Elena; Wang, Hao; Burman, Joachim; Duprez, Ida; Harris, Robert A.; LeBlanc, Katarina; Magnusson, Peetra U.; Brittebo, Eva B.; Loskog, Angelica

doi:10.1111/imm.12275

Cited by 41 publications

(38 citation statements)

References 53 publications

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“…In normal mice, MSCs or glia cells delivered by intranasal administration could bypass BBB and migrate to brain parenchyma and cerebrospinal fluid (CSF) [134]. In transgenic mice of Parkinson's disease (PD) and Alzheimer's disease (AD) models, MSCs were detected in the olfactory bulb (OB), cortex, amygdala, striatum, hippocampus, cerebellum, and brainstem after intranasal delivery, with majority of the MSCs found in the OB and the brainstem [135]. Although the mechanism of intranasal delivery was unclear, olfactory nerve pathways, trigeminal nerve pathways, vascular pathways, and lymphatic pathways were possibly involved [136].…”

Section: Routes Of Transplantationmentioning

confidence: 99%

Opportunities and Challenges: Stem Cell‐Based Therapy for the Treatment of Ischemic Stroke

Tang

Zhang

et al. 2015

CNS Neurosci Ther

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Stem cell-based therapy for ischemic stroke has been widely explored in animal models and provides strong evidence of benefits. In this review, we summarize the types of stem cells, various delivery routes, and tracking tools for stem cell therapy of ischemic stroke. MSCs, EPCs, and NSCs are the most explored cell types for ischemic stroke treatment. Although the mechanisms of stem cell-based therapies are not fully understood, the most possible functions of the transplanted cells are releasing growth factors and regulating microenvironment through paracrine mechanism. Clinical application of stem cell-based therapy is still in its infancy. The next decade of stem cell research in stroke field needs to focus on combining different stem cells and different imaging modalities to fully explore the potential of this therapeutic avenue: from bench to bedside and vice versa.

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Section: Routes Of Transplantationmentioning

confidence: 99%

Opportunities and Challenges: Stem Cell‐Based Therapy for the Treatment of Ischemic Stroke

Tang

Zhang

et al. 2015

CNS Neurosci Ther

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“…Until now, the migration of intranasally administered MSCs to a lesion and the efficacy of this treatment have been reported for a cerebral infarction model in mice, 12,22 an experimental autoimmune encephalomyelitis model in mice, 13 and a Parkinson's disease model in rats. 8 Surpris ingly, the cells have been observed in the spinal cord as well as in the cortex, cerebellum, and brainstem 4 hours after the intranasal administration in the rat model of Par kinson's disease.…”

Section: 10mentioning

confidence: 99%

“…Recently, the intranasal administra tion of BMSCs into lesioned brains of rodents has been reported. 5,9,12,13,22,24 After their administration by simple drops into the nostrils, BMSCs are thought to migrate into the brains through the olfactory nerve route or trigeminal ganglion route. From the point of view of minimizing in vasiveness, the intranasal route is thought to be the least invasive of all the routes mentioned above.…”

mentioning

confidence: 99%

Intranasal delivery of bone marrow stromal cells to spinal cord lesions

Ninomiya¹,

Iwatsuki²,

Ohnishi³

et al. 2015

SPI

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OBJECT The intranasal delivery of bone marrow stromal cells (BMSCs) or mesenchymal stem cells to the injured brains of rodents has been previously reported. In this study, the authors investigated whether BMSCs migrate to spinal cord lesions through an intranasal route and whether the administration affected functional recovery. METHODS Forty Sprague-Dawley rats that were subjected to spinal cord injuries at the T7–8 level were divided into 5 groups (injured + intranasal BMSC–treated group, injured + intrathecal BMSC–treated group, injured-only group, injured + intranasal vehicle–treated group, and injured + intrathecal vehicle–treated group). The Basso-Beattie-Bresnahan (BBB) scale was used to assess hind limb motor functional recovery for 2 or 4 weeks. Intralesionally migrated BMSCs were examined histologically and counted at 2 and 4 weeks. To evaluate the neuroprotective and trophic effects of BMSCs, the relative volume of the lesion cavity was measured at 4 weeks. In addition, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels in the CSF were evaluated at 2 weeks. RESULTS Intranasally administered BMSCs were confirmed within spinal cord sections at both 2 and 4 weeks. The highest number, which was detected in the intrathecal BMSC–treated group at 2 weeks, was significantly higher than that in all the other groups. The BBB score of the intranasal BMSC–treated group showed statistically significant improvements by 1 week compared with the control group. However, in the final BBB scores, there was a statistically significant difference only between the intrathecal BMSC–treated group and the control group. The cavity ratios in the BMSC-treated groups were smaller than those of the control groups, but the authors did not find any significant differences in the NGF and BDNF levels in the CSF among the treatment and control groups. CONCLUSIONS BMSCs reached the injured spinal cord through the intranasal route and contributed to the recovery of hind limb motor function and lesion cavity reduction. However, the effects were not as significant as those seen in the intrathecal BMSC–treated group.

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“…This method would minimize or eliminate the distribution of cellular grafts to peripheral organs and facilitate neurosurgical cell implantation [139] . Several studies have proven that intranasal transplantation promotes migration of infused MSCs to the sites of lesion [141,142] . Blood brain barrier (BBB), consisting of cellular interactions between brain microvascular endothelial cells (BMECs), astrocytes, pericytes, and neurons [143] , may restrict the number of stromal cells reaching injury sites.…”

Section: Methods To Promote the Homing Of Mscs In The Treatment Of Cnmentioning

confidence: 99%

Strategies to improve the migration of mesenchymal stromal cells in cell therapy

Chen

et al. 2017

Transl. Neurosci. Clin.

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KEYWORDSMSCs; migration; cell therapy; engraftment efficiency; neurological disorder Mesenchymal stromal/stem cells (MSCs) are multipotent cells under consideration as a potential new therapy for a variety of inflammatory diseases including certain neurological disorders. It is generally thought that the efficacy of cell therapy in attenuating damage after ischemia, inflammation, or injury depends on the quantity of transplanted cells recruited to the target tissue. However, only a small number of systematically infused MSCs can effectively migrate to target sites, which significantly decreases the efficacy of exogenous cell-based therapy. In this review, we discuss specific factors influencing MSC migration, and summarize current strategies that effectively promote the motility of MSCs. In addition, we describe several protocols to improve the migration of stromal cells into the nervous system and, therefore, enhance the efficiency of engraftment as means of treating neurological disorders.Citation Li G, Hu Y, Chen Y, Tang Z. Strategies to improve the migration of mesenchymal stromal cells in cell therapy. Transl. Neurosci. Clin. 2017, 3(3): 159-175.

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Intranasal delivery of central nervous system‐retargeted human mesenchymal stromal cells prolongs treatment efficacy of experimental autoimmune encephalomyelitis

Cited by 41 publications

References 53 publications

Opportunities and Challenges: Stem Cell‐Based Therapy for the Treatment of Ischemic Stroke

Opportunities and Challenges: Stem Cell‐Based Therapy for the Treatment of Ischemic Stroke

Intranasal delivery of bone marrow stromal cells to spinal cord lesions

Strategies to improve the migration of mesenchymal stromal cells in cell therapy

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