Human mesenchymal stromal cells ameliorate the phenotype of SOD1-G93A ALS mice

Zhao, Chengliang; Zhang, C.; Zhou, Shiyue; Xie, Youmei; Wang, Y.-H.; Huang, Hongyun; Shang, Yan Chang; Li, W.-Y.; Zhou, Chen; Yu, Menglei; Feng, Shan Wei

doi:10.1080/14653240701376413

Cited by 103 publications

(67 citation statements)

References 54 publications

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“…What is perhaps most pertinent, however, is that inflammatory demyelinated lesions were obvious throughout the CNS at this stage (day 50) and yet few or no hMSCs were disclosed. Rejection would be unlikely in view of the recognised immune suppressive effects of these cells [12]; others have likewise found no rejection of human MSCs in rodent recipients [8,17].…”

mentioning

confidence: 99%

Human mesenchymal stem cells abrogate experimental allergic encephalomyelitis after intraperitoneal injection, and with sparse CNS infiltration

Gordon

Pavlovska

Glover³

et al. 2008

Neuroscience Letters

113

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Multiple sclerosis is a currently incurable inflammatory demyelinating syndrome. Recent reports suggest that bone marrow derived mesenchymal stem cells may have therapeutic potential in experimental models of demyelinating disease, but various alternative mechanisms, ranging from systemic immune effects to local cell replacement, have been proposed. Here we used intraperitoneal delivery of human mesenchymal stem cells to help test (a) whether human cells can indeed suppress disease, and (b) whether CNS infiltration is required for any beneficial effect. We found pronounced amelioration of clinical disease but profoundly little CNS infiltration. Our findings therefore help confirm the therapeutic potential of mesenchymal stem cells, show that this does indeed extend to human cells, and are consistent with a peripheral or systemic immune effect of human MSCs in this model. Keywords Mesenchymal stem cells; Multiple sclerosis; Experimental allergic encephalomyelitisMultiple sclerosis is an acquired inflammatory demyelinating syndrome of unknown cause, and which is currently incurable. In many individuals, progressive disability occurs during the course of the disease, as a consequence of irreversible CNS damage. The ineffectiveness of current therapies has emphasised the importance of novel treatment approaches, and stem cells are widely held as having particular promise.Bone marrow derived mesenchymal stem cells can proliferate substantially, and can differentiate into cells of all three germ cell layers, including neural cells; moreover they are relatively accessible, could be used for autologous therapy, and are capable of entering the CNS (particularly when damaged) from the circulation [6,11]. They are therefore considered good candidates for early clinical stem cell therapeutic studies.Recently, reports have appeared suggesting that bone marrow-derived cells can ameliorate toxic and inflammatory experimental demyelinating disease following intravenous delivery [1,3,5,7,[13][14][15][16]. However, whether this effect is achieved through cell replacement and

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mentioning

confidence: 99%

Human mesenchymal stem cells abrogate experimental allergic encephalomyelitis after intraperitoneal injection, and with sparse CNS infiltration

Gordon

Pavlovska

Glover³

et al. 2008

Neuroscience Letters

113

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show abstract

“…Consequently, our results showing that intrathecal infusion of MSC is safe and feasible, in addition to data demonstrating MSC survival/ migration within the CNS [6,13] and effectiveness in neurological recovery [6,15], epitomize a weighty foundation for their use in the treatment of neurological patients.…”

Section: Discussionmentioning

confidence: 84%

“…The above assertion is supported by three major facts: a) MSC can differentiate outside the mesenchymal lineage into neurological precursors [5,9,10], b) after infusion of MSC to animals with genetic or experimental neurological diseases, MSC migrate and survive within the central nervous system [6,11] and contribute to the improvement/recovery of pre-symptomatic motor functions [6,7,[11][12][13] and c) MSC secrete several growth factors and chemokines that may create a neuroprotective environment favorable for tissue sparing and axonal regeneration [14,15 ].…”

Section: Introductionmentioning

confidence: 99%

“…Numerous studies have been performed to evaluate neuroplasticity, but not safety, after infusion (intravenous, intrathecal, subarachnoidal space or cortex) of MSC to mice models of motor neuron diseases [13,[16][17][18][19]. In turn, intrathecal infusion [12,20] emerges as an attractive option for cell delivery to treat neurological patients.…”

Section: Introductionmentioning

confidence: 99%

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The Intrathecal Infusion of Mesenchymal Stem Cells into Healthy Rabbits is Safe and Devoid of Neurological or Clinical Complications

Jj¹,

Pereira²,

Bartholomew³

et al. 2011

J Stem Cell Res Ther

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Background: Cellular, molecular and transplantation studies using mouse and rat models of neurological diseases have revealed that Mesenchymal Stem Cells (MSC) represent a reliable candidate for cellular therapies for neurological conditions, including Amyotrophic Lateral Sclerosis (ALS) and Spinal Cord Injury (SCI). However, evaluation of safety aspects associated with route and dose of cell infusion, pivotal issues in cell therapy, has not been tested in large animals.

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“…The therapeutic effect of MSCs may primarily capitalize on innate trophic support from themselves or from the delivery of augmented growth factors. Intraspinal, intracerebral, intrathecal, and intravenous injection of autologous MSCs in SOD1-G93A mice have also reported beneficial effects on disease progression, including slowed loss of motor neurons, improved motor function, and extended survival [43][44][45][46][47][48]. Given the fact that MSCs can deliver neurotrophic, anti-inflammatory, and immunomodulatory molecules [49,50], these cells are a promising treatment approach for ALS.…”

Section: Mesenchymal Stromal Cellsmentioning

confidence: 99%