Comparative miRNA-Based Fingerprinting Reveals Biological Differences in Human Olfactory Mucosa- and Bone-Marrow-Derived Mesenchymal Stromal Cells

Lindsay, Susan L.; Johnstone, Steven A.; McGrath, Michael A.; Mallinson, David J.; Barnett, Susan C.

doi:10.1016/j.stemcr.2016.03.009

Cited by 28 publications

(41 citation statements)

References 42 publications

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“…These cells could produce dopaminergic neurons in a rat model of Parkinson disease (Murrell et al, ) and recently, it was demonstrated that OM‐MSCs from the LP promote remyelination and the earlier recovery of gait coordination in a model of incomplete SCI (Lindsay et al, ). OM‐MSCs secrete factors that modulate OEC behavior in vitro , enhancing the extension of processes and their alignment along neurites, thereby promoting axon sheathing (Lindsay et al, ; Lindsay et al, ). OM‐MSC conditioned medium promoted myelination in vitro (Lindsay et al, ).…”

Section: Oecs In Spinal Cord Injury (Sci) Repairmentioning

confidence: 99%

Cell therapy for spinal cord injury with olfactory ensheathing glia cells (OECs)

Gómez

Sanchez

Portela-Lomba

et al. 2018

Glia

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The prospects of achieving regeneration in the central nervous system (CNS) have changed, as most recent findings indicate that several species, including humans, can produce neurons in adulthood. Studies targeting this property may be considered as potential therapeutic strategies to respond to injury or the effects of demyelinating diseases in the CNS. While CNS trauma may interrupt the axonal tracts that connect neurons with their targets, some neurons remain alive, as seen in optic nerve and spinal cord (SC) injuries (SCIs). The devastating consequences of SCIs are due to the immediate and significant disruption of the ascending and descending spinal pathways, which result in varying degrees of motor and sensory impairment. Recent therapeutic studies for SCI have focused on cell transplantation in animal models, using cells capable of inducing axon regeneration like Schwann cells (SchCs), astrocytes, genetically modified fibroblasts and olfactory ensheathing glia cells (OECs). Nevertheless, and despite the improvements in such cell-based therapeutic strategies, there is still little information regarding the mechanisms underlying the success of transplantation and regarding any secondary effects. Therefore, further studies are needed to clarify these issues. In this review, we highlight the properties of OECs that make them suitable to achieve neuroplasticity/neuroregeneration in SCI. OECs can interact with the glial scar, stimulate angiogenesis, axon outgrowth and remyelination, improving functional outcomes following lesion. Furthermore, we present evidence of the utility of cell therapy with OECs to treat SCI, both from animal models and clinical studies performed on SCI patients, providing promising results for future treatments.

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Section: Oecs In Spinal Cord Injury (Sci) Repairmentioning

confidence: 99%

Cell therapy for spinal cord injury with olfactory ensheathing glia cells (OECs)

Gómez

Sanchez

Portela-Lomba

et al. 2018

Glia

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“…Our own investigations have also revealed an important role for CXCL12 in human OM-MSC biology. OM-MSCs under the regulation of miR140-5p secrete more CXCL12 than BM-MSCs which is responsible for promoting rat CNS myelination in vitro to a greater extent than BM-MSCs (Lindsay et al., 2013, Lindsay et al, 2016). In the BM, CXCL12 has a range of HSC regulatory functions from retention (blocking their differentiation and migration) to quiescence and repopulation activity (Greenbaum et al., 2013, Schajnovitz et al., 2011).…”

Section: Introductionmentioning

confidence: 99%

“…Unfortunately, due to the technical variability in harvesting and growing cells from both BM and OM it is difficult to compare data across experiments. However, from the limited studies and our own data, which demonstrates OM-MSCs promote rat CNS myelination in vitro (Lindsay et al., 2010, Lindsay et al, 2016) and in vivo (Lindsay et al., submitted), we would postulate they may be an alternative candidate for the treatment in MS or other demyelinating diseases/injuries. Similarly they may be advantageous where neuroprotection or neurite outgrowth is important for repair eg retinitis pigmentosa, age-related macular degeneration, ALS, and stroke.…”

Section: Introductionmentioning

confidence: 99%

“…Similarly they may be advantageous where neuroprotection or neurite outgrowth is important for repair eg retinitis pigmentosa, age-related macular degeneration, ALS, and stroke. The identification that OM-MSCs secrete higher levels of the chemokine CXCL12 than BM-MSCs (Lindsay et al., 2016), which we and others have shown to be important in augmenting endogenous myelination (Maysami et al., 2006, Lindsay et al., 2013, Lindsay et al, 2016 Zilkha-Falb et al., 2016) also adds to the desirability as a candidate cell for transplantation. Lastly as MSCs are known to home to damaged tissue (Laroni et al., 2013, Eseonu and De Bari, 2015) and secrete a plethora of pro-repair factors, their use as a treatment is more beneficial than application of a chemokine alone (Allers et al., 2014, Joyce et al., 2010, Laroni et al., 2013).…”

Section: Introductionmentioning

confidence: 99%

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Are nestin-positive mesenchymal stromal cells a better source of cells for CNS repair?

Lindsay

Barnett

2017

Neurochemistry International

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In recent years there has been a great deal of research within the stem cell field which has led to the definition and classification of a range of stem cells from a plethora of tissues and organs. Stem cells, by classification, are considered to be pluri- or multipotent and have both self-renewal and multi-differentiation capabilities. Presently there is a great deal of interest in stem cells isolated from both embryonic and adult tissues in the hope they hold the therapeutic key to restoring or treating damaged cells in a number of central nervous system (CNS) disorders. In this review we will discuss the role of mesenchymal stromal cells (MSCs) isolated from human olfactory mucosa, with particular emphasis on their potential role as a candidate for transplant mediated repair in the CNS. Since nestin expression defines the entire population of olfactory mucosal derived MSCs, we will compare these cells to a population of neural crest derived nestin positive population of bone marrow-MSCs.

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“…However, a number of questions regarding MSC‐mediated specification of aNSCs and their oligodendroglial progeny remain unaddressed. Currently the identity of MSC‐CM derived compounds as well as the underlying mode of action are unknown, which is of additional interest considering the observation that not all MSCs are able to potentiate oligodendroglial processes (Lindsay, Johnstone, McGrath, Mallinson, & Barnett, ; Lindsay et al, ). Moreover, it is important to note that the majority of studies were performed with adult MSCs and it remains therefore to be shown whether the oligodendrogenic potential is restricted to adult cells or whether it strictly correlates with its bone (cell‐) origin.…”

Section: Introductionmentioning

confidence: 99%

Human mesenchymal factors induce rat hippocampal‐ and human neural stem cell dependent oligodendrogenesis

Jadasz

Tepe

Beyer

et al. 2017

Glia

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The generation of new oligodendrocytes is essential for adult brain repair in diseases such as multiple sclerosis. We previously identified the multifunctional p57kip2 protein as a negative regulator of myelinating glial cell differentiation and as an intrinsic switch of glial fate decision in adult neural stem cells (aNSCs). In oligodendroglial precursor cells (OPCs), p57kip2 protein nuclear exclusion was recently found to be rate limiting for differentiation to proceed. Furthermore, stimulation with mesenchymal stem cell (MSC)-derived factors enhanced oligodendrogenesis by yet unknown mechanisms. To elucidate this instructive interaction, we investigated to what degree MSC secreted factors are species dependent, whether hippocampal aNSCs respond equally well to such stimuli, whether apart from oligodendroglial differentiation also tissue integration and axonal wrapping can be promoted and whether the oligodendrogenic effect involved subcellular translocation of p57kip2. We found that CC1 positive oligodendrocytes within the hilus express nuclear p57kip2 protein and that MSC dependent stimulation of cultured hippocampal aNSCs was not accompanied by nuclear p57kip2 exclusion as observed for parenchymal OPCs after spontaneous differentiation. Stimulation with human MSC factors was observed to equally promote rat stem cell oligodendrogenesis, axonal wrapping and tissue integration. As forced nuclear shuttling of p57kip2 led to decreased CNPase-but elevated GFAP expression levels, this indicates heterogenic oligodendroglial mechanisms occurring between OPCs and aNSCs. We also show for the first time that dominant pro-oligodendroglial factors derived from human fetal MSCs can instruct human induced pluripotent stem cell-derived NSCs to differentiate into O4 positive oligodendrocytes.heterogeneity, inhibitors, intracellular protein shuttling, multiple sclerosis, myelin repair, neuroregeneration, oligodendrocyte Glia. 2018;66:145-160.wileyonlinelibrary.com/journal/glia

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Comparative miRNA-Based Fingerprinting Reveals Biological Differences in Human Olfactory Mucosa- and Bone-Marrow-Derived Mesenchymal Stromal Cells

Cited by 28 publications

References 42 publications

Cell therapy for spinal cord injury with olfactory ensheathing glia cells (OECs)

Cell therapy for spinal cord injury with olfactory ensheathing glia cells (OECs)

Are nestin-positive mesenchymal stromal cells a better source of cells for CNS repair?

Human mesenchymal factors induce rat hippocampal‐ and human neural stem cell dependent oligodendrogenesis

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