Meningeal Multipotent Cells: A Hidden Target for CNS Repair?

Axons in the adult mammalian nervous system can extend over formidable distances, up to one meter or more in humans. During development, axonal and dendritic growth requires continuous addition of new membrane. Of the three major kinds of membrane lipids, phospholipids are the most abundant in all cell membranes, including neurons. Not only immature axons, but also severed axons in the adult require large amounts of lipids for axon regeneration to occur. Lipids also serve as energy storage, signaling molecules and they contribute to tissue physiology, as demonstrated by a variety of metabolic disorders in which harmful amounts of lipids accumulate in various tissues through the body. Detrimental changes in lipid metabolism and excess accumulation of lipids contribute to a lack of axon regeneration, poor neurological outcome and complications after a variety of central nervous system (CNS) trauma including brain and spinal cord injury. Recent evidence indicates that rewiring lipid metabolism can be manipulated for therapeutic gain, as it favors conditions for axon regeneration and CNS repair. Here, we review the role of lipids, lipid metabolism and ectopic lipid accumulation in axon growth, regeneration and CNS repair. In addition, we outline molecular and pharmacological strategies to fine-tune lipid composition and energy metabolism in neurons and non-neuronal cells that can be exploited to improve neurological recovery after CNS trauma and disease.

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In Vivo Reprogramming for CNS Repair: Regenerating Neurons from Endogenous Glial Cells

Neuron ◽

10.1016/j.neuron.2016.08.004 ◽

2016 ◽

Vol 91 (4) ◽

pp. 728-738 ◽

Cited By ~ 60

Author(s):

Hedong Li ◽

Gong Chen

Keyword(s):

Glial Cells ◽

Cns Repair

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Adipocyte differentiation of multipotent cells established from human adipose tissue

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2004.01.053 ◽

2004 ◽

Vol 315 (2) ◽

pp. 255-263 ◽

Cited By ~ 205

Author(s):

Anne-Marie Rodriguez ◽

Christian Elabd ◽

Frédéric Delteil ◽

Julien Astier ◽

Cécile Vernochet ◽

...

Keyword(s):

Adipose Tissue ◽

Adipocyte Differentiation ◽

Human Adipose Tissue ◽

Multipotent Cells

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The neural crest population responding to endothelin-3 in vitro includes multipotent cells

Journal of Cell Science ◽

10.1242/jcs.110.14.1673 ◽

1997 ◽

Vol 110 (14) ◽

pp. 1673-1682 ◽

Cited By ~ 1

Author(s):

J.G. Stone ◽

L.I. Spirling ◽

M.K. Richardson

Keyword(s):

Neural Crest ◽

Schwann Cells ◽

Cell Types ◽

Developmental Potential ◽

Colony Assay ◽

Cellular Targets ◽

Multipotent Cells ◽

Endothelin 3

The peptide endothelin 3 (EDN3) is essential for normal neural crest development in vivo, and is a potent mitogen for quail truncal crest cells in vitro. It is not known which subpopulations of crest cells are targets for this response, although it has been suggested that EDN3 is selective for melanoblasts. In the absence of cell markers for different precursor types in the quail crest, we have characterised EDN3-responsive cell types using in vitro colony assay and clonal analysis. Colonies were analysed for the presence of Schwann cells, melanocytes, adrenergic cells or sensory-like cells. We provide for the first time a description of the temporal pattern of lineage segregation in neural crest cultures. In the absence of exogenous EDN3, crest cells proliferate and then differentiate. Colony assay indicates that in these differentiated cultures few undifferentiated precursors remain and there is a low replating efficiency. By contrast, in the presence of 100 ng/ml EDN3 differentiation is inhibited and most of the cells maintain the ability to give rise to mixed colonies and clones containing neural crest derivatives. A high replating efficiency is maintained. In secondary culture there was a progressive decline in the number of cell types per colony in control medium. This loss of developmental potential was not seen when exogenous EDN3 was present. Cell type analysis suggests two novel cellular targets for EDN3 under these conditions. Contrary to expectations, one is a multipotent precursor whose descendants include melanocytes, adrenergic cells and sensory-like cells; the other can give rise to melanocytes and Schwann cells. Our data do not support previous claims that the action of EDN3 in neural crest culture is selective for cells in the melanocyte lineage.

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The fate of cells in the tailbud of Xenopus laevis

Development ◽

10.1242/dev.127.2.255 ◽

2000 ◽

Vol 127 (2) ◽

pp. 255-267 ◽

Cited By ~ 4

Author(s):

R.L. Davis ◽

M.W. Kirschner

Keyword(s):

Xenopus Laevis ◽

Small Groups ◽

Neural Tube ◽

Cell Types ◽

Similar Distribution ◽

Germ Layer ◽

Cell Determination ◽

Multipotent Cells ◽

Axial Development

The vertebrate tailbud and trunk form very similar tissues. It has been a controversial question for decades whether cell determination in the developing tail proceeds as part of early axial development or whether it proceeds by a different mechanism. To examine this question more closely, we have used photoactivation of fluorescence to mark small neighborhoods of cells in the developing tailbud of Xenopus laevis. We show that, in one region of the tailbud, very small groups of adjacent cells can contribute progeny to the neural tube, notochord and somitic muscle, as well as other identified cell types within a single embryo. Groups averaging three adjacent cells at a later stage can contribute progeny with a similar distribution. Our data suggest that the tailbud contains multipotent cells that make very late germ-layer decisions.

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Mesenchymal Stem Cells after Polytrauma: Actor and Target

Stem Cells International ◽

10.1155/2016/6289825 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Markus Huber-Lang ◽

Rebecca Wiegner ◽

Lorenz Lampl ◽

Rolf E. Brenner

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Healing Process ◽

Severe Trauma ◽

Signaling Mechanisms ◽

Multipotent Cells ◽

Proliferation And Differentiation ◽

Tissue Trauma ◽

Molecular Patterns ◽

Severe Tissue

Mesenchymal stem cells (MSCs) are multipotent cells that are considered indispensable in regeneration processes after tissue trauma. MSCs are recruited to damaged areas via several chemoattractant pathways where they function as “actors” in the healing process by the secretion of manifold pro- and anti-inflammatory, antimicrobial, pro- and anticoagulatory, and trophic/angiogenic factors, but also by proliferation and differentiation into the required cells. On the other hand, MSCs represent “targets” during the pathophysiological conditions after severe trauma, when excessively generated inflammatory mediators, complement activation factors, and damage- and pathogen-associated molecular patterns challenge MSCs and alter their functionality. This in turn leads to complement opsonization, lysis, clearance by macrophages, and reduced migratory and regenerative abilities which culminate in impaired tissue repair. We summarize relevant cellular and signaling mechanisms and provide an up-to-date overview about promising future therapeutic MSC strategies in the context of severe tissue trauma.

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