Concise Review: Adult Mesenchymal Stem Cells, Adult Neural Crest Stem Cells, and Therapy of Neurological Pathologies: A State of Play

Neurosciences Unit and.
STEM CELLS TRANSLATIONAL MEDICINE (Impact Factor: 5.71). 04/2013; DOI: 10.5966/sctm.2012-0147


Adult stem cells are endowed with in vitro multilineage differentiation abilities and constitute an attractive autologous source of material for cell therapy in neurological disorders. With regard to lately published results, the ability of adult mesenchymal stem cells (MSCs) and neural crest stem cells (NCSCs) to integrate and differentiate into neurons once inside the central nervous system (CNS) is currently questioned. For this review, we collected exhaustive data on MSC/NCSC neural differentiation in vitro. We then analyzed preclinical cell therapy experiments in different models for neurological diseases and concluded that neural differentiation is probably not the leading property of adult MSCs and NCSCs concerning neurological pathology management. A fine analysis of the molecules that are secreted by MSCs and NCSCs would definitely be of significant interest regarding their important contribution to the clinical and pathological recovery after CNS lesions.

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    • "Similarly, human ESC-derived oligodendrocyte precursors did not survive past 8 days following intraventricular injection into mice with EAE, yet animals displayed decreased neurologic disability, and this was associated with increased numbers of regulatory T cells within the CNS (Kim et al., 2012a). These reports are consistent with growing evidence that transplanted stem cells rarely differentiate into cells of neural lineage, and their efficacy often appears to be through delivery of trophic factors (Blurton-Jones et al., 2009; Müller et al., 2006) or by modulating inflammation (Neirinckx et al., 2013). An important question that remains an area of ongoing work is to determine whether the sustained presence of Tregs after hNPC rejection continues to dampen neuroinflammation long term. "
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    ABSTRACT: Using a viral model of the demyelinating disease multiple sclerosis (MS), we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs) results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4+CD25+FOXP3+ regulatory T cells (Tregs) within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments.
    Full-text · Article · Jun 2014 · Stem Cell Reports
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    • "Because of the ability of MSCs to differentiate into bone and cartilage, their clinical application in musculoskeletal regeneration is actively being explored [3]. However, while there are claims of their potential to differentiate into hepatocytes and neurons [9, 10], solid evidence of differentiation that transcends the germ-layer boundaries remains scarce [11, 12]. The therapeutic efficacy of MSCs appears to be derived from their ability to secrete a wide array of bioactive molecules that are immune-modulatory, antiapoptotic, anti-inflammatory, proangiogenic, chemotactic, or stimulatory of tissue regeneration [13–19]. "
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    ABSTRACT: Mesenchymal stromal cells (MSCs) are currently being investigated in numerous clinical trials of tissue repair and various immunological disorders based on their ability to secrete trophic factors and to modulate inflammatory responses. MSCs have been shown to migrate to sites of injury and inflammation in response to soluble mediators including the chemokine stromal cell-derived factor-(SDF-)1, but during in vitro culture expansion MSCs lose surface expression of key homing receptors particularly of the SDF-1 receptor, CXCR4. Here we review studies on enhancement of SDF-1-directed migration of MSCs with the premise that their improved recruitment could translate to therapeutic benefits. We describe our studies on approaches to increase the CXCR4 expression in in vitro-expanded cord blood-derived MSCs, namely, transfection, using the commercial liposomal reagent IBAfect, chemical treatment with the histone deacetylase inhibitor valproic acid, and exposure to recombinant complement component C1q. These methodologies will be presented in the context of other cell targeting and delivery strategies that exploit pathways involved in MSC migration. Taken together, these findings indicate that MSCs can be manipulated in vitro to enhance their in vivo recruitment and efficacy for tissue repair.
    Full-text · Article · Dec 2013
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    • "MSCs, which might contain heterogeneous subpopulations of cells, are generally characterized as having the ability of differentiation into chondrocytes, osteoblasts, and adipocytes, and have no cell surface markers of hematopoietic cell lineages [32]. In addition, they adhere to the bottom of tissue culture dishes and expand into the shape of fibroblast-like spindle cells. "
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    ABSTRACT: Background: Although pathological involvements of diabetic polyneuropathy (DPN) have been reported, no dependable treatment of DPN has been achieved. Recent studies have shown that mesenchymal stem cells (MSCs) ameliorate DPN. Here we demonstrate a differentiation of induced pluripotent stem cells (iPSCs) into MSC-like cells and investigate the therapeutic potential of the MSC-like cell transplantation on DPN. Research design and methods: For induction into MSC-like cells, GFP-expressing iPSCs were cultured with retinoic acid, followed by adherent culture for 4 months. The MSC-like cells, characterized with flow cytometry and RT-PCR analyses, were transplanted into muscles of streptozotocin-diabetic mice. Three weeks after the transplantation, neurophysiological functions were evaluated. Results: The MSC-like cells expressed MSC markers and angiogenic/neurotrophic factors. The transplanted cells resided in hindlimb muscles and peripheral nerves, and some transplanted cells expressed S100 β in the nerves. Impairments of current perception thresholds, nerve conduction velocities, and plantar skin blood flow in the diabetic mice were ameliorated in limbs with the transplanted cells. The capillary number-to-muscle fiber ratios were increased in transplanted hindlimbs of diabetic mice. Conclusions: These results suggest that MSC-like cell transplantation might have therapeutic effects on DPN through secreting angiogenic/neurotrophic factors and differentiation to Schwann cell-like cells.
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