Differentiation of mesenchymal stem cells to support peripheral nerve regeneration in a rat model

Ladak, Adil; Olson, Jaret; Tredget, Edward E.; Gordon, Tessa

doi:10.1016/j.expneurol.2011.01.013

Cited by 156 publications

(149 citation statements)

References 43 publications

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“…Moreover, functional nerves have to be sacrificed as SCs donor resulting in loss of sensation, scarring and, possibly, neuroma formation. The limitations of harvesting autologous SCs, such as donor nerve sacrifice and donor site morbidity, have led to investigation of other cell types that provide similar trophic support to axon regeneration ( Ladak et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Use of poly(DL-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the Wharton's jelly of the umbilical cord for promoting nerve regeneration in axonotmesis: In vitro and in vivo analysis

et al. 2012

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Cellular systems implanted into an injured nerve may produce growth factors or extracellular matrix molecules, modulate the inflammatory process and eventually improve nerve regeneration. In the present study, we evaluated the therapeutic value of human umbilical cord matrix MSCs (HMSCs) on rat sciatic nerve after axonotmesis injury associated to Vivosorbs membrane. During HMSCs expansion and differentiation in neuroglial-like cells, the culture medium was collected at 48, 72 and 96 h for nuclear magnetic resonance (NMR) analysis in order to evaluate the metabolic profile. To correlate the HMSCs ability to differentiate and survival capacity in the presence of the Vivosorbs membrane, the [Ca 2þ ]i of undifferentiated HMSCs or neuroglial-differentiated HMSCs was determined by the epifluorescence technique using the Fura-2AM probe. The Vivosorbs membrane proved to be adequate and used as scaffold associated with undiffer-entiated HMSCs or neuroglial-differentiated HMSCs. In vivo testing was carried out in adult rats where a sciatic nerve axonotmesis injury was treated with undifferentiated HMSCs or neuroglial differentiated HMSCs with or without the Vivosorbs membrane. Motor and sensory functional recovery was evaluated throughout a healing period of 12 weeks using sciatic functional index (SFI), extensor postural thrust (EPT), and withdrawal reflex latency (WRL).Stereological analysis was carried out on regenerated nerve fibers. In vitro investigation showed the formation of typical neuroglial cells after differentiation, which were positively stained for the typical specific neuroglial markers such as the GFAP, the GAP-43 and NeuN.NMR showed clear evidence that HMSCs expansion is glycolysis-dependent but their differentiation requires the switch of the metabolic profile to oxidative metabolism. In vivo studies showed enhanced recovery of motor and sensory function in animals treated with transplanted undifferentiated and differentiated HMSCs that was accompanied by an increase in myelin sheath. Taken together, HMSC from the umbilical cord Wharton jelly might be useful for improving the clinical outcome after peripheral nerve lesion.

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Section: Introductionmentioning

confidence: 99%

Use of poly(DL-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the Wharton's jelly of the umbilical cord for promoting nerve regeneration in axonotmesis: In vitro and in vivo analysis

et al. 2012

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“…4) suggests that collagen supports cell adherence and proliferation. The seeded nMSCs are expected to function similarly to Schwann cells (SC) and support axonal regrowth by increasing their synthesis of surface cell adhesion molecules (CAMs) and secreting neurotrophic factors [28]. There were also minimal inflammation cells surrounding the conduit throughout the study (Fig.…”

Section: Discussionmentioning

confidence: 99%

Collagen-Coated Polylactic-Glycolic Acid (PLGA) Seeded with Neural-Differentiated Human Mesenchymal Stem Cells as a Potential Nerve Conduit*

Sulong¹,

Hassan²,

Ng³

et al. 2014

Adv Clin Exp Med

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Background. Autologous nerve grafts to bridge nerve gaps pose various drawbacks. Nerve tissue engineering to promote nerve regeneration using artificial neural conduits has emerged as a promising alternative. Objectives. To develop an artificial nerve conduit using collagen-coated polylactic-glycolic acid (PLGA) and to analyse the survivability and propagating ability of the neuro-differentiated human mesenchymal stem cells in this conduit. Material and Methods. The PLGA conduit was constructed by dip-molding method and coated with collagen by immersing the conduit in collagen bath. The ultra structure of the conduits were examined before they were seeded with neural-differentiated human mesenchymal stem cells (nMSC) and implanted sub-muscularly on nude mice thighs. The non-collagen-coated PLGA conduit seeded with nMSC and non-seeded non-collagen-coated PLGA conduit were also implanted for comparison purposes. The survivability and propagation ability of nMSC was studied by histological and immunohistochemical analysis. Results. The collagen-coated conduits had a smooth inner wall and a highly porous outer wall. Conduits coated with collagen and seeded with nMSCs produced the most number of cells after 3 weeks. The best conduit based on the number of cells contained within it after 3 weeks was the collagen-coated PLGA conduit seeded with neuro-transdifferentiated cells. The collagen-coated PLGA conduit found to be suitable for attachment, survival and proliferation of the nMSC. Minimal cell infiltration was found in the implanted conduits where nearly all of the cells found in the cell seeded conduits are non-mouse origin and have neural cell markers, which exhibit the biocompatibility of the conduits. Conclusions. The collagen-coated PLGA conduit is biocompatible, non-cytotoxic and suitable for use as artificial nerve conduits (Adv Clin Exp Med 2014, 23, 3, 353-362).

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“…These differentiated MSCs (dMSCs) have the advantage of being differentiated in a controlled manner, with both bone marrow and adipose-derived cells showing the ability to differentiate into SC-like cells [101,102,104,106]. These SC-like cells have a positive effect on neurite outgrowth on sensory dorsal root ganglion neurons in vitro [104,106] and, in recent studies, have been shown to have beneficial effects in vivo [102]. In the case of dASCs, these positive effects on neurite outgrowth may be attributed to increased level of BDNF and NGF versus that of their undifferentiated counterparts [108].…”

Section: Stem Cells: a Possible Alternative To Autologous Schwann Cellsmentioning

confidence: 99%

A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery

Daly

Yao

Zeugolis

et al. 2011

J. R. Soc. Interface.

481

508

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Microsurgical techniques for the treatment of large peripheral nerve injuries (such as the gold standard autograft) and its main clinically approved alternative-hollow nerve guidance conduits (NGCs)-have a number of limitations that need to be addressed. NGCs, in particular, are limited to treating a relatively short nerve gap (4 cm in length) and are often associated with poor functional recovery. Recent advances in biomaterials and tissue engineering approaches are seeking to overcome the limitations associated with these treatment methods. This review critically discusses the advances in biomaterial-based NGCs, their limitations and where future improvements may be required. Recent developments include the incorporation of topographical guidance features and/or intraluminal structures, which attempt to guide Schwann cell (SC) migration and axonal regrowth towards their distal targets. The use of such strategies requires consideration of the size and distribution of these topographical features, as well as a suitable surface for cell-material interactions. Likewise, cellular and molecular-based therapies are being considered for the creation of a more conductive nerve microenvironment. For example, hurdles associated with the short half-lives and low stability of molecular therapies are being surmounted through the use of controlled delivery systems. Similarly, cells (SCs, stem cells and genetically modified cells) are being delivered with biomaterial matrices in attempts to control their dispersion and to facilitate their incorporation within the host regeneration process. Despite recent advances in peripheral nerve repair, there are a number of key factors that need to be considered in order for these new technologies to reach the clinic.

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Differentiation of mesenchymal stem cells to support peripheral nerve regeneration in a rat model

Cited by 156 publications

References 43 publications

Use of poly(DL-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the Wharton's jelly of the umbilical cord for promoting nerve regeneration in axonotmesis: In vitro and in vivo analysis

Use of poly(DL-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the Wharton's jelly of the umbilical cord for promoting nerve regeneration in axonotmesis: In vitro and in vivo analysis

Collagen-Coated Polylactic-Glycolic Acid (PLGA) Seeded with Neural-Differentiated Human Mesenchymal Stem Cells as a Potential Nerve Conduit*

A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery

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