Trophic activity derived from bone marrow mononuclear cells increases peripheral nerve regeneration by acting on both neuronal and glial cell populations

Ribeiro-Resende, Victor Túlio; Pimentel‐Coelho, Pedro M.; Mesentier-Louro, Louise A.; Méndez, Raúl; Mello-Silva, J.P.C.; Cabral-da-Silva, Mauricio Castro; Mello, Fernando G. de; Reis, Ricardo Augusto de Melo; Mendez-Otero, Rosália

doi:10.1016/j.neuroscience.2008.12.059

Cited by 68 publications

(55 citation statements)

References 33 publications

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“…Some studies have reported that transplanted stem cells could promote peripheral nerve regeneration through host cell replacement, cell differentiation, or cell-tocell contact-mediated signaling. However, transplanted stem cells exhibit poor differentiation and survival [12,48]. Therefore, a paracrine mechanism triggered by growth factors and cytokines secreted by transplanted stem cells has been suggested to enhance peripheral nerve regeneration [49].…”

Section: Discussionmentioning

confidence: 99%

“…These factors were found to enhance peripheral nerve regeneration in previous studies. In addition, macrophage accumulation was reported to increase dramatically following bone marrow stem cell transplantation [12] as stem cells, including SHEDs, secrete monocyte chemotactic protein-1. Therefore, the accumulation of macrophages at an early stage after PNI accelerates debris removal increases the concentrations of growth factors and promotes the migration of SCs.…”

Section: Discussionmentioning

confidence: 99%

“…Macrophages, a phenotypically diverse population of immune cells, are integrated into both nerve degeneration and regeneration [8][9][10]. Macrophages reach the injury site within 24 h and reach a peak number within 2-3 days [11,12]. In PNI, macrophages, which are mainly recruited from circulation, disrupt and phagocytose axons, produce growth factors, and promote the migration of Schwann cells (SCs) [1,13].…”

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confidence: 99%

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Peripheral Nerve Regeneration by Secretomes of Stem Cells from Human Exfoliated Deciduous Teeth

Sugimura‐Wakayama

Katagiri

Osugi

et al. 2015

Stem Cells and Development

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Peripheral nerve regeneration across nerve gaps is often suboptimal, with poor functional recovery. Stem cell transplantation-based regenerative therapy is a promising approach for axon regeneration and functional recovery of peripheral nerve injury; however, the mechanisms remain controversial and unclear. Recent studies suggest that transplanted stem cells promote tissue regeneration through a paracrine mechanism. We investigated the effects of conditioned media derived from stem cells from human exfoliated deciduous teeth (SHED-CM) on peripheral nerve regeneration. In vitro, SHED-CM-treated Schwann cells exhibited significantly increased proliferation, migration, and the expression of neuron-, extracellular matrix (ECM)-, and angiogenesis-related genes. SHED-CM stimulated neuritogenesis of dorsal root ganglia and increased cell viability. Similarly, SHED-CM enhanced tube formation in an angiogenesis assay. In vivo, a 10-mm rat sciatic nerve gap model was bridged by silicon conduits containing SHED-CM or serum-free Dulbecco's modified Eagle's medium. Light and electron microscopy confirmed that the number of myelinated axons and axon-to-fiber ratio (G-ratio) were significantly higher in the SHED-CM group at 12 weeks after nerve transection surgery. The sciatic functional index (SFI) and gastrocnemius (target muscle) wet weight ratio demonstrated functional recovery. Increased compound muscle action potentials and increased SFI in the SHED-CM group suggested sciatic nerve reinnervation of the target muscle and improved functional recovery. We also observed reduced muscle atrophy in the SHED-CM group. Thus, SHEDs may secrete various trophic factors that enhance peripheral nerve regeneration through multiple mechanisms. SHED-CM may therefore provide a novel therapy that creates a more desirable extracellular microenvironment for peripheral nerve regeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Peripheral Nerve Regeneration by Secretomes of Stem Cells from Human Exfoliated Deciduous Teeth

Sugimura‐Wakayama

Katagiri

Osugi

et al. 2015

Stem Cells and Development

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“…Although the mechanisms whereby BMMCs promote angiogenesis in vivo remain unclear, our current coculture experiments indicate that BMMCs-induced proliferation of ECs is at least partially attributable to soluble factors. It has been reported that BMCs such as BMMCs [22,46,47] and MSCs [48][49][50] secrete multiple growth factors, including VEGF, glia-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and hepatocyte growth factor (HGF). In addition, they have been considered to be part of mechanisms responsible for angiogenic, antiapoptotic, and mitogenic effects after cell transplantation [51,52].…”

Section: Discussionmentioning

confidence: 99%

Bone Marrow Mononuclear Cells Promote Proliferation of Endogenous Neural Stem Cells Through Vascular Niches After Cerebral Infarction

et al. 2010

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Increasing evidence shows that administration of bone marrow mononuclear cells (BMMCs) is a potential treatment for various ischemic diseases, such as ischemic stroke. Although angiogenesis has been considered primarily responsible for the effect of BMMCs, their direct contribution to endothelial cells (ECs) by being a functional elements of vascular niches for neural stem/progenitor cells (NSPCs) has not been considered. Herein, we examine whether BMMCs affected the properties of ECs and NSPCs, and whether they promoted neurogenesis and functional recovery after stroke. We compared i.v. transplantations 1 3 10 6 BMMCs and phosphate-buffered saline in mice 2 days after cortical infarction. Systemically administered BMMCs preferentially accumulated at the postischemic cortex and periinfarct area in brains; cell proliferation of ECs (angiogenesis) at these regions was significantly increased in BMMCstreated mice compared with controls. We also found that endogenous NSPCs developed in close proximity to ECs in and around the poststroke cortex and that ECs were essential for proliferation of these ischemia-induced NSPCs. Furthermore, BMMCs enhanced proliferation of NSPCs as well as ECs. Proliferation of NSPCs was suppressed by additional treatment with endostatin (known to inhibit proliferation of ECs) following BMMCs transplantation. Subsequently, neurogenesis and functional recovery were also promoted in BMMCs-treated mice compared with controls. These results suggest that BMMCs can contribute to the proliferation of endogenous ischemia-induced NSPCs through vascular niche regulation, which includes regulation of endothelial proliferation. In addition, these results suggest that BMMCs transplantation has potential as a novel therapeutic option in stroke treatment.

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“…These factors may be released directly or, through cellto-cell contact and paracrine signaling, can stimulate endogenous SCs to upregulate secretory activity [5] . Increased recruitment of circulating macrophages into the area can potentiate this effect [6] . ECM proteins such as collagen I, collagen IV, fibronectin and laminin, and neurite guidance proteins such as netrin and ninjurin-2 have pro-regenerative effects [7,8] .…”

Section: Culture Mediummentioning

confidence: 99%

Augmenting peripheral nerve regeneration using stem cells: A review of current opinion

Fairbairn

Meppelink

Ng-Glazier

et al. 2015

WJSC

126

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Outcomes following peripheral nerve injury remain frustratingly poor. The reasons for this are multifactorial, although maintaining a growth permissive environment in the distal nerve stump following repair is arguably the most important. The optimal environment for axonal regeneration relies on the synthesis and release of many biochemical mediators that are temporally and spatially regulated with a high level of incompletely understood complexity. The Schwann cell (SC) has emerged as a key player in this process. Prolonged periods of distal nerve stump denervation, characteristic of large gaps and proximal injuries, have been associated with a reduction in SC number and ability to support regenerating axons. Cell based therapy offers a potential therapy for the improvement of outcomes following peripheral nerve reconstruction. Stem cells have the potential to increase the number of SCs and prolong their ability to support regeneration. They may also have the ability to rescue and replenish populations of chromatolytic and apoptotic neurons following axotomy. Finally, they can be used in non-physiologic ways to preserve injured tissues such as denervated muscle while neuronal ingrowth has not yet occurred. Aside from stem cell type, careful consideration must be given to differentiation status, how stem cells are supported following transplantation and how they will be delivered to the site of injury. It is the aim of this article to review current opinions on the strategies of stem cell based therapy for the augmentation of peripheral nerve regeneration.

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Trophic activity derived from bone marrow mononuclear cells increases peripheral nerve regeneration by acting on both neuronal and glial cell populations

Cited by 68 publications

References 33 publications

Peripheral Nerve Regeneration by Secretomes of Stem Cells from Human Exfoliated Deciduous Teeth

Peripheral Nerve Regeneration by Secretomes of Stem Cells from Human Exfoliated Deciduous Teeth

Bone Marrow Mononuclear Cells Promote Proliferation of Endogenous Neural Stem Cells Through Vascular Niches After Cerebral Infarction

Augmenting peripheral nerve regeneration using stem cells: A review of current opinion

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