Characterization of conditioned medium of cultured bone marrow stromal cells

Nakano, Norihiko; Nakai, Yoshiyasu; Seo, Tae-Boem; Yamada, Yoshihiro; Ohno, Takamasa; Yamanaka, A.; Nagai, Yoji; Fukushima, Masanori; Suzuki, Yoshiyuki; Nakatani, Toshio; Idé, Chizuka

doi:10.1016/j.neulet.2010.07.062

Cited by 102 publications

(72 citation statements)

References 17 publications

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“…BDNF administration decreases apoptosis and demyelination in a spinal cord compression model [74] and reduces astroglial scar formation [75]. Also, other factors, thus not described here, are known to be secreted by rat BMSCs: IGF-1, HGF, TGF-β1, EGF, SDF-1, MIP-1α/β, GM-CSF or FGF-2 [76], [77]. The fact that we didn't find those factors is first due to the fact that some of them were not included in our 90-protein array assay.…”

Section: Discussionmentioning

confidence: 88%

Conditioned Medium from Bone Marrow-Derived Mesenchymal Stem Cells Improves Recovery after Spinal Cord Injury in Rats: An Original Strategy to Avoid Cell Transplantation

et al. 2013

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Spinal cord injury triggers irreversible loss of motor and sensory functions. Numerous strategies aiming at repairing the injured spinal cord have been studied. Among them, the use of bone marrow-derived mesenchymal stem cells (BMSCs) is promising. Indeed, these cells possess interesting properties to modulate CNS environment and allow axon regeneration and functional recovery. Unfortunately, BMSC survival and differentiation within the host spinal cord remain poor, and these cells have been found to have various adverse effects when grafted in other pathological contexts. Moreover, paracrine-mediated actions have been proposed to explain the beneficial effects of BMSC transplantation after spinal cord injury. We thus decided to deliver BMSC-released factors to spinal cord injured rats and to study, in parallel, their properties in vitro. We show that, in vitro, BMSC-conditioned medium (BMSC-CM) protects neurons from apoptosis, activates macrophages and is pro-angiogenic. In vivo, BMSC-CM administered after spinal cord contusion improves motor recovery. Histological analysis confirms the pro-angiogenic action of BMSC-CM, as well as a tissue protection effect. Finally, the characterization of BMSC-CM by cytokine array and ELISA identified trophic factors as well as cytokines likely involved in the beneficial observed effects. In conclusion, our results support the paracrine-mediated mode of action of BMSCs and raise the possibility to develop a cell-free therapeutic approach.

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Section: Discussionmentioning

confidence: 88%

Conditioned Medium from Bone Marrow-Derived Mesenchymal Stem Cells Improves Recovery after Spinal Cord Injury in Rats: An Original Strategy to Avoid Cell Transplantation

et al. 2013

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“…MSCs secretomes present a high range of molecules, such as cytokines and growth factors 11, 30–32 . BDNF is a neurotrophin that, together with TrkB, its cognate receptor, is present throughout CNS 33 .…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF

Martins

Costa

Pedro

et al. 2017

Sci Rep

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Mesenchymal stem cells (MSCs) have been used for cell-based therapies in regenerative medicine, with increasing importance in central and peripheral nervous system repair. However, MSCs grafting present disadvantages, such as, a high number of cells required for transplantation and low survival rate when transplanted into the central nervous system (CNS). In line with this, MSCs secretome which present on its composition a wide range of molecules (neurotrophins, cytokines) and microvesicles, can be a solution to surpass these problems. However, the effect of MSCs secretome in axonal elongation is poorly understood. In this study, we demonstrate that application of MSCs secretome to both rat cortical and hippocampal neurons induces an increase in axonal length. In addition, we show that this growth effect is axonal intrinsic with no contribution from the cell body. To further understand which are the molecules required for secretome-induced axonal outgrowth effect, we depleted brain-derived neurotrophic factor (BDNF) from the secretome. Our results show that in the absence of BDNF, secretome-induced axonal elongation effect is lost and that axons present a reduced axonal growth rate. Altogether, our results demonstrate that MSCs secretome is able to promote axonal outgrowth in CNS neurons and this effect is mediated by BDNF.

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“…Nakano et al also showed that the secretome of BMSCs cultured in the supernatant of ischemic brain extracts was able to increase neuronal survival and neurite outgrowth of postnatal rat hippocampal neurons, through apoptosis suppression mechanisms [20]. These findings were correlated with the expression and secretion of IGF-1 (insulin-like growth factor 1), HGF (hepatocyte growth factor), VEGF (vascular endothelial growth factor), and TGF β 1 (transforming growth factor beta 1) by the BMSCs [20]. This was further confirmed by other studies in which, upon being cultured with extracts from ischemic and traumatic brain, BMSCs altered its gene expression profile when compared with uninjured control brain extracts [21, 22].…”

Section: Introductionmentioning

confidence: 99%

The Secretome of Bone Marrow and Wharton Jelly Derived Mesenchymal Stem Cells Induces Differentiation and Neurite Outgrowth in SH-SY5Y Cells

Pires

Sousa

Salgado

2014

Stem Cells International

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The goal of this study was to determine and compare the effects of the secretome of mesenchymal stem cells (MSCs) isolated from human bone-marrow (BMSCs) and the Wharton jelly surrounding the vein and arteries of the umbilical cord (human umbilical cord perivascular cells (HUCPVCs)) on the survival and differentiation of a human neuroblastoma cell line (SH-SY5Y). For this purpose, SH-SY5Y cells were differentiated with conditioned media (CM) from the MSCs populations referred above. Retinoic acid cultured cells were used as control for neuronal differentiated SH-SY5Y cells. SH-SY5Y cells viability assessment revealed that the secretome of BMSCs and HUCPVCs, in the form of CM, was able to induce their survival. Moreover, immunocytochemical experiments showed that CM from both MSCs was capable of inducing neuronal differentiation of SH-SY5Y cells. Finally, neurite lengths assessment and quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) analysis demonstrated that CM from BMSCs and HUCPVCs differently induced neurite outgrowth and mRNA levels of neuronal markers exhibited by SH-SY5Y cells. Overall, our results show that the secretome of both BMSCs and HUCPVCs was capable of supporting SH-SY5Y cells survival and promoting their differentiation towards a neuronal phenotype.

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Characterization of conditioned medium of cultured bone marrow stromal cells

Cited by 102 publications

References 17 publications

Conditioned Medium from Bone Marrow-Derived Mesenchymal Stem Cells Improves Recovery after Spinal Cord Injury in Rats: An Original Strategy to Avoid Cell Transplantation

Conditioned Medium from Bone Marrow-Derived Mesenchymal Stem Cells Improves Recovery after Spinal Cord Injury in Rats: An Original Strategy to Avoid Cell Transplantation

Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF

The Secretome of Bone Marrow and Wharton Jelly Derived Mesenchymal Stem Cells Induces Differentiation and Neurite Outgrowth in SH-SY5Y Cells

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