Conditioned Medium of Bone Marrow-Derived Mesenchymal Stromal Cells as a Therapeutic Approach to Neuropathic Pain: A Preclinical Evaluation

Neuropathic pain is a type of chronic pain caused by injury or dysfunction of the nervous system, without effective therapeutic approaches. Mesenchymal stromal cells (MSCs), through their paracrine action, have great potential in the treatment of this syndrome. In the present study, the therapeutic potential of MSC-derived conditioned medium (CM) was investigated in a mouse model of neuropathic pain induced by partial sciatic nerve ligation (PSL). PSL mice were treated by endovenous route with bone marrow-derived MSCs (1 × 106), CM, or vehicle. Gabapentin was the reference drug. Twelve hours after administration, neuropathic mice treated with CM exhibited an antinociceptive effect that was maintained throughout the evaluation period. MSCs also induced nonreversed antinociception, while gabapentin induced short-lasting antinociception. The levels of IL-1β, TNF-α, and IL-6 were reduced, while IL-10 was enhanced on sciatic nerve and spinal cord by treatment with CM and MSCs. Preliminary analysis of the CM secretome revealed the presence of growth factors and cytokines likely involved in the antinociception. In conclusion, the CM, similar to injection of live cells, produces a powerful and long-lasting antinociceptive effect on neuropathic pain, which is related with modulatory properties on peripheral and central levels of cytokines involved with the maintenance of this syndrome.

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The therapeutic potential of bone marrow-derived mesenchymal stromal cells on hepatocellular carcinoma

Liver International ◽

10.1111/liv.12338 ◽

2013 ◽

Vol 34 (3) ◽

pp. 330-342 ◽

Cited By ~ 15

Author(s):

Juan Bayo ◽

Mariano Marrodán ◽

Jorge B. Aquino ◽

Marcelo Silva ◽

Mariana G. García ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Bone Marrow ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Therapeutic Potential

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Aryl hydrocarbon receptor signaling pathway plays important roles in the proliferative and metabolic properties of bone marrow mesenchymal stromal cells

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmab122 ◽

2021 ◽

Author(s):

Yan Jia ◽

Youshan Zhao ◽

Zheng Zhang ◽

Lei Shi ◽

Ying Fang ◽

...

Keyword(s):

Bone Marrow ◽

Aryl Hydrocarbon Receptor ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Molecular Mechanisms ◽

Therapeutic Potential ◽

Aryl Hydrocarbon ◽

Receptor Signaling Pathway ◽

Metabolic Properties

Abstract Bone marrow mesenchymal stromal cells (BMMSCs) are widely sourced and easily amplified in vitro; thus, they have a great potential in the treatment of hemopathies. Recent findings suggested that BMMSCs express the aryl hydrocarbon receptor (AHR). However, few studies have reported on the regulation of proliferative behaviors and metabolism by AHR in BMMSCs. In the present study, we found that activating AHR reduced the proliferation of BMMSCs and enhanced their mitochondrial function, whereas inhibiting AHR exerted the opposite effects. This study may provide the basis for further unveiling the molecular mechanisms and therapeutic potential of AHR in BMMSCs.

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Augmenting emergency granulopoiesis with CpG conditioned mesenchymal stromal cells in murine neutropenic sepsis

Blood Advances ◽

10.1182/bloodadvances.2020002556 ◽

2020 ◽

Vol 4 (19) ◽

pp. 4965-4979 ◽

Cited By ~ 1

Author(s):

Julie Ng ◽

Fei Guo ◽

Anna E. Marneth ◽

Sailaja Ghanta ◽

Min-Young Kwon ◽

...

Keyword(s):

Bone Marrow ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Therapeutic Potential ◽

Neutrophil Extracellular Trap ◽

Differentiation Potential ◽

Neutropenic Sepsis ◽

Cpg Oligodeoxynucleotide ◽

Increased Risk

Abstract Patients with immune deficiencies from cancers and associated treatments represent a growing population within the intensive care unit with increased risk of morbidity and mortality from sepsis. Mesenchymal stromal cells (MSCs) are an integral part of the hematopoietic niche and express toll-like receptors, making them candidate cells to sense and translate pathogenic signals into an innate immune response. In this study, we demonstrate that MSCs administered therapeutically in a murine model of radiation-associated neutropenia have dual actions to confer a survival benefit in Pseudomonas aeruginosa pneumo-sepsis that is not from improved bacterial clearance. First, MSCs augment the neutrophil response to infection, an effect that is enhanced when MSCs are preconditioned with CpG oligodeoxynucleotide, a toll-like receptor 9 agonist. Using cytometry by time of flight, we identified proliferating neutrophils (Ly6GlowKi-67+) as the main expanded cell population within the bone marrow. Further analysis revealed that CpG-MSCs expand a lineage restricted progenitor population (Lin−Sca1+C-kit+CD150−CD48+) in the bone marrow, which corresponded to a doubling in the myeloid proliferation and differentiation potential in response to infection compared with control. Despite increased neutrophils, no reduction in organ bacterial count was observed between experimental groups. However, the second effect exerted by CpG-MSCs is to attenuate organ damage, particularly in the lungs. Neutrophils obtained from irradiated mice and cocultured with CpG-MSCs had decreased neutrophil extracellular trap formation, which was associated with decreased citrullinated H3 staining in the lungs of mice given CpG-MSCs in vivo. Thus, this preclinical study provides evidence for the therapeutic potential of MSCs in neutropenic sepsis.

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Effect of Quercetin 3-O-β-D-Galactopyranoside on the Adipogenic and Osteoblastogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stromal Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21218044 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8044

Author(s):

Jung Hwan Oh ◽

Fatih Karadeniz ◽

Youngwan Seo ◽

Chang-Suk Kong

Keyword(s):

Bone Marrow ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Therapeutic Potential ◽

Adipogenic Differentiation ◽

Bmp Signaling ◽

Human Bone ◽

Human Bone Marrow ◽

Differentiation Markers ◽

Beneficial Effects

Natural products, especially phenols, are promising therapeutic agents with beneficial effects against aging-related complications such as osteoporosis. This study aimed to investigate the effect of quercetin 3-O-β-D-galactopyranoside (Q3G), a glycoside of a common bioactive phytochemical quercetin, on osteogenic and adipogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). hBM-MSCs were induced to differentiate into osteoblasts and adipocytes in the presence or absence of Q3G and the differentiation markers were analyzed to observe the effect. Q3G treatment stimulated the osteoblastogenesis markers: cell proliferation, alkaline phosphatase (ALP) activity and extracellular mineralization. In addition, it upregulated the expression of RUNX2 and osteocalcin protein as osteoblastogenesis regulating transcription factors. Moreover, Q3G treatment increased the activation of osteoblastogenesis-related Wnt and bone morphogenetic protein (BMP) signaling displayed as elevated levels of phosphorylated β-catenin and Smad1/5 in nuclear fractions of osteo-induced hBM-MSCs. The presence of quercetin in adipo-induced hBM-MSC culture inhibited the adipogenic differentiation depicted as suppressed lipid accumulation and expression of adipogenesis markers such as PPARγ, SREBP1c and C/EBPα. In conclusion, Q3G supplementation stimulated osteoblast differentiation and inhibited adipocyte differentiation in hBM-MSCs via Wnt/BMP and PPARγ pathways, respectively. This study provided useful information of the therapeutic potential of Q3G against osteoporosis mediated via regulation of MSC differentiation.

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Fetal liver-conditioned medium induces hepatic specification from mouse bone marrow mesenchymal stromal cells: a novel strategy for hepatic transdifferentiation

Cytotherapy ◽

10.1080/14653240802360704 ◽

2008 ◽

Vol 10 (7) ◽

pp. 668-675 ◽

Cited By ~ 18

Author(s):

R-L. Pan ◽

Y. Chen ◽

R-L. Pan ◽

Y. Chen ◽

L-X. Xiang ◽

...

Keyword(s):

Bone Marrow ◽

Conditioned Medium ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Fetal Liver ◽

Mouse Bone Marrow ◽

Novel Strategy

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Myricetin 3-O-β-D-Galactopyranoside Exhibits Potential Anti-Osteoporotic Properties in Human Bone Marrow-Derived Mesenchymal Stromal Cells via Stimulation of Osteoblastogenesis and Suppression of Adipogenesis

Cells ◽

10.3390/cells10102690 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2690

Author(s):

Fatih Karadeniz ◽

Jung Hwan Oh ◽

Hyun Jin Jo ◽

Youngwan Seo ◽

Chang-Suk Kong

Keyword(s):

Bone Marrow ◽

Transcription Factors ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Intracellular Signaling ◽

Therapeutic Potential ◽

Adipogenic Differentiation ◽

Human Bone ◽

Human Bone Marrow ◽

Differentiation Markers

Natural bioactive substances are promising lead compounds with beneficial effects on various health problems including osteoporosis. In this context, the goal of this study was to investigate the effect of myricetin 3-O-β-D-galactopyranoside (M3G), a glycoside of a known bioactive phytochemical myricetin, on bone formation via osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). The hBM-MSCs were induced to differentiate into osteoblasts and adipocytes in the presence or absence of M3G and the differentiation markers were analyzed. Osteoblastogenesis-induced cells treated with M3G exhibited stimulated differentiation markers: cell proliferation, alkaline phosphatase (ALP) activity, and extracellular mineralization. In terms of intracellular signaling behind the stimulatory effect of M3G, the expression of RUNX2 and osteopontin transcription factors were upregulated. It has been shown that M3G treatment increased the activation of Wnt and BMP as a suggested mechanism of action for its effect. On the other hand, M3G treatment during adipogenesis-inducement of hBM-MSCs hindered the adipogenic differentiation shown as decreased lipid accumulation and expression of PPARγ, SREBP1c, and C/EBPα, adipogenic transcription factors. In conclusion, M3G treatment stimulated osteoblast differentiation and inhibited adipocyte differentiation in induced hBM-MSCs. Osteoblast formation was stimulated via Wnt/BMP and adipogenesis was inhibited via the PPARγ pathway. This study provided necessary data for further studies to utilize the therapeutic potential of M3G against osteoporosis via regulation of bone marrow stromal cell differentiation.

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