The Therapeutic Potential of Mesenchymal Stromal Cells for Regenerative Medicine: Current Knowledge and Future Understandings

Merimi, Makram; El-Majzoub, Rania; Lagneaux, Laurence; Agha, Douâa Moussa; Bouhtit, Fatima; Meuleman, Nathalie; Fahmi, Hassan; Lewalle, Philippe; Fayyad‐Kazan, Mohammad; Najar, Mehdi

doi:10.3389/fcell.2021.661532

Cited by 108 publications

(61 citation statements)

References 170 publications

(233 reference statements)

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“…The therapeutic potential of MSCs is linked to their immunoregulatory paracrine activity, with the secretion soluble factors (secretomes), including other growth factors, like vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF-2), insulin-like growth factor 1 (IGF-1), plateletderived growth factor (PDGF), and hepatocyte growth factor (HGF) [50]. Anti-inflammatory factors, such as interleukin-10 (IL-10), transforming growth factor beta 1 (TGF-β1), and mechanisms linked to exosome and mRNA release are also included with MSCs [51,52].…”

Section: Mscsmentioning

confidence: 99%

Therapeutic interventions of Amyotrophic Lateral Sclerosis (ALS)

Chakraborty¹,

Diwan²

2022

Neuro Neurosci

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Amyotrophic lateral sclerosis (ALS) is a non-demyelinating neurodegenerative disease mostly found in adults between 40 to 60 years old. This disease is usually prevalent in males, however it’s irrespective to the different genders. ALS is progressive and within 2-5 years of diagnosis ulimately ends with death. The majority of ALS cases is sporadic (90%) and is recorded without any defined aetiology. The other 10-12% of cases is recognized from mutations in more than 20 genes. The genes reported to cause ALS are Superoxide Dismutase 1 (SOD1), TAR DNA Binding Protein (TDP), Fused in Sarcoma, (FUS), Chromosome 9 Open Reading Frame 72 (c9orf72) and Vesicle-Associated Membrane-ProteinAssociated Protein B (VAPB). Furthermore, abnormal lipid metabolism with higher LDL/HDL ratio was reported in ALS patients. The aetiology of ALS is shown in the schematic diagram below (Figure 1) Due to the multi-nature of ALS causative factors and symptoms, there is no specific therapy for ALS today. However, this paper will touch on potential therapies that are in practice or may come up in the future. The goal is to maintain and improve the function of motor neuron, the well-being and quality of life for ALS patients. Until then, we have to rely on the symptomatic treatment and rehabilitative measures to support the patient’s quality of life.

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Section: Mscsmentioning

confidence: 99%

Therapeutic interventions of Amyotrophic Lateral Sclerosis (ALS)

Chakraborty¹,

Diwan²

2022

Neuro Neurosci

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“…Odontogenic MSCs have been isolated from dental tissue, including dental pulp ( Gronthos et al, 2000 ), exfoliated deciduous teeth ( Miura et al, 2003 ), periodontal ligaments ( Seo et al, 2004 ), dental follicles ( Morsczeck et al, 2005 ), apical papillae ( Sonoyama et al, 2006 ), papillae ( Tziafas and Kodonas, 2010 ) and periapical cysts ( Marrelli et al, 2013 ). Odontogenic MSCs have become an attractive source of autologous MSCs because they exhibit the characteristics of vasculogenesis and neurogenesis ( Liu et al, 2015 ), along with their good accessibility, low immunogenicity and high stemness ( Merimi et al, 2021 ). There has been some clinical evidence verifying the therapeutic effect of odontogenic MSCs in tissue regeneration.…”

Section: Introductionmentioning

confidence: 99%

Odontogenic MSC Heterogeneity: Challenges and Opportunities for Regenerative Medicine

et al. 2022

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Cellular heterogeneity refers to the genetic and phenotypic differences among cells, which reflect their various fate choices, including viability, proliferation, self-renewal probability, and differentiation into different lineages. In recent years, research on the heterogeneity of mesenchymal stem cells has made some progress. Odontogenic mesenchymal stem cells share the characteristics of mesenchymal stem cells, namely, good accessibility, low immunogenicity and high stemness. In addition, they also exhibit the characteristics of vasculogenesis and neurogenesis, making them attractive for tissue engineering and regenerative medicine. However, the usage of mesenchymal stem cell subgroups differs in different diseases. Furthermore, because of the heterogeneity of odontogenic mesenchymal stem cells, their application in tissue regeneration and disease management is restricted. Findings related to the heterogeneity of odontogenic mesenchymal stem cells urgently need to be summarized, thus, we reviewed studies on odontogenic mesenchymal stem cells and their specific subpopulations, in order to provide indications for further research on the stem cell regenerative therapy.

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“…The above-mentioned issues can be overcome by switching to the use of the MSC secretome. First, the regenerative effects of MSCs are largely mediated by secreted growth factors, cytokines, extracellular matrix components, biomolecules within extracellular vesicles, and transferred organelles [ 14 , 15 ]. Second, the use of the MSC secretome is devoid of the risks associated with the injection of cells.…”

Section: Introductionmentioning

confidence: 99%

Novel Potency Assay for MSC Secretome-Based Treatment of Idiopathic Male Infertility Employed Leydig Cells and Revealed Vascular Endothelial Growth Factor as a Promising Potency Marker

Monakova

Sagaradze

Basalova

et al. 2022

IJMS

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Idiopathic male infertility is a highly prevalent diagnosis in developed countries with no specific treatment options. Although empirical medical treatment is widely used to restore male fertility, its efficacy remains limited and inconclusively proven. Therefore, the development of novel therapeutic approaches in this field is a high-priority task. Since the failure of testicular microenvironment components might be involved in the pathogenesis of idiopathic male infertility, application of mesenchymal stromal cells (MSCs) as well as the MSC secretome is worth considering. Previously, we showed that the intratesticular injection of MSCs or the MSC secretome led to the recovery of spermatogenesis at least through replenishing the testicular microenvironment and its maintenance by MSC-secreted paracrine factors. However, the clinical use of such products has been limited to single trials to date. This may be due to the lack of relevant potency tests reflecting mechanisms of action of the MSC secretome in male infertility models. Based on the presumptive MSC secretome mode of action on the testicular microenvironment, we suggest a novel approach to test the potential efficacy of the MSC secretome for idiopathic male infertility treatment. It represents a potency assay based on evaluation of testosterone production by isolated Leydig cells. We demonstrated that the MSC secretome stimulated testosterone secretion by Leydig cells in vitro. We then hypothesized that among the major factors of the MSC secretome, vascular endothelial growth factor (VEGF) could be responsible for the observed effects, which we confirmed by the revealed correlation between the extent of stimulated testosterone production and VEGF concentration in the MSC secretome. The pilot results obtained from the doxorubicin-induced male infertility murine model also indicate the important impact of VEGF in the MSC secretome’s regenerative effects. Utilizing VEGF as a surrogate factor, a novel approach to study the potency of MSC secretome-based products for idiopathic male infertility treatment is suggested. Further validation is required for its implementation into the biopharmaceutical manufacturing process.

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The Therapeutic Potential of Mesenchymal Stromal Cells for Regenerative Medicine: Current Knowledge and Future Understandings

Abstract: Graphical AbstractThe road map of MSC review.

Cited by 108 publications

References 170 publications

Therapeutic interventions of Amyotrophic Lateral Sclerosis (ALS)

Therapeutic interventions of Amyotrophic Lateral Sclerosis (ALS)

Odontogenic MSC Heterogeneity: Challenges and Opportunities for Regenerative Medicine

Novel Potency Assay for MSC Secretome-Based Treatment of Idiopathic Male Infertility Employed Leydig Cells and Revealed Vascular Endothelial Growth Factor as a Promising Potency Marker

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