Influence of mesenchymal stem cell-derived extracellular vesicles in vitro and their role in ageing

Fafián-Labora, Juan; Morente-López, Miriam; Sánchez-Dopico, M.J.; Arntz, Onno J.; Loo, Fons A. J. van de; Toro, Javier de; Arufe, M.C.

doi:10.1186/s13287-019-1534-0

Cited by 41 publications

(42 citation statements)

References 29 publications

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“…Recently, it was demonstrated that incubation of old MSCs with exosomes from young MSCs reduced ageing markers and the mTOR pathway proteins, whereas up‐regulated the pluripotency markers in those cells. Further scrutiny showed that exosomal miRNA‐188‐3p was involved in ageing by regulating the mTOR complex 75 . These findings provide the idea that MSCs‐Exo may be used for the progress of novel therapies against ageing‐associated diseases.…”

Section: Distinct Effect Of Mscs‐exo On Ageingmentioning

confidence: 84%

Ageing and mesenchymal stem cells derived exosomes: Molecular insight and challenges

Ahmadi

Rezaie

2020

Cell Biochemistry & Function

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Ageing induces a great risk factor that participates in progressing various degenerative diseases morbidities. The main characteristic of ageing is the failure in maintaining homeostasis in the organs with a cellular senescence. Senescence is characterized by reduced cell growth, evade cellular death, and acquiring a senescence‐associated secretory phenotype (SASP). Mesenchymal stem cells (MSCs) are advantageous cells in regenerative medicine, exerting pleiotropic functions by producing soluble factors, such as exosomes. MSCs and their exosomes (MSCs‐Exo) kinetic are affected by ageing and other aged exosomes. Exosomes biogenesis from aged MSCs is accelerated and their exosomal cargoes, such as miRNAs, vary as compared to those of normal cells. Besides, exosomes from aged MSCs loss their regenerative potential and may negatively influence the function of recipient cells. MSCs‐Exo can improve ageing and age‐related diseases; however, the detailed mechanisms remain yet elusive. Although exosomes‐therapy may serve as a new approach to combat ageing, the translation of preclinical results to clinic needs more extensive investigation on exosomes both on their biology and related techniques. Overall, scrutiny on the effect of ageing on MSCs and vice versa is vital for designing novel therapy using MSCs with focus on the management of older individuals.

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Section: Distinct Effect Of Mscs‐exo On Ageingmentioning

confidence: 84%

Ageing and mesenchymal stem cells derived exosomes: Molecular insight and challenges

Ahmadi

Rezaie

2020

Cell Biochemistry & Function

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“…On the other hand, Oct4, the pluripotency markers which associated with the differentiation potential of BMSCs [43], decreased after differentiation. Oct4 was lower for cells cultured on the APB system than on TCF with signi cant difference after day 5 without GF, but lower with signi cant difference from day 3 with GF.…”

Section: Discussionmentioning

confidence: 96%

Pancreaticline Cell Differentiation of Bone Marrow Mesenchymal Stromal Cells in Acellular Pancreatic Scaffolds

Zhao

Wang

2020

Preprint

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Background: To evaluate the potential differentiation ability of bone mesenchymal stromal cells(BMSCs) to pancreatic line Cells on rat acellular pancreatic bioscaffold(APB) and the effect of differentiated BMSCs for chronic pancreatitis(CP) in vivo. Methods: After BMSCs were isolated and identified, they were dynamic cultured on the APB and static cultured in tissue culture flask(TCF),with or without the growth factors (GF) in both the culture system. The cytological behavior such as the proliferation and differentiation of BMSCs in all the above kinds of culture system were assessed by morphological observation, flow cytometry, ELASA analysis, qRT-PCR assay and western blot analysis. For the in vivo study, the pancreatic fibrosis and pathological score were evaluated. And also the expression of α-SMA, collagen type I and III, IL-10 in pancreas tissue were detected by ELASA. Results: 4ml/min was the most appropriate flow rate for the dynamic culture of BMSCs. The proliferation rate of BMSCs in the APB groups were significantly increased compared to TCF system. During the pancreatic line cell differentiation process, APB could induce BMSCs express markers such as PDX-1 and PTF-1 at higher mRNA levels. In contrast, the marker Oct 4 was expressed at a lower level in APB group. For the pancreatic functional cytoketatins including α-Amy, CK7, Flk-1, and C-peptide, they were all expressed at higher level in APB group. And metabolic enzymes secretion such as amylase and insulin were promoted significantly in APB system. By scanning electron microscope(SEM) and transmission electron microscopy(TEM), the ultrastructure of BMSCs in the APB group could further demonstrated the morphological characteristics of pancreatic-like cells. In vivo study,the expression of α-SMA, collagen type I and III in tissues were less in differentiated BMSCs treatment group, while the level of IL-10 in pancreatic tissue were higher in differentiated BMSCs treatment group with significant difference (P<0.05). In addition, in both in vitro and in vivo study, GF could significantly facilitate the function of proliferation, differentiation and pancreatic cell therapy. Conclusion: Together our data show the capacity of APB , 3D pancreatic biomatrix, promoting BMSCs differentiate toward pancreatic line phenotypes, and the considerable potential of using these cells for pancreatic cell therapies and tissue engineering.

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“…On the other hand, Oct4, the pluripotency markers which associated with the differentiation potential of BMSCs [40], decreased after differentiation. Oct4 was lower for cells cultured on the APB system than on TCF with signi cant difference after day 5 without GF, but lower with signi cant difference from day 3 with GF.…”

Section: Discussionmentioning

confidence: 96%

Pancreatic line Cell Differentiation of bone marrow Mesenchymal Stromal Cells in Acellular Pancreatic Scaffolds

Zhao

Wang

2020

Preprint

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Background: To evaluate the potential differentiation ability of bone mesenchymal stromal cells(BMSCs) to pancreatic line Cells on rat acellular pancreatic bioscaffold (APB). Methods: Fresh pancreata from 20 Adult Sprague Dawley rats (between 6 and 7 weeks old) were soaked and perfused using Easy-Load Digital Drive peristaltic pumps. After BMSCs were isolated and identified, they were dynamic cultured on the APB and static cultured in tissue culture flask(TCF). Based on whether the differentiation was induced by the growth factors (GF) in the culture system, our study was divided into 4 groups: BMSCs cultured in TCF without any GF(TCF-GF(-)), BMSCs cultured in TCF with GF(TCF-GF(+)), BMSCs cultured on APB without GF(APB-GF(-)), BMSCs cultured on APB with GF (APB-GF(+)).The cytological behavior such as the proliferation and differentiation of BMSCs in all the above kinds of culture system with or without GF were assessed by morphological observation, flow cytometry, ELASA analysis, qRT-PCR assay and western blot analysis. Results: 4ml/min was the most appropriate flow rate for the dynamic culture of BMSCs. Under culture conditions, BMSCs populations could attach to and proliferate within the APB. APB could promote the proliferation and viability of BMSCs significantly better in dynamic culture with optimal flow rate 4ml/min, when compared to the static culture system. Also, the proliferation rate of BMSCs in the APB groups were significantly increased compared to TCF system. During the pancreatic line cell differentiation process, APB could induce BMSCs into pancreatic-like cells which expressed markers such as pancreatic duodenal homeodomain containing transcription factor (PDX-1) and pancreatic exocrine transcription factor (PTF-1) higher at mRNA levels compared to TCF system. In contrast, the marker Oct4 (octamer-binding transcription factor 4) was expressed at a lower level in APB group. For the pancreatic functional cytoketatins including α-Amylase(α-Amy), cytokeratin 7(CK7), fetal liver kinase-1 (Flk-1),and C-peptide, they were all expressed at higher level in APB group than in the TCF group. And metabolic enzymes secretion such as amylase and insulin were promoted significantly in APB system. By scanning electron microscope(SEM) and transmission electron microscopy(TEM), the ultrastructure of BMSCs in the APB group could further demonstrated the morphological characteristics of pancreatic-like cells. In addition, in both the dynamic and static system, GF could significantly facilitate the function of proliferation, differentiation and cell engraftment . Conclusion: Together our data show the capacity of APB , 3D pancreatic biomatrix, promoting BMSCs differentiate toward pancreatic line phenotypes, and the considerable potential of using these cells for pancreatic cell therapies and tissue engineering.

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Influence of mesenchymal stem cell-derived extracellular vesicles in vitro and their role in ageing

Cited by 41 publications

References 29 publications

Ageing and mesenchymal stem cells derived exosomes: Molecular insight and challenges

Ageing and mesenchymal stem cells derived exosomes: Molecular insight and challenges

Pancreaticline Cell Differentiation of Bone Marrow Mesenchymal Stromal Cells in Acellular Pancreatic Scaffolds

Pancreatic line Cell Differentiation of bone marrow Mesenchymal Stromal Cells in Acellular Pancreatic Scaffolds

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