scholarly journals Role of Hyperglycemia in the Senescence of Mesenchymal Stem Cells

Author(s):  
Min Yin ◽  
Yan Zhang ◽  
Haibo Yu ◽  
Xia Li

The regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs) have laid a sound foundation for their clinical application in various diseases. However, the clinical efficiency of MSC treatments varies depending on certain cell characteristics. Among these, the roles of cell aging or senescence cannot be excluded. Despite their stemness, evidence of senescence in MSCs has recently gained attention. Many factors may contribute to the senescence of MSCs, including MSC origin (biological niche), donor conditions (age, obesity, diseases, or unknown factors), and culture conditions in vitro. With the rapidly increasing prevalence of diabetes mellitus (DM) and gestational diabetes mellitus (GDM), the effects of hyperglycemia on the senescence of MSCs should be evaluated to improve the application of autologous MSCs. This review aims to present the available data on the senescence of MSCs, its relationship with hyperglycemia, and the strategies to suppress the senescence of MSCs in a hyperglycemic environment.

2021 ◽  
Vol 234 ◽  
pp. 110203
Author(s):  
Shannon S. Connard ◽  
Renata L. Linardi ◽  
Kayla M. Even ◽  
Alix K. Berglund ◽  
Lauren V. Schnabel ◽  
...  

2017 ◽  
Vol 13 (4) ◽  
pp. 482-490 ◽  
Author(s):  
Guilherme Galvão dos Santos ◽  
Araceli Aparecida Hastreiter ◽  
Talita Sartori ◽  
Primavera Borelli ◽  
Ricardo Ambrósio Fock

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Hyun Sook Hong ◽  
Suna Kim ◽  
Youngsook Son

Bone marrow stem cells, especially, endothelial precursor cells (EPC), mesenchymal stem cells (MSC) or hematopoietic stem cell (HSC) are expected as reparative cells for the repair of a variety of tissue damages such as stroke and myocardial infarction, even though their role in the repair is not demonstrated. This report was investigated to find a role of Substance-p (SP) as a reparative agent in the tissue repair requiring EPC and MSC. In order to examine EPC (EPC SP ) and MSC (MSC SP ) mobilized by SP, we injected SP intravenously for consecutive 2 days and saline was injected as a vehicle. At 3 post injection, peripheral blood (PB) was collected.To get mesenchymal stem cells or endothelial progenitor cells, MNCs were incubated in MSCGM or EGM-2 respectively for 10 days. Functional characteristics of the EPC SP were proven by the capacity to form endothelial tubule network in the matrigel in vitro and in the matrigel plug assay in vivo. In contrast, MSC SP did not form a tube-like structure but formed a pellet-structure on matrigel. However, when both cells were premixed before the matrigel assay, much longer and branched tubular network was formed, in which a-SMA expressing MSC SP were decorating outside of the endothelial tube, especially enriched at the bifurcating point. MSC SP may contribute and reinforce elaborate vascular network formation in vivo by working as pericyte-like cells. Thus, the EPC SP and MSC SP were labeled with PKH green and PKH red respectively and their tubular network was examined. Well organized tubular network was formed, which was covered by PKH green labeled cells and was decorated in a punctate pattern by PKH red labeled cells. In order to investigate the role of EPC SP and MSC SP specifically in vivo, rabbit EPC SP and MSC SP were transplanted to full thickness skin wound. The vessel of EPC SP -transplanted groups was UEA-lectin+, which was not covered with a-SMA+ pericytes but EPC SP + MSC SP -transplanted groups showed, in part, a-SMA+ pericyte-encircled UEA-lectin+ vessels. This proved the specific role of MSC SP as pericytes. From these data, we have postulated that the collaboration of MSC and EPC is essential for normal vessel structure and furthermore, accelerated wound healing as ischemia diseases, which can be stimulated through by SP injection.


Author(s):  
Amanda Nogueira-Pedro ◽  
Edson Naoto Makiyama ◽  
Helena Regina Comodo Segreto ◽  
Ricardo Ambrósio Fock

2019 ◽  
Vol 9 (12) ◽  
pp. 358 ◽  
Author(s):  
Tatullo ◽  
Codispoti ◽  
Spagnuolo ◽  
Zavan

Promising researches have demonstrated that the alteration of biological rhythms may be consistently linked to neurodegenerative pathologies. Parkinson’s disease (PD) has a multifactorial pathogenesis, involving both genetic and environmental and/or molecular co-factors. Generally, heterogeneous alterations in circadian rhythm (CR) are a typical finding in degenerative processes, such as cell aging and death. Although numerous genetic phenotypes have been discovered in the most common forms of PD, it seems that severe deficiencies in synaptic transmission and high vesicular recycling are frequently found in PD patients. Neuron-to-neuron interactions are often ensured by exosomes, a specific type of extracellular vesicle (EV). Neuron-derived exosomes may carry several active compounds, including miRNAs: Several studies have found that circulating miRNAs are closely associated with an atypical oscillation of circadian rhythm genes, and they are also involved in the regulation of clock genes, in animal models. In this context, a careful analysis of neural-differentiated Mesenchymal Stem Cells (MSCs) and the molecular and genetic characterization of their exosome content, both in healthy cells and in PD-induced cells, could be a strategic field of investigation for early diagnosis and better treatment of PD and similar neurodegenerative pathologies. A novel MSC population, called human periapical cyst–mesenchymal stem cells (hPCy–MSCs), has demonstrated that it naively expresswa the main neuronal markers, and may differentiate towards functional neurons. Therefore, hPCy–MSCs can be considered of particular interest for testing of in vitro strategies to treat neurological diseases. On the other hand, the limitations of using stem cells is an issue that leads researchers to perform experimental studies on the exosomes released by MCSs. Human periapical cyst-derived mesenkymal stem cells can be a smart “lab-on-a-cell” to investigate neurodegenerative diseases and the related exosomes’ content alteration.


2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Doaa Aboalola ◽  
Victor K. M. Han

As mesenchymal stem cells (MSCs) are being investigated for regenerative therapies to be used in the clinic, delineating the roles of the IGF system in MSC growth and differentiation, in vitro, is vital in developing these cellular therapies to treat degenerative diseases. Muscle differentiation is a multistep process, starting with commitment to the muscle lineage and ending with the formation of multinucleated fibers. Insulin-like growth factor binding protein-6 (IGFBP-6), relative to other IGFBPs, has high affinity for IGF-2. However, the role of IGFBP-6 in muscle development has not been clearly defined. Our previous studies showed that in vitro extracellular IGFBP-6 increased myogenesis in early stages and could enhance the muscle differentiation process in the absence of IGF-2. In this study, we identified the signal transduction mechanisms of IGFBP-6 on muscle differentiation by placental mesenchymal stem cells (PMSCs). We showed that muscle differentiation required activation of both AKT and MAPK pathways. Interestingly, we demonstrated that IGFBP-6 could compensate for IGF-2 loss and help enhance the muscle differentiation process by triggering predominantly the MAPK pathway independent of activating either IGF-1R or the insulin receptor (IR). These findings indicate the complex interactions between IGFBP-6 and IGFs in PMSC differentiation into the skeletal muscle and that the IGF signaling axis, specifically involving IGFBP-6, is important in muscle differentiation. Moreover, although the major role of IGFBP-6 is IGF-2 inhibition, it is not necessarily the case that IGFBP-6 is the main modulator of IGF-2.


2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Min Tang ◽  
Rui Chen ◽  
Hao Wang ◽  
Guowei Sun ◽  
Fan Yin ◽  
...  

Obesity is a major risk factor for many chronic diseases, including diabetes, fatty livers, and cancer. Expansion of the adipose mass has been shown to be related to adipogenic differentiation of adipose-derived mesenchymal stem cells (ASCs). However, the underlying mechanism of this effect has yet to be elucidated. We found that osteopontin (OPN) is downregulated in ASCs and adipose tissues of obese mice and overweight human beings because of methylation on its promoter, indicating that OPN may affect the development of obesity. Silencing of OPN in wild-type ASCs promotes adipogenic differentiation, while reexpression of OPN reduced adipogenic differentiation in OPN−/− ASCs. The role of extracellular OPN in ASC differentiation was further demonstrated by supplementation and neutralization of OPN. Additionally, OPN suppresses adipogenic differentiation in ASCs through the C/EBP pathways. Consistent with these in vitro results, by intravenous injection of OPN-expressing adenovirus to the mice, we found OPN can delay the development of obesity and improve insulin sensitivity. Therefore, our study demonstrates an important role of OPN in regulating the development of obesity, indicating OPN might be a novel target to attenuate obesity and its complications.


2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Youwei Wang ◽  
Zhi-bo Han ◽  
Yong-ping Song ◽  
Zhong Chao Han

Mesenchymal stem cells (MSCs) hold great promise as therapeutic agents in regenerative medicine and autoimmune diseases, based on their differentiation abilities and immunosuppressive properties. However, the therapeutic applications raise a series of questions about the safety of culture-expanded MSCs for human use. This paper summarized recent findings about safety issues of MSCs, in particular their genetic stability in long-termin vitroexpansion, their cryopreservation, banking, and the role of serum in the preparation of MSCs.


2009 ◽  
Vol 81 (Suppl_1) ◽  
pp. 668-668 ◽  
Author(s):  
Hye-Jin Song ◽  
Sung-June Byun ◽  
Kang-Nyeong Heo ◽  
Jum-Soon Kim ◽  
Eung-Woo Park ◽  
...  

2021 ◽  
Author(s):  
Chen Zhang ◽  
Xueshuai Han ◽  
Jingkun Liu ◽  
Lei Chen ◽  
Ying Lei ◽  
...  

Ex vivo-expanded mesenchymal stem cells (MSCs) have been demonstrated to be a heterogeneous mixture of cells exhibiting varying proliferative, multipotential, and immunomodulatory capacities. However, the exact characteristics of MSCs remain largely unknown. By single-cell RNA sequencing of 61,296 MSCs derived from bone marrow and Wharton's jelly, we revealed five distinct subpopulations. The developmental trajectory of these five MSC subpopulations were mapped, revealing a differentiation path from stem-like active proliferative cells (APCs) to multipotent progenitor cells, followed by the branching into two paths - adipogenesis or osteochondrogenesis - and subsequent differentiation into unipotent prechondrocytes. The stem-like APCs, expressing the perivascular mesodermal progenitor markers CSPG4/MCAM/NES, uniquely exhibited strong proliferation and stemness signatures. Remarkably, the prechondrocyte subpopulation specifically expressed immunomodulatory genes and was able to suppress activated CD3+ T cell proliferation in vitro, supporting the role of this population in immunoregulation. In summary, our analysis mapped the heterogeneous subpopulations of MSCs and identified two subpopulations with potential functions in self-renewal and immunoregulation. Our findings advance the definition of MSCs by identifying the specific functions of its heterogeneous cellular composition, allowing for more specific and effective MSC application through the purification of its functional subpopulations.


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