Cell-Matrix Interactions Modulate Mesenchymal Stem Cell Response to Dynamic Compression

Author(s):  
Stephen D. Thorpe ◽  
Conor T. Buckley ◽  
Andrew J. Steward ◽  
Daniel J. Kelly

Unconfined cyclic compressive loading has been shown to promote the chondrogenic differentiation of agarose encapsulated mesenchymal stem cells (MSCs) in the absence of chondrogenic growth factors [1, 2]. However, in general robust chondrogenesis has not been reported as a result of mechanical stimulation alone; with biochemical stimulation through TGF-β supplementation yielding a more potent pro-chondrogenic effect [2, 3].

2018 ◽  
Vol 6 (2) ◽  
pp. 312-326 ◽  
Author(s):  
Yilu Ni ◽  
Zhurong Tang ◽  
Jirong Yang ◽  
Yongli Gao ◽  
Hai Lin ◽  
...  

Various scaffolds have been studied in the formation of cell niches and regulation of mesenchymal stem cells (MSCs) behaviors.


2021 ◽  
Vol 22 (16) ◽  
pp. 8637
Author(s):  
David A. Hart

Mesenchymal stem cells, also called medicinal signaling cells (MSC), have been studied regarding their potential to facilitate tissue repair for >30 years. Such cells, derived from multiple tissues and species, are capable of differentiation to a number of lineages (chondrocytes, adipocytes, bone cells). However, MSC are believed to be quite heterogeneous with regard to several characteristics, and the large number of studies performed thus far have met with limited or restricted success. Thus, there is more to understand about these cells, including the molecular recognition systems that are used by these cells to perform their functions, to enhance the realization of their potential to effect tissue repair. This perspective article reviews what is known regarding the recognition systems available to MSC, the possible systems that could be looked for, and alternatives to enhance their localization to specific injury sites and increase their subsequent facilitation of tissue repair. MSC are reported to express recognition molecules of the integrin family. However, there are a number of other recognition molecules that also could be involved such as lectins, inducible lectins, or even a MSC-specific family of molecules unique to these cells. Finally, it may be possible to engineer expression of recognition molecules on the surface of MSC to enhance their function in vivo artificially. Thus, improved understanding of recognition molecules on MSC could further their success in fostering tissue repair.


2010 ◽  
Vol 38 (9) ◽  
pp. 2896-2909 ◽  
Author(s):  
Stephen D. Thorpe ◽  
Conor T. Buckley ◽  
Tatiana Vinardell ◽  
Fergal J. O’Brien ◽  
Veronica A. Campbell ◽  
...  

2021 ◽  
Author(s):  
Ganesan Jothimani ◽  
Surajait Pathak ◽  
Suman Dutta ◽  
Asim K. Duttaroy ◽  
Antara Banerjee

Abstract Background The mesenchymal stem cells (MSCs) have enormous therapeutic potential owing to their multi-lineage differentiation and self-renewal properties. MSCs express growth factors, cytokines, chemokines, and non-coding regulatory RNAs with immunosuppressive, anti-tumor, and migratory properties. MSCs also release several anti-cancer molecules via extracellular vesicles, that act as pro-apoptotic/tumor suppressor factors. This study aimed to identify the stem cell-derived secretome that could exhibit anti-cancer properties through molecular profiling of cargos in MSC-derived exosomes. Methods Human umbilical cord mesenchymal stem cells (hUCMSCs) were isolated from umbilical cord tissues and cultured expanded. After that, exosomes were isolated from the hUCMSC conditioned medium. The miRNA profiling of hUCMSCs and hUCMSC-derived exosomes was performed, followed by functional enrichment analysis. Results The miRNA expression profile and gene ontology (GO) depicts the differential expression patterns of high and less-expressed miRNAs that are delineated to be involved in the regulation of the apoptosis process. The LCMS/MS data and GO analysis indicate that hUCMSC secretomes are involved in several oncogenic and inflammatory signaling cascades. Conclusion Primary human MSCs releases miRNAs and growth factors via exosomes that are increasingly implicated in intercellular communications, and hUCMSC-exosomal miRNAs may have a critical influence in regulating cell death and apoptosis of cancer cells.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4263-4263
Author(s):  
Shawdee Eshghi ◽  
Jing Zhang ◽  
Linda G. Griffith ◽  
Harvey F. Lodish

Abstract The hematopoietic stem cell niche is the set of soluble growth factors, cell-cell and cell-matrix interactions that contribute to stem cell self renewal in the bone marrow. While cytokines and cell-cell interactions have been well documented, cell-matrix interactions in the niche are less understood. Integrins are a class of highly conserved cell adhesion molecules that are important in hematopoietic development and homing. However the specific role of integrins in mediating adhesion to extracellular matrix in the hematopoietic stem cell niche is unknown. The terminal stages of erythropoiesis in the fetal liver provide a good model system with which to develop several of the assays to be used with HSCs. Using flow cytometry, murine fetal liver erythroid progenitors can be separated at four distinct stages of development based on expression of CD71 and Ter119. Further FACS and quantitative PCR analysis revealed that α4β1 integrin is significantly downregulated over the course of erythroid differentiation. Using a centrifugation assay, we determined that this change is accompanied by a loss of adhesion to fibronectin, and that adhesion to fibronectin is blocked by addition of anti-integrin antibodies. Finally, fetal liver progenitor cells adhered to comb co-polymer surfaces engineered to present peptides specifically recognized by α4β1 integrins. By determining the integrin profile expressed by hematopoietic stem cells and measuring stem cell adhesion to ECM in a similar manner, we can begin to understand how these specific interactions present developmental cues important to maintaining the stem cell phenotype in vivo, in addition to leading to design parameters for ex vivo culture systems.


2012 ◽  
Vol 44 (2) ◽  
pp. 69-73 ◽  
Author(s):  
Ľ. Danišovič ◽  
I. Varga ◽  
Š. Polák

2015 ◽  
Vol 21 (19-20) ◽  
pp. 2618-2628 ◽  
Author(s):  
Alessandro Bertolo ◽  
Fanny Arcolino ◽  
Simona Capossela ◽  
Anna Rita Taddei ◽  
Martin Baur ◽  
...  

Author(s):  
Megan J. Farrell ◽  
Tiffany L. Zachry ◽  
Robert L. Mauck

Mesenchymal stem cells (MSCs) are a clinically attractive alternative to chondrocytes for the development of engineered cartilage tissue owing to their ease of isolation and chondrogenic potential [1]. However, the mechanical properties of MSC-based constructs have yet to match those of native cartilage or of chondrocyte-based constructs cultured similarly [1]. One route for improving these properties may be the application of mechanical stimulation, as normal cartilage development and homeostatic maintenance is dependent on force transduction. In a tissue engineering context, dynamic compression applied to chondrocyte-seeded hydrogels modulates both matrix production and mechanical properties [2, 3]. Similarly, when MSCs are embedded in 3D hydrogels, expression of chondrogenic markers and cartilaginous ECM synthesis are differentially regulated by dynamic compressive loading [4, 5]. Indeed, we have recently shown that long-term dynamic loading initiated after a pre-culture period of 21 days in pro-chondrogenic medium improves matrix distribution and the compressive properties of MSC-seeded constructs [5]. Interestingly, when loading was initiated after a single day of culture, mechanical properties failed to develop [6, 7], suggesting that elaboration of matrix was required prior to dynamic loading in order to positively direct construct maturation. When chondrocytes are embedded in agarose, the initial growth phase is characterized by the establishment of a dense pericellular matrix (PCM). At early times in culture, before these islands of PCM become connected into an interterritorial matrix, cells are protected from bulk deformation applied to the gel [8]. In a recent study, we showed that clonal heterogeneity in stem cell populations determines the rate at which this PCM forms, with some MSC clones rapidly establishing a dense PCM, while others fail to develop a robust PCM (and so continue to deform with gel deformation) through several weeks in culture [9]. To further this investigation, this study charted the culture time-dependent changes in ECM connectivity and MSC deformation under basal and chondrogenic conditions.


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