Differential adhesion and fibrinolytic activity of mesenchymal stem cells from human bone marrow, placenta, and Wharton’s jelly cultured in a fibrin hydrogel

Abstract

Mesenchymal stem cells isolated from different tissues should share associated markers and the capability to differentiate to mesodermal lineages. However, their behavior varies in specific microenvironments. Herein, adhesion and fibrinolytic activity of mesenchymal stem cells from placenta, bone marrow, and Wharton’s jelly were evaluated in fibrin hydrogels prepared with nonpurified blood plasma and compared with two-dimensional cultures. Despite the source, mesenchymal stem cells adhered through focal adhesions positive for vinculin and integrin αV in two dimensions, while focal adhesions could not be detected in fibrin hydrogels. Moreover, some cells could not spread and stay rounded. The proportions of elongated and round phenotypes varied, with placenta mesenchymal stem cells having the lowest percentage of elongated cells (~10%). Mesenchymal stem cells degraded fibrin at distinct rates, and placenta mesenchymal stem cells had the strongest fibrinolytic activity, which was achieved principally through the plasminogen–plasmin axis. These findings might have clinical implications in tissue engineering and wound healing therapy.

Mechanosensitive regulation of stanniocalcin-1 by zyxin and actin-myosin in human mesenchymal stromal cells

“…In line with this, in 3D environments (alginate hydrogels and ESP scaffolds), fewer focal adhesions formed and STC1 secretion increased. A reduced number of focal adhesions and actin stress fibers have been previously reported in a number of studies in both hydrogels [37][38][39][40][41][42][43][44][45] and ESP scaffolds. 35,36 The increase of STC1 in 3D cultures has been shown before in different 3D culture systems.…”

“…35,36 We have also seen that 3D alginate hydrogels show the same trend, in line with results published by others. [37][38][39][40][41][42][43][44][45] Indeed, when stained for zyxin, hMSCs cultured in 3D RGD-modified alginate hydrogels or 3D ESP scaffolds displayed very few zyxin positive focal adhesions, while many large focal adhesions were observed in 2D TCP ( Figure 4A). As expected, STC1 secretion was increased 5.7 ± 1.0x (P < .001) in 3D alginate and 6.0 ± 1.4x (P < .001) in 3D ESP.…”

Hypoxia-Mesenchymal Stem Cells Inhibit Intra-Peritoneal Adhesions Formation by Upregulation of the IL-10 Expression

“…Adhesion formation following abdominal surgery may develop serious health problems ranging from severe pain up to bowel obstruction [1], [2], [3], [4], [5]. To decrease the IPAs event, MSCs administration has been performed either by topical or via systemic vein, however, the adhesion formation is occurred as yet [6], [7], [8]. The unique characteristic of mesothelial cells is considered as one of the failure factors of MSCs treatment due to the robust ability of this cell in modulating serosal inflammation than the other cells [17].…”

“…These immunoregulatory properties of MSCs are due to their ability to suppress the inflammatory milieu by releasing several anti-inflammatory cytokines such as IL-10, IDO, PGE2, TGF-b, HGF and nitric oxide [6]. Several studies of MSCs have been performed to prevent IPAs, such as decreasing the inflammatory response and fibrin formation as well as increasing fibrin lysis [7], [8]. However, intraperitoneal MSCs are yet ineffective in preventing IPAs although they can control the inflammatory process [9].…”

Regulation of inflammatory microenvironment using a self-healing hydrogel loaded with BM-MSCs for advanced wound healing in rat diabetic foot ulcers

“…These elements create an optimal environment to encourage high quality wound healing. 16,17 However, the beneficial properties are often mitigated by the formation of cracks in the traditional hydrogels. As a result, the integrity of network structures and the mechanical characteristics of bulk gels have limited their practical application.…”