Soft Matrix Combined With BMPR Inhibition Regulates Neurogenic Differentiation of Human Umbilical Cord Mesenchymal Stem Cells

Abstract

Stem cells constantly encounter as well as respond to a variety of signals in their microenvironment. Although the role of biochemical factors has always been emphasized, the significance of biophysical signals has not been studied until recently. Additionally, biophysical elements, like extracellular matrix (ECM) stiffness, can regulate functions of stem cells. In this study, we demonstrated that soft matrix with 1-10 kPa can induce neural differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs). Importantly, we used a combination of soft matrix and bone morphogenetic protein receptor (BMPR) inhibition to promote neurogenic differentiation of hUC-MSCs. Furthermore, BMPR/SMADs occurs in crosstalk with the integrinβ1 downstream signaling pathway. In addition, BMPR inhibition plays a positive role in maintaining the undifferentiated state of hUC-MSCs on the hydrogel substrate. The results provide further evidence for the molecular mechanisms via which stem cells convert mechanical inputs into fateful decisions.

Gelatin methacrylate hydrogel loaded with brain‐derived neurotrophic factor enhances small molecule‐induced neurogenic differentiation of stem cells from apical papilla

“…37 In regard to neurogenic differentiation, soft matrix with 1-10 kPa favored neural differentiation of human umbilical cord mesenchymal stem cells. 35 Consistently, in our study, the average elastic moduli of 5% (wt/vol) GelMA hydrogels was 3.21 ± 0.54 kPa which was within the range of 1-10 kPa. Therefore, 5% (wt/vol) GelMA hydrogel was selected to be utilized in further experiments to provide a 3D microenvironment for neurogenic differentiation.…”

“…NSCs have been reported to display morphological changes in response to varying substrate stiffness, 33 with relatively softer substrata being more conducive for neuronal differentiation and maturation. 34,35 Thus, in this study, we fabricated 5%, 10%, and 15%…”

Substrate stiffness mediates osteogenic and adipogenic differentiation of osteosarcoma through the PIEZO1 / ITGB1 -YAP -EZH2 signaling pathway

“…However, recent studies have shown that mesenchymal stem cells (MSCs), which are similar in origin to osteosarcoma cells, show different differentiation trends under different matrix stiffnesses. MSCs on soft substrates tend to neural and adipogenic differentiation, while MSCs on stiff substrates tended to cartilage and osteogenic differentiation (17,18,19,20). Based on the above evidence, we speculate that a similar phenomenon may also exist in osteosarcoma.…”

Multipotent Human Mesenchymal Stem/Stromal Cells: An Updated Review on Historical Background, Recent Trends and Advances in their Clinical Applications

“…For example, culture on rigid surfaces can induce osteogenic and adipogenic differentiation [9,69,70]. Soft tissues and surfaces induce MSCs towards the myogenic and neurogenic lineages [71][72][73][74][75]. Thus the stiffness of a surface or microenvironment can influence the expression of markers and shape of MSCs both in vivo and in vitro ( Figure 3) [76][77][78].…”