Wnt signaling regulates the proliferation potential and lineage commitment of human umbilical cord derived mesenchymal stem cells

Inhibition versus activation of canonical Wnt-signaling, to promote chondrogenic differentiation of Mesenchymal Stem Cells. A review.

“…Summarizing the impact of Wnt signaling on lineage commitment of MSCs, the authors concluded that a shift of differentiation potential after the inhibition of Wnt signaling by Quercetin was evident, driving MSCs towards the osteogenic lineage. 19 Eslaminejad et al investigated the effect of two Gsk-3β inhibitors on the GAG content of cartilage produced by human marrow MSCs during in vitro chondrogenesis. MSCs were centrifuged into small aggregates and provided with a chondrogenic medium supplemented with either LiCl or SB216763.…”

Current understanding of the mesenchymal stem cell-derived exosomes in cancer and aging

“…The chief application listed for the umbilical cord (UC) derived exosomes are in cutaneous wound healing. The possible mechanism for such positive modulation of these exosomes is attributed to enhanced angiogenesis through the Wnt/β-catenin pathway [ 4 , 23 ]. Many studies have reported the benefits of such cell free therapy in combatting colitis in a mouse model, inflammatory bowel diseases, in fracture healing, in immunosuppression, and in a mouse model of acute liver failure, myocardial infarction, and autoimmune uveitis [2] .…”

The Role of Notch and Wnt Signaling in MSC Communication in Normal and Leukemic Bone Marrow Niche

“…The canonical Wnt/β-catenin pathway sustains proliferation and renewal of MSCs; therefore, the use of pharmacological modulators of the pathway has brought several informations. The activation of the canonical Wnt/β-catenin pathway with lithium chloride or exogenous ligands, such as Wnt1 and Wnt3a, promotes MSC expansion by maintaining their clonogenic properties, but inhibits osteogenic, and adipogenic commitment (Liu et al, 2009(Liu et al, , 2011Jothimani et al, 2020).…”

“…One key mechanism of the suppressive role of Wnt/β-catenin on adipogenesis is the reduced expression of adipogenic transcription factors CCAAT/enhancer binding protein alpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma (PPARgamma) (Ross et al, 2000;Yuan et al, 2016). However, the use of Wnt/β-catenin inhibitors, such as Quercitin, reduce MSC proliferation and multipotency by favoring their osteogenic commitment and inhibiting both the chondrogenic and the adipogenic differentiation (Qu et al, 2013;Narcisi et al, 2015;Jothimani et al, 2020;Volleman et al, 2020). This model failed to explain the positive contribution of canonical Wnt in bone homeostasis in vivo (Wagner et al, 2020).…”

“…In fact, a tight crosstalk between canonical and non-canonical Wnt leads to functional antagonism during osteogenic differentiation (Baksh et al, 2007), and osteogenic suppression induced by Wnt1 and Wnt3a is correlated with reduced Ror2/JNK levels (Gaur et al, 2005;Liu et al, 2009). Therefore, these studies proposed a binary view where the activation of Wnt/β-catenin through exogenous ligands, such as Wnt3a, may suppress both osteoblastic gene expression and MSC osteogenic differentiation with decreased matrix mineralization, while the activation of the non-canonical pathway has an opposite effects (Boland et al, 2004;Jothimani et al, 2020). Moreover, the activation of canonical pathway suppresses the non-canonical pathway and vice versa.…”