Platelet-derived growth factor receptor beta identifies mesenchymal stem cells with enhanced engraftment to tissue injury and pro-angiogenic property

Abstract

Mesenchymal stem cells (MSCs) are heterogeneous likely consisting of subpopulations with various therapeutic potentials. Here we attempted to acquire a subset of MSCs with enhanced effect in wound healing. We found that human placental MSCs expressing platelet-derived growth factor (PDGF) receptor (PDGFR)-β exhibited greater proliferation rates and generated more colony-forming unit-fibroblast (CFU-F), compared to PDGFR-β MSCs. Notably, PDGFR-β MSCs expressed higher levels of pro-angiogenic factors such as Ang1, Ang2, VEGF, bFGF and PDGF. When 10 GFP-expressing MSCs were topically applied into excisional wounds in mice, PDGFR-β MSCs actively incorporated into the wound tissue, resulting in enhanced engraftment (3.92 ± 0.31 × 10 remained in wound by 7 days) and accelerated wound closure; meanwhile, PDGFR-β MSCs tended to remain on the top of the wound bed with significantly fewer cells (2.46 ± 0.26 × 10) engrafted into the wound, suggesting enhanced chemotactic migration and engraftment of PDGFR-β MSCs into the wound. Real-Time PCR and immunostain analyses revealed that the expression of PDGF-B was upregulated after wounding; transwell migration assay showed that PDGFR-β MSCs migrated eightfold more than PDGFR-β MSCs toward PDGF-BB. Intriguingly, PDGFR-β MSC-treated wounds showed significantly enhanced angiogenesis compared to PDGFR-β MSC- or vehicle-treated wounds. Thus, our results indicate that PDGFR-β identifies a subset of MSCs with enhanced chemotactic migration to wound injury and effect in promoting angiogenesis and wound healing, implying a greater therapeutic potential for certain diseases.

Comprehensive analysis of skeletal muscle- and bone-derived mesenchymal stem/stromal cells in patients with osteoarthritis and femoral neck fracture

“…We also screened in vitro expanded MSCs for gene expression of several markers of MSCs that were identified previously either in bone (e.g., leptin receptor, Gremlin 1) [3,33], cartilage (e.g., Gremlin 1) [3], or muscle (e.g., PW1, CD56, ACTA2A) [1] regeneration or in wound healing (e.g., PDGFRB) [34]. The present study shows that LEPR is significantly lower in patients with OA compared to patients with OP and the controls in bonederived MSCs.…”

c-Jun Overexpression Accelerates Wound Healing in Diabetic Rats by Human Umbilical Cord-Derived Mesenchymal Stem Cells

“…Patients with diabetes mellitus (DM) often experience impaired wound healing, which leads to the formation of chronic ulcers. The underlying pathogenesis is primarily accounted for by a weakened immune system [1], insufficient angiogenesis [2], impaired proliferation and migration of keratinocytes and fibroblasts [3], and diminished production of healing-related growth factors such as vascular endothelial growth factor (VEGF) [4], insulin-like growth factor 1 (IGF-1) [5], transforming growth factor-beta (TGF-β) [6], and platelet-derived growth factor (PDGF) [7].…”

Isolation and Culture of Human Stem Cells from Apical Papilla under Low Oxygen Concentration Highlight Original Properties

“…We investigated the expression of classical MSC markers (CD73, CD90, CD105) and also that of other markers described as "stemness/proliferative-linked" markers like CD49f, stage-specific human embryonic antigen-4 (SSEA4), CD24 and PDGFRβ [44][45][46][47]. We observed that the MSC phenotype was not affected by the [O 2 ] since the percentage of positive cells for the classical MSC markers was similar in both conditions ( Figure 4A).…”

“…Among the different markers analyzed, CD49f and SSEA4 remained highly expressed under low [O 2 ] in comparison with ambient air. In contrast, PDGFRβ, which is enriched in human placental MSCs with elevated colony forming unit efficiency [45], was moderately expressed in SCAPs irrespective of cell growth conditions and the percentage of positive cells was rather decreased under low [O 2 ]. In addition, CD24 expression, which may refer to the number of committed progenitors cells in the papilla tissue, was not differentially expressed in our cell growth conditions [44].…”