TGF-β1 Pretreatment Improves the Function of Mesenchymal Stem Cells in the Wound Bed

Abstract

The wound healing process initiates after injury to a tissue and involves a series of orchestrated events to minimize the invasion of foreign matters such as bacteria and efficiently regenerate the damaged tissue. A variety of cells must be recruited to the tissue during wound healing. However, this process is severely disrupted in patients suffering from chronic illness, including diabetes, leading to impaired healing or non-healing wounds. Current avenues of treatment include negative-pressure therapy, wound debridement, growth factor replacement, and cell-based therapies. Among these therapies, mesenchymal stem cells (MSCs) delivery to the wound holds a very high promise due to the innate abilities of MSCs that include immunogenicity, plasticity, and self-renewal. Bone marrow derived MSCs have been shown to promote more rapid wound healing by increased cytokine production in diabetic mice. However, the lack of understanding of the mechanical and chemical interaction of the transplanted MSCs with the factors present in the regenerative niches limits their efficacy in the wound bed. In this study, we sought to understand how the changes in MSC biochemical and biophysical properties can affect their function in vitro and in vivo. We demonstrate that pretreatment of MSCs with the mechano-stimulatory soluble factor transforming growth factor (TGF-β1), which is highly expressed in injury sites, improves wound closure in a syngeneic murine wound model. This improved wound closure correlated with increased invasion into the wound bed. In vitro studies demonstrated that TGF-β1 pretreatment expedited wound closure by increasing adhesion, traction force, and migration even after removal of the stimulus. Furthermore, this response was mediated by the cytoskeletal protein focal adhesion kinase. Taken together, this study suggests that defined chemical stimuli can benefit site specific adaptability of MSCs to improve their function and therapeutic usefulness.

Senescence of bone marrow-derived mesenchymal stem cells from patients with idiopathic pulmonary fibrosis

“…TGF-β1 also plays an important role in directing fate decision in B-MSCs and modulating regenerative function of B-MSCs [ 26 – 28 ]. We analyzed the response to TGF-β1 stimulation on control and IPF B-MSCs at 24 h and 72 h. At 24 h, IPF-MSCs expressed higher levels of interleukin (IL)-6 (a well-known factor of SASP) than control cells (data not shown).…”

Platelet “first responders” in wound response, cancer, and metastasis

“…Platelet release of TGF-β and extracellular matrix (ECM) tension, help drive fibroblasts to transition into a myofibroblast phenotype that help with repair [180,181]. It also enhances mesenchymal stem cells (MSCs) differentiation and functions as a mechano-stimulatory factor to improve wound closure [182]. Platelet TGF-β also helps neutrophils infiltrate into wounds that are replaced by macrophages.…”

Regenerative potential of partially differentiated mesenchymal stromal cells in a mouse model of a full-thickness skin wound

“…5) ). It has been previously demonstrated that MSCs increase the rate of wound closure in full thickness skin wounds (Ghosh et al, 2017[ 11 ]). Moreover, MSCs promote skin appendages regeneration (Xia et al, 2017[ 37 ]).…”