Pre-conditioning Strategies for Mesenchymal Stromal/Stem Cells in Inflammatory Conditions of Livestock Species

Abstract

Mesenchymal stem/stromal cells (MSCs) therapy has been a cornerstone of regenerative medicine in humans and animals since their identification in 1968. MSCs can interact and modulate the activity of practically all cellular components of the immune response, either through cell-cell contact or paracrine secretion of soluble mediators, which makes them an attractive alternative to conventional therapies for the treatment of chronic inflammatory and immune-mediated diseases. Many of the mechanisms described as necessary for MSCs to modulate the immune/inflammatory response appear to be dependent on the animal species and source. Although there is evidence demonstrating an in vitro immunomodulatory effect of MSCs, there are disparate results between the beneficial effect of MSCs in preclinical models and their actual use in clinical diseases. This discordance might be due to cells' limited survival or impaired function in the inflammatory environment after transplantation. This limited efficacy may be due to several factors, including the small amount of MSCs inoculated, MSC administration late in the course of the disease, low MSC survival rates in vivo, cryopreservation and thawing effects, and impaired MSC potency/biological activity. Multiple physical and chemical pre-conditioning strategies can enhance the survival rate and potency of MSCs; this paper focuses on hypoxic conditions, with inflammatory cytokines, or with different pattern recognition receptor ligands. These different pre-conditioning strategies can modify MSCs metabolism, gene expression, proliferation, and survivability after transplantation.

Mesenchymal stem cells in fibrotic diseases—the two sides of the same coin

“…The complex microenvironment that internal and external MSCs faced and encountered in fibrosis diseases could bring opposite outcomes for their functions. Based on this information, pre-conditioning strategies for MSCs have been encouraged to be used in preclinical and clinical trials, including physical and chemical pre-conditioning strategies such as hypoxic conditions, with inflammatory cytokines, or with different pattern recognition receptor ligands [ 268 , 269 ].…”

Mesenchymal Stem Cell Conditioned Medium Modulates Inflammation in Tenocytes: Complete Conditioned Medium Has Superior Therapeutic Efficacy than Its Extracellular Vesicle Fraction

“…In addition to the stem cell source, differences in secretome composition are significant when comparing fetal or adult donors [ 75 , 76 ]. Furthermore, pre-conditioning of the donor cells either with various compounds or by modification of the culture conditions leads to altered secretome profiles [ 77 , 78 , 79 , 80 ]. Another big obstacle when comparing CM and its subfraction is the standardization strategy for studies, the optimal dosage of the treatment, and the number of doses.…”

Mesenchymal stromal cells modulate infection and inflammation in the uterus and mammary gland

“…This potential use of MSC in cattle was recently discussed [7]. Some in-vitro and in-vivo studies demonstrated encouraging immunomodulating, antiinflammatory and antimicrobial effects in mammary and uterus cell systems and animal models [5,[8][9][10][11][12][13]. However, the feasibility and efficacy of MSC-based therapy for mastitis and metritis are still unknown and further research is required.…”