Mesenchymal Stem Cells Modulate the Functional Properties of Microglia via TGF-β Secretion

Abstract

The results of this study showed that microglia functional properties may be modulated depending on the composition and quantity of mesenchymal stromal cell (MSC)-secreting factors. Transforming growth factor (TGF)-β is proposed as a modulator of microglia functional properties among MSC-secreting factors, and this study aligns with a previous clinical study by these same authors. TGF-β releasing capacity could be an important factor enhancing the therapeutic efficacy of MSCs in clinical trials.

Enhanced alleviation of aGVHD by TGF‐β1‐modified mesenchymal stem cells in mice through shifting MΦ into M2 phenotype and promoting the differentiation of Treg cells

“…48 Furthermore, as demonstrated previously, TGF-β1 can increase the differentiation of M2-like macrophages which function in wound healing and immunoregulation. 49,50 Taken together, these studies partially explain why infusion of MSC-TGF-β1 increased the M2-like macrophages in our murine aGVHD models. However, the precise underlying mechanism how M2 macrophage polarizated and functioned is quite sophisticated and still unknown in our current study, which need further illustration.…”

Repeated Intrathecal Mesenchymal Stem Cells for Amyotrophic Lateral Sclerosis

“…In previous studies, we proposed that intrathecal BM‐MSC injection in ALS possibly results in increased peripheral and central Tregs with IL‐4, IL‐10, and TGF‐β elevation in peripheral blood mononuclear cells of ALS patients, and switches microglia functional phenotypes toward anti‐inflammatory type 29. This leads to an anti‐inflammatory environment in the central nervous system in agreement with results of CSF biomarker analysis in a previous phase 1 study10 and the present phase 2 trial.…”

“…Another mechanism of BM‐MSCs could be an anti‐inflammatory M2 phenotypic “switch” away from the toxic or proinflammatory microglial form (M1), known to play an important role in accelerating neuronal death, thus increasing the rate of disease progression in patients with ALS 31. In addition, we previously reported that TGF‐β, secreted by BM‐MSCs, increases the phagocytic activity and anti‐inflammatory functions of microglial cells 29. Collectively, the plausible mechanisms of BM‐MSC therapy for slowing the progression of ALS shown in this trial may include increase of CSF anti‐inflammatory cytokines, the known paracrine effect of secreting neurotrophic factors, and other undetermined positive actions of BM‐MSCs.…”

Comparison of the paracrine activity of mesenchymal stem cells derived from human umbilical cord, amniotic membrane and adipose tissue

“…After primary experiments, MSCs are now valued for their multilineage differentiation, which enables action through direct regeneration. However, the current leading approach is that paracrine action by MSC‐derived soluble factors is a primary mechanism by which this population enhances regeneration of the injured tissues and organs . Moreover, MSCs evoke very small to minimal immune reactivity as they suppress the proliferation of lymphocytes and are believed to be safe for allogeneic transplantation …”

“…In a neurodegenerative disease model, MSC‐conditioned media inhibited proinflammatory cytokine expression and improved phagocytosis in lipopolysaccharide‐stimulated microglia. It is supposed that TGF‐β acts by inhibiting the nuclear factor‐κB pathway and by restoring the TGF‐β pathway in microglia cells, which turns them into an inflammation‐resolving phenotype …”