ADSC-conditioned media elicit an ex vivo anti-inflammatory macrophage response

Abstract

Obesity-associated inflammatory mechanisms play a key role in the pathogenesis of metabolic-related diseases. Failure of anti-inflammatory control mechanisms within adipose tissue and peripheral blood mononuclear cells (PBMCs) have been implicated in disease progression. This study investigated the efficacy of allogeneic adipose tissue-derived mesenchymal stem cells conditioned media (ADSC-CM) to counteract persistent inflammation by inducing an anti-inflammatory phenotype and cytokine response within PBMCs derived from patients with and without metabolic syndrome. Forty six (n=46) mixed ancestry females (18 - 45 years) were subdivided into a) healthy lean (HL) (n=10) (BMI < 25 kg/m2), b) overweight/obese (OW/OB) (BMI ≥ 25 kg/m2, < 3 metabolic risk factors) (n=22) and c) metabolic syndrome (MetS) (visceral adiposity , ≥ 3 metabolic risk factors) (n=14) groups. Body composition (DXA scan), metabolic (cholesterol, HDL, LDL, triglycerides, blood glucose) and inflammatory profiles (38-Plex cytokine panel) were determined. PBMCs were isolated from whole blood and treated ex vivo with either i) autologous participant-derived serum ii) ADSCs-CM or iii) a successive treatment regime. The activation status (CD11b+) and intracellular cytokine (IL6, IL10, TNFa) expression were determined in M1 (CD68+CD206-CD163-) and M2 (CD68+CD163+ CD206+) macrophage populations using flow cytometry. ADSC-CM treatment, promoted a M2 macrophage phenotype and induced IL10 expression, this was most pronounced in the OW/OB group. This response is likely mediated by multiple complementing factors within ADSC-CM, yet to be identified. This study is the first to demonstrate the therapeutic potential of ADSC-CM to restore the inflammatory balance in immune compromised obese individuals.

Prospective application of exosomes derived from adipose‐derived stem cells in skin wound healing: A review

“…Adipose stem cells exhibit characteristics similar to MSCs. A study exploring the efficacy of allogeneic adipose tissue‐derived mesenchymal stem cell conditioned media (ADSC‐CM) to counteract persistent inflammation firstly illustrated the therapeutic potential of ADSC‐CM to restore the inflammatory balance in immune‐compromised obese individuals . ADSC‐Exos also displayed protective effects for osteoarthritis (OA) through the possible mechanism of downregulating senescence‐associated β‐galactosidase activity, thus reducing the production of inflammatory mediators .…”

Effects of Adipose Tissue-Derived Stem Cells Transplanted to a Bone Defect after Irradiation

“…Thangarajan et al 24) suggested that the paracrine effect of the ADSCs on the wound healing process has the effect of inducing the endogenous stem cells in the injured region to initiate the healing process. Furthermore, It was suggested that the ADSC transplantation had the effect of reducing the inflammatory response [25][26][27] . It has been reported that ADSCs increase the production of VEGF under hypoxic culture conditions 13,14) .…”

Exosomes contribution in COVID-19 patients’ treatment

“…Failure of anti-inflammatory control mechanisms within adipose tissue and peripheral blood mononuclear cells (PBMCs) have been implicated in disease progression. More importantly, ADSCs can distinguish between M1 and M2 macrophages and inducing their polarization into the anti-inflammatory profile M2 [ 34 ]. Also, ADSCs ensure the inactivation of T cells through secreting IL-10, TGF-β and impair B lymphocytes function [ 35 ].…”