Human Adipose Stromal/Stem Cells from Obese Donors Show Reduced Efficacy in Halting Disease Progression in the Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis

Abstract

Multiple sclerosis is an autoimmune disease that affects the white matter of the central nervous system and involves inflammation and demyelination. The recent advances in our understanding of adipose-derived stromal/stem cells (ASCs) and the utilization of these cells in clinical settings to treat diseases have made it essential to identify the most effective ASCs for therapy. Studies have not yet investigated the impact of obesity on the therapeutic efficacy of ASCs. Obesity is characterized by adipocyte hyperplasia and hypertrophy and can extend to metabolic and endocrine dysfunction. Investigating the impact obesity has on ASC biology will determine whether these cells are suitable for use in regenerative medicine. The therapeutic efficacy of ASCs isolated from lean subjects (body mass index [BMI] < 25; lnASCs) and obese subjects (BMI > 30; obASCs) were determined in murine experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. Compared with the EAE disease-modifying effects of lnASCs, obASCs consistently failed to alleviate clinical symptoms or inhibit inflammation in the central nervous system. When activated, obASCs expressed higher mRNA levels of several pro-inflammatory cytokines compared with lnASCs. Additionally, conditioned media (CM) collected from the obASCs markedly enhanced the proliferation and differentiation of T cells; whereas, CM from lnASC did not. These results indicate that obesity reduces, or eliminates, the anti-inflammatory effects of human ASCs such that they may not be a suitable cell source for the treatment of autoimmune diseases. The data suggest that donor demographics may be particularly important when identifying suitable stem cells for treatment.

Insight into the development of obesity: functional alterations of adipose‐derived mesenchymal stem cells

“…A transcriptomic analysis indicates an inhibited osteogenic pattern in obese ASCs . Moreover, obese ASCs from both subcutaneous and visceral adipose depots differentiated much less toward osteogenic lineage than ASCs from non‐obese controls , supported by the data from other research groups . These observations suggest that the osteogenic differentiation is compromised in obesity, which is in line with the finding that obesity compromises bone reconstitution and fracture healing .…”

The transplantation of mesenchymal stem cells derived from unconventional sources: an innovative approach to multiple sclerosis therapy

“…An interesting recent study in 2016 (Strong et al 2016) emphasizes the importance of the choice of AD-MSCs donor. Researchers compared the efficacy of intraperitoneal injection of allogenic AD-MSCs (1 × 10 6 ) taken from lean healthy donors (lnASCs) with allogenic AD-MSCs from obese subjects (obASCs) in EAE mice.…”

Stem Cell Therapy: A Promising Therapeutic Approach for Multiple Sclerosis

“…The therapeutic potential of AdMSCs in a mouse model of peripheral nerve sciatic crush has been demonstrated (65). The therapeutic efficacy of AdMSCs isolated from lean and obese persons indicated that obesity reduces the anti-inflammatory effects of human AdMSCs such that they may not be a suitable cell source for the treatment of autoimmune diseases (66). AdMSCs are a valuable source of adult MSC with neuronal differentiation ability, and are a useful remedy to treat neurodegenerative diseases (67).…”