An Investigation of the Effects of Human Serum, Altered by Exercise, on Mesenchymal Stem Cell Characteristics

Abstract

Human bone marrow mesenchymal stem cells (hBM-MSCs) have become an attractive source for the treatment of a number of injuries and diseases due to their unique therapeutic properties. However, their clinical use has many inherent challenges. Exercise, a non-pharmacological stimulus, has been reported to promote stem cell actions, though, limited knowledge exists regarding the mechanisms by which this occurs. One avenue through which exercise can potentially enable the exploitation of BM-MSC therapeutic properties is through the generation and alteration of a number of exercise-induced biochemical and metabolic factors present within the peripheral circulation, for which MSCs also possess receptors. Therefore, this thesis investigated the effect of metabolic and biochemical factors, generated and altered by acute and regular exercise, that were present within the serum, on MSC characteristics. hBM-MSC culture media was supplemented with serum obtained from a recreationally active (ACTIVE) population at pre- and post-exercise time points following exercise at 85% (ACTIVELT85) and 115% (ACTIVELT115) of lactate threshold, and an inactive (INACTIVE) population under resting conditions. Control conditions were represented by hBM-MSCs incubated in commercially available media, DMEM+10%FBS and MSCBM-CD+SingleQuot. When compared to the hBM-MSC response to pre-exercise serum, relative to the change in the housekeeping gene (HKG) expression, hBM-MSC peroxisome proliferator-activated receptor γ (PPARG) expression was 24% and 11% (p > 0.05) greater, and runt-related transcription factor 2 (RUNX2) expression 24% and 2% greater (p > 0.05) greater in response to serum obtained from post-exercise time points in ACTIVELT85 and ACTIVELT115 trials, respectively. When compared to the hBM-MSC response to MSCBM-CD+SingleQuot, relative to the change in the HKG, hBM-MSC PPARG expression was 57% and 146% greater following incubation with ACTIVE and INACTIVE serum, respectively (p < 0.05), whereas RUNX2 expression was 53% (p < 0.05) and 5% (p > 0.05) lower in response to ACTIVE and INACTIVE serum. In response to these culture conditions, hBM-MSCs displayed a greater degree of proliferation, and also exported more [d5]phenylalanine labelled protein per hour, following incubation with human serum compared to the control conditions (p < 0.05). These findings suggest that metabolic and biochemical changes which occurred in response to acute exercise did not alter hBM-MSC characteristics, in the variables analysed, but the milieu created by regular exercise did. For the infusion of MSCs into injured or diseased patients, this may suggest that their microenvironment might affect the MSC function and treatment outcome.

Date of Award	Jun 2018
Original language	English
Awarding Institution	University of Brighton
Supervisor	Peter Watt (Supervisor), Anna Guildford (Supervisor) & Yannis Pitsiladis (Supervisor)