PMID- 30631282 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1664-042X (Print) IS - 1664-042X (Electronic) IS - 1664-042X (Linking) VI - 9 DP - 2018 TI - Systemic Factors During Metabolic Disease Progression Contribute to the Functional Decline of Adipose Tissue-Derived Mesenchymal Stem Cells in Reproductive Aged Females. PG - 1812 LID - 10.3389/fphys.2018.01812 [doi] LID - 1812 AB - It is known that advanced metabolic disorders such as type 2 diabetes compromise the functional and regenerative capacity of endogenous adipose-tissue resident stem cells (ADSCs). It is, however, still unclear at which stage of disease progression ADSCs become compromised and whether systemic factors contribute to their functional decline. It was therefore hypothesized that inflammatory changes in the systemic microenvironment during distinct stages of disease progression negatively affect the functional capacity of ADSCs. A total of forty-seven (n = 47) black African reproductive aged females (32 +/- 8 years; mean +/- SD) were included in this study and subdivided into: (a) healthy lean (C; body mass index, BMI /= 25 kg/m(2)), (c) obese metabolic syndrome (MetS; BMI >/= 30 kg/m(2)), and (d) type 2 diabetes mellitus (T2DM; previously diagnosed and on treatment) groups. Participants underwent anthropometric assessments and a DXA scan to determine their body composition and adipose indices. Each persons' systemic metabolic- (cholesterol, HDL, LDL, triglycerides, and blood glucose) and inflammatory profiles (CRP, SDF1alpha, TNFalpha, IL6, IL8, IL10, and IFNy) were also evaluated. Participant-derived serum was then used to treat an ADSC cell line in vitro and its effect on viability (MTT-based assay), proliferation (BrdU), migration (wound healing assay), and osteogenic differentiation assessed. When exposed to serum derived from overweight/obese individuals (with or without metabolic syndrome), both the proliferative and migratory responses of ADSCs were less pronounced than when exposed to healthy control serum. Serum IL6 concentrations were identified as a factor influencing the proliferation of ADSCs, suggesting that long-term disruption to the systemic cytokine balance can potentially disrupt the proliferative responses of ADSCs. Obese participant-derived serum (with and without metabolic syndrome) furthermore resulted in lipid accumulation during osteogenic differentiation. This study, therefore demonstrated that systemic factors in obese individuals, regardless of the presence of metabolic syndrome, can be detrimental to the multifunctional properties of ADSCs. FAU - Seboko, Ascentia M AU - Seboko AM AD - Division of Endocrinology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. FAU - Conradie, M M AU - Conradie MM AD - Division of Endocrinology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. FAU - Kruger, M J AU - Kruger MJ AD - Division of Endocrinology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. FAU - Ferris, William Frank AU - Ferris WF AD - Division of Endocrinology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. FAU - Conradie, Magda AU - Conradie M AD - Division of Endocrinology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. FAU - van de Vyver, Mari AU - van de Vyver M AD - Division of Endocrinology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. LA - eng PT - Journal Article DEP - 20181218 PL - Switzerland TA - Front Physiol JT - Frontiers in physiology JID - 101549006 PMC - PMC6315119 OTO - NOTNLM OT - adipogenesis OT - adipose tissue OT - body composition OT - cytokines OT - interleukin 6 OT - mesenchymal stem cells OT - obesity OT - osteogenesis EDAT- 2019/01/12 06:00 MHDA- 2019/01/12 06:01 PMCR- 2018/12/18 CRDT- 2019/01/12 06:00 PHST- 2018/03/19 00:00 [received] PHST- 2018/12/04 00:00 [accepted] PHST- 2019/01/12 06:00 [entrez] PHST- 2019/01/12 06:00 [pubmed] PHST- 2019/01/12 06:01 [medline] PHST- 2018/12/18 00:00 [pmc-release] AID - 10.3389/fphys.2018.01812 [doi] PST - epublish SO - Front Physiol. 2018 Dec 18;9:1812. doi: 10.3389/fphys.2018.01812. eCollection 2018.