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Kiara Boodhoo, Mare Vlok, David L Tabb, Kathryn H Myburgh, and Mari van de Vyver

Chronic wounds are a serious and debilitating complication of diabetes. A better understanding of the

dysregulated healing responses following injury will provide insight into the optimal time frame for

therapeutic intervention. In this study a direct comparison was done between the healing dynamics and

the proteome of acute and obese diabetic wounds on day 2 and day 7 following injury. Full thickness

excisional wounds were induced on obese diabetic (B6.Cg-lepob/J, ob/ob, n=14) (blood glucose

423,25±127,92 mg/dL) and wild-type control (C57BL/6J, n=14) (blood glucose 186,67±24,5 mg/dL)

mice. Histological analysis showed no signs of healing in obese DM wounds whereas complete wound

closure/ re-epithelization, the formation of granulation tissue and signs of re-vascularization was evident

in acute wounds on day 7. In obese DM wounds, substance P deficiency and increased MMP-9 activity

on day 2 coincided with increased cytokine/chemokine levels within wound fluid. LC-MS/MS identified

906 proteins, of which 23 (Actn3, Itga6, Epb41, Sncg, Nefm, Rsp18, Rsp19, Rpl22, Macroh2a1, Rpn1,

Ppib, Snrnp70, Ddx5, Eif3g, Tpt1, FABP5, Cavin1, Stfa1, Stfa3, Cycs, Tkt, Mb, Chmp2a) were

differentially expressed in wounded tissue on day 2 (p<0.05; >2 fold) and 6 (Cfd, Ptms, Hp, Hmga1,

Cbx3, Syap1) (p<0.05; >2 fold) on day 7. A large number of dysregulated proteins on day 2 was

associated with an inability to progress into the proliferative stage of healing and suggest that early

intervention might be pivotal for effective healing outcomes. The proteomic approach highlighted the

complexity of obese DM wounds in which the dysregulation involves multiple regulatory pathways and

biological processes.

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Maria Jacoba Kruger, Maria Martha Conradie, Magda Conradie, and Mari van de Vyver

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.