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, 15 (6), 842-850

Systemic Administration of Rejuvenated Adipose-Derived Mesenchymal Stem Cells Improves Liver Metabolism in Equine Metabolic Syndrome (EMS)- New Approach in Veterinary Regenerative Medicine

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Systemic Administration of Rejuvenated Adipose-Derived Mesenchymal Stem Cells Improves Liver Metabolism in Equine Metabolic Syndrome (EMS)- New Approach in Veterinary Regenerative Medicine

Krzysztof Marycz et al. Stem Cell Rev Rep.

Abstract

Equine metabolic syndrome (EMS) is characterized by adiposity, insulin dysregulation and increased risk for laminitis. Increased levels of specific liver enzymes in the peripheral blood are typical findings in horses diagnosed with EMS. Current management of EMS is based on caloric restriction and increased physical activity. However, new potential treatment options are arising such as the transplantation of autologous adipose stem cells (ASC). However, cytophysiological properties of ASC derived from EMS horses are impaired which strongly limits their therapeutic potential. We hypothesized, that in vitro pharmacotherapy of those cells with 5-azacytidine (AZA) and resveratrol (RES) before their clinical application can reverse the aged phenotype of those cells and improve clinical outcome of autologous therapy. A 9 year old Dutch Warmblood Horse used for driving, was presented with severe obesity, insulin resistance. After EMS diagnosis, the animal received three intravenous injections of autologous, AZA/RES treated ASCs at weekly intervals. The therapeutic effect was assessed by the analysis of liver specific enzymes in the blood. ASC-transplantation reduced levels of glutamate dehydrogenase (GLDH), gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH) and aspartate transaminase (AST). This case report demonstrates the therapeutic potential of this intervention for EMS as well as apt utility of autologous, rejuvenated ASC injections.

Keywords: Adipose derived stem cells; Cell therapy; Equine metabolic syndrome; Liver; Mesenchymal stem cells.

Conflict of interest statement

Authors declare that there is no conflict of interest.

Figures

Fig. 1
Fig. 1
Results of the oral sugar test in an 8-year old Dutch warmblood horse with obesity. Plasma glucose (a) and plasma insulin (a) concentrations were measured over 150 min after oral administration of glucose
Fig. 2
Fig. 2
Alamar blue assay (a) was performed to determine the proliferation rate of cells (a). Untreated cells served as a control group (CTRL and EMS). PDT (b) was decreased while the mitochondrial membrane potential (c) increased in the experimental group. AZA/RES treatment increased SOD activity with (d) and enhanced osteogenic differentiation (e). Results are expressed as mean ± SD. Statistical significance is indicated as asterisk (*) when comparing the result to ASCEMS, and as hashtag (#) when comparing to ASC from healthy horse (CTRL). ##P < .01, **P < .01, ***P < .001. (Reproduced from Marycz et al. [35] under the Creative Commons Attribution License https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156237/)
Fig. 3
Fig. 3
Evaluation of GLDG and GGT(a), LDH and AST (b) and AP (c) levels in the serum an 8-year-old Dutch warmblood horse before and after intravenous administration of AZA/RES treated ASCs
Fig. 4
Fig. 4
Results of the GLDH, GGT, LDH, AST and AP measurements in different time points shown as a heat map. Lower values highlighted in green highest in red

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