Extracellular Nucleotide Hydrolysis in Dermal and Limbal Mesenchymal Stem Cells: A Source of Adenosine Production

• Published in: Journal of cellular biochemistry 2017-08, Vol.118 (8), p.2430-2442
• Main Authors: Naasani, Liliana I. Sous, Rodrigues, Cristiano, de Campos, Rafael Paschoal, Beckenkamp, Liziane Raquel, Iser, Isabele C., Bertoni, Ana Paula Santin, Wink, Márcia R.
• Format: Article
• Language: English
• Subjects: Accumulation; Adenosine; Adenosine - metabolism; Adenosine Triphosphatases - genetics; Adenosine Triphosphatases - metabolism; Adenosine triphosphate; Adenosine Triphosphate - metabolism; Adipogenesis - genetics; Adipogenesis - physiology; AMP; Antigens, CD34 - genetics; Antigens, CD34 - metabolism; Apoptosis; ATP; Biochemistry; Biocompatibility; Biomarkers; Biomedical materials; CD105 antigen; CD14 antigen; CD34 antigen; CD44 antigen; CD45 antigen; CD73; CD73 antigen; Cell Differentiation - genetics; Cell Differentiation - physiology; Cell proliferation; Chondrogenesis - genetics; Chondrogenesis - physiology; Degradation; DERMAL MESENCHYMAL STEM CELLS; Dermatology; Differentiation; Endoglin - genetics; Endoglin - metabolism; Enzymatic activity; Humans; Hyaluronan Receptors - genetics; Hyaluronan Receptors - metabolism; Hydrolysis; Information processing; Leukocyte Common Antigens - genetics; Leukocyte Common Antigens - metabolism; Ligands; LIMBAL MESENCHYMAL STEM CELLS; Limbus Corneae - cytology; Lipopolysaccharide Receptors - genetics; Lipopolysaccharide Receptors - metabolism; Mesenchymal stem cells; Mesenchymal Stromal Cells - metabolism; Mesenchyme; Metabolism; mRNA; MSCs; NTPDases; Nucleotides; Nucleotides - metabolism; Oncogene Proteins - genetics; Oncogene Proteins - metabolism; Ophthalmology; Osteogenesis - genetics; Osteogenesis - physiology; Physiology; PURINERGIC SIGNALING; Pyrophosphatases - genetics; Pyrophosphatases - metabolism; Repair; Rims; Side effects; Skin; Skin - cytology; Stem cells; Therapeutic applications; Tissues
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.25909

ABSTRACT Human Limbal (L‐MSCs) and Dermal Mesenchymal Stem Cell (D‐MSCs) possess many properties that increase their therapeutic potential in ophthalmology and dermatology. It is known that purinergic signaling plays a role in many aspects of mesenchymal stem cells physiology. They release and respond to purinergic ligands, altering proliferation, migration, differentiation, and apoptosis. Therefore, more information on these processes would be crucial for establishing future clinical applications using their differentiation potential, but without undesirable side effects. This study evaluated and compared the expression of ecto‐nucleotidases, the enzymatic activity of degradation of extracellular nucleotides and the metabolism of extracellular ATP in D‐MSCs and L‐MSCs, isolated from discard tissues of human skin and sclerocorneal rims. The D‐MSCs and L‐MSCs showed a differentiation potential into osteogenic, adipogenic, and chondrogenic lineages and the expression of markers CD105+, CD44+, CD14−, CD34−, CD45−, as expected. Both cells hydrolyzed low levels of extracellular ATP and high levels of AMP, leading to adenosine accumulation that can regulate inflammation and tissue repair. These cells expressed mRNA for ENTPD1, 2, 3, 5 and 6, and CD73 that corresponded to the observed enzymatic activities. Thus, considering the degradation of ATP and adenosine production, limbal MSCs are very similar to dermal MSCs, indicating that from the aspect of extracellular nucleotide metabolism L‐MSCs are very similar to the characterized D‐MSCs. J. Cell. Biochem. 118: 2430–2442, 2017. © 2017 Wiley Periodicals, Inc. In our molecular analysis, both human limbal (L‐MSCs) and dermal mesenchymal stem cell (D‐MSCs) express CD73 and NTPDases (NT) 1,2,3,5, and 6. Comparing both cells, L‐MSCs express higher levels of NT3 mRNA, while D‐MSCs express higher levels of NT1. However, in our enzymatic activity analysis, we demonstrated that in both cells, the ATP and ADP degradation is low when compared to AMP hydrolysis. At the end, as result of the high hydrolytic activity of the CD73 enzyme, there will be an abundant production of adenosine, which in turn, can exert many roles in the extracellular space interacting with other cells.