title: Adipose tissue and bone marrow-derived stem cells react similarly in an ischaemia-like microenvironment.
abstract: Mesenchymal stem cells (MSCs) from adipose tissue and bone marrow are promising cell sources for autologous cell therapy of nerve injuries, as demonstrated by their intrinsic neurotrophic potential. However, extensive death of transplanted cells limits their full benefits. This study investigated the effects of ischaemia (metabolically induced by sodium azide and 2-deoxyglucose) and serum-derived mitogens on the viability and functional profile of MSCs in vitro. MSCs were more susceptible to combined, rather than individual, blockade of glycolysis and oxidative phosphorylation. Apoptosis and autophagy were involved in ischaemia-induced cell death. Chemical ischaemia alone and serum withdrawal alone induced a similar amount of cell death, with significantly different intracellular ATP maintenance. Combined ischaemia and serum deprivation had additive effects on cell death. Expression of the extracellular matrix (ECM) molecules laminin and fibronectin was attenuated under ischaemia and independent of serum level; however, BDNF and NGF levels remained relatively constant. Strong upregulation of VEGF and to a lesser extent angiopoietin-1 was observed under ischaemia but not in serum withdrawal conditions. Importantly, this study demonstrated similar reactions of MSCs derived from adipose and bone marrow tissue, in ischaemia-like and mitogen-deprived microenvironments in terms of viability, cellular energetics, cell death mechanisms and expression levels of various growth-promoting molecules. Also, the results suggest that ischaemia has a larger impact on the ability of MSCs to survive transplantation than withdrawal of mitogens.
authors.affiliation: Department of Integrative Medical Biology, Section of Anatomy, Umeå University, Sweden.
authors.forename: Kai-Hei
authors.initials: KH
authors.lastname: Tse
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kingham
authors.forename: Lev N
authors.initials: LN
authors.lastname: Novikov
authors.forename: Mikael
authors.initials: M
authors.lastname: Wiberg
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D060833:Cellular Microenvironment / Q000187:drug effects; D003847:Deoxyglucose / Q000633:toxicity; D007511:Ischemia / Q000139:chemically induced / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008954:Models, Biological; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D044967:Serum; D019810:Sodium Azide / Q000633:toxicity
chemical_list: D015415:Biomarkers; D011506:Proteins; D019810:Sodium Azide; D003847:Deoxyglucose