Ex vivo antioxidant preconditioning improves the survival rate of bone marrow stem cells in the presence of wound fluid.
Yashar Mehrbani AzarCarola U NieslerMari van de VyverPublished in: Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society (2020)
The advancement of autologous mesenchymal stem cell (MSC) therapy for the treatment of non-healing diabetic wounds is hampered by endogenous MSC dysfunction and limited viability of cells post-transplantation into the pathological wound environment. The development of effective strategies to restore the functional capabilities of these impaired MSCs prior to transplantation may be a key to their ultimate success as wound repair mediators. The current study therefore investigated whether antioxidant preconditioning [7.5 mM N-acetylcysteine (NAC) + 0.6 mM ascorbic 2-phosphate (AAP)] could restore the growth rate, migration ability and viability of impaired MSCs and whether this restored state is maintained in the presence of diabetic wound fluid (DWF). Healthy control (source: wild type, C57BL/6J mice) (n = 12) and impaired/diabetic MSCs (source: obese prediabetic, B6.Cg-Lepob/J mice) (n = 12) were isolated from the bone marrow of mice. Treatment groups post-isolation were as follow: (a) No treatment (baseline phenotype): MSCs expanded in standard growth media (SGM) (±8 days) and only exposed to growth media. (b) DWF (baseline response): MSCs expanded in SGM (±8 days) followed by exposure to DWF (24 hours, 48 hours, 96 hours). (c) Antioxidant preconditioning (preconditioned phenotype): MSCs expanded in the presence of NAC/AAP (±8 days). (d) Antioxidant preconditioning + DWF (preconditioned response): MSCs expanded in the presence of NAC/AAP (±8 days) followed by exposure to DWF (24 hours, 48 hours, 96 hours). The results demonstrated that expansion of MSCs (both healthy control and impaired diabetic) in the presence of combined NAC/AAP treatment improved ex vivo MSC viability and protected MSCs in the presence of DWF. Despite improved viability, AAP/NAC could however not rescue the reduced proliferation and migration capacity of impaired diabetic MSCs. The protective effect of NAC/AAP preconditioning against the toxicity of DWF could however be a potential strategy to improve cell number post-transplantation.
Keyphrases
- mesenchymal stem cells
- bone marrow
- umbilical cord
- transcription factor
- cell therapy
- wound healing
- stem cells
- oxidative stress
- type diabetes
- wild type
- metabolic syndrome
- anti inflammatory
- adipose tissue
- high fat diet induced
- cerebral ischemia
- combination therapy
- insulin resistance
- bariatric surgery
- skeletal muscle
- cell proliferation
- brain injury
- genome wide analysis
- cell death
- high resolution
- endoplasmic reticulum stress
- subarachnoid hemorrhage
- platelet rich plasma
- free survival