title: Sub-physiological oxygen levels optimal for growth and survival of human atrial cardiac stem cells.
abstract: Cardiac stem cells reside in niches where the oxygen levels are close to 3%. For cytotherapy, cells are conventionally expanded in ambient oxygen (21% O2) which represents hyperoxia compared to the oxygen tension of niches. Cardiosphere-derived cells (CDCs) are then transplanted to host tissue with lower-O2levels. The high-O2gradient can reduce the efficacy of cultured cells. Based on the assumption that minimizing injury due to O2gradients will enhance the yield of functionally efficient cells, CDCs were cultured in 3% O2and compared with cells maintained in ambient O2. CDCs were isolated from human right atrial explants and expanded in parallel in 21 and 3% oxygen and compared with regard to survival, proliferation, and retention of stemness. Increased cell viability even in the tenth passage and enhanced cardiosphere formation was observed in cells expanded in 3% O2. The cell yield from seven passages was fourfold higher for cells cultured in 3% O2. Preservation of stemness in hypoxic environment was evident from the proportion of c-kit-positive cells and reduced myogenic differentiation. Hypoxia promoted angiogenesis and reduced the tendency to differentiate to noncardiac lineages (adipocytes and osteocytes). Mimicking the microenvironment at transplantation, when shifted to 5% O2, viability and proliferation rate were significantly higher for CDCs expanded in 3% O2. Expansion of CDCs, from atria in sub-physiological oxygen, helps in obtaining a higher yield of healthy cells with better preservation of stem cell characteristics. The cells so cultured are expected to improve engraftment and facilitate myocardial regeneration.
authors.affiliation: Division of Cellular and Molecular Cardiology, Sree ChitraTirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, 695011, India.
authors.forename: Deepthi Sreerengam
authors.initials: DS
authors.lastname: RajendranNair
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, SreeChitraTirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, 695011, India.
authors.forename: Jayakumar
authors.initials: J
authors.lastname: Karunakaran
authors.affiliation: Division of Cellular and Molecular Cardiology, Sree ChitraTirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, 695011, India. renuka@sctimst.ac.in.
authors.forename: Renuka R
authors.initials: RR
authors.lastname: Nair
mesh_terms: D015687:Cell Hypoxia; D049109:Cell Proliferation; D002470:Cell Survival; D006325:Heart Atria / Q000166:cytology / Q000378:metabolism; D006801:Humans; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D010100:Oxygen
keywords: Cardiac stem cells; Cardiosphere-derived cells; Human atrial explants; Myocardial regeneration; Niche oxygen levels