title: Vasculogenic stem cell mobilization and wound recruitment in diabetic patients: increased cell number and intracellular regulatory protein content associated with hyperbaric oxygen therapy.
abstract: Diabetic patients undergoing hyperbaric oxygen therapies (HBO(2)T) for refractory lower extremity neuropathic ulcers exhibit more than a twofold elevation (p=0.004) in circulating stem cells after treatments and the post-HBO(2)T CD34(+) cell population contains two- to threefold higher levels of hypoxia inducible factors-1, -2, and -3, as well as thioredoxin-1 (p<0.003), than cells present in blood before HBO(2)T. Skin margins obtained from 2-day-old abdominal wounds exhibit higher expression of CD133, CD34, hypoxia inducible factor-1, and Trx-1 vs. margins from refractory lower extremity wounds and expression of these proteins in all wounds is increased due to HBO(2)T (p<0.003). HBO(2)T is known to mobilize bone marrow stem cells by stimulating nitric oxide synthase. We found that nitric oxide synthase activity is acutely increased in patients' platelets following HBO(2)T and remains elevated for at least 20 hours. We conclude that HBO(2) T stimulates vasculogenic stem cell mobilization from bone marrow of diabetics and more cells are recruited to skin wounds.
authors.affiliation: Institute for Environmental Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104-6068, USA. sthom@mail.med.upenn.edu
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Thom
authors.forename: Tatyana N
authors.initials: TN
authors.lastname: Milovanova
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.forename: Veena M
authors.initials: VM
authors.lastname: Bhopale
authors.forename: Elena M
authors.initials: EM
authors.lastname: Sorokina
authors.forename: Günalp
authors.initials: G
authors.lastname: Uzun
authors.forename: D Scot
authors.initials: DS
authors.lastname: Malay
authors.forename: Michael A
authors.initials: MA
authors.lastname: Troiano
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Hardy
authors.forename: David S
authors.initials: DS
authors.lastname: Lambert
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Logue
authors.forename: David J
authors.initials: DJ
authors.lastname: Margolis
mesh_terms: D001707:Biopsy, Needle; D001792:Blood Platelets / Q000201:enzymology; D002465:Cell Movement; D017719:Diabetic Foot / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D006801:Humans; D006931:Hyperbaric Oxygenation; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000097:blood; D013234:Stem Cells / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D052250:Nitric Oxide Synthase Type III