Physiologically significant effects of pH and oxygen tension on granulopoiesis

Hevehan, Diane L.; Papoutsakis, E. T.; Miller, William M.

doi:10.1016/s0301-472x(99)00150-2

Cited by 71 publications

(64 citation statements)

References 46 publications

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“…In addition, hypoxic gradients may be important in regulating progenitor trafficking [48]. Exposure to hypoxia in vitro increased the maturation rate of CD34+ cells, while maintaining early precursors in a quiescent state [23,24]. The current authors did not observe preferential release of less immature precursors in more hypoxaemic COPD patients; rather, all CD34+ subpopulations tested were uniformly decreased (table 4).…”

Section: Discussionmentioning

confidence: 53%

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Circulating haemopoietic and endothelial progenitor cells are decreased in COPD

Palange¹

2006

European Respiratory Journal

177

133

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Circulating CD34+ cells are haemopoietic progenitors that may play a role in tissue repair. No data are available on circulating progenitors in chronic obstructive pulmonary disease (COPD).Circulating CD34+ cells were studied in 18 patients with moderate-to-severe COPD (age: mean¡SD 68¡8 yrs; forced expiratory volume in one second: 48¡12% predicted) and 12 controls, at rest and after endurance exercise. Plasma concentrations of haematopoietic growth factors (FMS-like tyrosine kinase 3 (Flt3) ligand, kit ligand), markers of hypoxia (vascular endothelial growth factor (VEGF)) and stimulators of angiogenesis (VEGF, hepatocyte growth factor (HGF)) and markers of systemic inflammation (tumour necrosis factor (TNF)-a, interleukin (IL)-6, IL-8) were measured.Compared with the controls, the COPD patients showed a three-fold reduction in CD34+ cell counts (3.3¡2.5 versus 10.3¡4.2 cells?mL -1 ), and a 50% decrease in AC133+ cells. In the COPD patients, progenitor-derived haemopoietic and endothelial cell colonies were reduced by 30-50%. However, four COPD patients showed progenitor counts in the normal range associated with lower TNF-a levels. In the entire sample, CD34+ cell counts correlated with exercise capacity and severity of airflow obstruction. After endurance exercise, progenitor counts were unchanged, while plasma Flt3 ligand and VEGF only increased in the COPD patients. Plasma HGF levels were higher in the COPD patients compared with the controls and correlated inversely with the number of progenitor-derived colonies.In conclusion, circulating CD34+ cells and endothelial progenitors were decreased in chronic obstructive pulmonary disease patients and could be correlated with disease severity.

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Section: Discussionmentioning

confidence: 53%

“…In vitro, very low arterial oxygen tension preserved early haemopoietic progenitors [23], while promoting their differentiation [24]. No study addressed the effects of mild hypoxaemia on circulating CD34+ cells and subpopulations in vivo in COPD patients.…”

Section: Cd34+ Cells In Copd P Palange Et Almentioning

confidence: 99%

Circulating haemopoietic and endothelial progenitor cells are decreased in COPD

Palange¹

2006

European Respiratory Journal

177

133

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“…At 22°C, glucose, which is abundantly present in CPDA-1 (2.9 g/dl), is metabolized rapidly into lactate and CO 2 , resulting in a drop in pH. Deviation of culture pH has been shown to affect both the cloning efficiency and differentiation potential of progenitor cells, 36,37 and indeed in separate experiments with mononuclear cells, a pH of 6.8 or lower negatively influenced CFU-GM recovery. Therefore, we hypothesized that either a strong buffer or an alternative to glucose, resulting in less lactate production, should be used.…”

Section: Discussionmentioning

confidence: 99%

Storage of unprocessed G-CSF-mobilized whole blood in a modified Leibovitz's L15 medium preserves clonogenic capacity for at least 7 days

Kreuk

Jonkhoff

Zevenbergen

et al. 2001

Bone Marrow Transplant

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Summary:Autologous stem cell transplantation using unprocessed, G-CSF-mobilized whole blood (WB) is a simple, cost-reducing procedure and supports high-dose chemotherapy regimens not exceeding 72 h. Thereafter, clonogenic capacity rapidly decreases if routine anticoagulants are used for storage. In order to increase clinical applicability, we investigated the requirements for optimal preservation of unprocessed WB for 7 days. During storage at 22؇C in CPDA-1, a decrease in pH was noted, which was at least partially responsible for the low recovery of clonogenic cells. Subsequently, WB cells were stored in various cell culture media (RPMI 1640, ␣-MEM, X-VIVO15, CellGro SCGM and Leibovitz's L15 medium) containing either serum, serum-free substitutes or no additives. Leibovitz's L15 showed significantly better CFU-GM recoveries than the other media. Using a calcium-free modification of L15 medium (added 3:10 to WB), 94 ؎ 24% of CD34 ؉ cells, 41 ؎ 14% of BFU-E, 56 ؎ 17% CFU-GM and 90 ؎ 14% of LTC-IC were preserved during storage for 7 days at 22؇C. Storage at 4؇C was also feasible, but showed less optimal recoveries of 52 ؎ 29% (CD34), 32 ؎ 10% (BFU-E), 13 ؎ 7% (CFU-GM) and 58 ؎ 9% (LTC-IC). The expression of CD38, Thy-1, c-kit, AC133, L-selectin and CXCR4 on CD34-positive cells remained unchanged. In conclusion, a modified Leibovitz's L15 medium better meets the metabolic requirements of a high-density cell culture and allows safe storage of G-CSF mobilized WB for at least 7 days. The results encourage further exploration of WB transplants stored for 7 days for clinical use. Bone Marrow Transplantation (2001) 28, 145-155.

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“…41 On each day of analysis, 3 mL of culture media was centrifuged at 200 g for 15 min to pellet cells. In initial experiments, the pH of the resultant supernatant was measured immediately (Method 1).…”

Section: Cell Culture For Media and Il-3 Source Evaluationmentioning

confidence: 99%