Global strategy for asthma management and prevention

Much of the work conducted on adult stem cells has focused on mesenchymal stem cells (MSCs) found within the bone marrow stroma. Adipose tissue, like bone marrow, is derived from the embryonic mesenchyme and contains a stroma that is easily isolated. Preliminary studies have recently identified a putative stem cell population within the adipose stromal compartment. This cell population, termed processed lipoaspirate (PLA) cells, can be isolated from human lipoaspirates and, like MSCs, differentiate toward the osteogenic, adipogenic, myogenic, and chondrogenic lineages. To confirm whether adipose tissue contains stem cells, the PLA population and multiple clonal isolates were analyzed using several molecular and biochemical approaches. PLA cells expressed multiple CD marker antigens similar to those observed on MSCs. Mesodermal lineage induction of PLA cells and clones resulted in the expression of multiple lineage-specific genes and proteins. Furthermore, biochemical analysis also confirmed lineage-specific activity. In addition to mesodermal capacity, PLA cells and clones differentiated into putative neurogenic cells, exhibiting a neuronal-like morphology and expressing several proteins consistent with the neuronal phenotype. Finally, PLA cells exhibited unique characteristics distinct from those seen in MSCs, including differences in CD marker profile and gene expression.

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Human Adipose Tissue Is a Source of Multipotent Stem Cells

Asthma is a serious health problem throughout the world During the past two decades, many scientific advances have improved our understanding of asthma and ability to manage and control it effectively However, recommendations for asthma care need to be adapted to local conditions, resources and services Since it was formed in 1993, the Global Initiative for Asthma, a network of individuals, organisations and public health officials, has played a leading role in disseminating information about the care of patients with asthma based on a process of continuous review of published scientific investigations A comprehensive workshop report entitled "A Global Strategy for Asthma Management and Prevention", first published in 1995, has been widely adopted, translated and reproduced, and forms the basis for many national guidelines The 2006 report contains important new themes First, it asserts that "it is reasonable to expect that in most patients with asthma, control of the disease can and should be achieved and maintained," and recommends a change in approach to asthma management, with asthma control, rather than asthma severity, being the focus of treatment decisions The importance of the patient-care giver partnership and guided self-management, along with setting goals for treatment, are also emphasised

https://erj.ersjournals.com/content/erj/31/1/143.full.pdf

Global strategy for asthma management and prevention: GINA executive summary.

Our laboratory has recently characterized a population of cells from adipose tissue, termed processed lipoaspirate (PLA) cells, which have multi-lineage potential similar to bone-marrow-derived mesenchymal stem cells (MSCs). This study is the first comparison of PLA cells and MSCs isolated from the same patient. No significant differences were observed for yield of adherent stromal cells, growth kinetics, cell senescence, multi-lineage differentiation capacity, and gene transduction efficiency. Adipose tissue is an abundant and easily procured source of PLA cells, which have a potential like MSCs for use in tissue-engineering applications and as gene delivery vehicles.

Comparison of Multi-Lineage Cells from Human Adipose Tissue and Bone Marrow

Studies of oral corticosteroid dose and loss of bone mineral density have reported inconsistent results. In this meta-analysis, we used information from 66 papers on bone density and 23 papers on fractures to examine the effects of oral corticosteroids on bone mineral density and risk of fracture. Strong correlations were found between cumulative dose and loss of bone mineral density and between daily dose and risk of fracture. The risk of fracture was found to increase rapidly after the start of oral corticosteroid therapy (within 3 to 6 months) and decrease after stopping therapy. The risk remained independent of underlying disease, age and gender. We conclude that oral corticosteroid treatment using more than 5 mg (of prednisolone or equivalent) daily leads to a reduction in bone mineral density and a rapid increase in the risk of fracture during the treatment period. Early use of preventive measures against corticosteroid-induced osteoporosis is recommended.

/pdf/the-epidemiology-of-corticosteroid-induced-osteoporosis-a-4ra3qtx7u3.pdf

The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis.

In the UK, over 250 000 patients take continuous oral glucocorticoids (GCs), yet no more than 14% receive any therapy to prevent bone loss, a major complication of GC treatment. Bone loss is rapid, particularly in the first year, and fracture risk may double. This review, based wherever possible on clinical evidence, aims to provide easy-to-use guidance with wide applicability. A treatment algorithm is presented for adults receiving GC doses of 7.5 mg day(-1) or more for 6 months or more. General measures, e.g. alternative GCs and routes of administration, and therapeutic interventions, e.g. cyclical etidronate and hormone replacement, are recommended.

A UK Consensus Group on management of glucocorticoid‐induced osteoporosis: an update

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], but not 24,25-(OH)2D3, stimulates the alkaline phosphatase activity of cultured human bone cell populations. The stimulatory effect of the sterol was dose dependent (10−10–10−7 m), evident by 24 h, and observed over a range of cell densities. Analysis of the radiolabeled collagens synthesised by human bone cell cultures indicated the synthesis of predominantly type I collagen. In the presence of l,25-(OH)2b3, but not 24,25-(OH)2D3, there was a dose-dependent (10−11–10−9 m) increase in radiolabeled proline incorporation into collagenase-digestible protein and in the amount of collagen synthesized, expressed as a percentage of the total protein synthesis. The effect of 1,25-(OH)2D3 was observed over a range of cell densities and appeared to be specific for the synthesis of type I collagen. The stimulatory effect of 1,25- (QH)2D3 on alkaline phosphatase activity and the increase in proline incorporation into collagenase-digestible protein were accompanied by a dose-de...

1,25-Dihydroxyvitamin D3 and human bone-derived cells in vitro: effects on alkaline phosphatase, type I collagen and proliferation.

Bone marrow stromal cells are believed to play a major role in bone formation as a major source of osteoprogenitor cells, however, very little is known about how the osteogenic differentiation of these cells is regulated by systemic hormones and local growth factors. We examined the effects of TGF-β and its interaction with 1,25(OH)2 Vitamin D3 [1,25(OH)2D3] on the differentiation and proliferation of human bone marrow stromal cells (hBMSC) in secondary cultures. Alkaline phosphatase (ALP) activity was inhibited by TGF-β (0.1–10 ng/ml) and increased by 1,25(OH)2D3 (50 nM), however, co-treatment of TGF-β and 1,25(OH)2D3 synergistically enhanced ALP activity with maximal stimulation occurring at about 8 days after treatment. This synergistic effect was independent of proliferation because, in contrast to TGF-β alone, combined treatment with TGF-β and 1,25(OH)2D3 had no effect on hBMSC proliferation. As no synergistic effect was seen with combinations of 1,25(OH)2D3 and other osteotrophic growth factors, including BMP-2, IGF-I, and basic fibroblast growth factor (bFGF), it would seem likely that the synergistic interaction is specific for TGF-β. The increased ALP activity was due to an enhancement of 1,25(OH)2D3-induced ALP activity by TGF-β, rather than vice versa. In contrast, TGF-β inhibited 1,25(OH)2D3-induced osteocalcin production. Taken together, these results indicate that TGF-β and 1,25(OH)2D3 act synergistically to stimulate the recruitment of BMSC to the osteoblast lineage. This interaction may play an important role in bone remodeling.

Regulation of Osteogenic Differentiation of Human Bone Marrow Stromal Cells: Interaction Between Transforming Growth Factor-β and 1,25(OH)2 Vitamin D3 In Vitro

http://portlandpress.com/clinsci/article-pdf/64/2/38P/461565/cs064038pc.pdf

Human Bone Cells in Culture. A Novel System for the Investigation of Bone Cell Metabolism

1. We have observed previously that extracellular ATP acting at P2-purinoceptors promotes the production of prostaglandin E2 by human articular chondrocytes, and that this response is enhanced synergistically by interleukin-1 beta. Since other cytokines that influence the metabolism of articular cartilage may have a similar effect, we have investigated whether tumour necrosis factor-alpha also modulates the stimulation of the production of prostaglandin E2 in these cells by ATP. 2. Tumour necrosis factor-alpha enhanced the response of cultured human articular chrondrocytes to a maximally stimulating concentration of ATP (100 mumol/l). This effect was present when the cells were co-incubated with tumour necrosis factor-alpha and ATP for 4 h, was augmented when the cells were also preincubated with the cytokine for 24 h, and remained constant or decline on extending the preincubation period to 72 h. The enhancement of responsiveness to ATP by tumour necrosis factor-alpha was dose-dependent, and the minimum effective concentration (6 pmol/l) did not consistently increase prostaglandin E2 production when the cytokine was tested alone. The presence of tumour necrosis factor-alpha during the incubation with ATP was required for maximum enhancement of the response. Tumour necrosis factor-alpha did not alter the minimum concentration of ATP that stimulated production of prostaglandin E2. 3. Cytokines such as interleukin-1 and tumour necrosis factor-alpha are involved in the pathogenesis of some forms of arthritis, and these data provide additional evidence that their actions in articular cartilage may be modulated by other agents which originate from chondrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Rgg Russell

Papers

A UK Consensus Group on management of glucocorticoid‐induced osteoporosis: an update

1,25-Dihydroxyvitamin D3 and human bone-derived cells in vitro: effects on alkaline phosphatase, type I collagen and proliferation.

Regulation of Osteogenic Differentiation of Human Bone Marrow Stromal Cells: Interaction Between Transforming Growth Factor-β and 1,25(OH)2 Vitamin D3 In Vitro

Human Bone Cells in Culture. A Novel System for the Investigation of Bone Cell Metabolism

Induction of enhanced responsiveness of human articular chondrocytes to extracellular ATP by tumour necrosis factor-alpha.