Camilla Drexler

Human platelet lysate can replace fetal bovine serum for clinical-scale expansion of functional mesenchymal stromal cells.

BACKGROUND: Human multipotent mesenchymal stromal cells (MSCs) are promising candidates for a growing spectrum of regenerative and immunomodulatory cellular therapies. Translation of auspicious experimental results into clinical applications has been limited by the dependence of MSC propagation from fetal bovine serum (FBS).

Sclerostin and its association with physical activity, age, gender, body composition, and bone mineral content in healthy adults.

CONTEXT Sclerostin is produced by osteocytes and inhibits bone formation through the Wnt/β-catenin-signaling pathway. Only limited data are available on circulating sclerostin levels in healthy subjects. OBJECTIVE We aimed to evaluate the correlation between sclerostin and physical activity, anthropometric, and biochemical variables. DESIGN, SETTING, AND PARTICIPANTS We conducted a cross-sectional observational study in 161 healthy adult men and premenopausal women aged 19 to 64 yr (mean age, 44 ± 10). INTERVENTION(S) There were no interventions. MAIN OUTCOME MEASURE(S) Serum sclerostin levels were associated with body composition, bone mineral density, physical activity, and various biochemical parameters. RESULTS A positive correlation between age and sclerostin in both men (r = 0.37; P < 0.001) and premenopausal women (r = 0.66; P < 0.001) was found. Men had significantly higher sclerostin levels than women (49.8 ± 17.6 vs. 37.2 ± 15.2 pmol/liter; P < 0.001). However, after adjustment for age, bone mineral content (BMC), physical activity, body mass index (BMI), and renal function, sclerostin levels did not differ (P = 0.543). Partial correlation analysis adjusted for age, gender, and kidney function revealed a significant positive correlation between sclerostin levels and BMC, bone mineral density, BMI, and android/gynoid fat and a significant negative correlation with serum osteocalcin and calcium. The most physically active quartile had significantly lower sclerostin levels compared to the least active quartile in a univariate analysis. CONCLUSIONS In healthy adults, sclerostin serum levels correlate positively with age, BMI, and BMC and negatively with osteocalcin and calcium. Further studies in larger populations are needed to confirm our findings and to better understand their clinical implications.

Rapid Large-Scale Expansion of Functional Mesenchymal Stem Cells from Unmanipulated Bone Marrow Without Animal Serum

Adult mesenchymal stem cells (MSCs) are considered as valuable mediators for tissue regeneration and cellular therapy. This study was performed to develop conditions for regularly propagating a clinical quantity of > 2 x 10(8) MSCs without animal serum from small bone marrow (BM) aspiration volumes within short time. We established optimized culture conditions with pooled human platelet lysate (pHPL) replacing fetal bovine serum (FBS) for MSC propagation. MSC quality, identity, purity, and function were assessed accordingly. Biologic safety was determined by bacterial/fungal/mycoplasma/endotoxin testing and genomic stability by array comparative genomic hybridization (CGH). We demonstrate that unmanipulated BM can be used to efficiently initiate MSC cultures without the need for cell separation. Just diluting 1.5-5 mL heparinized BM per 500 mL minimum essential medium supplemented with L-glutamine, heparin, and 10% pHPL sufficiently supported the safe propagation of 7.8 +/- 1.5 x 10(8) MSCs within a single 11- to 16-day primary culture under defined conditions. This procedure also resulted in sustained MSC colony recovery. MSC purity, immune phenotype, and in vitro differentiation potential fully matched current criteria. Despite high proliferation rate, MSCs showed genomic stability in array CGH. This easy single-phase culture procedure can build the basis for standardized manufacturing of MSC-based therapeutics under animal serum-free conditions for dose-escalated cellular therapy and tissue engineering.

Blood donor screening for parvovirus B19 in Germany and Austria

BACKGROUND: Although the main transmission pathway of parvovirus B19 (B19) is typically via the respiratory route, several transfusion‐transmitted infections have been reported. To increase blood safety, all blood donations to our blood donor service have been screened by a B19 minipool real‐time nucleic acid testing (NAT) since April 2000. Additional customers have been screened since the summer of 2003.

Adverse events and safety issues in blood donation—A comprehensive review

Although blood donation is generally safe, a variety of risks and complications exist, the most common being iron deficiency, vasovagal reactions and citrate-related events. In the last decades, extensive efforts have significantly improved recipient and product safety, but there is still great potential to optimise donor care. Many therapies in modern medicine depend on the prompt availability of blood products, therefore it is crucial to maintain a motivated and healthy donor pool in view of a limited number of healthy volunteers willing and able to give blood or blood components. We present a comprehensive review on adverse events addressing all types of blood donation including whole blood, plasma, platelet, peripheral blood stem cell, leucocyte and bone marrow donation. In addition, we outline strategies for the prevention and treatment of these events and give a blueprint for future research in this field.

Tetragametic chimerism detected in a healthy woman with mixed-field agglutination reactions in ABO blood grouping

BACKGROUND: The case of a healthy woman with serologic blood group AB and her biologic father showing blood group O was investigated. Further analysis, including blood, buccal swabs, and nail clippings, revealed a tetragametic chimerism.

Blood group chimerism.

Purpose of reviewWith improved methods for detecting chimeras and growing numbers of stem cell transplantations, blood group and other forms of chimerism are observed with increasing frequency. This review will focus on the state of science and new insights into the multifaceted subject of blood group chimerism. Recent findingsRecognition that the immune system tolerates chimeric cells under certain conditions has led to efforts to elucidate related immune-modulating processes. The chimeric state following transplantation of hematopoietic stem cells, as well as after solid organ transplantation, is of special interest. Also, chimerism is considered to be a potential trigger for certain autoimmune diseases. Natural chimerism is more frequent than previously recognized. Using improved laboratory techniques, investigators can often trace chimeric tissues to their origin. New therapeutic strategies have been applied after stem cell transplantation depending on the chimeric state. Also, recent research has resulted in methods for determining chimerism in maternal peripheral blood that reflect fetal blood type and certain congenital diseases. SummaryThe subject of human chimerism has evolved from a curiosity of nature to an important field of research and, potentially, holds the key to advancing our understanding of the fundamental mechanisms of immune tolerance.

The particle gel immunoassay as a rapid test to rule out heparin-induced thrombocytopenia?

Heparin-induced thrombocytopenia (HIT) is a prothrombotic condition characterized by a platelet decrease of 50% or thrombosis with a temporal relationship of 1 to 2 weeks after the initiation of heparin. These surrogate markers are useful for the clinical assessment but are hardly applicable in multimorbid patients with clinical conditions that mimic HIT. Platelet activation assays (heparin-induced platelet activation [HIPA] and serotonin release assay) and platelet factor 4 (PF4)/polyanion enzyme-linked immunosorbent assay (ELISA) confirm HIT. HIPA and serotonin release assay are highly specific, but they are laborious and require selected donor platelets and extended experience. High titer immunoglobulin (Ig)G antibodies correlate with clinical HIT, but ELISA is also time-consuming. The alternative heparin/PF4-antigen particle gel immunoassay (PaGIA) is easy, provides results within 1 hour, and detects mainly IgG but also IgA/M antibodies. We evaluated the specificity and sensitivity of PaGIA in relation to HIPA and ELISA in 285 patients with an undetermined likelihood for HIT with the intention to validate it as a rapid assay to exclude HIT.

Identification of 14 new alleles at the fucosyltransferase 1, 2, and 3 loci in Styrian blood donors, Austria

BACKGROUND: Genes for fucosyltransferases 1 (FUT1:H), 2 (FUT2:Secretor), and 3 (FUT3:Lewis) encode enzymes crucial for ABH and Lewis blood group antigen synthesis. They are highly polymorphic and ethnically and geographically specific.

A novel ABO O allele caused by a large deletion covering two exons of the ABO gene identified in a Caucasian family showing discrepant ABO blood typing results.

The presence of ABO subgroup alleles and unusual O alleles often is associated with discrepant serologic findings in ABO blood group typing. In the ABO gene of a Caucasian female and her daughters who had aberrant ABO phenotypes, a novel ABO O allele characterized by a large deletion that included two exons was identified.