About

TruCulture

A Whole Blood Collection and Culture Tube for Standardized Functional Immunophenotyping Procedures

TruCulture tubes are designed to capture immune cell activity at the time and place of sample collection, thereby minimizing the bias and variability introduced by sample shipping and manipulation. These revolutionary tubes consist of an integrated whole-blood collection and leukocyte culture system that is reliable, simple to use and does not require specialized laboratory equipment. TruCulture enables researchers to reproducibly ascertain information about immune responses to stress or stimulation, including responses to novel therapeutics. The ex vivo TruCulture procedure preserves physiological cellular interactions to more accurately reflect the complexities of the human immune system, bringing added value to immune monitoring in clinical trials.

TruCulture Procedure

TruCulture tubes are pre-loaded with cell culture media and immune stimulant(s) or drug candidates. Blood is drawn directly into the TruCulture tube and incubated in a dry heat block. Supernatants are collected by simply inserting a valve separator to separate cells from the culture supernatant.

TruCulture Procedure, Collect

01. COLLECT

Draw 1 mL of blood directly into the TruCulture Tube and break off the plunger.

TruCulture Procedure, MIX

02. MIX

Gently invert tube to mix 3 to 5 times

TruCulture Procedure, Incubate

03. INCUBATE

Place tube in 37ºC heat block for up to 24 or 48 hours.

TruCulture Procedure, separate

04. SEPARATE

Manually insert valve to separate supernatant from the cells. Collect supernatant and cell layer for downstream analysis.

TruCulture Tube Components

Order TruCulture

Applications

TruCulture Applications

TruCulture has been utilized as a whole-blood stimulation system by researchers and drug developers in several fields to reliably measure immune response for the following applications.

  • Pharmacodynamics (including dose response)
  • Functional immune cell analysis
  • Disease characterization
  • Patient stratification
  • Genotype – to – Phenotype association studies
  • Vaccine Development
    • Antigen recall
    • Early safety studies
    • Profile the functional immune status of clinical trial participants

The use of TruCulture for vaccine development has been highlighted by two key examples:

  1. Safety and immunogenicity of SARS-CoV-2 recombinant protein vaccine formulations in healthy adults: interim results of a randomized, placebo-controlled, phase 1-2, dose-ranging study. (2021) Goepfert PA, et al. Lancet Infectious Disease. https://doi.org/10.1016/S1473-3099(21)00147-X

Supplementary Material including TruCulture details and figures, view here.

For the two-dose cohort, pre-vaccination and post-vaccination blood samples (D1, D22, D36) were collected into three types of TruCulture tubes:

1) Recombinant SARS-CoV-2 spike protein

2) Negative control (TruCulture media only)

3) Positive control (SEB + CD28)

Cytokines from supernatants were measured at Rules-Based Medicine. Production of Th1 associated cytokines (IFNg, IL-2 and TNFa) were elevated compared to Th2 associated cytokines (IL-4, IL-5, IL-13) on D22 and D36 whereas neutralizing antibodies were not significantly detected until D36. The AS03 adjuvant formulation generated stronger humoral and cell mediated immunity signals relative to the AF03 adjuvant. This study illustrates that TruCulture can be a vital tool for vaccine clinical trials to profile antigen specific T cell responses.

2. Flu Antigen Recall Responses using TruCulture with OptiMAP and SIMOA Analysis(2019) Hwang SA, et al.

The recall response of flu hemagglutinin (HA) antigens was examined in healthy adults vaccinated with the 2018-2019 annual flu vaccine. The TruCulture tubes used were:

  1. Null (TruCulture media only)
  2. Staphylococcal enterotoxin B (SEB)
  3. Null tubes spiked with 1.25mg each of 4 different recombinant HA proteins.

All samples were incubated for 48 hours at 37oC. Supernatant were collected and analyzed using the OptiMAP panel. No inflammatory cytokines were detected in the null tubes from either the baseline or 2 weeks post-vaccination samples. There were no differences in cytokine production in the SEB stimulated samples between the baseline and 2 weeks post-flu vaccination timelines. For flu HA stimulated samples, there was a significant increase in production of GM-CSF, IFN-­, IL-1‑, IL-6, IL-12p70, IL-23, and TNF-a at 2 weeks post-flu vaccination compared to samples collected at baseline. Additionally, flu HA stimulated samples post vaccination also demonstrated increased production of type I inteferons, as analyzed by SIMOA. These data demonstrate that TruCulture in conjunction with OptiMAP and SIMOA are useful tools for investigating antigen specific responses.

In another pertinent example:

Our partners at, The Institut Pasteur, demonstrated the indispensable benefits of TruCulture in The Milieu Intérieur (“Environment Within”) project. Briefly, the Milieu Intérieur project is working to establish the determinants of a healthy immune response by identifying the genetic, epigenetic and environmental factors that contribute to the observed heterogeneity of immune responses. The challenge of the project is to establish the boundaries of a healthy immune response, and to that end, the Milieu Intérieur Project recruited 1,000 healthy individuals stratified across age (five-decades of life from age 20 – 69), and gender (1:1 gender ratio). TruCulture tubes were an integral part of the Milieu Intérieur clinical study, used as a standardized method for monitoring human response to immune stimulation.

To define the boundaries of a healthy immune response, The Milieu Intérieur project combined the use of TruCulture whole blood culture system with the use of stimuli to define the protein signatures induced by (i) medically relevant bacteria, fungi and viruses; (ii) agonists specific for defined host sensors; (iii) clinically employed cytokines; and (iv) activators of T cell immunity.

Visit The Milieu Intérieur website for more information on the project, publications, protocols, and data exploration.

View an Overview of The Milieu Intérieur Project:

Advantages

Advantages of TruCulture

  • Integrated closed sterile instant whole blood collection and culture system.
  • Standardized to ensure consistent performance across multiple users and clinical sites.
  • Reliable, easy to use, and reproducible – eliminates the need for cell manipulation.
  • Retains all blood components, granulocytes, platelets, red blood cells, soluble factors and Fc receptor expressing cells.
  • Only inexpensive heat block needed, no lab equipment nor centrifugation steps.
  • Has been successfully deployed in hundreds of clinical drug trials.

Disadvantages of Traditional PBMC

  • Separate blood collection and specialized cell culture procedures.
  • Extensive manipulation, processing, and often freezing/shipping prior to culturing.
  • Requires technical expertise with increased variability across users and clinical sites.
  • Requires CO2 incubator, biosafety cabinet, centrifuge, media, and cell culture plastics.
  • Culture procedures/conditions are difficult to standardize for clinical trial applications.
  • Open, less sterile, artificial system.
  • Poor reproducibility.

Traditional pharmacodynamic whole blood experiments are generally short in duration (2-6 hrs) as a consequence of poor culture conditions leading to premature termination of the normal physiological immune response. A longer more robust response usually provides higher sensitivity and greater relevance than short incubation times that may only lead to the release of stored pre-synthesized mediators.

Publications

View Peer-Reviewed Publications Citing TruCulture

Bibliography

TruCulture

2021

Sex-specific differences in peripheral blood leukocyte transcriptional response to LPS are enriched for HLA region and X chromosome genes (2021) Stein MM, Conery M, Magnaye KM, Clay SM, Billstrand C, Nicolae R, Naughton K, Ober C, Thompson EE Scientific Reports
 
Therapy Indications
TruCulture
 
First-in-human study of the safety, tolerability, pharmacokinetics and pharmacodynamics of ALPN-101, a dual CD28/ICOS antagonist, in healthy adult subjects (2021) Yang J, Lickliter JD, Hilson JL, Means GD, Sanderson RJ, Carley K, Tercero A, Manjarrez KL, Wiley JR, Peng SL Clinical and Translational Science
Novel approaches to develop biomarkers predicting treatment responses to TNF-blockers (2021) Mezghiche I, Yahia-Cherbal H, Rogge L, Bianchi E Expert Review of Clinical Immunology
Machine learning-based single cell and integrative analysis reveals that baseline mDC predisposition predicts protective Hepatitis B vaccine response (2021) Aevermann B, Shannon CP, Novotny M, Ben-Othman R, Cai B, Zhang Y, Ye JC, Kobor MS, Gladish N, Lee A, Blimke TM, Hancock RE, Llibre A, Duffy D, Koff WC, Sadarangani M, Tebbutt SJ, Kollmann TR, Scheuermann RH medRxiv
Novel signatures associated with systemic lupus erythematosus clinical response to IFN-a/-? inhibition (2021) Seridi L, Cesaroni M, Orillion A, Schreiter J, Chevrier M, Marciniak S, Migone TS, Stohl W, Chatham WW, Furie RA, Benson J, Jordan J Lupus
Primary human dendritic cells and whole-blood based assays to evaluate immuno-modulatory properties of heat-killed commensal bacteria (2021) Norton JE Jr., Kommineni S, Akrivoulis P, Gutierrez DA, Hazuda DJ, Swaminathan G Vaccines
Differential response induced by LPS and MPLA in immunocompetent and septic individuals (2021) Vega CA, Karakike E, Bartolo F, Mouton W, Cerrato E, Brengel-Pesce K, Giamarellos-Bourboulis EJ, Mallet F, Trouillet-Assant S Clinical Immunology
Characterization of the pathophysiological determinants of diarrheagenic Escherichia coli infection using a challenge model in healthy adults (2021) van Hoffen E, Mercenier A, Vidal K, Benyacoub J, Schloesser J, Kardinaal A, Lucas-van de Bos E, van Alen I, Rogero I, Duintjer K, Berendts A, Albers R, Kleerebezem M, Bruggencate ST Scientific Reports
Functional immune reconstitution early after allogeneic hematopoietic cell transplantation: A comparison of pre- and post-transplantation cytokine responses in stimulated whole-blood (2021) Gjaerde LK, Brooks PT, Andersen NS, Friss LS, Kornblit B, Petersen SL, Schjodt I, Nielsen SD, Ostrowski SR, Sengelov H Scandinavaian Journal of Immunology
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2020

Association of occupational exposures with ex vivo functional immune response in workers handling carbon nanotubes and nanofibers (2020) Schubauer-Berigan MK, Dahm MM, Toennis CA, Sammons DL, Eye T, Kodali V, Zeidler-Erdely PC, Erdely A Nanotoxicology
Application of the TruCulture® whole blood stimulation system for immune response profiling in cattle (2020) O'Brien MB, McLoughlin RM, Meade KG Veterinary Immunology and Immunopathology
Characterisation of the pharmacodynamic effects of the P2X7 receptor antagonist JNJ-54175446 using an oral dexamphetamine challenge model in healthy males in a randomised, double-blind, placebo-controlled, multiple ascending dose trial. (2020) Recourt K, van der Aart J, Jacobs G, de Kam M, Drevets W, van Nueten L, Kanhal K, Siebenga P, Zuiker R, Ravenstijn P, Timmers M, van Gerven J, de Boer P Journal of Psychopharmacology
 
Therapy Indications
TruCulture
Neurological Disease
 
Systematic investigation of polyurethane biomaterial surface roughness on human immune responses in vitro (2020) Segan S, Jakobi M, Khokhani P, Klimosch S, Billing F, Schneider M, Martin D, Metzger U, Biesemeier A, Xiong X, Mukherjee A, Steuer H BioMed Research International
 
Therapy Indications
TruCulture
Inflammation and Immune Response
Miscellaneous
 
Innate Immune Stimulation of Whole Blood Reveals IFN-1 Hyper-Responsiveness in Type 1 Diabetes (2020) Rodrigues KB, Dufort MJ, Llibre A, Speake C, Jubayer Rahman M, Bondet V, Quiel J, Linsley PS, Greenbaum CJ, Duffy D, Tarbell KV Diabetologia
Systemic juvenile idiopathic arthritis and recurrent macrophage activation syndrome due to a CASP1 variant causing inflammasome hyperactivation (2020) Jorgensen SE, Christiansen M, Host C, Glerup M, Mahler B, Lausten MM, Gad HH, Hartmann R, Herlin T, Mogensen TH Rheumatology
Comparison of host immune responses to LPS in human using an immune profiling panel, in vivo endotaxemia versus ex vivo stimulation (2020) Tawfik DM, Lankelma JM, Vachot L, Cerrato E, Pachot A, Wiersinga WJ, Textoris J Scientific Reports
Towards standardization of immune functional assays (2020) Mouton W, Albert-Vega C, Boccard M, Bartolo F, Oriol G, Lopez J, Pachot A, Textoris J, Mallet F, Brengel-Pesce K, Trouillet-Assant S Clinical Immunology
Results of the phase I open label clinical trial SAKK 06/14 assessing safety of intravesical instillation of VPM1002BC, a recombinant mycobacterium bacillus calmette guerin (BCG), in patients with non-muscle invasive bladder cancer and previous failure of conventional BCG therapy (2020) Rentsch CA, Bosshard P, Mayor G, Rieken M, Puschel H, Wirth G, Cathomas R, Parzmair GP, Grode L, Eisele B, Sharma H, Gupta M, Gairola S, Shaligram U, Goldenberger D, Spertini F, Audran R, Enoui M, Beradi S, Hayoz S, Wicki A Oncoimmunology
 
Therapy Indications
TruCulture
Cancer
 
Impact of carbohydrate-reduced nutrition in septic patients on ICU: study protocol for a prospective randomised controlled trial (2020) Rahmel T, Hubner M, Koos B, Wolf A, Willemsen KM, Straub G, Effinger D, Adamzik M, Kreth S BMJ Open
Preoperative TruCulture whole blood cytokine response predicts postoperative inflammation in pancreaticoduodenectomy patients - a pilot cohort study (2020) Aasvang EK, Pitter S, Hansen CP, Storkholm JH, Krohn PS, Burgdorf SK, Von Stemann JH, Lundgren JD, Nielsen SD, Kehlet H, Ostrowski SR Scandinavian Journal of Immunology
Safety and efficacy of neurostimulation with a miniaturised vagus nerve stimulation device in patients with multidrug-refractory rheumatoid arthritis: a two-stage multicentre, randomised pilot study (2020) Genovese MC, Gaylis NB, Sikes D, Kivitz A, Horowitz DL, Peterfy C, Glass EV, Levine YA, Chernoff D The Lancet Rheumatology
Preclinical investigations and a first-in-human phase I trial of M4112, the first dual inhibitor of indoleamine 2,3-dioxygenase 1 and tryptophan 2,30dioxygenase 2, in patients with advanced solid tumors (2020) Naing A, Eder JP, Piha-Paul SA, Gimmi C, Hussey E, Zhang S, Hildebrand V, Hosagrahara V, Habermehl C, Moisan J, Papadopoulos KP Journal for ImmunoTherapy of Cancer
 
Therapy Indications
TruCulture
Cancer
Immuno-oncology
 
First-in-human, single- and multiple-ascending dose studies in healthy subjects to assess pharmacokinetics, pharmacodynamics, and safety/tolerability of iberdomide, a novel cereblon E3 ligase modulator (2020) Ye Y, Gaudy A, Schafer P, Thomas M, Weiss D, Chen N, Liu L, Xue Y, Carayannopoulos L, Palmisano M Clinical Pharmacology in Drug Development
Deciphering heterogeneity of septic shock patients using immune functional assays: a proof of concept study (2020) Albert Vega C, Oriol G, Bartolo F, Lopez J, Pachot A, Rimmele T, Venet F, Leray V, Monneret G, Delwarde B, Brengel-Pesce K, Textoris J, Mallet F, Trouillet-Assant S Scientific Reports
Immune profiling enables stratification of patients with active TB disease or M. tuberculosis infection (2020) Duffy D, Nemes E, Llibre A, Rouilly V, Musvosvi M, Smith N, Filander E, Africa H, Mabwe S, Jaxa L, Charbit B, Mulenga H, the Milieu Interieur Consortium, Tameris M, Walzl G, Malherbe S, Thomas S, Hatherill M, Bilek N, Scriba TJ, Albert ML Clinical Infectious Diseases
 
Therapy Indications
TruCulture
 
Transcutaneous auricular vagus nerve stimulation reduces pain and fatigue in patients with systemic lupus erythematosus: a randomised, double-blind, sham-controlled pilot trial (2020) Aranow C, Atish-Fregoso Y, Lesser M, Mackay M, Anderson E, Chavan S, Zanos TP, Datta-Chaundhuri T, Bouton C, Tracey KJ, Diamond B Annals of the rheumatic diseases
Immune response profiling of patients with spondyloarthritis reveals signalling networks mediating TNF-blocker function in vivo (2020) Menegatti S, Guillemot V, Latis E, Yahia-Cherbal H, Mittermuller D, Rouilly V, Mascia E, Rosine N, Koturan S, Millot G, Leloup C, Duffy D, Gleizes A, Hacein-Bey-Abina S, Milieu interieur Consortium, Sellam J, Berenbaum F, Miceli C, Dougados M, Bianchi E, Rogge L Ann Rheum Dis
Characterization of LY2775240, a selective phosphodiesterase-4 inhibitor, in nonclinical models and in healthy subjects (2020) Patel DR, Urva S, Ho S, Buckman CJ, Ma Y, Lim J, Sissons SE, Zuniga MS, Philips D, Cox K, Dairaghi D Clinical and Translational Science
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2019

VaccHemInf Project: protocol for a prospective cohort study of efficacy, safety and characterisation of immune functional response to vaccinations in haematopoietic stem cell transplant recipients (2019) Conrad A, Boccard M, Valour F, Alcazer V, Tovar Sanchez AT, Chidiac C, Laurent F, Vanhems P, Salles G, Brengel-Pesce K, Meunier B, Trouillet-Assant S, Ader F, Lyyon HEMINF Study Group BMJ Journals
Social history and exposure to pathogen signals modulate social status effects on gene regulation in rhesus macaques (2019) Sanz J, Maurizio PL, Snyder-Mackler N, Simons ND, Voyles T, Kohn J, Michopoulos V, Wilson M, Tung J, Barreiro LB bioRxiv
Early changes in immune, coagulation, and organ function after clinical and experimental polytrauma (2019) Halbgbauer Repositorium der Universität Ulm
Exploring and redefining Autoimmune polyendocrine syndrome type 1 (2019) Bruserud Skipnes Kommunikasjon, University of Bergen
Synovial fluid biomarkers associated with osteoarthritis severity reflect macrophage and neutrophil related inflammation. (2019) Haraden CA, Huebner JL, Hsueh MF, Li YJ, Kraus VB Arthritis Research & Therapy
Immune function as predictor of infectious complications and clinical outcome in patients undergoing solid organ transplantation (the ImmuneMo:SOT study): a prospective non-interventional observational trial. (2019) Drabe CH, Sorensen SS, Rasmussen A, Perch M, Gustafsson F, Rezahosseini O, Lundgren JD, Osrowski SR, Nielson SD BMC Infectious Diseases
T cell phenotypes are associated with serum IgE levels in Amish and Hutterite children (2019) Hrusch CL, Stein MM, Gozdz J, Holbreich M, Von Mutius E, Vercelli D, Ober C, Sperling AI Journal of Allergy and Clinical Immunology
Type I Interferon Predicts an Alternate Immune System Phenotype in Systemic Lupus Erythematosus (2019) Thanarajasingam U, Muppirala AN, Jensen MA, Ghodke-Puranik Y, Dorschner JM, Vsetecka DM, Amin S, Makol A, Ernste F, Osborn T, Moder K, Chowdhary V, Niewold TB ACR Open Rheumatology
 
Therapy Indications
TruCulture
 
Functional immune monitoring in severely injured patients - a pilot study. (2019) Halbgebauer R, Kllermann S, Schafer F, Weckbach S, Weiss M, Barth E, Bracht H, Kalbitz M, Gebhard F, Huber-Lang MS, Perl M Scandinavian Journal of Immunology
Autoinflammatory disease with corneal and mucosal dyskeratosis caused by a novel NLRP1 variant (2019) Herlin T, Jorgensen SE, Host C, Mitchell PS, Christensen MH, Lausten M, Larsen DA, Schmidt FI, Christiansen M, Mogensen TH Rheumatology
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2018

A decade of research on the 17q12-21 asthma locus: Piecing together the puzzle (2018) Stein MM, Thempson EE, Schoettler N, Helling BA, Magnaye KM, Stanhope C, Igartua C, Morin A, Washinton C, Nicolae D, Bonnelykke K, Ober C J Allergy Clin Immunol 2018
 
Therapy Indications
TruCulture
Pulmonary
 
IL-17 blockade with secukinumab in peripheral spondyloarthritis impacts synovial immunopathology without compromising systemic immune responses (2018) van Mens LJJ, van de Sande MGH, Menegatti S, Chen S, Blijdorp ICP, de Jong HM, Fluri IA, Latuhihin TE, van Kuijk AWR, Rogge L, Yeremenko NG, Baeten DLP Arthritis Rheumatol
Cereblon modulator iberdomide induces degradation of the transcription factor Ikaros and Aiolos: immunomodulation in healthy volunteers and relevance to systemic lupus erythematosus (2018) Schafer PH, Ye Y, Wu L, Kosek J, Ringheim G, Yang Z, Liu L, Thomas M, Palmisano M, Chopra R Ann Rheum Dis
Standardized Immunomonitoring: Separating the Signals from the Noise (2018) Duffy D Trends in Biotechnology
 
Therapy Indications
Immuno-oncology
TruCulture
Miscellaneous
 
Effects of an FcyRIIA polymorphism on leukocyte gene expression and cytokine responses to anti-CD3 and anti-CD28 antibodies (2018) Stein MM, Hrusch CL, Sperling AI, Ober C Genes and Immunity
Identifying the etiology and pathophysiology underlying stunting and environmental enteropathy: study protocol of the AFRIBIOTA project (2018) Vonaesch P, Randremanana R, Gody JC, Collard JM, Giles-Vernick T, Doria M, Vigan-Womas I, Rubbo PA, Etienne A, Andriatahirintsoa EJ, Kapel N, Brown E, Huus KE, Duffy D, Finlay BB, Hasan M, Hunald FA, Robinson A, Manirakiza A, Wegener-Parfrey L, Vray M, Sansonetti PJ BMC Pediatrics
Parent of origin gene expression in a founder population identifies two new candidate imprinted genes at known imprinted regions (2018) Mozaffari SV, Stein MM, Magnaye KM, Nicolae DL, Ober C PLoS One
 
Therapy Indications
TruCulture
 
Clinical pharmacokinetics, pharmacodynamics, safety, and tolerability of JNJ-54175446, a brain permeable P2X7 antagonist, in a randomised single-ascending dose study in healthy participants (2018) Timmers M, Ravenstijn P, Xi L, Triana-Baltzer G, Furey M, Van Hemelryck S, Biewenga J, Ceusters M, Bhattacharya A, van den Boer M, van Nueten L, de Boer P Journal of Psychopharmacology
 
Therapy Indications
TruCulture
Neurological Disease
 
Dominace rank-associated gene expression is widespread, sex-specific, and a precursor to high social status in wild male baboons (2018) Lea AJ, Akinyi MY, Nyakundi R, Mareri P, Kariuki T, Alberts SC, Archie EA, Tung J PNAS
 
Therapy Indications
TruCulture
 
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2017

Effects of Traumeel (Tr14) on recovery and inflammatory immune response after repeated bouts of exercise: a double-blind RCT. (2017) Muders K, Pilat C, Deuster V, Frech T, Krüger K, Pons-Kuhnemann J, Mooren FC Eur J Appl Physiol.
Dietary Buglossoides Arvensis Oil Increases Circulating n-3 Ployunsaturated Fatty Acids in a Dose Dependent Manner and Enhances Lipopolysaccharide-Stimulated Whole Blood Interleukin-10-A Randomized Placebo-Controlled Trial. (2017) Lefort N, LeBlanc R, Surette M Nutrients
 
Therapy Indications
Cytokines/Chemokine
TruCulture
 
Impact of Maternal antibodies and infant gut microbiota on the immunogenicity of rotacirus vaccines in African, Indian, and European infants: protocol for a prospective cohort study. (2017) Sindhu KN, Cunliffe N, Peak M, Turner M, Darby A, Grassly N, Gordon M, Dube Q, Babji S, Praharaj I, Verghese V, Iturriza-Gomara M, Kang G BMJ
Standardized whole blood stimulation improves immunomonitoring of induced immune responses in multi-center study (2017) Duffy D, Rouilly V, Braudeau C, Corbière V, Djebali R, Ungeheuer MN, Josien R, LaBrie ST, Lantz O, Louis D, Martinez-Caceres E, Mascart F, Ruiz de Morales JG, Ottone C, Redjah L, Guen N, Savenay A, Schmolz M, Toubert A, Albert ML Clin Immunol
Altered Immune Activation and IL-23 Signaling in Response to Candida albicans in Autoimmune Polyendocrine Syndrome Type 1 (2017) Bruserud O, Bratland E, Hellesen A, Delaleu N, Reikvam H, Oftedal BE, and Wolff A Front Immunol.
Immunodepression after CPB: Cytokine dynamics and clinics after pediatric cardiac surgery – A prospective trial (2017) Justus G, Walker C, Rosenthal LM, Berger F, Miera O, Schmitt KR Cytokine
Identifying baseline immune-related biomarkers to predict clinical outcome of immunotherapy (2017) Gnjatic S, Bronte V, Brunet LR, Butler MO, Disis ML, Galon J, Hakansson LG, Hanks BA, Karanikas V, Khleif SN, Kirkwood JM, Miller LD, Schendel DJ, Tanneau I, Wigginton JM and Butterfield LH J Immunother Cancer
 
Therapy Indications
Cancer
Immuno-oncology
TruCulture
 
The REAnimation Low Immune Status Markers (REALISM) project: a protocol for broad characterisation and follow-up of injury-induced immunosuppression in intensive care unit (ICU) critically ill patients (2017) Rol ML, Venet F, Rimmele T, Moucadel V, Cortez P, Quemeneur L, Gardiner D, Griffiths A, Pachot A, Textoris J, Monneret G, On behalf of the REALISM study group BMJ Open
Effect of DHA supplementation on oxylipin levels in plasma and immune cell stimulated blood. (2017) Schuchardt JP, Ostermann AI, Stork L, Fritzsch S, Kohrs H, Greupner T, Hahn A, Schebb NH Prostaglandins Leukot Essent Fatty Acids
Randomized clinical study of safety, pharmacokinetics, andpharmacodynamics of RIPK1 inhibitor GSK2982772 in healthyvolunteers (2017) Weisel K, Scott NE, Tompson DJ, Votta BJ, Madhavan S, Povey K, Wolstenholme A, Simeoni M, Rudo T, Richards-Peterson L, Sahota T, Wang JE, Lich J, Finger J, Verticelli A, Reilly M, Gough PJ, Harris PA, Bertin J, Wang M Pharmacol Res Perspect.
Distinctive roles of age, sex, and genetics in shaping transcriptional variation of human immune responses to microbial challenges. (2017) Piasecka B, Duffy D, Urrutia A, Quach H, Patin E, Posseme C, Bergstedt J, Charbit B, Rouilly V, MacPherson CR, Hasan M, Albaud B, Gentien D, Fellay J, Albert ML, Quintana-Murci L, Milieu Intérieur Consortium Proc Natl Acad Sci U S A
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2016

Coordinated Activation of Toll-Like Receptor8 (TLR8) and NLRP3 by the TLR8 Agonist, VTX-2337, Ignites Tumoricidal Natural Killer Cell Activity (2016) Dietsch GN, Lu H, Yang Y, Morishima C, Chow LQ, Disis ML, Hershberg RM PLoS ONE
 
Therapy Indications
Cancer
TruCulture
 
Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children (2016) Stein MM, Hrusch CL, Gozdz J, Igartua C, Pivniouk V, Murray SE, Ledford JG, Marques Dos Santos M, Anderson RL, Metwali N, Neilson JW, Maier RM, Gilbert JA, Holbreich M, Thorne PS, Martinez FD, Von Mutius E, Vercelli D, Ober C, Sperling AI New England Journal of Medicine
Biological stress systems, adverse life events and the improvement of chronic multi-site musculoskeletal pain across a 6-year follow-up. (2016) Generaal E, Vogelzangs N, Macfarlane GJ, Geenen R, Smit JH, de Geus EJ, Dekker J, Penninx BW. J Pain
 
Therapy Indications
TruCulture
 
Social status alters immune regulation and response to infection in macaques (2016) Snyder-Mackler N, Sanz J, Kohn JN, Brinkworth JF, Morrow S, Shaver AO, Grenier JC, Pique-Regi R, Johnson ZP, Wilson ME, Barreiro LB, Tung J Science
Exercise-induced cytokine changes in antigen stimulated whole-blood cultures compared to serum (2016) Pilat C, Krüger K, Frech T, Mooren FC J Immunol Methods.
Vagus Nerve Stimulation Inhibits Cytokine Production and Attenuates Disease Severity in Rheumatoid Arthritis (2016) Koopman FA, Chavan SS, Miljko S, Grazio S, Sokolovic S, Schuurman PR, Mehta AD, Levine YA, Faltys M, Zitnik R, Tracey KJ, Tak PP PNAS
Effects of Traumeel (Tr14) on Exercise-Induced Muscle Damage Response in Healthy Subjects: A Double-Blind RCT (2016) Muders K, Pilat C, Deuster V, Frech T, Kruger K, Pons-Kuhnemann J, Mooren F-C Mediators of Inflammation
Standardized Whole-Blood Transcriptional Profiling Enables the Deconvolution of Complex Induced Immune Responses (2016) Urrutia A, Duffy D, Rouilly V, Posseme C, Djebali R, Illanes G, Libri V, Albaud B, Gentien D, Piasecka B, Hasan M, Fontes M, Quintana-Murci L, Albert Matthew l, Abel L, Alcover A, Astrom K, Bousso P, Bruhns P, Cumano A, Demangel C, Deriano L, Di santo J, Dromer F, Eberl G, Enninga J, Fellay J, Freitas A, Gelpi O, Gomperts-Boneca I, Hercberg S, Lantz O, Leclerc C, Mouquet H, Pellegrini S, Pol S, Rogge L, Sakuntabhai A, Schwartz O, Schwikowski B, Shorte S, Soumelis V, Tangy F, Tartour E, Toubert A, Ungeheuer M-N, Quintana-Murci L, Albert Matthew Cell Reports
 
Therapy Indications
TruCulture
 
Noninvasive Transcutaneous Vagus Nerve Stimulation Decreases Whole Blood Culture-Derived Cytokines and Chemokines: A Randomized, Blinded, Healthy Control Pilot Trial (2016) Lerman I, Hauger R, Sorkin L, Proudfoot J, Davis B, Huang A, Lam K, Simon B, Baker DG Neuromodulation: Technology at the Neural Interface
Immune Monitoring Technology Primer: Immunoprofiling of Antigen-Stimulated Blood (2016) Brunet LR, LaBrie S, Hagemann T Journal for Immunotherapy of Cancer
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2015

Immune cell profiling to guide therapeutic decisions in rheumatic diseases. (2015) Ermann J, Rao DA, Teslovich NC, Brenner MB, Raychaudhuri S. Nat Rev Rheumatol. 2015 Jun 2. doi: 10.1038/nrrheum.2015.71. [Epub ahead of print]
Cd4+ T-Cell Profiles and Peripheral Blood Ex-Vivo Responses to T-Cell Directed Stimulation Delineate Copd Phenotypes (2015) Roberts MEPH, Brandon W.; Brohawn, Philip; Pilataxi, Fernanda; Guo, Xiang; Kuziora, Michael; Bowler, Russell P.; White, Wendy I. Chronic Obstructive Pulmonary Diseases
 
Therapy Indications
TruCulture
 
The Milieu Intérieur Study — an Integrative Approach for Study of Human Immunological Variance (2015) Thomas S, Rouilly V, Patin E, Alanio C, Dubois A, Delval C, Marquier L-G, Fauchoux N, Sayegrih S, Vray M, Duffy D, Quintana-Murci L, Albert ML, Abel L, Alcover A, Bousso P, Bruhns P, Cumano A, Daëron M, Delval C, Demangel C, Deriano L, Di Santo J, Dromer F, Eberl G, Enninga J, Freitas A, Gelpi O, Gomperts-Boneca I, Hercberg S, Lantz O, Leclerc C, Mouquet H, Pellegrini S, Pol S, Rogge L, Sakuntabhai A, Schwartz O, Schwikowski B, Shorte S, Soumelis V, Tangy F, Tartour E, Toubert A, Ungeheuer M-N, Quintana-Murci L, Albert ML Clinical Immunology
Identification of circulatory biomarkers from clinical trial samples (2015) Brunet LR, Bodman-Smith K, Bodman-Smith M, Kassam Z, Dalgleish A, LaBrie S and Hagemann T J Immunother Cancer
Late Stage Cancer Patients Remain Highly Responsive to Immune Activation by the Selective TLR8 Agonist Motolimod (VTX-2337) (2015) Dietsch GN, Randall TD, Gottardo R, Northfelt DW, Ramanathan RK, Cohen PA, Manjarrez KL, Newkirk M, Bryan JK, Hershberg RM Clinical Cancer Research
Specificity of human anti-variable heavy (VH) chain autoantibodies and impact on the design and clinical testing of a VH domain antibody antagonist of TNF-a receptor 1 (2015) Cordy JC, Morley PJ, Wright TJ, Birchler MA, Lewis AP, Emmins R, Chen YZ, Powley WM, Bareille PJ, Wilson R, Tonkyn J, Bayliffe AI, Lazaar AL. Clin Exp Immunol.
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2014

Oxidative stress and reduced responsiveness of challenged circulating leukocytes following pulmonary instillation of metal-rich particulate matter in rats. (2014) Erdely A, Antonini JM, Young SH, Kashon ML, Gu JK, Hulderman T, Salmen R, Meighan T, Roberts JR, Zeidler-Erdely PC. Part Fibre Toxicol. 2014 Aug 15;11:34. doi: 10.1186/s12989-014-0034-8.
 
Therapy Indications
TruCulture
 
Exploring effects of a natural combination medicine on exercise-induced inflammatory immune response: A double-blind RCT (2014) Pilat C, Frech T, Wagner A, Krüger K, Hillebrecht A, Pons-Kühnemann J, Scheibelhut C, Bödeker RH, Mooren FC Scand J Med Sci Sports. 2014 Jun 12
Functional Analysis via Standardized Whole-Blood Stimulation Systems Defines the Boundaries of a Healthy Immune Response to Complex Stimuli (2014) Duffy D, Rouilly V, Libri V, Hasan M, Beitz B, David M, Urrutia A, Bisiaux A, LaBrie ST, Dubois A, Boneca IG, Delval C, Thomas S, Rogge L, Schmolz M, Quintana-Murci L, Albert ML Immunity Volume 40, Issue 3, 20 March 2014, Pages 436–450
Immunomodulatory Activities of a Concentrated Fruit and Vegetable Juice Tested in a Randomized, Placebo-Controlled, Double-Blind Clinical Trial in Healthy Volunteers (2014) Schmolz M, März RW, Schaudt M, Schaudt C, Lauster C Food and Nutrition Sciences, Vol. 5 No. 4, 2014, pp. 341-350
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2013

Placebo-Controlled Randomized Clinical Trial on the Immunomodulating Activities of Low- and High-Dose Bromelain after Oral Administration – New Evidence on the Antiinflammatory Mode of Action of Bromelain (2013) Müller S, März R, Schmolz M, Drewelow B, Eschmann K, Meiser P Phytotherapy Research
Identification of a molecular profile associated with immune status in first onset schizophrenia patients (2013) Herberth M, Rahmoune H, Schwarz E, Koethe D, Harris LW, Kranaster L, Witt SH, Spain M, Barnes A, Schmolz M, Leweke MF, Guest PC, Bahn S Clin Schizophr Relat Psychoses
Autoantibodies to Variable Heavy (VH) Chain Ig Sequences in Humans Impact the Safety and Clinical Pharmacology of a VH Domain Antibody Antagonist of TNF-a Receptor 1 (2013) Holland MC, Wurthner JU, Morley PJ, Birchler MA, Lambert J, Albayaty M, Serone AP, Wilson R, Chen Y, Forrest RM, Cordy JC, Lipson DA, Bayliffe AI Journal of Clinical Immunology, July 2013
 
Therapy Indications
Cytokines/Chemokine
TruCulture
 
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2012

Intraindividual long term stability and response corridors of cytokines in healthy volunteers detected by a standardized whole-blood culture system for bed-side application (2012) Mueller SC, März R, Schmolz M, Drewelow B BMC Med Res Methodol. 2012 Aug 1;12(1):112
 
Therapy Indications
Cytokines/Chemokine
TruCulture
 
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2011

Effects of Echinaforce® treatment on ex vivo-stimulated blood cells (2011) Ritchie MR, Gertsch J, Klein P, Schoop R Phytomedicine. 2011 Jul 15;18(10):826-31
Discrimination of agonist and antagonist forms of CXCL10 in biologic samples (2011) Casrouge A, Bisiaux A, Stephen L, Schmolz M, Mapes J, Pfister C, Pol S, Mallet V, Albert ML Clin Exp Immunol. 2012 Jan;167(1):137-48
Phagocytosis and digestion of pH-sensitive fluorescent dye (Eos-FP) transfected E. coli in whole blood assays from patients with severe sepsis and septic shock (2011) Schreiner L, Huber-Lang M, Weiss ME, Hohmann H, Schmolz M, Schneider EM J Cell Commun Signal. 2011 Jun;5(2):135-44
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2010

Synthetic Ligands Against TLR2-9 in TruCulture - whole blood assays distinguish clinical stages of SIRS (trauma) and sepsis (2010) Bindja J, Weiss ME, Schmolz M, Stein GM, Mapes J, Schneiderhan-Marra N, Joos TO, Schneider EM TSIS Mar 9-13th
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2008

"Host Tissue Damage" Signal ATP Impairs IL-12 and IFNgamma Secretion in LPS Stimulated Whole Human Blood. (2008) Nalos M, Huang S, Sluyter R, Khan A, Santner-Nanan B, Nanan R, McLean AS Intensive Care Med 34: 1891-1897.
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2004

Validation of a new highly standardised, lab-independent whole-blood leukocyte function assay for clinical trials (ILCS). (2004) Schmolz M, Hurst TL, Bailey DM, Powell JR, Forsey RJ, Thompson JM, Williams C, Pawelec G Exp Gerontol 39: 667-671.
 
Therapy Indications
Miscellaneous
TruCulture
 

Case Studies

Milieu Intérieur: Personalized Immune Response Monitoring

“We hope to advance the promise of personalized medicine with functional biomarkers.”
Dr. Matthew Albert, Director of the Department of Immunology; Co-Director and Founder of the Center for Human Immunology at Institut Pasteur; Adjunct Faculty at Cochin Hospital

Applications of TruCulture in Chronic infection

“What makes our project unique is our ability to induce standardized immune responses…possible because of the reproducibility of the TruCulture system.”
Dr. Darragh Duffy, Laboratory of Dendritic Cell Biology, Department of Immunology, Institut Pasteur

Statistical Analysis and Mathematical Modeling of Data Derived from TruCulture

“[Using TruCulture] we get high quality data with very little variation.”
Pr. Magnus Fontes, Director of the International Group for Data Analysis, Institut Pasteur

Stimulants

Stimulants

Part # Description Type
782-001411 SARS-CoV-2 Spike Protein (2019 nCoV) Spike Protein
TBD SARS-CoV-2 Spike Protein (Delta variant) Spike Protein
782-001086 Null TruCulture Tubes (no stimulant) Control
782-001291 NegCo Control
782-001219 TNF-alpha (TNFa 10ng/ml) Cytokine
782-001277 Interferon beta (TC Tubes IFN-beta) Cytokine
782-001278 Interleukin-1beta + tumor necrosis factor-alpha (IL-1b+TNFa) Cytokine
782-001272 Adenosine Triphosphate + Lipopolysaccharide, high concentration (ATP+LPS-EB) NLRP3 Inflammasome / TLR4 Ligand
782-001273 Lauroyl-γ-D-glutamyl-meso-diaminopimelic acid (C12-iE-DAP) NOD Ligand
782-001125 CD3/CD28 TruCulture Tubes (CD3+CD28) T-Cell
782-001416 TStim TruCulture Tubes T-Cell
782-001202 CD3 TruCulture Tubes (CD3) T-Cell
782-001259 Zymosan TruCulture Tubes (ZYM) TLR2 Ligand
782-001274 Fibroblast-stimulating Lipopeptide (FSL-1) TLR2 Ligand
782-001282 Polyinosinic:polycytidylic acid (Poly I:C) TLR3 Ligand
782-001087 LPS TruCulture Tubes (LPS) TLR4 Ligand
782-001264 Resiquimod R848 (R848) TLR7/8 Ligand
782-001269 Gardiquimod (GDQ) TLR7/8 Ligand

If the stimulant you’d like to use in our TruCulture tubes is not listed, please fill out this form to request it. One of our experts will contact you to discuss the feasibility of your request. Thank you for your interest in TruCulture.

Analysis

RBM provides quantitative measurement of immune related proteins from TruCulture supernatants. Whether your specific application requires a broad range or a focused set of analytes, RBM’s panels are designed to meet your needs.

TruCulture® OptiMAP is an immunoassay testing panel validated and optimized to quantify the effect of TruCulture stimulations.  It is a cost-effective test comprised of 13 biomarkers that captures the diversity of responses to microbial, viral, and T cell stimulants.

OptiMAP Biomarkers

Click or mouse over biomarkers for more information. Analytes included in this MAP are subject to change.
Don't See Your Biomarker? Request It »
1. Epithelial-Derived Neutrophil-Activating Protein 782. Granulocyte-Macrophage Colony-Stimulating Factor
3. Interferon gamma4. Interleukin-1 beta
5. Interleukin-106. Interleukin-12 Subunit p70
7. Interleukin-138. Interleukin-17
9. Interleukin-210. Interleukin-23
11. Interleukin-612. Interleukin-8
13. Tumor Necrosis Factor alpha
MAP Volume Required
OptiMAP v. 1.0 TruCulture Supernatant 100 μL

OptiMAP Design

A total of 106 immune-related biomarkers were tested on TruCulture samples taken from healthy subjects. A careful selection of the key stimulants listed below were used to monitor a wide range of immune response pathways.  From the 106 candidate biomarkers, we selected a subset of 13 assays that were useful in distinguishing responses to individual stimuli while also revealing population variances.

Microbial stimulants: LPS, IL-1β, TNF-α, BCG, HK C. albicans, HK E. coli, HK S. aureus

Viral stimulants: Poly IC, R848, IFN- α/β

T cell stimulants:  SEB, anti-CD3/CD28

Principle component analysis of 25 normal subjects each tested with 12 TruCulture stimuli and responses monitored with either 106 protein biomarkers or an optimized panel of 13 protein biomarkers. Both analyses show a similar ability to segregate responses by the various stimuli, indicating the utility and efficiency of the OptiMAP panel.

 

For a more comprehensive understanding of functional immune cell activity, TruCulture supernatant can be tested on any of our Human MAP products. The tubes are also compatible with flow cytometry and gene expression analysis.

Multiplex immunoassay analysis of TruCulture supernatants is conducted in our CLIA-certified testing laboratory.

Order TruCulture

Every order starts with a quote.

To get your quote, contact RBM or choose an option below:

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Co-Developing new tubes

To co-develop Truculture tubes of interest, please contact us.
RBM can evaluate your stimuli of interest for sterility, solubility, dose response, short and long-term stability, and reproducibility.

Support

RBM is proud to provide excellent customer support

Let us know how we can help you using one of the following options:

Frequently Asked Questions
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Gene Expression Analysis of TruCulture with NanoString nCounter
SARS-CoV-2/COVID-19 Research

Application Notes

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