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Gibco - Model HPLM - Human Plasma-Like Medium
Create physiologically relevant cell culture models. Gibco Human Plasma-like Medium (HPLM) is a new formulation designed to resemble the natural cellular environment found in the body, mimicking the metabolic profile of human plasma. The widely used classic synthetic cell culture media, including MEM, DMEM, RPMI 1640, and DMEM/F-12 contain glucose, amino acids, vitamins, and salts at concentrations that in large part do not reflect those found in human plasma. These media also lack additional plasma components needed to mimic the metabolic profile of human plasma. When studying cancer and other diseases, results with more physiological relevance will enable researchers to improve their understanding of human function and illness.
Gibco HPLM contains the same salt concentrations found in human plasma, as well as the same concentrations of over 60 polar metabolites, such as amino acids, nucleic acids, sugars, and small organic acids. In resembling the natural cellular environment found in the body, HPLM provides researchers the ability to study the impact of physiologically relevant cell media on their specific applications.
When supplemented with fetal bovine serum (FBS), HPLM is capable of supporting cell growth and viability that are comparable to that of conventional basal media formulations supplemented with FBS. For most cell lines, adaptation is not required to transition from conventional medium to HPLM.
- Physiologically relevant -designed to resemble the natural cellular environment found in the body formulated with more than 60 polar metabolites and salt concentrations
- Peer reviewed- extensive research publications completed using HPLM formulation
- Easy to use- direct replacement for your current media when supplemented with FBS
Graphical abstract summary: “Among the most prominent was an inhibition of de novo pyrimidine synthesis—an effect traced to uric acid, which is 10-fold higher in the blood of humans than of mice and other non-primates. We find that uric acid directly inhibits uridine monophosphate synthase (UMPS) and consequently reduces the sensitivity of cancer cells to the chemotherapeutic agent 5-fluorouracil. Thus, media that better recapitulates the composition of human plasma reveals unforeseen metabolic wiring and regulation, suggesting that HPLM should be of broad utility.”
Reproduced with permission from: Cantor JR, Abu-Remaileh M, Kanarkek N et al. (2017) Physiologic medium rewires cellular metabolism and reveals uric acid as an endogenous inhibitor of UMP synthase. Cell 169: 258–272.E17. doi: 10.1016/j.cell.2017.03.023.
Graphical abstract summary: “The composition of human plasma differs from conventional media, and we hypothesized that such differences could impact immune cell physiology. Here, we showed that relative to the medium typically used to culture lymphocytes (RPMI), a physiologic medium (human plasma-like medium; HPLM) induced markedly different transcriptional responses in human primary T cells and in addition, improved their activation upon antigen stimulation. We found that this medium-dependent effect on T cell activation is linked to Ca2+, which is six-fold higher in HPLM than in RPMI. Thus, a medium that more closely resembles human plasma has striking effects on T cell biology, further demonstrates that medium composition can profoundly affect experimental results, and broadly suggests that physiologic media may offer a valuable way to study cultured immune cells."
Reproduced with permission from: Leney-Greene MA, Boddapati AK, Su HC et al. (2020) Human plasma-like medium improves T lymphocyte activation. iScience 23:100759. doi: 10.1016/j.isci.2019.100759.
Human Plasma-like Medium Improves T Lymphocyte Activation
Leney-Greene MA, Boddapati AK, Su HC, Cantor JR, Lenardo MJ. iScience. 2020;23(1):100759.
- Research area: Immunology
- Cell lines: Peripheral blood mononuclear cells (PBMCs), T lymphocytes
- Objective: Test the impact of HPLM versus RPMI on T-lymphocyte activation
- Findings: “Our data broadly highlight the fact that commonly used conditions used to culture and examine T lymphocytes in vitro may not be ideal for metabolic studies, and we also specifically identify one extracellular component (calcium) that can be easily considered by others in the field. Our approach also further demonstrates the value of using HPLM to improve the modeling capacity of in vitro cell culture systems.”
Lineage-Specific Silencing of PSAT1 Induces Serine Auxotrophy and Sensitivity to Dietary Serine Starvation in Luminal Breast Tumors
Choi BH, Conger KO, Selfors LM, Coloff JL. bioRxiv 2020.06.19.161844.
- Research area: Cancer therapy, gene expression metabolism
- Cell lines and culture conditions: Luminal and basal human breast tumors:
- HCC1 806, MCF7, MCF7-EMPTY, MCF7-PSAT1
- Cells were grown in human plasma-like medium according to the published formulation (Cantor et al., 2017) with 5% dialyzed FBS. Media was changed at least every two days.
- Objective: Identify differences in metabolic gene expression that may limit pathway redundancy and create therapeutic vulnerabilities
- Findings: “In summary, our studies of lineage-dependent gene expression in breast cancer have revealed a novel vulnerability in serine metabolism specifically in luminal breast tumors. Lineage-specific suppression of PSAT1 induces serine auxotrophy in luminal breast cancer cells and sensitizes them serine starvation. These findings demonstrate that lineage-dependent gene 10 expression is sufficient to limit pathway redundancy and create therapeutic vulnerabilities that could be taken advantage of to target specific subtypes of tumors.”
Inhibiting both proline biosynthesis and lipogenesis synergistically suppresses tumor growth
Liu M, Wang Y, Yang C, Ruan Y, Bai C, Chu Q, Cui Y, Chen C, Ying G, Li B. J Exp Med. 2020 Mar 2;217(3):e20191226.
- Research area: Cancer metabolism
- Cell lines: HeLa, MDA-MB-231, MCF-7, A549, HepG2, 8133, SKOV3, and mouse 4T1 cells
- Objectives:
- To build up an electron balance model to reveal the chemical mechanism of metabolic reprogramming under hypoxia
- HPLM was used to test cellular metabolism at physiological (5%), hypoxic (0.5%), and normal oxygen (20%) concentrations
- Findings: “Overall, our model suggests a promising combination of targets to control tumor growth under hypoxia. Moreover, this treatment can be further intensified by blocking electron transfer established on our concept. Therefore, it is anticipated that the model of electron balance developed in the current study could help us to better understand cancer metabolism and its therapeutic application in the future.”
CRISPR screens in physiologic medium reveal conditionally essential genes in human cells
Nicholas JR, Kimberly SH, Charles HA, Heather RK, Ross W.S, David M.S, Jason RC.bioRxiv2020.08.31.275107
- Research type: Cancer biology
- Cell lines: K562, MOLM-13, SUDHL4, and NOMO1
- Objective: To explore how medium composition influences gene essentiality of human cancer cell lines cultured in traditional medium versus HPLM
- Findings: “To explore how medium composition influences gene essentiality, we performed CRISPR-based screens of human cancer cell lines cultured in traditional versus human plasma-like medium (HPLM). Sets of medium-dependent fitness genes span several cellular processes and can vary with both natural cell-intrinsic diversity and the specific combination of basal and serum components that comprise typical culture media. Our findings reveal the profound impact of medium composition on gene essentiality in human cells, and also suggest general strategies for using genetic screens in HPLM to uncover new cancer vulnerabilities and gene-nutrient interactions.”