BioSpherix, Ltd.

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Have your cell cultures been naughty this year, or nice?
Happy Holidays, from the BioSpherix family.

Enhanced Self-Renewal of HSC Under Physioxia:
Physioxia induces downregulation of Tet2 in Hematopoietic Stem Cells, report Aljoufi et al.

Read more (open access): https://ashpublications.org/blood/article/doi/10.1182/blood.2022015499/485747/Physioxia-induced-Downregulation-of-Tet2-in

Workshop on Measurement Needs for Biofabrication of Tissue Engineered Medical Products Goal: discuss and identify measurement needs for characterizing biofabricated, tissue en

Physioxia Influences Gene Methylation:
Dogan et al. use physiological oxygen to examine epigenetic modification in pluripotent stem cells.

Read more (open access): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9148100/

Alliance Formed to Create AI Tools for Biomanufacturing The goal of the alliance is to allow cell-based therapies to be manufactured cost-effectively with superior efficacy and safety.

Osteogenesis and HIF Signaling in the Clinic: An in-depth review of recent progress in HIF-regulated bone regeneration provides evidence for novel tissue repair strategies.

Read more: https://pubmed.ncbi.nlm.nih.gov/35913258/

HIF signaling: A new propellant in bone regeneration - PubMed Bone tissue destruction leads to severe pain, physical flaws, and loss of motility. Bone repair using biocompatible and osteo-inductive scaffolds is regarded as a viable and potential therapeutic approach. However, for large-scale bone regeneration, oxygen and nutrient supply have become limiting fa...

Altering O2 in Solid Tumor Studies:
Herrera-Campos et al. review the role of hyperoxia and the immune system in novel treatments for solid tumors.

Read more (open access): https://www.mdpi.com/2072-6694/14/11/2740/htm

Implications of Hyperoxia over the Tumor Microenvironment: An Overview Highlighting the Importance of the Immune System Hyperoxia is used in order to counteract hypoxia effects in the TME (tumor microenvironment), which are described to boost the malignant tumor phenotype and poor prognosis. The reduction of tumor hypoxic state through the formation of a non-aberrant vasculature or an increase in the toxicity of the....

Identifying EV Uptake Signals in Pancreatic Cancer: Nigri et al. mimic pathophysiologic conditions to identify a potential target for therapeutic intervention into aggressive pancreatic ductal carcinoma.

Read more (open access): https://pubmed.ncbi.nlm.nih.gov/35917363/

CD9 mediates the uptake of extracellular vesicles from cancer-associated fibroblasts that promote pancreatic cancer cell aggressiveness - PubMed In pancreatic ductal adenocarcinoma (PDAC), signaling from stromal cells is implicated in metastatic progression. Tumor-stroma cross-talk is often mediated through extracellular vesicles (EVs). We previously reported that EVs derived from cancer-associated stromal fibroblasts (CAFs) that are abundan...

Intestinal Wound Healing and HIF: Steiner et al. review the double-edged sword HIF present over the course of the metabolic response to chronic intestinal inflammation.

Read more: https://pubmed.ncbi.nlm.nih.gov/35912990/

Hypoxia-inducible factor as a bridge between healthy barrier function, wound healing, and fibrosis - PubMed The healthy mammalian intestine is lined by a single layer of epithelial cells. These cells provide a selectively permeable barrier to luminal contents and normally do so in an efficient and effective manner. Barrier function in the healthy mucosa is provided via several mechanisms including epithel...

Relevant miRNA patterns under pathophysioxia:
Majewska et al. study the role of PTEN in kidney cancer by mimicking the TME in vitro.

Read more (open access): https://pubmed.ncbi.nlm.nih.gov/35625614/

miRNA Pattern in Hypoxic Microenvironment of Kidney Cancer-Role of PTEN - PubMed MicroRNAs are post-transcriptional regulators of gene expression, and disturbances of their expression are the basis of many pathological states, including cancers. The miRNA pattern in the context of tumor microenvironment explains mechanisms related to cancer progression and provides a potential t...

Neuroinflammation Regulation Therapies Tested Using Hypoxia: Wang et al. recreate pathophysiological conditions to study neuroprotection after cardiac arrest-induced brain injury.

Read more: https://pubmed.ncbi.nlm.nih.gov/35921049/

Neuroprotection of NSC Therapy is Superior to Glibenclamide in Cardiac Arrest-Induced Brain Injury via Neuroinflammation Regulation - PubMed Cardiac arrest (CA) is common and devastating, and neuroprotective therapies for brain injury after CA remain limited. Neuroinflammation has been a target for two promising but underdeveloped post-CA therapies: neural stem cell (NSC) engrafting and glibenclamide (GBC). It is critical to understand w...

Goldilocks, Radiation, and Cataracts in Space:
Richard B. Richardson details the role of oxygen in cataract development in US astronauts.

Read more (open access): https://pubmed.ncbi.nlm.nih.gov/35917999/

The role of oxygen and the Goldilocks range in the development of cataracts induced by space radiation in US astronauts - PubMed This article explores the role that oxygen levels in US spacecraft from 1961 to 1998 have on the development of cataracts induced by space radiation in astronauts and whether oxygen levels are well accounted for in experimental studies examining cataractogenesis. The first epidemiological report in....

Physioxia Diminishes Cellular Iron Dependency: New biosensors uncover altered cell metabolism in this study by Sevimli et al.

Read more (open access): https://www.sciencedirect.com/science/article/pii/S221323172200091X

Nitric oxide biosensor uncovers diminished ferrous iron-dependency of cultured cells adapted to physiological oxygen levels Iron is an essential metal for cellular metabolism and signaling, but it has adverse effects in excess. The physiological consequences of iron deficie…

Simulating Pathological Hypoxia to Study Neurodegeneration:
Thinard et al. discuss a novel approach to therapy at the blood brain barrier.

Read more (open access): https://www.mdpi.com/1999-4923/14/7/1418

“Endothelial Antibody Factory” at the Blood Brain Barrier: Novel Approach to Therapy of Neurodegenerative Diseases The failures of anti-β-amyloid immunotherapies suggested that the very low fraction of injected antibodies reaching the brain parenchyma due to the filtering effect of the BBB may be a reason for the lack of therapeutic effect. However, there is no treatment, as yet, for the amyotrophic lateral...

Oxygen Controls the Lymphovascular-Immune Ensemble:
Schito et al. review the role of hypoxia in the lymphatic system's response to cancer.
Read more: https://www.cell.com/trends/cancer/fulltext/S2405-8033(22)00095-4?

Hypoxia orchestrates the lymphovascular–immune ensemble in cancer The lymphatic system is a major component of the tumor microenvironment, wherein lymphovascular remodeling occurs as a response to low O2 (hypoxia), resulting in metastatic dissemination and patient mortality. Further to this notion, recent data have brought forth an expanded view of lymphatics, bey...

B Cell Function, Development, and Metabolism are Regulated by HIF: A comprehensive review by Zhang et al. of immunoregulation by hypoxia and hypoxia-inducible factors.

Read more (open access): https://www.frontiersin.org/articles/10.3389/fimmu.2022.967576/full

Hypoxia and hypoxia-inducible factor signals regulate the development, metabolism, and function of B cells Hypoxia is a common hallmark of healthy tissues in physiological states or chronically inflamed tissues in pathological states. Mammalian cells sense and adapt to hypoxia mainly through hypoxia-inducible factor (HIF) signaling. Many studies have shown that hypoxia and HIF signaling play an important...

A Novel Photosynthetic Gel for Wound Healing:
Developing novel treatments can require novel approaches, like that of Zhu et al., who mimicked peripheral artery disease in vitro to develop a novel topical gel to enhance localized hyperoxygenation.

Read more (open access): https://www.nature.com/articles/s41598-022-14085-1

A novel photosynthetic biologic topical gel for enhanced localized hyperoxygenation augments wound healing in peripheral artery disease - Scientific Reports Peripheral artery disease and the associated ischemic wounds are substantial causes of global morbidity and mortality, affecting over 200 million people worldwide. Although advancements have been made in preventive, pharmacologic, and surgical strategies to treat this disease, ischemic wounds, a con...

Mimicking the TME in Immunotherapy Studies:
Ma et al. discuss drug resistance and epigenetic vulnerability in triple negative breast cancer.

Read more (open access): https://pubmed.ncbi.nlm.nih.gov/35840558/

Hypoxia induces HIF1α-dependent epigenetic vulnerability in triple negative breast cancer to confer immune effector dysfunction and resistance to anti-PD-1 immunotherapy - PubMed The hypoxic tumor microenvironment has been implicated in immune escape, but the underlying mechanism remains elusive. Using an in vitro culture system modeling human T cell dysfunction and exhaustion in triple-negative breast cancer (TNBC), we find that hypoxia suppresses immune effector gene expre...

Improving Tox Assay Predictability with Physioxia:
Human renal proximal tubular epithelial cells exhibit in vivo-like properties in co-culture under physiological oxygen, Piossek et al. report.
Read more: https://pubmed.ncbi.nlm.nih.gov/35533734/

Physiological oxygen and co-culture with human fibroblasts facilitate in vivo-like properties in human renal proximal tubular epithelial cells - PubMed Reliable prediction of compound mediated nephrotoxicity in humans is still unsatisfactory irrespective of the recent advancements in in silico, in vitro and in vivo models. Therefore, current in vitro approaches need refinement to better match the human in vivo situation, specifically with regard to...

Extracellular vesicles require proper conditions:
Almeria et al. detail how MSC produce more heterogeneous EVs when the upstream culture conditions are uncontrolled.

Read more (open access): https://pubmed.ncbi.nlm.nih.gov/35501833/

Heterogeneity of mesenchymal stem cell-derived extracellular vesicles is highly impacted by the tissue/cell source and culture conditions - PubMed Extracellular vesicles (EVs) are cell-derived membrane structures exerting major effects in physiological as well as pathological processes by functioning as vehicles for the delivery of biomolecules to their target cells. An increasing number of effects previously attributed to cell-based therapies...

Creating relevant pathophysiology in vitro:
Cheng et al. control oxygen around primary human trophoblasts to study autophagy-lysosomal machinery in early-onset preeclampsia.
Read more (open access): https://pubmed.ncbi.nlm.nih.gov/35628454/

Hypoxia-Reoxygenation Impairs Autophagy-Lysosomal Machinery in Primary Human Trophoblasts Mimicking Placental Pathology of Early-Onset Preeclampsia - PubMed We have previously described that placental activation of autophagy is a central feature of normal pregnancy, whereas autophagy is impaired in preeclampsia (PE). Here, we show that hypoxia-reoxygenation (H/R) treatment dysregulates key molecules that maintain autophagy-lysosomal flux in primary huma...

Controlling cell phenotype in tissue constructs : Decellularized extracellular matrix scaffolds and hypoxic priming improves the phenotype of degenerate intervertebral disc cells, Penolazzi et al. report.
Read more: https://pubmed.ncbi.nlm.nih.gov/35537547/

Decellularized extracellular matrix-based scaffold and hypoxic priming: A promising combination to improve the phenotype of degenerate intervertebral disc cells - PubMed These results open new avenues to engineer IVD by demonstrating that appropriate stimuli are able to dampen the degenerated IVD cell phenotype and to promote anabolic activity in cells which are constitutively characterized by poor reparative capacity.

Discovering new treatment modalities by mimicking the TME: Qin et al. study androgen biosynthesis and hormone therapy resistance in prostate cancer.
Read more: https://pubmed.ncbi.nlm.nih.gov/35536859/

Culture Oxygen Drives MSC Metabolism: Olesen et al. discuss respiration and metabolic adaptation to low oxygen tension in mesenchymal stromal cells.
Read more (open access): https://www.sciencedirect.com/science/article/pii/S2589936822000056

Diversity of respiratory parameters and metabolic adaptation to low oxygen tension in mesenchymal stromal cells Cell metabolism has been shown to play an active role in regulation of stemness and fate decision. In order to identify favorable culture conditions f…

Congratulations to Emma Warner, who finished her Summer Scholar project successfully in the Xvivo System at WFIRM with the help of the incredible Katie Benson!

Interview: How does room air affect cancer drug screening?
Professor Harikrishna Nakshatri joins CSO Dr. Alicia Henn to discuss culturing cancer cells under physiologic oxygen for better drug development.

Watch the full interview: https://www.youtube.com/watch?v=PeEiHSIkOvw&t=386s

Hari Nakshatri Cytocentric Visionary Here Cytocentric Visionary Dr. Harikrishna Nakshatri tell us about his latest paper and his revolutionary idea to screen drugs under physioxic conditions bef...

Penolazzi et al. promote the discogenic phenotype of degenerate IVD cells in vitro by mimicking their hypoxic niche.

Read more: https://pubmed.ncbi.nlm.nih.gov/35537547/

Decellularized extracellular matrix-based scaffold and hypoxic priming: A promising combination to improve the phenotype of degenerate intervertebral disc cells - PubMed These results open new avenues to engineer IVD by demonstrating that appropriate stimuli are able to dampen the degenerated IVD cell phenotype and to promote anabolic activity in cells which are constitutively characterized by poor reparative capacity.

Tumor signaling and hypoxia: Qin et al. investigate HIF2a as a potential therapeutic target for prostate cancer.

Read more: https://pubmed.ncbi.nlm.nih.gov/35536859/

Hypoxia-reoxygenation couples 3βHSD1 enzyme and cofactor upregulation to facilitate androgen biosynthesis and hormone therapy resistance in prostate cancer - PubMed Androgen deprivation therapy suppresses tumor androgen receptor (AR) signaling by depleting circulating testosterone and is a mainstay treatment for advanced prostate cancer. Despite initial treatment response, castration-resistant prostate cancer nearly always develops and remains driven primarily....