3-D traditional /Organoid Models & the HuCells that build them

Yvonne Adams, Anja T.R. Jensen (University of Copenhagen) manufactured Organioids using Neuromics' Primary Human Astrocytes and Human Brain Microvascular Endothelial Cells to study Plasmodium falciparum erythrocyte membrane protein 1 variants induce cell swelling and disrupt the blood–brain barrier in cerebral malaria.

Cerebral malaria (CM) is caused by the binding of Plasmodium falciparum–infected erythrocytes (IEs) to the brain microvasculature, leading to inflammation, vessel occlusion, and cerebral swelling.

Image 1: 3D BBB spheroids are composed of three different cell types. (A) FACS histogram showing pericytes (NG2, neural/glial antigen 2), astrocytes (GFAP, glial fibrillary acidic protein), and human cerebral microvascular endothelial cells (hCMEC/D3 and CD31).

Image2: ICAM-1–enriched microvilli and transmigratory ring/docking structures on brain hCMEC/D3 endothelial cells. (A–C) hCMEC/D3 brain endothelial cells were incubated with parasites.

This is first time the presence of intact, mature P. falciparum IEs within brain microvascular endothelial cells both in vitro and in vivo.  The data on the enhanced binding and internalization of IEs suggest that the same approach will be necessary to counteract not only the effects of cytoadhesion but also the subsequent contribution to potentially lethal brain swelling in CM.

Explore more topics on 3-D "in-vivo" Like HuCell Models

We are always excited to showcase innovative publications utilizing our reagents. We take immense pride in providing researchers and professionals with reliable and consistent products that unlock new possibilities in their fields. Today, we delve into another new study using some of of our primary human brain cells.

Researchers from the University of Nottingham have released two new publications using our primary human brain microvascular endothelial cells (cat. HEC02), brain pericytes (cat. HMP104), and brain astrocytes (cat. HMP202) to build an in vitro blood-brain barrier (BBB) model. Last week, we highlighted the first publication, where the impact of exposure to Substance P (SP) on the BBB was evaluated. You can check out the blog post to learn more.

Image: Astrocytes stained with S100 beta.

Then, to our pleasant surprise, we saw the researchers cited our cells in another BBB related publication. This time, the investigators looked into some of the mechanisms behind neuroinflammation seen in ischaemic stroke and other disorders. They found that inhibition of Rho kinase neutralized the disruptive effects of TNF-α on BBB integrity. You can read the full study here.

As always, Neuromics greatly appreciates when our products are used in publications. The most recent publication shared by customers took advantage of our mouse Tuj-1 antibody (Cat.#MO15013). In this publication, researchers describe how they created an ex vivo 3D vascularized neural constructs that mimics the function of the blood-brain barrier.

Image: The neurovascular interface containing Tuj1+ (green) neurons differentiated from NSCs (in spaces surrounding the vasculature network) and Claudin-5+ (red) endothelial cells (inside the microfluidic channels). Scale bar, 500 μm. Image citation below

Citation:

Haibing Yue, Kai Xie, Xianglin Ji, Bingzhe Xu, Chong Wang, and Peng Shi. (2020). Vascularized Neural Constructs for Ex-Vivo Reconstitution of Blood-Brain Barrier Function. Biomaterials. doi: 10.1016/j.biomaterials.2020.119980

Learn more...

With COVID-19 affecting the globe for well over a year at this point, many researchers have shifted their focus to the virus. While there are many COVID-19 related questions still needing answers, it is incredible what the scientific community has achieved in such a short period of time.

Our reagents have been used by customers in a handful of publications that have helped us learn more about the virus. We've just added a new page to our website to compile all these publications. Visit it here.

Image: Detected auto Ig levels in specific cell types, including our human small intestine endothelial cells.

Included is a publication from researchers at Emory University comparing the plasma of COVID-19 patients to healthy patients to study the pathogenesis of severe COVID-19. In this research, they used our Human Small Intestine Endothelial Cells (cat.# HEC15). Check out this blog post to learn more.

A second publication utilizes our Human Brain Microvascular Endothelial Cells (cat.# HEC02) to find a microRNA capable of targeting Neuropilin-1, a transmembrane glycoprotein that plays a role in the cellular entry of the SARs-CoV-2 virus. Learn more.

As always, Neuromics greatly appreciates when our products are used in publications. The most recent publication shared by customers took advantage of our mouse Tuj-1 antibody (Cat.#MO15013). In this publication, researchers describe how they created an ex vivo 3D vascularized neural constructs that mimics the function of the blood-brain barrier.

Image: The neurovascular interface containing Tuj1+ (green) neurons differentiated from NSCs (in spaces surrounding the vasculature network) and Claudin-5+ (red) endothelial cells (inside the microfluidic channels). Scale bar, 500 μm. Image citation below

Citation:

Haibing Yue, Kai Xie, Xianglin Ji, Bingzhe Xu, Chong Wang, and Peng Shi. (2020). Vascularized Neural Constructs for Ex-Vivo Reconstitution of Blood-Brain Barrier Function. Biomaterials. doi: 10.1016/j.biomaterials.2020.119980

Learn more...

Just how important is the tumor microenvironment (TME) in cancer research? As a supplier of primary human cancer-associated fibroblasts (CAFs), we’re exposed to plenty of studies looking into their role. One big theme: it’s becoming ever clearer that cancer treatments must take CAFs and their role in the TME into account.

Image: 3D organotypic colorectal tumor model surrounded by CAFs (vimentin, green) (a). Organoids are larger and more plentiful when CAFs are incorporated than without CAFs (b & c).

In a newly released paper, a team of researchers from the University of Akron builds 3D organoids with patient-derived colorectal tumor samples to study prospective cancer treatments. They compare how organoids develop, prosper, and react to treatments when they are with and without colorectal tumor CAFs (cat. CAF115) provided by Neuromics.

In this study, the authors developed a 3D functional human microvascular network in a microfluidic device. The established model enables Neuromics GFP-labeled human umbilical vein endothelial cellsto form vessel-like microtissues and have physiological functions which are closer to cells in human blood vessels. The perfusable microvasculature allows the delivery of nutrients, and oxygen, as well as flow-induced mechanical stimuli into the luminal space of the endothelium. The microflow effectively mimic the blood flow in human vessels.

With colorectal cancer (CRC) being one of the most prevalent cancers worldwide, understanding chemotherapy resistance in the CRC tumor microenvironment (TME) is an important goal. As we’ve seen in many other publications using our human cancer-associated fibroblasts (CAFs), CAFs play a huge role in the TME.

Our CAFs have been used in a handful of studies in 2D and 3D TME models, where they demonstrate their ability to complicate treatment objectives. Overall, the mechanisms by which CAFs contribute to chemotherapy resistance in the TME are poorly understood. 

Image: DKK1 expression in Neuromics colorectal CAFs when subjected to chemotherapeutic agents.

Researchers from the University of Kentucky utilized our colorectal CAFs (cat. CAF115) in a new paper examining these mechanisms. In their cell models, they found that CAFs secrete DKK1, a protein associated with tumor growth and metastasis, when subjected to chemotherapy treatments for CRC. Their results identified CAF-secreted DKK1 as a major player in resistance to treatment. Furthermore, they recommend looking into treatments that target DKK1 to counteract chemotherapy resistance.

You can check out the full paper here.

When researchers employ our human primary cancer associated fibroblasts (CAFs) in their tumor microenvironment models, they consistently find stark differences between 2D and 3D. Through 3D co-culture, investigators recognize that their models mirror in vivo tumors more closely than in 2D.

This makes our CAFs invaluable, enabling drug discovery research that better mimics the tumor microenvironment. Furthermore, over the last few years, we've seen the observation across many of our CAF types, including pancreatic, colorectal, breast, and now, ovarian.

Image: Human ovarian cancer cell lines (SKOV3 and OVACR8) along with Neuromics ovarian CAFs (cat. CAF112) in 2D and 3D ovarian cancer models.