MD Biosciences Blog

IL-23 induced Psoriasis-like Preclinical Model of Inflammation

Posted by MD Biosciences on Aug 8, 2013 7:17:00 AM

MD Biosciences focuses on rapid and cost effective models of psoriasis involving the IL-23/TH17 axis in order to provide companies alternatives to complex and costly xenotransplantation models for screening. With the earlier launch of the IMQ-induced model and now the IL-23 psoriasis model, MD Biosciences offers a range of rapid models for dermal conditions such as dermatitis and psoriasis. 

Recent psoriasis research has focused extensively on the IL-23/TH17 axis. While previously thought to be mainly a Th1 mediated disease, evidence has shifted to a new population of IL-17 producing Th17 cells and the involvement in a variety of autoimmune diseases including psoriasis. The development and maintenance of Th17 cells has been linked to IL-23, a key cytokine involved in the development of autoimmunity. With the focus of research on the IL-23/TH17 role in psoriasis, a number of novel therapeutics are currently in clinical trials that target this pathway.

MD Biosciences is currently working with a biopharmaceutical company in evaluating novel therapeutics that target this pathway. While models of psoriasis such as xenotransplantation models have traditionally been the most commonly used, they are complex and cost prohibitive for screening. MD Biosciences research group has validated rapid and cost effective preclinical models for screening psoriatic therapeutics. In addition to the IMQ-induced psoriasis model launched last year, the most recent model to be validated is the IL-23 induced model of psoriasisform inflammation.

ear thickness data in IL-23 psoriasis modelThe IL-23 psoriasis model is 21 days long and involves the injection of IL-23 into the ear of C57Bl/6, which produces psoriasis-like inflammation that is dependent on IL-22. IL-22 induces keratinocyte proliferation and epidermal hyperplasia contributing to epidermal thickening. “We are continually looking to the most recent research clinical findings. With the number of clinical trials involving targets in the IL-23/Th17 pathway, offering rapid preclinical models of psoriasis involving this pathway allows biopharma companies to cost-effectively screen potentially novel therapeutics. This is important for companies in early discovery to be able to evaluate compounds in a clinically relevant model of psoriasisform inflammation.”

Background on Th17 in psoriasis pathology

While the pathology of psoriasis is not completely understood, there are complex un- derlying mechanisms, which involve the interplay between epidermal keratinocytes, leukocytes such as dendritic cells and APCs, and vascular endothelium. Epidermal keratinocytes and vascular endothelial cells are active participants in the psoriasis inflammatory process via secreted cytokines and growth factors along with the upregulation of signaling and adhesion molecules on their surfaces. TGFb1 is elevated and released by keratinocytes, which when combined with activated dendritic cells is sufficient to generate TH17 cells in skin-draining lymph nodes inducing cutaneous inflammation. Intracellular signaling induces expression of IL-23R on developing Th17 cells promoting responsiveness to IL-23, the key cytokine in the survival and proliferation of Th17 cells. Th17 cells secrete a range of pro-inflammatory cytokines such as IL-6, IL-17A, IL-17F, IL-21, IL-22 and TNF-α . In psoriasis, IL-23 plays an important role with genetic alterations of IL-23p40 and IL-23R leading to enhanced IL-23 production increasing psoriasis susceptibility and indeed injection of the IL-17 supporting cytokine, IL-23, into the skin of mice can induce psoriasis-like inflammation. The main cellular source of IL-17A in psoriasis-like skin inflammation are γδ T cells located specifically in the dermal layers and expansion of Th17 cells producing inflammation and these cells are required to initiate the IL-23 driven processes.

About MD Biosciences

MD Biosciences is a Research Group and Preclinical Contract Research Organization (CRO) providing services and products for biotech/pharmaceutical, medical device and animal health and companies engaged in inflammations & neurology research. With specialized laboratories located in Minnesota, Glasgow, and Israel, our panel of internationally recognized experts provides in-depth expertise and technologies to overcome challenges and provide total solutions to the drug discovery market.

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The information in this press release should be considered accurate only as of the date of the release. MDB has no intention of updating and specifically disclaims any duty to update the information in these press releases.

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Topics: Dermal

3D Human Skin System w/Co-Cultures & Vasclr tech. Closely Resembles Human Skin

Posted by MD Biosciences on Jul 31, 2012 9:29:00 AM

MD Biosciences, in collaboration with Fraunhofer IGB, announces a revolutionary, in vitro 3D human skin equivalent (HSE) system. The model enables scientists to measure the penetration, resorption, metabolism and epidermal impedance in a human skin equivalent system Penetration across the layers is visible, enabling the determination of intracellular drug transport. The system offers two uptake routes for drugs:

  • Direct uptake by cells following topical administration
  • Deposition in skin cells following administration of drug through vascular system

The 3D HSE is a two-layered structure closely resembling natural human skin. The dermis layer is composed of dermal fibroblasts, embedded in a biomatrix consisting of tissue-typical matrix proteins. This serves as a scaffold for epidermal keratinocytes seeded on them. The keratinocytes differentiate into a multilevel epidermis with Stratum basale, Stratum spinosum, Stratum granulosum and Stratum corneum. Due to the interaction of fibroblasts and keratinocytes between the dermal and epidermal sections of the skin model, a functional basal membrane consisting of matrix proteins is developed. 

3D human skin equivalent system with co-cultures and vascularized technology, preclinical in vitro CRO

 

Additionally, the HSE system can be vascularized using BioVaSc technology:

  • De-cellularized jejunum for the appropriate scaffold material
  • Tubular structures are seeded with microvascularized endothelial cells leading to the synthesis of extracellular matrix including capillaries
  • Uniform tissue is made with no separation of layers or shrinking of skin enabling longer cultures

The vascularized 3D HSE system serves as an important advancement in the area of skin equivalents for use as a drug development tool. It eliminates many of the challenges associated with other commercially available skin equivalents such as low barrier properties, skin shrinkage due to inefficient scaffolds, short term culture limitations and lack of blood vasculature. By incorporating tissue-specific cells, the technology can be applied to multiple areas beyond skin such as infections, wounds, tumors and organs. To discuss how this technology can advance your particular program, contact MD Biosciences.

 

About MD Biosciences

MD Biosciences is a Preclinical and Clinical Contract Research Organization (CRO) providing services for biotech/pharmaceutical, medical device and animal health. Our core therapeutic focus is in inflammation/autoimmune, neurology/CNS disorders, pain and cardiovascular as well as the interplay between the inflammatory, neurology and cardiovascular systems. Our approach is to work backwards from the clinic, understanding what the clinicians would expect from an active compound. This approach and understanding enables the development of models and biomarkers that help break the preclinical/clinical barrier and provide more clinically relevant data at earlier stages.

 

About Fraunhofer IGB

Fraunhofer IGB develops and optimizes processes and products in the fields of medicine, pharmacy, chemistry, the environment and energy. Fraunhofer combines the highest scientific quality with professional expertise in fields of competence always with a view to economic efficiency and sustainability. Fraunhofer IGB is one of more than 80 research units of the Fraunhofer-Gesellschaft, Europe’s largest non-profit organization for application-oriented research. Fraunhofer IGB has obtained a patent for the three-dimensional human skin equivalent (patent ID: EP 1 290 145 B1) and in 2009 developed the biological vascularized matrix (BioVaSc) winning a technology prize for “human-centered” technology by the Fraunhofer-Gesellschaft.

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The information in this press release should be considered accurate only as of the date of the release. MDB has no intention of updating and specifically disclaims any duty to update the information in these press releases.

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Topics: Dermal

Preclinical Imiquimod-induced Psoriasis-like Skin Inflammation Model

Posted by MD Biosciences on May 1, 2012 2:12:00 PM

A Rapid 10 day preclinical efficacy study that produces lesions highly representative of human psoriatic lesions.

Wednesday, May 2, 2012, St. Paul, MN – The most common models for evaluating skin-related inflammation are time consuming and expensive. While they provide valuable data, they don’t allow for rapid and cost effective evaluation of therapeutics earlier in the preclinical pipeline. In response to this need for more convenient and cost effective models, researchers (Van der Fits et al, 2009) developed a model using Imiquimod (IMQ) to induce psoriasis-like inflammation.

Imiquimod is a potent immune activator that is traditionally used to treat virus-associated skin abnormalities and precancerous skin lesions. However it can exacerbate psoriasis (both at the treated area and at distant skin sites) during topical treatment. Application of IMQ to mouse skin results in the influx of various cells of the immune system as well as hyperplasia of the epidermis that is critically dependent on IL-23 and IL-17.

MD Biosciences now offers the IMQ-induced model of skin inflammation as part of its portfolio of efficacy services. The model is 10 days long and the lesions closely resemble that of human psoriatic lesions with erythema, skin thickening and epidermal alterations such as acanthosis and parakeratosis. Subjects are given a psoriasis score depending on the degree of erythema, scaling and thickening. Analysis includes clinical score of the back, ear thickness and histology of both the ear and back.

 

Image: histology on psoriatic lesions (B-D) compared to that of a naive sample (A) in the IMQ-induced model of skin inflammation. For additional data, please visit the IMQ-induced model.

histology of the skin in the IMQ-induced psoriasis-like model of skin inflammation, preclinical CRO

 

About MD Biosciences

MD Biosciences is a Preclinical Contract Research Organization (CRO) providing services and products for biotech/pharmaceutical, medical device and animal health and companies engaged in inflammations & neurology research. With specialized laboratories located in Minnesota, Glasgow, and Israel, our panel of internationally recognized experts provides in-depth expertise and technologies to overcome challenges and provide total solutions to the drug discovery market.

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The information in this press release should be considered accurate only as of the date of the release. MDB has no intention of updating and specifically disclaims any duty to update the information in these press releases.

Read More

Topics: Dermal