Multiple-Condition Analysis in a Retrievable Subcutaneous Animal Model for Drug Screening on Full Pancreatic Tissue

Tim W G M Spitters1,2, Parker L Andersen1,2, Chloé Martel1,2

  • 1Laboratoire de bio-ingénierie et de biophysique de l'Université de Sherbrooke, Department of Chemical and Biotechnological Engineering, Université de Sherbrooke, Sherbrooke, Canada.

Insights

A new in vivo model using full pancreatic digests in alginate beads offers a better platform for testing pancreas disease therapeutics. This approach reduces costs and time while improving accuracy for drug development.

Area of Science:

  • Biomedical Engineering
  • Regenerative Medicine
  • Drug Discovery

Background:

  • Current in vitro models lack physiological relevance for pancreas research.
  • This limitation hinders the development of effective treatments for pancreas-related diseases.
  • Existing models often lead to biased and unreliable drug testing results.

Purpose of the Study:

  • To develop a novel in vivo model for evaluating pancreatic therapeutics.
  • To create a model that preserves the complex interactions within pancreatic tissue.
  • To establish a cost-effective and time-efficient platform for drug testing.

Main Methods:

  • Developed an in vivo model using full pancreatic digests embedded in alginate beads.
  • Implanted four different conditions subcutaneously within the same animal for direct comparison.
  • Retrieved explants after 5-day implantation for analysis of survival, function, and organization.

Main Results:

  • Demonstrated proof-of-principle by showing effects of hyaluronic acid and vascular endothelial growth factor.
  • Validated the model's ability to assess overall pancreatic digest function and endothelial cell behavior.
  • Utilized metabolism (MTT) assays, dithizone staining, and glucose-stimulated insulin secretion for analysis.

Conclusions:

  • The developed in vivo model accurately reflects pancreatic tissue behavior and drug responses.
  • This platform simplifies drug testing, reduces animal usage, and enhances therapeutic development for pancreatic diseases.
  • The model's adaptability makes it suitable for various research needs in pancreas-related studies.

Related Concept Videos

Carbohydrate Digestion00:57

Carbohydrate Digestion

Carbohydrate digestion and metabolism break down simple and complex carbohydrates from food into saccharides (i.e., sugars) for the body to use as energy. Carbohydrate digestion starts in the mouth during mastication, or chewing. The masticated carbohydrates remain intact in the stomach. Digestion resumes in the duodenum of the small intestine, where pancreatic alpha-amylase and brush border enzymes of the microvilli convert complex carbohydrates to monosaccharides. Finally, the monosaccharides...
122.6K
Lipid Digestion01:06

Lipid Digestion

Lipids are large molecules that are generally not water-soluble. Since most of the digestive enzymes in the human body are water-based, there are specific steps the body must take to break down lipids and make them available for use.
99.5K
Bioequivalence of Drugs: Drugs with Multiple Indications01:09

Bioequivalence of Drugs: Drugs with Multiple Indications

The concept of therapeutic equivalence (TE) in drugs with multiple indications is complex. A generic drug may be therapeutically equivalent to a brand-name product for one specific indication, but this doesn't necessarily mean it's equivalent for all other indications. Evidence of TE in one patient group and bioequivalence shown in healthy volunteers can support—but not confirm—TE for other indications. However, definitive proof requires individual clinical studies for each...
162
Retrieval01:12

Retrieval

Retrieval is the process of getting information out of memory storage and back into conscious awareness. This ability is essential for daily tasks like brushing hair and teeth, driving to work, and performing job duties. Retrieval occurs in three ways: recall, recognition, and relearning.
Recall involves accessing information without cues, such as during an essay test, where individuals must retrieve facts and concepts from memory unaided. Another example is remembering the name of a colleague...
447
What is Monogastric Digestion?01:50

What is Monogastric Digestion?

The human body contains a monogastric digestive system. In a monogastric digestive system, the stomach only contains one chamber in which it digests food. Several other animal species also have monogastric digestive systems, including pigs, horses, dogs, and birds. This chapter, however, focuses on the human digestive system.
75.4K
ER Retrieval Pathway01:45

ER Retrieval Pathway

In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
4.8K