High throughput screening: Compounding the advantage of the (Adult) Mesenchymal Stem Cell model system in vitro

Images of human mesenchymal stem cells sourced from various tissues; L to R, MSCs from tooth pulp, human umbilical cord tissue, and adipose tissue (Copyright Transcell Oncologics Pvt Ltd, India).
Lakshman Varanasi, PhD, Science Associate    September 24, 2020

Mesenchymal stem cells are borne of the embryonal mesenchyme. The stem cells progenitors give rise to the spectrum of connective tissues in the human body. The MSCs endure until adulthood, much beyond the lifespan of the mesenchyme. Scientists, through laborious effort, have managed to develop methods of preserving and culturing MSCs without loss of their stemness. Although difficult to isolate from adult tissue, they can be easily collected from human umbilical cord tissue, discarded wisdom or milk tooth pulp, and non-diabetic adult lipoaspirates. MSCs interact with T-lymphocytes and have immunomodulatory properties, among others, that make them appropriate for the treatment of severe and acute conditions, such as sepsis and ARDS (the latter now known to be typical of COVID-19). Because they mimic human physiology better than an animal model, they are rightly considered a better model system for examining the toxicity of chemicals intended for human use. These are routinely made to differentiate into a connective tissue type for in-vitro testing of toxicity, or efficacy of drug candidates (Pharmacokinetics is not possible in individual cells, or even groups of cells). The fundamental physiological processes underlying a condition, or a developmental pathway and fate can be systematically parsed/ reductively examined using the versatile MSC platform in combination with high throughput screening (HTS). Indeed HTS, by virtue of the sheer volume of chemicals that it can assay in a single run, bypasses the hypothesis-based approach, identifies those of interest and hitherto unknown, and compounds manifold the advantage the MSCs confer. MSCs have been explored for high throughput drug screening for assaying pharmaceutical cytotoxicity and genotoxicity, and are now considered a mature platform for this purpose. Properties in addition to toxicity, such as immunomodulatory or inhibitory effects can also be studied. For instance, Kozisek et al report a high throughput technique for screening compounds that “prime” MSCs for the efficient uptake of DNA that is not delivered via a viral vehicle, in essence, endowing the MSCs with additional properties. Likewise, the identification of novel molecules that can prevent the undesired differentiation of MSCs into bone (osteocytes) and cartilage (chondrocytes), as in arthritis.

A high throughput screening robot arm readies to receive a plate from an assay plate reader (Above); A robot arm handles an assay plate (below). Courtesy: National Institute of Allergy and Infectious Diseases.

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