Abstract
Most therapeutics are based on the traditional method of reductionism where a clinically defined condition is broken down into a defined biochemical pathway underlying the condition, then a target in the pathway is identified, followed by developing a drug to interact with the target, modifying the target such that the disease is ameliorated. Biology acts as a system, therefore reductionist approaches to developing therapeutics are limited in therapeutic value because disease or traumatized tissue involves multiple underlying pathways, only a part of the pathways underlying the disease is manipulated by the traditional therapeutic. Much data regarding stem cells shows that their beneficial effects are not restricted to their ability to differentiate, but is more likely due in large part to their ability to release a multitude of molecules. Stem cells release potent combinations of factors that modulate the composition of the cellular milieu to evoke a multitude of responses from neighboring cells. Therefore, stem cells represent a natural systems-based biological factory for the production and release of a multitude of molecules that interact with the system of biomolecular circuits underlying an indication. Current research includes efforts to define, stimulate, enhance, and harness stem cell released molecules (SRM) to develop systems-therapeutics.
Highlights
In the postgenomic era, where even individual somatic cells display genetic heterogeneity [1], knowing the sequence of the genome has limited predictive value in disease diagnosis and treatment [2, 3]
As opposed to traditional reductionist approaches, where one molecule is developed to target and perturb one pathway in a system, stem cells actively contribute to their environment by releasing multiple cytokines, growth factors, extracellular matrix (ECM) molecules, micro-RNA, antioxidants, and other molecules that act either on themselves or on neighboring cells to exert their therapeutic actions (Figure 1)
Studies continue to demonstrate that most organ systems of the body have a resident pool of dormant somatic, tissuespecific stem cells ready to be activated in the case of injury or disease
Summary
In the postgenomic era, where even individual somatic cells display genetic heterogeneity [1], knowing the sequence of the genome has limited predictive value in disease diagnosis and treatment [2, 3]. The pharmaceutical industry has realized the need to develop innovative strategies and new technologies to identify and develop new drug candidates, moving away from the over reliance of nonpredictive genetic tools [4]. Many more systems biology-based analytical tools are being used and further developed such as proteomics, genomics, or connectomics to name a few, and metabolomics has seen further development into such subdisciplines as tracer-based metabolomics [10]. The rationale behind those terms, using omics, is to convey that the proteins, or genes, or connections in the brain need to be thought of as operating within a system. Unlike the use of systems biology in describing a circuit within biology or describing analytical methods of drug development, the development of therapeutics that act in a systems manner rather than a in reductionist manner has received little attention
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