Abstract
The potential rapid advance of regenerative medicine was obstructed by findings that stimulation of human body regeneration is a much tougher mission than expected after the first cultures of stem and progenitor cells were established. In this mini review, we focus on the ambiguous role of growth factors in regeneration, discuss their evolutionary importance, and highlight them as the “cure and the cause” for successful or failed attempts to drive human body regeneration. We draw the reader's attention to evolutionary changes that occurred in growth factors and their receptor tyrosine kinases (RTKs) and how they established and shaped response to injury in metazoans. Discussing the well-known pleiotropy of growth factors, we propose an evolutionary rationale for their functioning in this specific way and focus on growth factors and RTKs as an amazing system that defines the multicellular nature of animals and highlight their participation in regeneration. We pinpoint potential bottlenecks in their application for human tissue regeneration and show their role in fibrosis/regeneration balance. This communication invites the reader to re-evaluate the functions of growth factors as keepers of natively existing communications between elements of tissue, which makes them a fundamental component of a successful regenerative strategy. Finally, we draw attention to the epigenetic landscape that may facilitate or block regeneration and give a brief insight into how it may define the outcome of injury.
Highlights
One of the paradigms in regenerative biology and medicine is that the adult stem cell (SC) is the cornerstone of tissue renewal and regeneration
Its functions are regulated by the nervous system, providing rapid response, and by endocrine stimuli transmitted by hormones, growth factors, and cytokines acting via specific receptors
We may conclude that growth factors (GFs) are an evolutionary established unique system that provides tissue formation in development and via receptor tyrosine kinases (RTKs) and their signaling axes supports homeostasis, cell integration, and tissue renewal
Summary
One of the paradigms in regenerative biology and medicine is that the adult stem cell (SC) is the cornerstone of tissue renewal and regeneration. Its functions are regulated by the nervous system, providing rapid response, and by endocrine stimuli transmitted by hormones, growth factors, and cytokines acting via specific receptors. These systems provide an array of signals required to support tissue homeostasis and repair after damage. SC alone is not the optimal object for application in regenerative medicine since it depends on the regulatory circuits of the tissue (much related to the “niche” term) and lacks functional autonomy. Probably the only effective “stem cell therapy” known to rebuild a functional organ from adult SC to date is bone marrow transplantation [1]
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