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REVIEW: Biochemical Regulation of Regenerative Processes by Growth Factors and Cytokines: Basic Mechanisms and Relevance for Regenerative Medicine#

P. I. Makarevich1,2,a*, A. Yu. Efimenko1,2, and V. A. Tkachuk1,2,3

1Lomonosov Moscow State University, Institute for Regenerative Medicine, Medical Research and Education Center, 119991 Moscow, Russia

2Lomonosov Moscow State University, Faculty of Fundamental Medicine, 119991 Moscow, Russia

3Institute of Experimental Cardiology, National Medical Research Center of Cardiology, 121552 Moscow, Russia

# The article is dedicated to the 80th anniversary of the Department of Biochemistry, Faculty of Biology, Lomonosov Moscow State University (see Volume 84, Issue 11, 2019).

* To whom correspondence should be addressed.

Received June 15, 2019; Revised September 30, 2019; Accepted October 16, 2019
Regenerative medicine that had emerged as a scientific and medical discipline at end of 20th century uses cultured cells and tissue-engineered structures for transplantation into human body to restore lost or damaged organs. However, practical achievements in this field are far from the promising results obtained in laboratory experiments. Searching for new directions has made apparent that successful solution of practical problems is impossible without understanding the fundamental principles of the regulation of development, renewal, and regeneration of human tissues. These aspects have been extensively investigated by cell biologists, physiologists, and biochemists working in a specific research area often referred to as regenerative biology. It is known that during regeneration, growth factors, cytokines, and hormones act beyond the regulation of individual cell functions, but rather activate specific receptor systems and control pivotal tissue repair processes, including cell proliferation and differentiation. These events require numerous coordinated stimuli and, therefore, are practically irreproducible using single proteins or low-molecular-weight compounds, i.e., cannot be directed by applying classical pharmacological approaches. Our review summarizes current concepts on the regulatory mechanisms of renewal and regeneration of human tissues with special attention to certain general biological and evolutionary aspects. We focus on the biochemical regulatory mechanisms of regeneration, in particular, the role of growth factors and cytokines and their receptor systems. In a separate section, we discussed practical approaches for activating regeneration using small molecules and stem cell secretome containing a broad repertoire of growth factors, cytokines, peptides, and extracellular vesicles.
KEY WORDS: regenerative medicine, stem cell, growth factor, cytokine, intracellular signaling, receptor tyrosine kinase

DOI: 10.1134/S0006297920010022