Clinical-instrumental and morphological evaluation of the effect of autologous dermal fibroblasts administration Vadim Zorin 1,2 , Alla Zorina 3 , Vladimir Cherkasov 3 *, Roman Deev 4 , Pavel Kopnin 2 and Artur Isaev 1 1 OJSC ‘Human Stem Cells Institute’, Business Development Department, Moscow, Russia 2 Research Institute of carcinogenesis, RAMS, Moscow, Russia 3 OJSC ‘Human Stem Cells Institute’, Regenerative Medicine Department, Moscow, Russia 4 OJSC ‘Human Stem Cells Institute’, R&D Department, Moscow, Russia Abstract Basic molecular mechanisms, associated with the main cell population of the dermis – fibroblasts – are the basis of skin aging. The number of functionally active fibroblasts in the skin and their biosyn- thetic activity decreases with age, thus enhancement of their cell density with synthetically active cells is accepted as a one of the most effective methods. The objective of the present study was to evaluate the safety and effectiveness of intradermal administration of autologous dermal fibroblasts in a year after treatment of 17 patients, aged 45–65 years. Results obtained with modern instrumental skin diagnostic methods (vacuum cutometry, optical profilometry, VISIA photometric analysis, etc.) demonstrate the safety and clinical effectiveness of dermal autofibroblast therapy: after transplanta- tion, cultured autofibroblasts keep their biosynthetic activity and produce extracellular matrix for at least 12 months. As a result, remodelling of the dermis microstructures is observed, accompanied by a progressive increase of collagen content and thickness of the dermis (up to 62.5 ±6.7% in 12 months). This is clinically expressed by increase of skin elasticity (24.0 ±4.3% in periorbital area) and thickness of the skin, and by decrease in the number and depth of wrinkles (46 ±7% by the end of observation period). Copyright © 2014 John Wiley & Sons, Ltd. Received 18 November 2013; Revised 16 July 2014; Accepted 3 November 2014 Keywords autologous fibroblasts; cell therapy; SPRS therapy; aging of skin; regenerative medicine 1. Introduction Skin aging is based on fundamental molecular mecha- nisms which are associated with the primary dermal cell population – fibroblasts. The main function of fibroblasts is to produce, organize and renew intercellular dermal matrix (Fisher et al., 2008; Sorrell and Caplan, 2009). It is known that dermal fibroblasts, the heterogeneous cell population, which consists of all fibroblastic programmed differentiation from multipotent mesenchymal stromal cell, progenitor cells and differentiated fibroblasts up to fi- nally differentiated fibrocytes, are the main effectors in skin physiology (Sorrell and Caplan, 2009). They control composition and structure of intercellular matrix via feedback-regulated synthesis of collagen, elastin and cyto- sol, as well as involvement in degradation of the compo- nents (Zhukova et al., 2009). With age, the number of functionally active fibroblasts is decreased in the skin, the balance between synthesis and degradation processes of intercellular matrix is disrupted, their biosynthetic activity is reduced and the collagen content (the main structural dermal component) is decreased (Varani et al., 2006; Fisher et al., 2008; Sorrell and Caplan, 2009). It is shown that collagen pro- duction in skin of elderly persons (aged over 80 years) in comparison with the young (aged 18–29 years) is re- duced on average by 75%, and the total number of fibro- blasts is decreased by an average of 35% (Fisher et al., 2002). Such processes manifest as decreased skin thick- ness, decreased elasticity and wrinkle formation. Boss et al. showed, in 2000, that intradermal administration of autologous dermal fibroblasts (autoDF) *Correspondence to: Vladimir Cherkasov, OJSC ‘Human Stem Cells Institute’, Regenerative Medicine Department, Moscow, Russia; PO Box 373, Bld 2, 3 Gubkina Street, Moscow 119333, Russia. E-mail: cherkasov@hsci.ru Copyright © 2014 John Wiley & Sons, Ltd. JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE RESEARCH ARTICLE J Tissue Eng Regen Med (2014). Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/term.1976