FIBROBLASTS AND TISSUE CELL THERAPY

Fibroblasts are the main cells of the connective tissue of the skin. They were discovered more than 150 years ago and named from the Latin fibra — fiber and the Greek blastos — germ, sprout.

The function of fibroblasts is the synthesis of extracellular matrix components (collagen, elastin, reticulin, hyaluronic acid), that is, what makes the skin supple and smooth. Unfortunately, the number of divisions of fibroblasts is limited from 50 to 60 divisions, after which the cells are not renewed and the skin (tissue) loses its former splendor. But, a new technology for isolating one’s own fibroblasts, reproduction and introduction into problem areas solves this problem.

Over the past 20 years, we have been using the mobilization and storage of autologous fibroblasts for cosmetic programs, not only as a renewal of the pool of our own young fibroblasts, but for remodeling the tissue niche of stem cells.
Fibroblasts found in connective tissues constitute the stem cell niche, especially in organs such as the skin. A new study has shown a redox activation mechanism of the transcription factor JunB, which, through the simultaneous activation of p16INK4A and repression of insulin growth factor-1 (IGF-1), initiates the acceleration of fibroblast aging. Fibroblast aging severely disrupts the metabolic and structural niche, and its important interactions with various stem cells thus cause depletion of stem cell pools and depletion of skin tissues.
Suppressing JunB in a fibroblast niche-specific manner – by restoring IGF-1 and p16 levels – restores skin stem cell pools and overall skin tissue integrity. www.cell.com/cell-reports/fulltext/S2211-1247(21)01077-9

Maintains a healthy and youthful condition of your skin for a long time. Mor et al. proved that when transplanting normal fibroblasts into the skin of cancer patients, no tumors form at the injection site, while transplanting cancer cells always gives tumors. Hayflick and Moorhead (1961) confirmed that normal fibroblasts do not form tumors when transplanted into cancer patients. The safety of the use of fibroblasts was studied by Keller et al., 2000, they proved that fibroblasts obtained after 60 years did not lose their ability to multiply and produce collagen. The procedure is approved for use by the FDA USA and on the territory of the Russian Federation. Our experience in the application of technology is more than twenty years.

CELL THERAPY IN COSMETOLOGY

MSCs have been recognized as therapeutic agents for skin regeneration and rejuvenation. The skin can be damaged as a result of wounds caused by cutting or tearing of tissue, as well as burns. Skin aging is a natural process that can be exacerbated by environmental pollution, exposure to ultraviolet radiation, alcohol, tobacco and malnutrition. MSCs have healing abilities that can be applied to damaged and aging skin. In skin regeneration, MSCs increase cell proliferation and neovascularization, and reduce inflammation in skin lesions. In skin rejuvenation, MSCs lead to the production of collagen and elastic fibers, inhibition of the activation of metalloproteinases, and contribute to protection against aging caused by ultraviolet radiation. MSCs derived from induced pluripotent stem cells (iPSCs) are potentially advanced MSCs that are suitable for cell therapy. www.mdpi.com/1422-0067/22/5/2410

REGENERATION OF CARTILAD TISSUE

New approaches support the concept of MSCs as signaling and modulating cells exerting their influence through trophic and immune mediation rather than as cell replacement therapy.

The advantages of allogeneic cells as a ready-to-use product with well-defined characteristics of cell surface marker expression, proliferative capacity and differentiation capacity are well known. There is more emphasis on allogeneic cell sources. Moreover, the understanding of immunomodulatory mechanisms and the role of trophic factors in the interactions of articular chondrocytes and MSCs is considered, which offer possible targets for assessing the activity of MSCs in vivo in the intra-articular environment. stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/sctm.20-0552

Growth factors secreted by platelets initiate genes involved in the formation of the extracellular matrix in human fibroblasts.
Whole transcriptome sequencing and gene ontology enrichment (GO) analysis of PRGF-treated fibroblasts revealed the induction of several genes involved in extracellular matrix (ECM) formation. Real-time PCR analysis of PRGF-treated fibroblasts and skin explants confirmed the induction of genes associated with ECM, specifically transforming growth factor-induced beta protein (TGFBI), fibronectin 1 (FN1), matrix metalloproteinase-9 (MMP-9), transglutaminase 2 (TGM2), fermitin family member 1 (FERMT1), collagen type I alpha 1 (COL1A1), disintegrin and metalloproteinase 19 (ADAM19), serpin family member 1 (SERPINE1) and lysyl oxidase-like 3 (LOXL3).
The induction of these genes was time dependent and partly dependent on the epidermal growth factor receptor (EGFR). Moreover, PRGF induced fibroblast migration and proliferation. Taken together, the observed effects of PRGF on human fibroblasts may contribute to the underlying mechanisms that support the beneficial wound healing effects of platelet concentrate products.