Scarring and Skin Fibrosis Reversal with Regenerative Surgery and Stem Cell Therapy

Abstract

Skin scarring and fibrosis affect millions of people worldwide, representing a serious clinical problem causing physical and psychological challenges for patients. Stem cell therapy and regenerative surgery represent a new area of treatment focused on promoting the body's natural ability to repair damaged tissue. Adipose-derived stem cells (ASCs) represent an optimal choice for practical regenerative medicine due to their abundance, autologous tissue origin, non-immunogenicity, and ease of access with minimal morbidity for patients. This review of the literature explores the current body of evidence around the use of ASCs-based regenerative strategies for the treatment of scarring and skin fibrosis, exploring the different surgical approaches and their application in multiple fibrotic skin conditions. Human, animal, and in vitro studies demonstrate that ASCs present potentialities in modifying scar tissue and fibrosis by suppressing extracellular matrix (ECM) synthesis and promoting the degradation of their constituents. Through softening skin fibrosis, function and overall quality of life may be considerably enhanced in different patient cohorts presenting with scar-related symptoms. The use of stem cell therapies for skin scar repair and regeneration represents a paradigm shift, offering potential alternative therapeutic avenues for fibrosis, a condition that currently lacks a cure.

Keywords: adipose stem cells; cell therapy; extracellular matrix; fat grafting; fibrosis; lipofilling; lipotransfer; regenerative medicine; regenerative surgery; scar; stromal vascular fraction.

Figure 1

The wound healing response. The stages of wound healing following injury involve hemostasis, inflammation, proliferation, and remodeling. Fibroblasts play a crucial role in the formation of cutaneous scars post-injury. Inhibition of these cells leads to a more regenerative phenotype, resulting in reduced scarring. Reproduced with permission from Jones et al., Transfusions, published by Wiley, 2019 [7].

Figure 2

Cellular mechanism of skin fibrosis. Fibroblast activation plays a critical role in the development of fibrosis. A blood vessel (Bv), neutrophils (Ne), macrophages (Mc), and mast cells (Ma) are indicated. ECM: extracellular matrix. Reproduced from Fertala et al., Biomolecules; published by MDPI, 2023 [11].

Figure 3

Fat grafting technique. The adipose tissue is harvested from the abdomen, inner thighs, knees, or hips (A); it is processed via centrifugation at 3000 rpm per 3 minutes to concentrate the fraction rich in ASCs (B); after discarding the upper and lower parts, the purified adipose tissue rich with ASCs is then available to be grafted in the recipient site (C).

Figure 4

SVF and ASCs. The diagram illustrates different options for processing the adipose tissue to obtain progenitors cells (SVF, stromal vascular fraction, or ASCs, adipose-derived stem cells). Option (A) (in green) shows the passages that start with collagenase digestion (1) leading to enzymatically obtained SVF (e-SVF), which is a heterogeneous cell population mainly composed of ASCs, perivascular cells, endothelial cells, inflammatory cells, cell debris, and erythrocytes obtained from the lipoaspirate after collagenase digestion. After culture expansion (3), e-SVF yields a homogeneous population of plastic-adherent cells, the ASCs, that are described as CD31−, CD34+, CD45−, CD90+, CD105−, and CD146−. Option (B) (in blue) shows an alternative method to select mechanically obtained SVF (m-SVF) suspended in a solution mainly composed of broken adipocytes and cell debris.

Figure 5

PRP consists of peripheral blood collection (A); centrifugation to separate the blood into different components (B); and selection of the fraction of plasma rich with platelets for injection at the recipient site (C).

Figure 6

Commonalities among different fibrotic skin conditions successfully treated with ASCs-based therapies.

Figure 7

Fat grafting for reversing scars. The image represents an example of a facial scar treated with fat grafting by our team.

Figure 8

Mechanism of action. The diagram illustrates how fat grafting and ASCs-based therapies reduce scarring and skin fibrosis with a combination of mechanical (1) and paracrine (2) effects. The latter is mediated mainly by the ASCs, which can release cytokines and growth factors with pro-angiogenetic, immunomodulatory, and trophic effects.