Hopes and Limits of Adipose-Derived Stem Cells (ADSCs) and Mesenchymal Stem Cells (MSCs) in Wound Healing

Abstract

Adipose tissue derived stem cells (ADSCs) are mesenchymal stem cells identified within subcutaneous tissue at the base of the hair follicle (dermal papilla cells), in the dermal sheets (dermal sheet cells), in interfollicular dermis, and in the hypodermis tissue. These cells are expected to play a major role in regulating skin regeneration and aging-associated morphologic disgraces and structural deficits. ADSCs are known to proliferate and differentiate into skin cells to repair damaged or dead cells, but also act by an autocrine and paracrine pathway to activate cell regeneration and the healing process. During wound healing, ADSCs have a great ability in migration to be recruited rapidly into wounded sites added to their differentiation towards dermal fibroblasts (DF), endothelial cells, and keratinocytes. Additionally, ADSCs and DFs are the major sources of the extracellular matrix (ECM) proteins involved in maintaining skin structure and function. Their interactions with skin cells are involved in regulating skin homeostasis and during healing. The evidence suggests that their secretomes ensure: (i) The change in macrophages inflammatory phenotype implicated in the inflammatory phase, (ii) the formation of new blood vessels, thus promoting angiogenesis by increasing endothelial cell differentiation and cell migration, and (iii) the formation of granulation tissues, skin cells, and ECM production, whereby proliferation and remodeling phases occur. These characteristics would be beneficial to therapeutic strategies in wound healing and skin aging and have driven more insights in many clinical investigations. Additionally, it was recently presented as the tool key in the new free-cell therapy in regenerative medicine. Nevertheless, ADSCs fulfill the general accepted criteria for cell-based therapies, but still need further investigations into their efficiency, taking into consideration the host-environment and patient-associated factors.

Adipose derived stem cells (ADSCs) Immunomodulation Impact on Skin Tissue Repair

“…Using a specific mussel-inspired nanostructure scaffold derived ADSCs to shift macrophages from M1 to M2 immunomodulatory profile, to enhance vascularization thus accelerating wound closure [64]. This result also suggests the crosstalk between ADSCs and local immune cells to address the inflammatory status of their microenvironment which appear to be potentiated by direct cell-cell contact [32,75].…”

“…The impact of microenvironment changing on ADSCs functionality, on their induction of proliferation, differentiation and migration has already been reported [32][33][34][35]72]. Reciprocally, ADSCs are reported to address this microenvironment in vitro, their conditioned media was reported to activate macrophages and to increase the secretion of TNF and IL-10 anti-inflammatory cytokines stimulating thus wound healing [37,73].…”

“…TFG-β, secreted by ADSCs and other epithelial cells is involved in the inflammatory, proliferative and remodeling phases of wound healing [32]. Together with IL-1β and IL-6, this factor increases macrophages recruitment, and their polarization from M1 to M2 [31] leading to a phase of secretion of anti-inflammatory cytokines [65,66].…”

“…Therefore, ADSCs can be differentiated towards a desired cell phenotype as a result of microenvironment stimulation or by an appropriate composition of cell culture media. Indeed, ADSC's functions are modulated by the composition and the presence of immune cells of their microenvironment and change their behavior in response to the nature of biomolecules, cytokines or cellular profile present [32][33][34][35][36]. Their conditioned media has the ability to induce macrophages to secrete IL-10 and TNF anti-inflammatory cytokines, and at the other side to decrease the secretion of the pro-inflammatory cytokines [28,37].…”

Clinical Translational Potential in Skin Wound Regeneration for Adipose-Derived, Blood-Derived, and Cellulose Materials: Cells, Exosomes, and Hydrogels

“…There have been considerable advancements in the understanding of the biochemical pathways and mechanisms underlying skin regenerative therapies, leading to explorations into the use of cells and cell-derived cytokines and exosomes, as well as hydrogels (recently reviewed in [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]) ( Table 1 ). While decellularized dermal scaffolds are routinely employed [ 20 ], only a PDGF (Platelet Derived Growth Factor)-related product has received regulatory approval among the cytokines, while no cell therapy has widespread approval in the U.S. [ 21 , 22 ].…”