Adipose-Derived Stem Cells from Systemic Sclerosis Patients Maintain Pro-Angiogenic and Antifibrotic Paracrine Effects In Vitro

Abstract

Innovative therapies based on autologous adipose-derived stem/stromal cells (ASC) are currently being evaluated for treatment of systemic sclerosis (SSc). Although paracrine angiogenic and antifibrotic effects are considered the predominant mechanisms of ASC therapeutic potential, the impact of SSc on ASC paracrine functions remains controversial. In this study, phenotype, senescence, differentiation potential, and molecular profile were determined in ASC from SSc patients (SSc-ASC) (n = 7) and healthy donors (HD-ASC) (n = 7). ASC were co-cultured in indirect models with dermal fibroblasts (DF) from SSc patients or endothelial cells to assess their pro-angiogenic and antifibrotic paracrine effects. The angiogenic activity of endothelial cells was measured in vitro using tube formation and spheroid assays. DF collagen and alpha smooth muscle actin (αSMA) content were quantified after five days of co-culture with ASC. Differentiation capacity, senescence, and mRNA profiles did not differ significantly between SSc-ASC and HD-ASC. SSc-ASC retained the ability to stimulate angiogenesis through paracrine mechanisms; however, functional assays revealed reduced potential compared to HD-ASC. DF fibrosis markers were significantly decreased after co-culture with SSc-ASC. Together, these results indicate that SSc effects do not significantly compromise the angiogenic and the antifibrotic paracrine properties of ASC, thereby supporting further development of ASC-based autologous therapies for SSc treatment.

Immunomodulatory Effect of Adipose-Derived Stem Cells: The Cutting Edge of Clinical Application

“…In this regard, contradictory results are available about the properties of ASCs isolated from patients affected by autoimmune and chronic inflammatory diseases. For example, some reports demonstrated that ASCs from patients affected by systemic sclerosis show the same phenotypical and functional characteristics of their healthy counterparts (Scuderi et al, 2013;Capelli et al, 2017;Velier et al, 2019), while Griffin et al (2017) observed that ASCs from sclerodermic patients showed identical phenotype and differentiation capacity of those from healthy donors, but displayed reduced proliferation and migration capacity. Whilst, the presence of cardiovascular risk factors in cardiac patients seems to reduce ASC pluripotency and self-renewal, thus discouraging their autologous use in the clinical setting (Dimmeler and Leri, 2008;Krawiec et al, 2016).…”

Mesenchymal Stem/Stromal Cells in Immunity and Disease: A Better Understanding for an Improved Use

“…Such therapy was safe, well tolerated, and associated with possible transient, beneficial, clinical and peripheral immune-tolerogenic effects [3]. Velier, M. et al indicated that adipose-derived stem/stromal cells (ASC) from systemic sclerosis (SSs) patients maintain pro-angiogenic and anti-fibrotic paracrine effects in vitro, thereby supporting further development of ASC-based autologous therapies for SSc treatment [4]. Buyl, K. et al pointed out the responses and characteristics of MSCs from adipose tissue, following expansion and inflammatory priming that substantially modulated the expression of 28 molecules implicated in immune regulation [5].…”

Extracellular matrix-based biomaterials as adipose-derived stem cell delivery vehicles in wound healing: a comparative study between a collagen scaffold and two xenografts

“…Histology and immunohistochemistry analyses showed the absence of a fibrotic response, as indicated by a lower scar index than the sham and no increase of cellularity in the wounds. In general, cell-loaded materials, even though they were loaded with half of the cells that were delivered through the direct injection approach, exhibited low levels of total collagen, high levels of mature collagen and high angiogenesis potential, which further advocate the paracrine antifibrotic effect, regenerative/ remodelling capacity and vascularisation competence of ADSCs [54][55][56]. The injected hADSCs resulted in higher collagen deposition, which could be related to a slower activity during the remodelling phase [57,58].…”