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Generation and analysis of spheroids from human primary skin myofibroblasts: an
experimental system to study myofibroblasts deactivation
#MMPMID28725488
Granato G
; Ruocco MR
; Iaccarino A
; Masone S
; Calì G
; Avagliano A
; Russo V
; Bellevicine C
; Di Spigna G
; Fiume G
; Montagnani S
; Arcucci A
Cell Death Discov
2017[]; 3
(?): 17038
PMID28725488
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Myofibroblasts are activated fibroblasts involved in tissue repair and cancer.
They are characterized by de novo expression of ?-smooth muscle actin (?-SMA),
immunoregulatory phenotype and paracrine interaction with normal and tumorigenic
cells leading to cell proliferation. At the end of wound-healing myofibroblasts
undergo apoptotic cell death, whereas in vitro-activated fibroblasts are also
subjected to a programmed necrosis-like cell death, termed nemosis, associated
with cyclooxygenase-2 (COX-2) expression induction and inflammatory response.
Furthermore, myofibroblasts form clusters during wound healing, fibrotic states
and tumorigenesis. In this study, we generated and analysed clusters such as
spheroids from human primary cutaneous myofibroblasts, which represent a part of
stromal microenvironment better than established cell lines. Therefore, we
evaluated apoptotic or necrotic cell death, inflammation and activation markers
during myofibroblasts clustering. The spheroids formation did not trigger
apoptosis, necrotic cell death and COX-2 protein induction. The significant
decrease of ?-SMA in protein extracts of spheroids, the cytostatic effect exerted
by spheroids conditioned medium on both normal and cancer cell lines and the
absence of proliferation marker Ki-67 after 72?h of three-dimensional culture
indicated that myofibroblasts have undergone a deactivation process within
spheroids. The cells of spheroids reverted to adhesion growth preserved their
proliferation capability and can re-acquire a myofibroblastic phenotype.
Moreover, the spontaneous formation of clusters on plastic and glass substrates
suggests that aggregates formation could be a physiological feature of cutaneous
myofibroblasts. This study represents an experimental model to analyse
myofibroblasts deactivation and suggests that fibroblast clusters could be a cell
reservoir regulating tissues turnover.
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