EFFECT OF MICE INJURY SERUM INDUCTING MSC ACTIVE : INCREASE OF VEGF,

PDGF, TGF, IL10

Introduction

Optimal wound healing requires a complex series of biological events suchas cell migration,
proliferation, ECM remodeling and angiogenesis (Wu Y, 2007). Studies on BM-MSC, ASC and
amnion-derived progenitor cell administration to dermal wounds have demonstrated such
acceleration ( Fu X, 2009). Upon closer examination, it was determined that MSCs increased
blood perfusion and reduced tissue necrosis in ischemic models through stimulation of
angiogenesis (SH raganath, 2012)

BM-MSCs induced neovascularization through secretion of the pro-angiogenic factors Ang-1

and VEGF within the wound beds (Wu Y, 2007). ASCs implanted into chronic dermal wounds
enhanced granulation tissue thickness, epithelialization and capillary formation by secreting
angiogenic cytokines such as bFGF, PDGF, VEGF and HGF (Nie CD, 2009)

The inflammatory response that activated to restore tissue injury shares various molecular targets
and signaling pathways with the carcinogenic process, such as apoptosis, increased proliferation
rate, and angiogenesis. Several inflammatory mediators, such as TNF-, IL-6, TGF-, and IL-10
(Landskron Glauben,2014)

Tumor necrosis factor- (TNF-), a pro-inflammatory cytokine, is expressed in ischemic and

injured tissues . TNF- plays a key role not only in inflammatory response but also in repair
processes of injured tissues (B. Jiang, 2010).

TNF--treated human adipose tissue-derived MSCs (hASCs) have been shown to secrete various
protein factors, including cytokines, extracellular matrix, proteases, and protease inhibitors.

In response to tumor necrosis factor alpha (TNF), stem cells increase the release of paracrine
factors by a p38 mitogen activated protein kinase (MAPK) and STAT3 dependent mechanism
(Son BR, 2007).

The mechanism for the superior paracrine efficacy of MSCIEC-6(IR) is related to a higher secretion
of regenerative, immunomodulatory and trafficking molecules, including the pivotal factor IGF-
1, induced by TNF- IL-1 and nitric oxide. Pre-activation of MSCs with TNF-, IL-1 and
nitric oxide enhances its paracine effects on RIII via a heme oxygenase-1 dependent mechanism,
which may help us to maximize the paracrine potential of MSCs. (Hao Chen, 2015).

However, the involvement how much of level TNF- CM-induced MSC angiogenesis and repair
of injury tissues has not been explored.
In this study we explored the question wether TNF Alpha pre activation MSC secreting
angiogenic cytokines in vitro.