TY - JOUR
T1 - Medium conditioned by human mesenchymal stromal cells reverses low serum and hypoxia-induced inhibition of wound closure
AU - Kosol, Wilai
AU - Kumar, Suneel
AU - Marrero-BerrÍos, Ileana
AU - Berthiaume, Francois
N1 - Funding Information:
This work was partially supported by the New Jersey Commission on Spinal Cord Injury Research ( CSCR15IRG010 ). Wilai Kosol was supported by the Louis Stokes Alliances for Minority Participation, the ARESTY Research Center at Rutgers University, and a Norman and Ruth Feller Rosenberg Fellowship. Ileana Marrero-Berríos was supported by training grants from NIGMS ( T32GM008339 ) and the U. S. Department of Education GAANN ( P200A150131 ). We thank Paulina Krzyszczyk and Rick Cohen from the Department of Biomedical Engineering at Rutgers University for technical assistance.
Funding Information:
This work was partially supported by the New Jersey Commission on Spinal Cord Injury Research (CSCR15IRG010). Wilai Kosol was supported by the Louis Stokes Alliances for Minority Participation, the ARESTY Research Center at Rutgers University, and a Norman and Ruth Feller Rosenberg Fellowship. Ileana Marrero-Berr?os was supported by training grants from NIGMS (T32GM008339) and the U. S. Department of Education GAANN (P200A150131). We thank Paulina Krzyszczyk and Rick Cohen from the Department of Biomedical Engineering at Rutgers University for technical assistance.
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2020/2/5
Y1 - 2020/2/5
N2 - Chronic wounds, such as pressure ulcers, are a common complication of impaired peripheral circulation, such as in advanced diabetes. Factors secreted by mesenchymal stromal cells (MSCs) have been shown to enhance wound healing in vitro and in vivo. However, there is little understanding of the impact of the chronic wound environment, namely the limited supply of nutrients and oxygen, on the ability of wound cells to respond to MSCs. In this study, we first established the effects of hypoxia (1% O2) and low serum (1% serum) concentration on the proliferation and migration of keratinocytes. We found that hypoxia and low serum significantly slowed down these processes. Next, we found that supplementation with human MSC-concentrated conditioned media (hMSC-CM) enhanced both cell migration and proliferation in the presence of hypoxia and low serum. Furthermore, low serum and hypoxia decreased cell spreading and F-actin expression, which was reversed in the presence of hMSC-CM. Several wound healing mediators were identified in hMSC-CM, including IL-5, IL-6, IL-8, IL-9, IP-10, MCP-1, FGF-2, and VEGF. This study suggests that the concentrated secretome of human MSCs can reverse the inhibitory effect of hypoxia and low serum on keratinocyte proliferation and migration. This phenomenon may contribute to the beneficial effects of hMSC-CM on wound healing in vivo.
AB - Chronic wounds, such as pressure ulcers, are a common complication of impaired peripheral circulation, such as in advanced diabetes. Factors secreted by mesenchymal stromal cells (MSCs) have been shown to enhance wound healing in vitro and in vivo. However, there is little understanding of the impact of the chronic wound environment, namely the limited supply of nutrients and oxygen, on the ability of wound cells to respond to MSCs. In this study, we first established the effects of hypoxia (1% O2) and low serum (1% serum) concentration on the proliferation and migration of keratinocytes. We found that hypoxia and low serum significantly slowed down these processes. Next, we found that supplementation with human MSC-concentrated conditioned media (hMSC-CM) enhanced both cell migration and proliferation in the presence of hypoxia and low serum. Furthermore, low serum and hypoxia decreased cell spreading and F-actin expression, which was reversed in the presence of hMSC-CM. Several wound healing mediators were identified in hMSC-CM, including IL-5, IL-6, IL-8, IL-9, IP-10, MCP-1, FGF-2, and VEGF. This study suggests that the concentrated secretome of human MSCs can reverse the inhibitory effect of hypoxia and low serum on keratinocyte proliferation and migration. This phenomenon may contribute to the beneficial effects of hMSC-CM on wound healing in vivo.
KW - Cytokines and growth factors
KW - Hypoxia
KW - Mesenchymal stromal cells
KW - Proliferation and migration
KW - Scratch assay
KW - Secretome
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U2 - 10.1016/j.bbrc.2019.11.071
DO - 10.1016/j.bbrc.2019.11.071
M3 - Article
C2 - 31761327
AN - SCOPUS:85077613292
VL - 522
SP - 335
EP - 341
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -