TY - JOUR
T1 - Anti-Inflammatory and Anti-Fibrotic Effects of Human Amniotic Membrane Mesenchymal Stem Cells and Their Potential in Corneal Repair
AU - Navas, Alejandro
AU - Magaña-Guerrero, Fátima Sofía
AU - Domínguez-López, Alfredo
AU - Chávez-García, César
AU - Partido, Graciela
AU - Graue-Hernández, Enrique O.
AU - Sánchez-García, Francisco Javier
AU - Garfias, Yonathan
N1 - Publisher Copyright:
© 2018 The Authors. Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press
PY - 2018/12
Y1 - 2018/12
N2 - Acute ocular chemical burns are ophthalmic emergencies requiring immediate diagnosis and treatment as they may lead to permanent impairment of vision. The clinical manifestations of such burns are produced by exacerbated innate immune response via the infiltration of inflammatory cells and activation of stromal fibroblasts. New therapies are emerging that are dedicated to repair mechanisms that improve the ocular surface after damage; for example, transplantation of stem cells (SC) has been successfully reported for this purpose. The pursuit of easily accessible, noninvasive procedures to obtain SC has led researchers to focus on human tissues such as amniotic membrane. Human amniotic mesenchymal SC (hAM-MSC) inhibits proinflammatory and fibrotic processes in different diseases. hAM-MSC expresses low levels of classical MHC-I and they do not express MHC-II, making them suitable for regenerative medicine. The aim of this study was to evaluate the effect of intracameral injection of hAM-MSC on the clinical manifestations, the infiltration of inflammatory cells, and the activation of stromal fibroblasts in a corneal alkali-burn model. We also determined the in vitro effect of hAM-MSC conditioned medium (CM) on α-SMA+ human limbal myofibroblast (HLM) frequency and on release of neutrophil extracellular traps (NETs). Our results show that intracameral hAM-MSC injection reduces neovascularization, opacity, stromal inflammatory cell infiltrate, and stromal α-SMA+ cells in our model. Moreover, in in vitro assays, CM from hAM-MSC decreased the quantity of α-SMA+ HLM and the release of NETs. These results suggest that intracameral hAM-MSC injection induces an anti-inflammatory and anti-fibrotic environment that promotes corneal wound healing. Stem Cells Translational Medicine 2018;7:906–917.
AB - Acute ocular chemical burns are ophthalmic emergencies requiring immediate diagnosis and treatment as they may lead to permanent impairment of vision. The clinical manifestations of such burns are produced by exacerbated innate immune response via the infiltration of inflammatory cells and activation of stromal fibroblasts. New therapies are emerging that are dedicated to repair mechanisms that improve the ocular surface after damage; for example, transplantation of stem cells (SC) has been successfully reported for this purpose. The pursuit of easily accessible, noninvasive procedures to obtain SC has led researchers to focus on human tissues such as amniotic membrane. Human amniotic mesenchymal SC (hAM-MSC) inhibits proinflammatory and fibrotic processes in different diseases. hAM-MSC expresses low levels of classical MHC-I and they do not express MHC-II, making them suitable for regenerative medicine. The aim of this study was to evaluate the effect of intracameral injection of hAM-MSC on the clinical manifestations, the infiltration of inflammatory cells, and the activation of stromal fibroblasts in a corneal alkali-burn model. We also determined the in vitro effect of hAM-MSC conditioned medium (CM) on α-SMA+ human limbal myofibroblast (HLM) frequency and on release of neutrophil extracellular traps (NETs). Our results show that intracameral hAM-MSC injection reduces neovascularization, opacity, stromal inflammatory cell infiltrate, and stromal α-SMA+ cells in our model. Moreover, in in vitro assays, CM from hAM-MSC decreased the quantity of α-SMA+ HLM and the release of NETs. These results suggest that intracameral hAM-MSC injection induces an anti-inflammatory and anti-fibrotic environment that promotes corneal wound healing. Stem Cells Translational Medicine 2018;7:906–917.
KW - Corneal repair
KW - Inflammation
KW - NETs
KW - hAM-MSC
KW - α-SMA myofibroblasts
UR - http://www.scopus.com/inward/record.url?scp=85053348038&partnerID=8YFLogxK
U2 - 10.1002/sctm.18-0042
DO - 10.1002/sctm.18-0042
M3 - Artículo
C2 - 30260581
SN - 2157-6564
VL - 7
SP - 906
EP - 917
JO - Stem Cells Translational Medicine
JF - Stem Cells Translational Medicine
IS - 12
ER -