TY - JOUR
T1 - Hypoxic conditioned medium from mesenchymal stem cells promotes lymphangiogenesis by regulation of mitochondrial-related proteins
AU - Lee, Chang Youn
AU - Kang, Jin Young
AU - Lim, Soyeon
AU - Ham, Onju
AU - Chang, Woochul
AU - Jang, Dae Hyun
N1 - Publisher Copyright:
© 2016 Lee et al.
PY - 2016/3/11
Y1 - 2016/3/11
N2 - Background: Recently, cell-based therapeutic lymphangiogenesis has emerged and provided hope for lymphatic regeneration. Previous studies have demonstrated that secretomes of mesenchymal stem cells (MSCs) facilitate the regeneration of various damaged tissues. This study was conducted to evaluate the lymphangiogenic potential of hypoxic conditioned media (HCM) from MSCs. Methods: To investigate the effects of MSC-secreted factors in starved human lymphatic endothelial cells (hLEC), hLECs were treated with endothelial basal medium (EBM)-2 (control), normoxic conditioned media (NCM), or HCM in vitro and in vivo. Results: MSCs expressed lymphangiogenic factors including EGF, FGF2, HGF, IGF-1, and VEGF-A and -C. hLECs were treated with each medium. hLEC proliferation, migration, and tube formation were improved under HCM compared with NCM. Moreover, expression of mitochondrial-related factors, MFN1and 2, were improved in HCM-treated hLECs. Lymphedema mice injected with HCM showed markedly decreased lymphedema via increased lymphatic vessel formation when compared with EBM-2- or NCM-treated mice. Conclusions: This study suggested that HCM from MSCs contain high levels of secreted lymphangiogenic factors and promote lymphangiogenesis by regulating mitochondrial-related factors. Thus, treatment with HCM may be a therapeutic strategy for lymphedema.
AB - Background: Recently, cell-based therapeutic lymphangiogenesis has emerged and provided hope for lymphatic regeneration. Previous studies have demonstrated that secretomes of mesenchymal stem cells (MSCs) facilitate the regeneration of various damaged tissues. This study was conducted to evaluate the lymphangiogenic potential of hypoxic conditioned media (HCM) from MSCs. Methods: To investigate the effects of MSC-secreted factors in starved human lymphatic endothelial cells (hLEC), hLECs were treated with endothelial basal medium (EBM)-2 (control), normoxic conditioned media (NCM), or HCM in vitro and in vivo. Results: MSCs expressed lymphangiogenic factors including EGF, FGF2, HGF, IGF-1, and VEGF-A and -C. hLECs were treated with each medium. hLEC proliferation, migration, and tube formation were improved under HCM compared with NCM. Moreover, expression of mitochondrial-related factors, MFN1and 2, were improved in HCM-treated hLECs. Lymphedema mice injected with HCM showed markedly decreased lymphedema via increased lymphatic vessel formation when compared with EBM-2- or NCM-treated mice. Conclusions: This study suggested that HCM from MSCs contain high levels of secreted lymphangiogenic factors and promote lymphangiogenesis by regulating mitochondrial-related factors. Thus, treatment with HCM may be a therapeutic strategy for lymphedema.
KW - Hypoxic conditioned media
KW - Lymphangiogenesis
KW - Lymphatic endothelial cells
KW - Mesenchymal stem cells
KW - Mitochondrial-related protein
UR - https://www.scopus.com/pages/publications/84960336432
U2 - 10.1186/s13287-016-0296-1
DO - 10.1186/s13287-016-0296-1
M3 - Article
C2 - 26968383
AN - SCOPUS:84960336432
SN - 1757-6512
VL - 7
JO - Stem Cell Research and Therapy
JF - Stem Cell Research and Therapy
IS - 1
M1 - 38
ER -