The Roles of Podoplanin-Positive/Podoplanin-Negative Cells from Adipose-Derived Stem Cells in Lymphatic Regeneration.
Animals
Biomarkers
/ metabolism
Cells, Cultured
Cytokines
/ metabolism
Disease Models, Animal
Endothelial Cells
/ physiology
Female
Green Fluorescent Proteins
Lymphangiogenesis
/ physiology
Lymphatic Vessels
/ physiology
Lymphedema
/ physiopathology
Membrane Glycoproteins
/ metabolism
Mesenchymal Stem Cells
/ physiology
Mice, Inbred C57BL
Mice, Transgenic
Neovascularization, Physiologic
/ physiology
Phenotype
Journal
Plastic and reconstructive surgery
ISSN: 1529-4242
Titre abrégé: Plast Reconstr Surg
Pays: United States
ID NLM: 1306050
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
entrez:
28
1
2020
pubmed:
28
1
2020
medline:
6
2
2020
Statut:
ppublish
Résumé
Secondary lymphedema is a refractory disease, for which adipose-derived stem cells have shown some therapeutic potential. However, the mechanism of this action remains poorly understood. The authors identified podoplanin-expressing adipose-derived stem cells, which allowed them to divide adipose-derived stem cells into podoplanin-positive and podoplanin-negative groups that they characterized in vitro. The authors then used a mouse hindlimb model for lymphedema to trace the fate of podoplanin-positive, podoplanin-negative, and unsorted adipose-derived stem cells in vivo. When induced in culture, podoplanin-positive cells were noted to up-regulate the expression of lymphatic endothelial cell markers, including LYVE-1, and assumed a cobblestone morphology. In addition, a substantial increase in lymphangiogenic cytokines was detected in the podoplanin-positive supernatant. The above findings were largely absent from the podoplanin-negative and unsorted groups. In the mouse model, the implanted cells relieved the limb lymphedema by promoting lymphangiogenesis, with the podoplanin-positive group showing the most significant effect. Immunocolocalization further revealed that the podoplanin-positive cells incorporated into lymphatic vessels were positive for LYVE-1. These data demonstrated that actions by means of both paracrine and differentiation pathways were involved in the adipose-derived stem cell-mediated therapeutic effects. The podoplanin-positive cells possessed lymphatic paracrine and differentiation abilities and may represent lymphatic endothelial cell precursor cells. The podoplanin-negative cells, which constitute a considerable proportion of the adipose-derived stem cells, may play an important paracrine role by secreting mesenchymal stem cell-related factors.
Sections du résumé
BACKGROUND
BACKGROUND
Secondary lymphedema is a refractory disease, for which adipose-derived stem cells have shown some therapeutic potential. However, the mechanism of this action remains poorly understood.
METHODS
METHODS
The authors identified podoplanin-expressing adipose-derived stem cells, which allowed them to divide adipose-derived stem cells into podoplanin-positive and podoplanin-negative groups that they characterized in vitro. The authors then used a mouse hindlimb model for lymphedema to trace the fate of podoplanin-positive, podoplanin-negative, and unsorted adipose-derived stem cells in vivo.
RESULTS
RESULTS
When induced in culture, podoplanin-positive cells were noted to up-regulate the expression of lymphatic endothelial cell markers, including LYVE-1, and assumed a cobblestone morphology. In addition, a substantial increase in lymphangiogenic cytokines was detected in the podoplanin-positive supernatant. The above findings were largely absent from the podoplanin-negative and unsorted groups. In the mouse model, the implanted cells relieved the limb lymphedema by promoting lymphangiogenesis, with the podoplanin-positive group showing the most significant effect. Immunocolocalization further revealed that the podoplanin-positive cells incorporated into lymphatic vessels were positive for LYVE-1.
CONCLUSIONS
CONCLUSIONS
These data demonstrated that actions by means of both paracrine and differentiation pathways were involved in the adipose-derived stem cell-mediated therapeutic effects. The podoplanin-positive cells possessed lymphatic paracrine and differentiation abilities and may represent lymphatic endothelial cell precursor cells. The podoplanin-negative cells, which constitute a considerable proportion of the adipose-derived stem cells, may play an important paracrine role by secreting mesenchymal stem cell-related factors.
Identifiants
pubmed: 31985635
doi: 10.1097/PRS.0000000000006474
pii: 00006534-202002000-00030
doi:
Substances chimiques
Biomarkers
0
Cytokines
0
Gp38 protein, mouse
0
Membrane Glycoproteins
0
Green Fluorescent Proteins
147336-22-9
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
420-431Références
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