Systematic Reviews
Copyright ©The Author(s) 2020.
World J Stem Cells. Jul 26, 2020; 12(7): 676-687
Published online Jul 26, 2020. doi: 10.4252/wjsc.v12.i7.676
Table 1 Adipose-derived stem cell-based treatment of lymphedema in animal studies
YearRef.AnimalLocation and methodsGroupsCell type used for characterization and numberImplantation methodsAssessmentResults
2011Hwang et al[25]6-8-wk-old female BALB/c miceHindlimb, Circumferential incision and electrocautery5 groups (n = 5 for each group): Normal, control, hADSCs, VEGF-C hydrogel, hADSCs/VEGF-C hydrogelPKH-26-labeled hADSCs N/AIn combination with VEGF-C gelatin hydrogel subcutaneous injectionDermal edema depth measurement using Vernier calipersCo-administration of hADSCs and VEGF-C decreased dermal edema depth and increased lymphatic vessel intensity
H&E staining
IFC (LYVE-1) for lymphatic vessel intensity
2012Shimizu et al[26]7-8-wk-old male C57BL/6J miceTail 2 mm-wide circumferential annulus of the skin excision at 10 mm distal to the tail base, excluding a 4 mm2 dermal flap located at the ventral side3 groups (n = 12 for each group): Sham, PBS, and freshly isolated ADRCsFreshly isolated ADRCs 2 × 106Local injectionTail thickness measurementLocal injection of ADRCs significantly reduced lymphedema ADRC implantation accelerated lymphangiogenesis ADRC implantation enhanced recruitment of M2 macrophages, to serve as lymphatic endothelial progenitor cells
IHC analysis (LVYE-1)
IFC staining (LYVE-1, CD11-b, CD163)
2015Ackermann et al[27]10-wk-old male C57BL/6J miceTail Circumferential 5 mm-wide full thickness excision at a 10 mm distance from the base of the tail3 groups: Saline, PRP, and ASCAllogenic 3 passages FACS analyzed (CD31−/CD45−/CD29+/CD90+ cellsInjectionAngiogenesis (anti-CD31 staining)Wounds treated by PRP and ASC healed faster and showed a significantly increased epithelialization
Laser Doppler imaging for microcirculationApplication of PRP induced a significantly increased lymphangiogenesis, while application of ASC did not induce any significant change, in this regard.
Lymphangiogenesis (anti-LYVE1 staining)
Corrosion casting for microvascular architecture
Digital planimetry for wound healing
2015Yoshida et al[28]Male C57BL/6J miceRight hindlimb, 30-gray x irradiation, surgical lymph node dissection, and 2-mm gap creation4 groups (n = 20 for each group with different cell numbers)Allogenic up to 5 passages 0, 106, 105, 104Subcutaneous injectionCircumference measurementNumber of lymphatic vessels significantly increased at 2 wk
Near-infrared video camera for lymphatic flow assessment
IHC for quantitation of lymphatic vessels (LYVE, VEGF-C, VEGFR, and EGFP)No direct detection of ADSCs involving lymphangiogenesis by EGFP at 2 wk or chromosome FISH at 2 wk and 4 wk
XY chromosome FISH analysis
2017Hayashida et al[29]10-wk-old male C57BL/6J miceLeft hindlimb, 30-Gy X-ray irradiation, surgical lymph node dissection, and 5-mm gap creation4 groups (n = 5 for each group): Control, VLNT, ADSCs, VLNT-plus/ADSCs-plusAllogenic 1-3 passages at 104VLNT, subcutaneouslyNear-infrared video camera for lymphatic flow assessmentIncreased number of lymphatic vessels
Water-displacement plethysmometer for hind-paw volumetry testInduced lymphatic flow drainage to the circulatory system
IHC for tissue quantification of lymphatic vessels (LYVE-1, VEGF-C, and VEGF-R3)
B16 mouse melanoma cells for functional analysis of lymphatic vessels and nodes