title: Therapeutic lymphangiogenesis using stem cell and VEGF-C hydrogel.
abstract: Lymphedema is a manifestation of lymphatic system insufficiency. It arises from primary lymphatic dysplasia or secondary obliteration after lymph node dissection or irradiation. Although improvement of swelling can be achieved by comprehensive non-operative therapy, treatment of this condition requires lifelong care and good compliance. Recently molecular-based treatments using VEGF-C have been investigated by several researchers. We designed the present study to determine whether the therapeutic efficacy of implanted human adipose-derived stem cells (hADSCs) could be improved by applying a gelatin hydrogel containing VEGF-C (VEGF-C hydrogel) to the site of tissue injury in a lymphedema mouse model. Four weeks after the operation, we evaluated edema and determined lymphatic vessel density at various post-operative time points. Mice treated with hADSCs and VEGF-C hydrogel showed a significantly decreased dermal edema depth compared to the groups of mice that received hADSCs only or VEGF-C hydrogel only. Immunohistochemical analysis also revealed that the hADSC/VEGF-C hydrogel group showed significantly greater lymphatic vessel regeneration than all the other groups. hADSCs were detected in the implantation sites of all mice in the hADSC/VEGF-C group, and exhibited a lymphatic endothelial differentiation phenotype as determined by co-staining PKH-labeled hADSCs for the lymphatic marker LYVE-1. Our results suggest that co-administration of hADSCs and VEGF-C hydrogel has a substantial positive effect on lymphangiogenesis.
authors.affiliation: Department of Physical and Rehabilitation Medicine, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Hwang
authors.forename: In Gul
authors.initials: IG
authors.lastname: Kim
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Shuyu
authors.initials: S
authors.lastname: Piao
authors.forename: David S
authors.initials: DS
authors.lastname: Lee
authors.forename: Tae Seung
authors.initials: TS
authors.lastname: Lee
authors.forename: Jeong Chan
authors.initials: JC
authors.lastname: Ra
authors.forename: Ji Youl
authors.initials: JY
authors.lastname: Lee
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D005780:Gelatin / Q000737:chemistry; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry / Q000494:pharmacology*; D042583:Lymphangiogenesis; D008209:Lymphedema / Q000628:therapy*; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D012038:Regeneration / Q000502:physiology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D042582:Vascular Endothelial Growth Factor C / Q000494:pharmacology*
chemical_list: D001672:Biocompatible Materials; D042582:Vascular Endothelial Growth Factor C; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005780:Gelatin