Mesenchymal stromal cells of human umbilical cord Wharton's jelly accelerate wound healing by paracrine mechanisms.
OBJECTIVE
Mesenchymal stromal cells (MSC) can be isolated from the perivascular connective tissue of umbilical cords, called Wharton's jelly. These human umbilical cord perivascular cells (HUCPVC) might provide therapeutic benefits when treating skeletal or cutaneous malformations in neonatal patients.


METHODS
HUCPVC were isolated, and their proliferation rate, marker expression and multilineage differentiation potential determined. HUCPVC or their conditioned medium (HUCPVC-CM) was injected into the excisional wound of a mouse splinted-wound model. The effects of the treatment on wound closure were examined by morphohistochemical and gene expression analyses.


RESULTS
HUCPVC expressed typical MSC markers and could differentiate into osteoblastic and adipogenic lineages. HUCPVC transplanted into the mouse wound accelerated wound closure. Immunohistologic analysis showed that the HUCPVC accelerated wound healing by enhancing collagen deposition and angiogenesis via paracrine mechanisms. Furthermore, treatment with HUCPVC-CM alone significantly enhanced wound closure. HUCPVC-CM increased the number of anti-inflammatory M2 macrophages expressing resistin-like molecule (RELM)-α/CD11b and promoted neovessel maturation. Quantitative polymerase chain reaction (PCR) analysis showed that HUCPVC-CM increased the expression of tissue-repairing cytokines interleukin (IL)-10, transforming growth factor (TGF)-β1, vascular endothelial growth factor (VEGF)-1 and angiopoietin-1 at the healing wound.


CONCLUSIONS
Our results show that HUCPVC promotes wound healing via multifaceted paracrine mechanisms. Together with their ability to differentiate into the osteogenic linage, HUCPVC may provide significant therapeutic benefits for treating wounds in neonatal patients.
Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya 466 – 8550, Japan.
Ryutaro
R
Shohara
Akihito
A
Yamamoto
Sachiko
S
Takikawa
Akira
A
Iwase
Hideharu
H
Hibi
Fumitaka
F
Kikkawa
Minoru
M
Ueda
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism; D002452:Cell Count; D002469:Cell Separation; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000187:drug effects; D019899:Paracrine Communication / Q000187:drug effects; D014470:Umbilical Cord / Q000098:blood supply / Q000166:cytology*; D059631:Wharton Jelly / Q000166:cytology*; D014945:Wound Healing / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D017077:Culture Media, Conditioned