The use of glandular-derived stem cells to improve vascularization in scaffold-mediated dermal regeneration.
Clinical success in tissue regeneration requires improvements in vascularization capacity of scaffolds. Several efforts have been made in this field including cellular and acellular technologies. In this work we combined the use of stem cells derived from pancreas or submandibular glands expressing green fluorescent protein (GFP(+)) with a commercially available scaffold for dermal regeneration. Cells were isolated, characterized and seeded in a scaffold for dermal regeneration. Scaffolds containing cells were used to induce dermal regeneration in a full skin defect model. After 3 weeks of in vivo regeneration, tissues were harvested and vascularization was analyzed. Results showed that gland-derived stem cells displayed stem cell features and presented multipotential differentiation capacity because they were able to differentiate in cell types representing the 3 different germ layers. After seeding, cells were homogeneously distributed and formed focal adhesions with the scaffold. Metabolic assays showed that cells can be cultured for at least 3 weeks in the scaffold. In vivo, the presence of pancreatic or submandibular stem cells significantly enhanced the vascularization compared to empty scaffolds. Presence of gland-derived stem cells in the regenerating tissue was confirmed by the detection of GFP expression in the wound area. In order to explore the possible mechanisms behind the improvement in vascular regeneration, in vitro experiments were performed, showing that gland-derived stem cells could contribute by angiogenic and vasculogenic mechanisms to this process. Our results suggest that the combined use of stem cells derived from glands and scaffold for dermal regeneration could be a rational alternative to improve vascularization in scaffold-mediated dermal regeneration.
Egaña
José T
JT
Department of Plastic and Hand Surgery, University of Lübeck, Germany. tomasega@gmail.com
Danner
Sandra
S
Kremer
Mathias
M
Rapoport
Daniel H
DH
Lohmeyer
Jörn A
JA
Dye
Julian F
JF
Hopfner
Ursula
U
Lavandero
Sergio
S
Kruse
Charli
C
Machens
Hans-Günther
HG
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D001808:Blood Vessels / Q000473:pathology; D002454:Cell Differentiation; D002470:Cell Survival; D003094:Collagen / Q000737:chemistry; D020405:Dermis / Q000473:pathology; D004338:Drug Combinations; D049452:Green Fluorescent Proteins / Q000737:chemistry; D007797:Laminin / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D011509:Proteoglycans / Q000737:chemistry; D012038:Regeneration; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D013234:Stem Cells / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds
D001672:Biocompatible Materials; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D049452:Green Fluorescent Proteins; D003094:Collagen