Microencapsulated VEGF gene-modified umbilical cord mesenchymal stromal cells promote the vascularization of tissue-engineered dermis: an experimental study.
OBJECTIVE
Tissue-engineered dermis (TED) is thought to be the best treatment for skin defect wounds; however, lack of vascular structures in these products can cause slow vascularization or even transplant failure. We assessed the therapeutic potential of microencapsulated human umbilical cord mesenchymal stromal cells (hUCMSCs) expressing vascular endothelial growth factor (VEGF) in vascularization of TED.


METHODS
hUCMSCs were isolated by means of enzymatic digestion and identified by means of testing biological characteristics. hUCMSCs were induced to differentiate into dermal fibroblasts in conditioned induction media. Collagen-chitosan laser drilling acellular dermal matrix (ADM) composite scaffold was prepared by means of the freeze dehydration and dehydrothermal cross-linking method. hUCMSC-derived fibroblasts were implanted on composite scaffolds to construct TED. TED with microencapsulated VEGF gene-modified hUCMSCs was then transplanted into skin defect wounds in pigs. The angiogenesis of TED at 1 week and status of wound healing at 3 weeks were observed.


RESULTS
The collagen-chitosan laser ADM composite has a uniform microporous structure. This composite has been used to grow hUCMSC-derived fibroblasts in vitro and to successfully construct stem cell-derived TED. Microencapsulated VEGF gene-modified hUCMSCs were prepared with the use of a sodium alginate-barium chloride one-step encapsulation technology. Seven days after the transplantation of the stem cell-derived TED and microencapsulated VEGF gene-modified hUCMSCs into the skin defect wounds on the backs of miniature pigs, the VEGF expression increased and the TED had a higher degree of vascularization. Re-epithelialization of the wound was completed after 3 weeks.


CONCLUSIONS
Microencapsulated VEGF gene-modified hUCMSCs can effectively improve the vascularization of TED and consequently the quality of wound healing.
Department of Plastic Surgery, Affiliated Beijing Shijitan Hospital, Capital Medical University, Beijing, People's Republic of China; Department of Burn and Plastic Surgery, Burns Institute, The First Affiliated Hospital of PLA General Hospital, Beijing, People's Republic of China.
Yanfu
Y
Han
Department of Plastic Surgery, PLA General Hospital, Beijing, People's Republic of China.
Ran
R
Tao
School of Electrical and Information Engineering, Wuhan Institute of Technology, Wuhan, People's Republic of China.
Yanqing
Y
Han
Department of Burn and Plastic Surgery, Burns Institute, The First Affiliated Hospital of PLA General Hospital, Beijing, People's Republic of China.
Tianjun
T
Sun
Department of Burn and Plastic Surgery, Burns Institute, The First Affiliated Hospital of PLA General Hospital, Beijing, People's Republic of China. Electronic address: cjk304@126.com.
Jiake
J
Chai
Department of Plastic Surgery, Affiliated Beijing Shijitan Hospital, Capital Medical University, Beijing, People's Republic of China.
Guang
G
Xu
Department of Plastic Surgery, Affiliated Beijing Shijitan Hospital, Capital Medical University, Beijing, People's Republic of China.
Jing
J
Liu
D000818:Animals; D002214:Capsules / Q000378:metabolism*; D002478:Cells, Cultured; D048271:Chitosan / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D020405:Dermis / Q000098:blood supply / Q000293:injuries / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000502:physiology*; D018014:Gene Transfer Techniques; D048091:Guided Tissue Regeneration; D064593:Heterografts; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D023421:Models, Animal; D018919:Neovascularization, Physiologic; D012871:Skin Diseases / Q000628:therapy*; D016038:Skin Transplantation; D013552:Swine; D013556:Swine, Miniature; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000706:statistics & numerical data; D019076:Transgenes / Q000235:genetics; D014470:Umbilical Cord / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing
D002214:Capsules; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen; D048271:Chitosan
microencapsulation; tissue-engineered dermis; umbilical cord mesenchymal stromal cells; vascular endothelial growth factor; vascularization; wound healing