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微囊化 VEGF 基因修饰的脐带间充质基质细胞促进组织工程化真皮的血管化:一项实验研究。

Microencapsulated VEGF gene-modified umbilical cord mesenchymal stromal cells promote the vascularization of tissue-engineered dermis: an experimental study.

机构信息

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.

Department of Plastic Surgery, PLA General Hospital, Beijing, People's Republic of China.

出版信息

Cytotherapy. 2014 Feb;16(2):160-9. doi: 10.1016/j.jcyt.2013.10.014.


DOI:10.1016/j.jcyt.2013.10.014
PMID:24438897
Abstract

BACKGROUND AIMS: 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.

摘要

背景目的:组织工程真皮(TED)被认为是治疗皮肤缺损创面的最佳方法;然而,这些产品中缺乏血管结构会导致血管化缓慢,甚至移植失败。我们评估了表达血管内皮生长因子(VEGF)的微囊化人脐带间充质基质细胞(hUCMSCs)在 TED 血管化中的治疗潜力。

方法:通过酶消化法分离 hUCMSCs,并通过生物学特性检测进行鉴定。hUCMSCs 在条件诱导培养基中诱导分化为真皮成纤维细胞。通过冷冻干燥和去水热交联法制备胶原-壳聚糖激光钻削脱细胞真皮基质(ADM)复合支架。将 hUCMSC 源性成纤维细胞植入复合支架上构建 TED。然后将微囊化 VEGF 基因修饰的 hUCMSCs 转染 TED 并移植到猪皮肤缺损创面。观察 1 周时 TED 的血管生成情况和 3 周时创面愈合情况。

结果:胶原-壳聚糖激光 ADM 复合支架具有均匀的微孔结构。该复合支架已用于体外培养 hUCMSC 源性成纤维细胞,并成功构建干细胞源性 TED。采用海藻酸钠-氯化钡一步包埋技术制备微囊化 VEGF 基因修饰的 hUCMSCs。将干细胞源性 TED 和微囊化 VEGF 基因修饰的 hUCMSCs 移植到小型猪背部皮肤缺损创面 7 天后,VEGF 表达增加,TED 的血管化程度更高。3 周后,创面完成再上皮化。

结论:微囊化 VEGF 基因修饰的 hUCMSCs 可有效改善 TED 的血管化,从而提高创面愈合质量。

相似文献

[1]
Microencapsulated VEGF gene-modified umbilical cord mesenchymal stromal cells promote the vascularization of tissue-engineered dermis: an experimental study.

Cytotherapy. 2014-2

[2]
Transplantation of microencapsulated cells expressing VEGF improves angiogenesis in implanted xenogeneic acellular dermis on wound.

Transplant Proc. 2010-6

[3]
The healing of full-thickness burns treated by using plasmid DNA encoding VEGF-165 activated collagen-chitosan dermal equivalents.

Biomaterials. 2010-11-10

[4]
Preparation of microencapsulated VEGF gene-modified human umbilical cord mesenchymal stem cells and in vitro culture.

Eur Rev Med Pharmacol Sci. 2013-1

[5]
[Effects of different artificial dermal scaffolds on vascularization and scar formation of wounds in pigs with full-thickness burn].

Zhonghua Shao Shang Za Zhi. 2012-2

[6]
Umbilical Cord Mesenchymal Stem Cells Combined With a Collagenfibrin Double-layered Membrane Accelerates Wound Healing.

Wounds. 2015-5

[7]
[Mechanisms and effects of biosynthesis and apoptosis in repair of full-thickness skin defect with collagen-chitosan dermal stent].

Zhonghua Zheng Xing Wai Ke Za Zhi. 2009-5

[8]
[Effects of gelatin methacrylate anhydride hydrogel loaded with small extracellular vesicles derived from human umbilical cord mesenchymal stem cells in the treatment of full-thickness skin defect wounds in mice].

Zhonghua Shao Shang Yu Chuang Mian Xiu Fu Za Zhi. 2024-4-20

[9]
[EXPERIMENTAL STUDY ON HUMAN UMBILICAL CORD MESENCHYMAL STEM CELLS-ALGINATE WOUND DRESSING].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2015-9

[10]
Vascular endothelial growth factor-C promotes vasculogenesis, angiogenesis, and collagen constriction in three-dimensional collagen gels.

J Vasc Surg. 2005-4

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Alginate-polylysine-alginate (APA) microencapsulated transgenic human amniotic epithelial cells ameliorate fibrosis in hypertrophic scars.

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[2]
Mesenchymal stem cell therapy in diabetic foot ulcer: An updated comprehensive review.

Health Sci Rep. 2024-4-21

[3]
Mesenchymal Stem Cells in Soft Tissue Regenerative Medicine: A Comprehensive Review.

Medicina (Kaunas). 2023-8-10

[4]
Scaffold-based delivery of mesenchymal stromal cells to diabetic wounds.

Stem Cell Res Ther. 2022-8-20

[5]
Recent strategies for enhancing the therapeutic efficacy of stem cells in wound healing.

Stem Cell Res Ther. 2021-11-25

[6]
Systematic Review of the Application of Perinatal Derivatives in Animal Models on Cutaneous Wound Healing.

Front Bioeng Biotechnol. 2021-9-24

[7]
Advancements in the Delivery of Growth Factors and Cytokines for the Treatment of Cutaneous Wound Indications.

Adv Wound Care (New Rochelle). 2021-11

[8]
Growth Factor Gene-Modified Mesenchymal Stem Cells in Tissue Regeneration.

Drug Des Devel Ther. 2020

[9]
Metformin prevents murine ovarian aging.

Aging (Albany NY). 2019-6-10

[10]
Human umbilical cord mesenchymal stem cells implantation accelerates cutaneous wound healing in diabetic rats via the Wnt signaling pathway.

Eur J Med Res. 2019-2-8

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