Transdifferentiation of Umbilical Cord-Derived Mesenchymal Stem Cells Into Epidermal-Like Cells by the Mimicking Skin Microenvironment

Published on Feb 20, 2015in The International Journal of Lower Extremity Wounds1.38
· DOI :10.1177/1534734615569913
Deyun Chen8
Estimated H-index: 8
(Chinese PLA General Hospital),
Haojie Hao23
Estimated H-index: 23
(Chinese PLA General Hospital)
+ 7 AuthorsXiaobing Fu23
Estimated H-index: 23
(Chinese PLA General Hospital)
Sources
Abstract
Human umbilical cord–derived mesenchymal stem cells (UC-MSCs) are multipotent, primitive, and have been widely used for skin tissue engineering. Their transdifferentiation is determined by the local microenvironment. In this study, we investigated the potential epidermal differentiation of UC-MSCs and the formation of epidermis substitutes in a 3-dimensional (3D) microenvironment, which was fabricated by UC-MSCs embedded into collagen–chitosan scaffolds (CCSs) combined with an air–liquid interface (ALI) culture system. Using fluorescence microscope, we observed that UC-MSCs were spindle-shaped and evenly distributed in the scaffold. Methyl thiazolyl blue tetrazolium bromide assay and Live/Dead assay indicated that the CCSs have good biocompatibility with UC-MSCs. Immunohistochemistry and western blotting assay showed that UC-MSCs on the surface of the CCSs were positive for the epidermal markers cytokeratin 19 and involucrin at 14 days. In addition, hematoxylin–eosin staining indicated that multilayered epidermis substitutes were established. The constructed epidermis substitutes were applied to treat full-thickness wounds in rats and proved to promote wound healing. In conclusion, manipulating the 3D microenvironment is a novel method for inducing the epidermal differentiation of MSCs to engineer epidermal substitutes, which provides an alternative strategy for skin tissue engineering.
References42
Newest
#1Nkemcho Ojeh (UWI: University of the West Indies)H-Index: 11
#2H Navsaria (Lond: University of London)H-Index: 6
The development of new wound therapies, such as bioengineered skin equivalents, is an ongoing process. Multi-potent mesenchymal stem cells (MSCs) give rise to many tissue lineages and have been implicated in wound healing making them a potential candidate for cell-based bioengineered products for injured tissue. In this study, we investigated the mesenchymal/epithelial interactions of cultured MSCs in comparison to cultured fibroblasts on epidermal proliferation, differentiation, and extracellul...
25 CitationsSource
#1Wang Li (SJTU: Shanghai Jiao Tong University)H-Index: 1
#2Bo Ye (SJTU: Shanghai Jiao Tong University)H-Index: 2
Last. Wei-Qiang Gao (SJTU: Shanghai Jiao Tong University)H-Index: 51
view all 5 authors...
Although human umbilical cord mesenchymal stem cells (hUC-MSCs) have been identified as a new source of MSCs for potential application in regenerative medicine, their full potential of differentiation has not been determined. In particular, whether they have the capability to differentiate into epithelial cells of endodermal origin such as the prostate epithelial cells is unknown. Here we report that when hUC-MSCs were combined with rat urogenital sinus stromal cells (rUGSSs) and transplanted in...
6 CitationsSource
#1Dongjie LiH-Index: 3
#2Jiake ChaiH-Index: 5
Last. Tianjun SunH-Index: 7
view all 5 authors...
Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) isolated from human umbilical Wharton’s Jelly are a population of primitive and pluripotent cells. In specific conditions, hUCMSCs can differentiate into various cells, including adipocytes, osteoblasts, chondrocytes, neurocytes, and endothelial cells. However, few studies have assessed their differentiation into epidermal cells in vitro. To assess the potential of hUCMSCs to differentiate into epidermal cells, a microporous membrane-...
16 CitationsSource
#1Waqar Hassan (UCD: University College Dublin)H-Index: 6
#2Udo Greiser (UCD: University College Dublin)H-Index: 23
Last. Wenxin Wang (UCD: University College Dublin)H-Index: 51
view all 3 authors...
Impaired wound healing remains a challenge to date and causes debilitating effects with tremendous suffering. Recent advances in tissue engineering approaches in the area of cell therapy have provided promising treatment options to meet the challenges of impaired skin wound healing such as diabetic foot ulcers. Over the last few years, stem cell therapy has emerged as a novel therapeutic approach for various diseases including wound repair and tissue regeneration. Several different types of stem...
172 CitationsSource
#1Lingying LiuH-Index: 10
#1Lingying LiuH-Index: 1
Last. Jundong DuH-Index: 4
view all 9 authors...
Background Severe burns are a common and highly lethal trauma. The key step for severe burn therapy is to promote the wound healing as early as possible, and reports indicate that mesenchymal stem cell (MSC) therapy contributes to facilitate wound healing. In this study, we investigated effect of human umbilical cord MSCs (hUC-MSCs) could on wound healing in a rat model of severe burn and its potential mechanism. Methods Adult male Wistar rats were randomly divided into sham, burn, and burn tran...
116 CitationsSource
Chronic or non-healing skin wounds present an ongoing challenge in advanced wound care, particularly as the number of patients increases while technology aimed at stimulating wound healing in these cases remains inefficient. Mesenchymal stem cells (MSCs) have proved to be an attractive cell type for various cell therapies due to their ability to differentiate into various cell lineages, multiple donor tissue types, and relative resilience in ex-vivo expansion, as well as immunomodulatory effects...
106 CitationsSource
#1Yi–Han Lin (NTUST: National Taiwan University of Science and Technology)H-Index: 1
#2Keng-Yen Fu (NDMC: National Defense Medical Center)H-Index: 7
Last. Niann-Tzyy Dai (NDMC: National Defense Medical Center)H-Index: 13
view all 14 authors...
Embryonic stem cells (ESCs) are pluripotent cells that can differentiate into various cell types, including keratinocyte-like cells, within suitable microniches. In this study, we aimed to investigate the effects of culture media, cell coculture, and a tissue-engineering biocomposite on the differentiation of mouse ESCs (MESCs) into keratinocyte-like cells and applied these cells to a surgical skin wound model. MESCs from BALB/c mice (ESC26GJ), which were transfected using pCX-EGFP expressing gr...
6 CitationsSource
#1Simat Siti Fatimah (UMS: Universiti Malaysia Sabah)H-Index: 5
#2Kien Hui Chua (UKM: National University of Malaysia)H-Index: 23
Last. Hayati Abdul Rahman (USIM: Universiti Sains Islam Malaysia)H-Index: 1
view all 6 authors...
Abstract Background aims The aim of the present study was to evaluate the effects of air-liquid interface on the differentiation potential of human amnion epithelial cells (HAECs) to skin-like substitute in organotypic culture. Methods HAECs at passage 1–2 were seeded onto a fibrin layer populated with human amnion mesenchymal cells to form the organotypic cultures. The organotypic HAECs were then cultured for 7, 14 and 21 d in two types of culture system: the submerged culture and the air-liqui...
12 CitationsSource
#1Hui-Min Wang (KMU: Kaohsiung Medical University)H-Index: 33
#2Yi-Ting Chou (KMU: Kaohsiung Medical University)H-Index: 4
Last. Mei-Ling Ho (KMU: Kaohsiung Medical University)H-Index: 34
view all 6 authors...
Skin wound healing is an important lifesaving issue for massive lesions. A novel porous scaffold with collagen, hyaluronic acid and gelatin was developed for skin wound repair. The swelling ratio of this developed scaffold was assayed by water absorption capacity and showed a value of over 20 g water/g dried scaffold. The scaffold was then degraded in time- and dose-dependent manners by three enzymes: lysozyme, hyaluronidase and collagenase I. The average pore diameter of the scaffold was 132.5±...
101 CitationsSource
#1Jun Liu (UMB: University of Maryland, Baltimore)H-Index: 15
#2Hockin H.K. XuH-Index: 89
Last. Carroll Ann Trotman (UMB: University of Maryland, Baltimore)H-Index: 4
view all 6 authors...
There has been little research on the seeding of human umbilical cord mesenchymal stem cells (hUCMSCs) in three-dimensional scaffolds for muscle tissue engineering. The objectives of this study were: (i) to seed hUCMSCs in a fibrin hydrogel containing fast-degradable microbeads (dMBs) to create macropores to enhance cell viability; and (ii) to investigate the encapsulated cell proliferation and myogenic differentiation for muscle tissue engineering. Mass fractions of 0–80% of dMBs were tested, a...
44 CitationsSource
Cited By11
Newest
#1Sara Vilabril (University of Aveiro)H-Index: 1
#2Sara Nadine (University of Aveiro)H-Index: 3
Last. João F. Mano (University of Aveiro)H-Index: 105
view all 8 authors...
The therapeutic effectiveness and biological relevance of technologies based on adherent cells depend on platforms that enable long-term culture in controlled environments. Liquid-core capsules have been suggested as semipermeable moieties with spatial homogeneity due to the high mobility of all components in their core. The lack of cell-adhesive sites in liquid-core structures often hampers their use as platforms for stem cell-based technologies for long-term survival and cell-directed self-org...
Source
#1Michaël Schreurs (Radboud University Nijmegen)H-Index: 1
#2C. Maarten Suttorp (Radboud University Nijmegen)H-Index: 1
Last. Frank A. D. T. G. Wagener (Radboud University Nijmegen)H-Index: 23
view all 8 authors...
: Cleft lip with or without cleft palate is a congenital deformity that occurs in about 1 of 700 newborns, affecting the dentition, bone, skin, muscles and mucosa in the orofacial region. A cleft can give rise to problems with maxillofacial growth, dental development, speech, and eating, and can also cause hearing impairment. Surgical repair of the lip may lead to impaired regeneration of muscle and skin, fibrosis, and scar formation. This may result in hampered facial growth and dental developm...
5 CitationsSource
#1Fereshteh Shojaei (Shahrekord University of Medical Sciences)H-Index: 3
#2Shima Rahmati (Kurdistan University of Medical Sciences)H-Index: 5
Last. Mehdi Banitalebi Dehkordi (Shahrekord University of Medical Sciences)H-Index: 3
view all 3 authors...
: Mesenchymal stem cells (MSCs) accelerate wound healing but the harsh environment of wound site limits the engraftment, retention, and survival rate of transplanted cells. There are multiple approaches that amplify the therapeutic potential of MSCs. The MSCs derived from medical waste material, provide comparable regenerative abilities compared to traditional sources. The application of different scaffolds increases MSC delivery and migration into the wound. The spheroid culture of MSC increase...
12 CitationsSource
Mesenchymal stem cells (MSCs) are widely used in experimental research on cell therapy intended for the stimulation of repair processes in damaged tissues and organs. The present review summarizes the results of studies devoted to the possible directions of MSC differentiation after the transplantation of these cells into damaged nerves or special engineered structures of biological and artificial biodegradable materials that join the ends of a damaged nerve (nerve conduits). Data on exogenous M...
1 CitationsSource
#1Dinesh Murugan Girija (SRU: Sri Ramachandra University)H-Index: 6
#2Mangathayaru Kalachaveedu (SRU: Sri Ramachandra University)H-Index: 4
Last. Rajasekaran Subbarayan (SRU: Sri Ramachandra University)H-Index: 5
view all 4 authors...
: Gingival tissue is reportedly a promising, easily accessible, abundant resource of mesenchymal stem cells (MSC) for use in various tissue engineering strategies. Human gingival MSC (HGMSCs) were successfully isolated from gingival tissue and characterized. To analyze in a two-dimensional form, HGMSCs were cultured with basal medium and induced with 25 µg/ml of Acalypha indica. Quantitative real-time polymerase chain reaction (qPCR) and western blot analysis showed the presence of keratinocyte-...
4 CitationsSource
#1Biraja C. Dash (Yale University)H-Index: 16
#2Zhenzhen Xu (Yale University)H-Index: 3
Last. Henry C. Hsia (Yale University)H-Index: 13
view all 8 authors...
The normal wound healing process involves a well-organized cascade of biological pathways and any failure in this process leads to wounds becoming chronic. Non-healing wounds are a burden on healthcare systems and set to increase with aging population and growing incidences of obesity and diabetes. Stem cell-based therapies have the potential to heal chronic wounds but have so far seen little success in the clinic. Current research has been focused on using polymeric biomaterial systems that can...
41 CitationsSource
#1Ananya Barui (Indian Institute of Engineering Science and Technology, Shibpur)H-Index: 13
#2Farhan Chowdhury (SIU: Southern Illinois University Carbondale)H-Index: 21
Last. Pallab Datta (Indian Institute of Engineering Science and Technology, Shibpur)H-Index: 19
view all 4 authors...
Abstract Mesenchymal stromal/stem cells (MSCs) are multipotent cells that offer a promising outcome in the field of regenerative medicine. MSCs are present in various tissues including bone marrow, fat, skin, and placenta. The interest in clinical application of these mesoderm-derived MSCs is primarily fueled by their high self-renewal capacity and multipotency. Although, early studies indicated limited differentiation capacity of MSCs into same cell lineages from which they were isolated, subse...
21 CitationsSource
#1Xiao-Fei Zhang (WUT: Wuhan University of Technology)H-Index: 3
#2Jun Li (WHU: Wuhan University)H-Index: 1
Last. Xiaofeng Cui (WUT: Wuhan University of Technology)H-Index: 22
view all 6 authors...
Abstract A major challenge for clinical use of skin substitutes is insufficient host tissue integration leading to loosening and partial necrosis of the implant. In this present study, a three-dimensional (3D) coculture system constructed using human umbilical cord mesenchymal stem cells (uc-MSCs) and umbilical vein endothelial cells (HUVECs) encapsulated in gelatin methacryloyl (GelMA) hydrogels was evaluated to determine the outcomes of cell-cell interactions in vitro and in vivo . The results...
21 CitationsSource
#2Xiao Nong WangH-Index: 3
Last. Anne M. DickinsonH-Index: 42
view all 4 authors...
3 CitationsSource
#1Deyun Chen (Chinese PLA General Hospital)H-Index: 8
#2Haojie Hao (Chinese PLA General Hospital)H-Index: 23
Last. Weidong Han (Chinese PLA General Hospital)H-Index: 52
view all 4 authors...
Wound reepithelialization is a cooperative multifactorial process dominated by keratinocyte migration, proliferation, and differentiation that restores the intact epidermal barrier to prevent infection and excessive moisture loss. However, in wounds that exhibit impaired wound healing, such as chronic nonhealing wounds or hypertrophic scars, the reepithelialization process has failed. Thus, it is necessary to explore a suitable way to mitigate these abnormalities to promote reepithelialization a...
19 CitationsSource