Substance P and patterned silk biomaterial stimulate periodontal ligament stem cells to form corneal stroma in a bioengineered three-dimensional model

AimsTo explore the role of corneal-shaped static mechanical strain on the differentiation of human periodontal ligament stem cells (PDLSCs) into keratocytes and the possible synergistic effects of mechanics and inducing medium.MethodsPDLSCs were exposed to 3% static dome-shaped mechanical strain in a Flexcell Tension System for 3 days and 7 days. Keratocyte phenotype was determined by gene expression of keratocyte markers. Keratocyte differentiation (inducing) medium was introduced in the Flexcell system, either continuously or intermittently combined with mechanical stimulation. The synergistic effects of mechanics and inducing medium on keratocyte differentiation was evaluated by gene and protein expression of keratocyte markers. Finally, a multilamellar cell sheet was assembled by seeding PDLSCs on a collagen membrane and inducing keratocyte differentiation. The transparency of the cell sheet was assessed, and typical markers of native human corneal stroma were evaluated by immunofluorescence staining.ResultsDome-shaped mechanical stimulation promoted PDLSCs to differentiate into keratocytes, as shown by the upregulation of ALDH3A1, CD34, LUM, COL I and COL V. The expression of integrins were also upregulated after mechanical stimulation, including integrin alpha 1, alpha 2, beta 1 and non-muscle myosin II B. A synergistic effect of mechanics and inducing medium was found on keratocyte differentiation. The cell sheets were assembled under the treatment of mechanics and inducing medium simultaneously. The cell sheets were transparent, multilamellar and expressed typical markers of corneal stroma.ConclusionDome-shaped mechanical stimulation promotes differentiation of PDLSCs into keratocytes and has synergistic effects with inducing medium. Multilamellar cell sheets that resemble native human corneal stroma show potential for future clinical applications.

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“…The PDLSCs used in the present project have recently been characterised in another study of ours. 11 …”

Section: Methodsmentioning

confidence: 99%

Mechanical stress potentiates the differentiation of periodontal ligament stem cells into keratocytes

et al. 2018

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“…Silk fibroin, a natural protein extracted from Bombyx mori cocoons, can be formed into films and scaffolds with tunable degradation and mechanical strength with non-immunogenic responses in vivo [ 38 , 80 , 81 ]. Use of silk fibroin as a film or scaffolds for corneal tissue replacement [ 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 ] remains an active area of research, as outlined in Table 3 . Silk films and membranes can be fabricated through simple evaporation or electrospinning.…”

Section: Engineering a Cornea Mimetic: Mechanical Properties And Biomaterials Structurementioning

confidence: 99%

Recent Advances in Natural Materials for Corneal Tissue Engineering

et al. 2021

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Given the incidence of corneal dysfunctions and diseases worldwide and the limited availability of healthy, human donors, investigators are working to generate engineered cellular and acellular therapeutic approaches as alternatives to corneal transplants from human cadavers. These engineered strategies aim to address existing complications with human corneal transplants, including graft rejection, infection, and complications resulting from surgical methodologies. The main goals of these research endeavors are to (1) determine ideal mechanical properties, (2) devise methodologies to improve the efficacy of engineered corneal grafts and cell-based therapies, and (3) optimize transplantation of engineered tissue structures in the eye. Thus, recent innovations have sought to address these challenges through both in vitro and in vivo studies. This review covers recent work aimed at evaluating engineered materials, potential therapeutic cells, and the resulting cell-material interactions that lead to optimal corneal graft properties. Furthermore, we discuss promising strategies in corneal tissue engineering techniques and in vivo studies in animal models.

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“…Encapsulated PDLSCs and GMSCs in an alginate/hyaluronic acid three-dimensional scaffold promoted the regeneration of neurogenic tissue[ 54 ]. Besides, PDLSCs had the ability to differentiate into corneal stromal keratocyte-like cells[ 55 ] and constructed a multilamellar human corneal stromal-like tissue in vitro when seeded onto orthogonally aligned, multilayered silk membranes and supplemented with the neuropeptide substance P[ 56 ]. PDLSCs also could be directed to develop into retinal progenitors and islet-like cell clusters with competence for photoreceptor differentiation and secretion of insulin[ 57 , 58 ].…”

Section: Diverse Differentiation Of Dmscsmentioning

confidence: 99%

Multidifferentiation potential of dental-derived stem cells

Yin¹,

Luo²,

Feng³

et al. 2021

WJSC

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Tooth-related diseases and tooth loss are widespread and are a major public health issue. The loss of teeth can affect chewing, speech, appearance and even psychology. Therefore, the science of tooth regeneration has emerged, and attention has focused on tooth regeneration based on the principles of tooth development and stem cells combined with tissue engineering technology. As undifferentiated stem cells in normal tooth tissues, dental mesenchymal stem cells (DMSCs), which are a desirable source of autologous stem cells, play a significant role in tooth regeneration. Researchers hope to reconstruct the complete tooth tissues with normal functions and vascularization by utilizing the odontogenic differentiation potential of DMSCs. Moreover, DMSCs also have the ability to differentiate towards cells of other tissue types due to their multipotency. This review focuses on the multipotential capacity of DMSCs to differentiate into various tissues, such as bone, cartilage, tendon, vessels, neural tissues, muscle-like tissues, hepatic-like tissues, eye tissues and glands and the influence of various regulatory factors, such as non-coding RNAs, signaling pathways, inflammation, aging and exosomes, on the odontogenic/osteogenic differentiation of DMSCs in tooth regeneration. The application of DMSCs in regenerative medicine and tissue engineering will be improved if the differentiation characteristics of DMSCs can be fully utilized, and the factors that regulate their differentiation can be well controlled.

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Substance P and patterned silk biomaterial stimulate periodontal ligament stem cells to form corneal stroma in a bioengineered three-dimensional model

Cited by 15 publications

References 41 publications

Mechanical stress potentiates the differentiation of periodontal ligament stem cells into keratocytes

Mechanical stress potentiates the differentiation of periodontal ligament stem cells into keratocytes

Recent Advances in Natural Materials for Corneal Tissue Engineering

Multidifferentiation potential of dental-derived stem cells

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