Micronized acellular dermal matrix as an efficient expansion substrate and delivery vehicle of adipose‐derived stem cells for vocal fold regeneration

Qiang, Liang; Liu, Shiyu; Han, Pei; Li, Xiaofeng; Li, Xiaobing; Yu, Zhiwen; Liang, Yuanyuan; Deng, Zhihong; Jin, Yan

doi:10.1002/lary.23330

Cited by 23 publications

(32 citation statements)

References 46 publications

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“…We considered that the VFFs' ability to secrete ECM proteins might decrease after culture in vitro and implantatation in vivo. The dADSCs and ADSCs showed their capabilities to simulate the orderly composition of ECM proteins, as described in previous studies [9], [18], [19]. This may be related to the role of regulatory factors and the microenvironment after injury, although further research is needed to understand the relevant effective mechanisms.…”

Section: Discussionsupporting

confidence: 70%

Fibroblast-Like Cells Differentiated from Adipose-Derived Mesenchymal Stem Cells for Vocal Fold Wound Healing

Wei

et al. 2014

PLoS ONE

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Tissue engineering has revealed the potential to regenerate injured vocal folds, and identification of the most suitable seed cells has remained a hot topic of research. The aim of this study was to implant fibroblast-like cells differentiated from adipose-derived mesenchymal stem cells (ADSCs) in a canine acute vocal fold wound model. We then sought to characterize changes in the extracellular matrix (ECM) proteins of vocal fold lamina propria. For this purpose, ADSCs were induced to differentiate into fibroblasts under the regulation of connective tissue growth factor in vitro. Cell surface proteins were identified by immunofluorescence staining. Thirty vocal folds of 17 canines were injured by localized resection and injected with fibroblast-like cells (differentiated ADSCs, dADSCs), ADSCs or vocal fold fibroblasts (VFFs). The morphology of vocal folds was observed, and the characteristics of ECM protein components (collagen, elastin, hyaluronic acid, decorin and fibronectin) were evaluated by immunofluorescence staining from 15 days to 6 months following implantation. The results showed that in vitro, the dADSCs showed morphology and cell surface protein expression similar to those of VFFs. After implantation in vivo, the surfaces of the recipient vocal folds became almost smooth in the dADSCs and ADSCs groups at 6 months but remained slightly concave and stiff in the VFFs group. The elastin fluorescence intensity increased significantly and was maintained at a high level in the dADSCs group. The collagen fluorescence intensity increased slightly in the dADSCs and ADSCs groups, whereas it demonstrated a more irregular arrangement in the VFFs group. The fluorescence intensity of hyaluronic acid, decorin and fibronectin was similar between the three implanted groups. These results indicated that dADSCs may confer an advantage for vocal fold wound healing. Furthermore, dADSCs have the ability to secrete ECM components in vivo, particularly elastin, which may be beneficial for vocal fold vibration recovery.

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Section: Discussionsupporting

confidence: 70%

Fibroblast-Like Cells Differentiated from Adipose-Derived Mesenchymal Stem Cells for Vocal Fold Wound Healing

Wei

et al. 2014

PLoS ONE

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“…Previously reported methods to create vocal fold injury in the rabbit include Cup‐forceps biopsies, vocal fold stripping, laser ablation, and microflap incision . In some cases, the injury extended to the cartilaginous glottis or deep into muscle . As most current research in vocal fold tissue‐engineering focuses on the regeneration of the lamina propria, it would be advantageous to have an injury model for which the injury depth is largely confined to the lamina propria, does not involve total loss of the lamina propria, simulates vocal fold injuries in humans, and can be created with precision in a graded manner.…”

Section: Introductionmentioning

confidence: 99%

A rabbit vocal fold laser scarring model for testing lamina propria tissue‐engineering therapies

Mau

2014

The Laryngoscope

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Objectives/Hypothesis To develop a vocal fold scarring model using an ablative laser in the rabbit as a platform for testing bioengineered therapies for missing or damaged lamina propria. Study Design Prospective controlled animal study. Methods An optimal laser energy level was first determined by assessing the depths of vocal fold injury created by a Holmium:YAG laser at various energy levels on fresh cadaveric rabbit larynges. The selected energy level was then used to create controlled unilateral injuries in vocal folds of New Zealand white rabbits, with the contralateral folds serving as uninjured controls. After 4 weeks, the larynges were harvested and subjected to excised-larynx phonation with high-speed imaging and immunohistochemical staining for collagen types I and III, elastin, and hyaluronic acid (HA) with quantitative histological analysis. Results 1.8 joules produced full-thickness injury of the lamina propria without extensive muscle injury. After 4 weeks, the injured vocal folds vibrated with reduced amplitude (P = 0.036) in excised-larynx phonation compared to normal vocal folds. The injured vocal folds contained a higher relative density of collagen type I (P = 0.004), higher elastin (P = 0.022), and lower HA (P = 0.030) compared to normal controls. Collagen type III was unchanged. Conclusions With its potential for higher precision of injury, this laser vocal fold scarring model may serve as an alternative to scarring produced by cold instruments for studying the effects of vocal fold lamina propria bioengineered therapies. Level of Evidence N/A.

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“…Immediately after injury, 50 μL of solution containing 5.0 × 10 5 GFP‐labeled ASCs or 50 μL PBS was gently injected into the right thyroarytenoid muscle via a 30‐gauge needle affixed to a microsyringe. The injection layer was designed based on previous reports …”

Section: Methodsmentioning

confidence: 99%

“…Recently, mesenchymal stromal cells (MSCs) have attracted attention as a promising therapeutic cell population because they have multilineage potential and produce several growth factors . Adipose‐derived mesenchymal stromal cells (ASCs) and bone marrow‐derived mesenchymal stromal cells (BMSCs) are often used, and their restorative effects after vocal fold injury have been confirmed in animal models . ASCs have greater proliferating potency, are easily isolated, and 500 times more cells can be collected compared to BMSCs with an equivalent amount of tissue .…”

Section: Introductionmentioning

confidence: 99%

“…[3][4][5] Adipose-derived mesenchymal stromal cells (ASCs) and bone marrow-derived mesenchymal stromal cells (BMSCs) are often used, and their restorative effects after vocal fold injury have been confirmed in animal models. [6][7][8][9][10][11][12][13][14][15][16] ASCs have greater proliferating potency, are easily isolated, and 500 times more cells can be collected compared to BMSCs with an equivalent amount of tissue. 17 Our research group has confirmed the restorative effects of ASC transplantation in a rat model with a chronically scarred vocal fold.…”

Section: Introductionmentioning

confidence: 99%

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Adipose‐derived mesenchymal stromal cells prevented rat vocal fold scarring

et al. 2017

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Objectives/Hypothesis: This study aimed to reveal the effects of adipose-derived mesenchymal stromal cells (ASCs) on prevention of vocal fold scarring by investigating how the immediate ASCs transplantation into the injured rat vocal fold affect the levels of gene transcription and translation.Study Design: Prospective animal experiments with controls. Methods: ASCs harvested from green fluorescent protein transgenic rat (ASCs group) or saline (sham group) were injected into the thyroarytenoid muscle of Sprague-Dawley rats immediately after stripping the vocal fold. For histological examinations, larynges were extirpated at 3, 14, and 56 days after the injection. Quantitative real-time polymerase chain reaction (PCR) analyses were performed at 3 and 14 days after the injection.Results: Transplanted ASCs were detected only in larynges at day 3. At days 14 and 56, histological examination showed significantly higher amounts of hyaluronic acid and lower deposition of collagen in the ASCs group compared to the sham group. Real-time PCR revealed that the ASCs group showed low expression of procollagen (Col)1a1, Col1a3, matrix metalloproteinase (Mmp)1 and Mmp8 in each time points. The ASCs group showed high expression of fibroblast growth factor (Fgf)2 and Hepatocyte growth factor (Hgf) compared to the sham group at day 14.Conclusions: ASCs increased expressions of Fgf2 and Hgf, and suppressed excessive collagen deposition during vocal fold wound healing. Given the fact that ASCs survived no more than 14 days, ASCs were thought to induce upregulations of growth factors' genes in surrounding cells. These results suggested that ASCs have potential to prevent vocal fold scarring.

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Micronized acellular dermal matrix as an efficient expansion substrate and delivery vehicle of adipose‐derived stem cells for vocal fold regeneration

Abstract: MADM could be used as an efficient expansion substrate and delivery vehicle for ADSCs in vocal fold regeneration.

Cited by 23 publications

References 46 publications

Fibroblast-Like Cells Differentiated from Adipose-Derived Mesenchymal Stem Cells for Vocal Fold Wound Healing

Fibroblast-Like Cells Differentiated from Adipose-Derived Mesenchymal Stem Cells for Vocal Fold Wound Healing

A rabbit vocal fold laser scarring model for testing lamina propria tissue‐engineering therapies

Adipose‐derived mesenchymal stromal cells prevented rat vocal fold scarring

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