Macrophage Response to Allogeneic Adipose Tissue-Derived Stromal Cells in Hyaluronan-Based Hydrogel in a Porcine Vocal Fold Injury Model

King, Suzanne N.; Woo, Joo Hyun; Tang, Sharon; Thibeault, Susan L.

doi:10.1177/0003489417702923

Cited by 5 publications

(7 citation statements)

References 49 publications

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“…Previous flow cytometry in pigs after VF injury also found no difference in macrophage phenotype at 3 or 7 days among hydrogel with allogeneic porcine ASC, hydrogel injection alone, and injured control. 23 …”

Section: Discussionmentioning

confidence: 99%

A xenograft study of human adipose stromal cell‐based vocal fold mucosal replacement in rabbits

Tran

Alhiyari

Juarez

et al. 2022

Laryngoscope Investig Oto

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Objectives Vocal fold (VF) scarring, manifested by increased collagen, decreased glycosaminoglycans (GAGs), and disrupted elastic fibers, remains a negative consequence of VF injury or resection. The objective of this study is to compare four reconstructive options after Vf mucosal resection in rabbits. A Cell‐Based Outer Vocal fold Replacement (COVR) using human adipose‐derived mesenchymal stromal cells (hASCs) in fibrin scaffold is directly compared with a decellularized scaffold implant, hASC injection, and resection alone without reconstruction. The primary hypothesis is that the cells‐in‐scaffold construct better reconstitutes the VF structure than either cells or scaffold alone, or than healing by secondary intention. Methods A total of49 rabbits received bilateral VF cordectomy, followed by either COVR implant, decellularized scaffold implant, hASC injection, or no reconstruction (injured control group). Larynges were harvested after 6 weeks. Results Histology demonstrated greater lamina propria thickness, less collagen deposition, and more GAGs in COVR animals versus all other treatment groups. Evidence of persistent human cells was found in about half of the cell‐treated animals. RNA levels of fibrosis pathway and macrophage phenotype markers were statistically unchanged among treatment groups at 6 weeks. Conclusion These data support the efficacy of COVR implantation in restoring VF microstructure in rabbits. The intact COVR was required; isolated components of decellularized scaffold or injected hASC still produced histologic scarring. We propose that the unique bilayered cell structure within fibrin enables controlled matrix remodeling to minimize wound contraction and fibrosis, and to promote GAG deposition. Level of Evidence Basic science study

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Section: Discussionmentioning

confidence: 99%

A xenograft study of human adipose stromal cell‐based vocal fold mucosal replacement in rabbits

Tran

Alhiyari

Juarez

et al. 2022

Laryngoscope Investig Oto

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“…[38] Upon injury to the lamina propria, rapid neutrophil and monocyte recruitment from peripheral capillaries occurs, as demonstrated across experimental models of mice, [40] rats, [41][42][43][44] rabbits, [45] and pigs. [46,47] Li-Jessen's team applied multicolor flow cytometry to characterize temporal trajectories of neutrophils…”

Section: Immunological Profile Of the Vocal Foldsmentioning

confidence: 99%

“…For example, sourcing primary autologous (or even allogenic) vocal fold fibroblasts and epithelial cells is difficult due to the small size of the vocal folds and accessibility issues. [148,149] As such, other cell sources such as MSCs derived from bone marrow [150][151][152] or adipose [46,153] tissue and induced pluripotent stem cells (iPSCs) [154] have been sought for defected vocal fold treatments.…”

Section: Cell-based Therapiesmentioning

confidence: 99%

“…Memory cells present a significant obstacle to future injections using the same cell material therapy. Furthermore, the majority of cellular biomaterials have been applied for testing in xenogeneic [150][151][152]154,159] or allogenic [46,160] models, which can further exacerbate the inflammatory response, potentially masking the efficacy of the therapy.…”

Section: Cell-based Therapiesmentioning

confidence: 99%

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Progress in Vocal Fold Regenerative Biomaterials: An Immunological Perspective

Coburn

et al. 2021

Advanced NanoBiomed Research

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The vocal folds are functional organs located in the larynx that play a critical role in our daily breathing, speech, and swallowing functions. A key structural feature of the vocal folds is their delicate mucosa, which consists of a thin, layered epithelium and underlying extracellular matrix (ECM)-rich lamina propria. [1,2] Irreversible changes to the vocal fold mucosa, such as scarring, atrophy, and sulcus vocalis, require regenerative technologies to stimulate a controlled regrowth of the tissue. An increasing number of biomaterial systems have been proposed with the concurrent capability of refilling and regenerating severely damaged or absent vocal fold mucosae in situ (see review on public health significance in the study by Green et al. [3] ).Notably, as the vocal folds are located at the narrowest point of the airway, adverse hostÀbiomaterial responses can impair upper airway patency and create life-threatening complications. For instance, 2À5% of patients were reported to have postoperative inflammatory reactions including edema, dysphonia, and dyspnea to injectable biomaterials derived from hyaluronic acid (HA). [4][5][6] Although the incidence is rare, severe airway reactions could lead to an emergency admission for intensive care and require intubation procedures for breathing support. [5,7] Inevitably, this immunemediated rejection response is detrimental to the longevity, performance, and integration of the biomaterial in the vocal fold mucosa.Upon biomaterial introduction into a host, the immune system quickly responds to the iatrogenic trauma and foreign

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“…Valerie et al [96] showed that transplanting ASCs into a chronic scar could regenerate the VF by dissolving the excess collagen fibers that form the scar tissue and restoring the normal structure of elastic fibers. King et al [97] used ASCs embedded in a hyaluronan scaffold for VF scarring. These researchers investigated the macrophage inflammatory response to allogeneic ASCs and concluded that the constructs were biocompatible.…”

Section: New Strategies For Vf Scar Including Regenerative Medicinmentioning

confidence: 99%

Pathophysiology of Fibrosis in the Vocal Fold: Current Research, Future Treatment Strategies, and Obstacles to Restoring Vocal Fold Pliability

Kumai

2019

IJMS

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Communication by voice depends on symmetrical vibrations within the vocal folds (VFs) and is indispensable for various occupations. VF scarring is one of the main reasons for permanent dysphonia and results from injury to the unique layered structure of the VFs. The increased collagen and decreased hyaluronic acid within VF scars lead to a loss of pliability of the VFs and significantly decreases their capacity to vibrate. As there is currently no definitive treatment for VF scarring, regenerative medicine and tissue engineering have become increasingly important research areas within otolaryngology. Several recent reviews have described the problem of VF scarring and various possible solutions, including tissue engineered cells and tissues, biomaterial implants, stem cells, growth factors, anti-inflammatory cytokines antifibrotic agents. Despite considerable research progress, these technical advances have not been established as routine clinical procedures. This review focuses on emerging techniques for restoring VF pliability using various approaches. We discuss our studies on interactions among adipose-derived stem/stromal cells, antifibrotic agents, and VF fibroblasts using an in vitro model. We also identify some obstacles to advances in research.

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Macrophage Response to Allogeneic Adipose Tissue-Derived Stromal Cells in Hyaluronan-Based Hydrogel in a Porcine Vocal Fold Injury Model

Abstract: The ASC-constructs were biocompatible; they did not influence the macrophage inflammatory response or provoke increases in collagen expression. Long-term engraftment was confirmed.

Cited by 5 publications

References 49 publications

A xenograft study of human adipose stromal cell‐based vocal fold mucosal replacement in rabbits

A xenograft study of human adipose stromal cell‐based vocal fold mucosal replacement in rabbits

Progress in Vocal Fold Regenerative Biomaterials: An Immunological Perspective

Pathophysiology of Fibrosis in the Vocal Fold: Current Research, Future Treatment Strategies, and Obstacles to Restoring Vocal Fold Pliability

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