Medical Hypotheses 82 (2014) 781–783

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Medical Hypotheses

journal homepage: www.elsevier .com/locate /mehy

Transplantation of adipose-derived stem cells combinedwith decellularized cartilage ECM: A novel approachto nasal septum perforation repair

http://dx.doi.org/10.1016/j.mehy.2014.03.0250306-9877/� 2014 Elsevier Ltd. All rights reserved.

⇑ Corresponding author at: Department of Otolaryngology, Peking UniversityInternational Hospital, Peking University, No. 1, Life Science Park Road, ChangpingDistrict, 102206 Beijing, China. Tel./fax: +86 10 82315710.

E-mail addresses: menghangwang@gmail.com (M. Wang), yulish68@163.com(L. Yu).

1 Co-corresponding author at: Department of Otolaryngology, Peking UniversityPeople’s Hospital, Peking University, No. 11, Xizhimen South Street, Xicheng District,100044 Beijing, China. Tel.: +86 10 66583755.

Menghang Wang a,b,⇑, Lisheng Yu c,1

a Department of Otolaryngology, Peking University International Hospital, Peking University, No. 1, Life Science Park Road, Changping District, 102206 Beijing, Chinab Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Chinac Department of Otolaryngology, Peking University People’s Hospital, Peking University, No. 11, Xizhimen South Street, Xicheng District, 100044 Beijing, China

a r t i c l e i n f o a b s t r a c t

Article history:Received 4 August 2013Accepted 24 March 2014

Nasal septal perforation, a defect of the nasal mucoperichondrium and cartilage, may induce epistaxis,persistent rhinorrhea and nasal obstruction. Cell-based tissue engineering is a promising therapeuticmethod for the treatment of nasal septal perforation. However, lack of an adequate source of cells andunsuitable biomaterials greatly hinder the development of cell-based therapy. In this paper, we proposedthe application of adipose-derived stem cells combined with decellularized cartilage ECM as a potentialgraft for the damaged nasal septum, which could help to repair the mucosal and cartilage tissues in thetreatment of nasal septal perforation. This new technology could play a novel role in the repair of nasalseptal perforation, and in regeneration of damaged nasal cartilage.

� 2014 Elsevier Ltd. All rights reserved.

Introduction

Nasal septal perforation, an anatomic defect of the nasalseptum, is commonly caused by trauma, nasal surgery, inhaledirritants, infectious disorders and neoplasms [1]. With the increas-ingly widespread abuse of powdered cocaine, cocaine-inducednasal septal perforation is occurring more frequently in thedrug-abusing population [2]. Repair of nasal septal perforation isdifficult for otolaryngology specialists and facial plastic surgeons,because the surgical area lacks sufficient mucosal and cartilagestissue [3]. Therefore, the development of new technologies torepair nasal septal perforation is important to improve patients’quality of life.

Stem-cell-based therapy provides the potential for repair andregeneration of damaged cartilage tissue in the treatment of nasalseptal perforation. Adipose-derived stem cells (ADSCs) derivedfrom adipose tissue are an accessible and abundant source of stemcells for translational clinical research, and can be differentiatedinto multiple cell lineages, including adipocytes, chondrocytes,

osteoblasts, myocytes and neuronal cells [4]. Compared with otherstem cells, ADSCs are superior seed cells for autologous celltransplantation in promoting cartilage regeneration, as they canbe obtained by minimally-invasive procedures and exhibit highproliferation rates in culture [5]. Recently, ADSCs have emergedas an alternative treatment option for degenerative disc diseaseand cartilage degeneration [6,7]. Therefore, the ADSC hasimportant merits in regenerative clinical application and can beconsidered as a strategy for future cartilage tissue engineering.

Transplantation of stem cells or ADSCs into damaged tissueswas performed in a previous study [8]. However, the therapeuticuses of these cells are limited by multiple factors [9]. Recently,tissue engineering has focused on the importance of developingan in vitro stem cell microenvironment for transplanted cells topromote their proliferation and tissue-specific differentiation.Decellularized cartilage extracellular matrix (DECM) couldprovide such an expansion microenvironment, allowing the pro-duction of large quantities of high-quality cells for cartilage tissueengineering [10]. The stem cell niche acts to regulate cellularbehavior and enhance cell proliferation and chondrogenic poten-tial [11–13]. The structural and biomechanical properties ofDECM that are similar to native tissue depend on preservationof structural proteins. The DECM comprises a three-dimensional(3D) microenvironment, regulates multiple molecular signalingpathways and exerts control over the multi-potentiality andself-renewal ability of stem cells [14].

782 M. Wang, L. Yu / Medical Hypotheses 82 (2014) 781–783

Hypothesis

Based on previous reports, in this paper, we hypothesized thattransplantation of ADSCs combined with decellularized cartilageECM into the injured nasal septum would provide a noveltreatment for nasal septal perforation patients.

Evaluation of the hypothesis

The evaluation of this hypothesis can be carried out from thefollowing aspects:

(1) In recent years, human ADSCs have proved to be an attrac-tive and readily-available cell source for cartilage tissueengineering. ADSCs are multipotent and can differentiateinto various cell types, including osteocytes, cartilage cells,vascular endothelial cells and cardiomyocytes [15]. Recentstudies revealed that cartilage engineered from differenti-ated ADSCs in an alginate biodegradable scaffold was ableto repair tracheal cartilage defects. The chondrogenic differ-entiation potential of ADSCs is attractive, and may be appli-cable to cartilage tissue engineering [16].

(2) New biological scaffolds, such as DECM, represent the nativeextracellular matrix (ECM) properties of cartilage tissues andprovide potential alternative approaches for nasal cartilagetissue repair and regeneration. The utilization of biologi-cally-engineered DECM for reconstructive surgery in nasalseptal perforation may provide an accessible tissue sourceand avoid the limitation of autologous tissue grafts. Decellu-larization can preserve the native cartilage ECM, especiallycollagen and elastin fibers, but remove antigenic and cellularcomponents that would initiate an immune response [17].The ECM can provide biomechanical properties similar tonative tissue, modulate stem cells’ behavior, repair thedamaged cartilage tissue and guide the development ofnew tissues with biophysical cues [18]. In addition, region-specific cues are important in the differentiation of syno-vium-derived stem cells and other stem cells, and providecertain biochemical factors which guide differentiation ofthe stem cells [19]. Thus, ECM may play a role in mediatingchondrogenic differentiation of ADSCs.

(3) Surgical repair of septal perforations is a particularlychallenging operation. It is a difficult problem for the otolar-yngologist and facial plastic surgeons to solve. Nasal perfora-tion destroys the integrity of the cartilaginous framework,induces erosion of the nasal mucoperichondrium and resultsin ischemic necrosis of nasal septal cartilage [1,18]. Success-ful repair of nasal perforations should aim to restore nasalseptal cartilage, improve nasal epithelium and mucoperic-hondrium, and enhance mucous clearance. Tissue-engi-neered cartilage has become a significant focus forbiomedicine in recent years [20]. Many different biomaterialscaffolds have been considered for production of tissue-engineered cartilage including both synthetic and naturalmaterials [11]. Therefore, such an approach may provideinsights into the regeneration of nasal cartilage in patients.

Discussion

Cell-based tissue engineering is a potential therapeutic methodfor the treatment of mucosal and cartilage tissue defects in cases ofnasal septal perforation. However, transplanted stem cells areespecially vulnerable to a lack of a suitable growth microenviron-ment at the transplant site. Decellularized cartilage extracellularmatrix (DECM) provides a novel cell growth system for tissue

engineering, constituting a three-dimensional (3D) microenviron-ment which can house the transplanted cells and influence stemcell proliferation and differentiation [12]. Moreover, it has beendemonstrated that several signal transduction pathways, such asbrain-derived neurotrophic factor–phosphatidylinositol 30-ki-nase/Akt (PI3K/Akt), MAPK and extracellular signal regulatedkinase (ERK) signaling pathway, are reportedly involved in ECMregulation of specific cellular processes, such as cell growth anddifferentiation [21,22]. Recently, it was revealed that the chondro-genic effects of ECM on cells might be due to the regulation ofNotch signals. The Notch pathway and b1-integrins co-modulategrowth factor receptors in the maintenance of the stem cellpopulation [23]. Another report demonstrated that the Wnt path-way modulates the proliferation of stem cells and promotes theirdifferentiation potential [24].

An adequate cell source and suitable biomaterials greatlyimprove cell-based therapy [25]. Reconstruction of the in vitromicroenvironment and obtaining a suitable stem cell source arebecoming an urgent issue for cartilage tissue engineering. In thispaper, we hypothesized that transplantation of ADSCs combinedwith decellularized cartilage ECM into the injured nasal septumwould provide a novel treatment for nasal septal perforationpatients.

Although we propose that ADSCs combined with decellularizedcartilage ECM might play important roles in repair and regenera-tion of nasal septal perforation, many questions need to beaddressed before this technology can be applied clinically.

Conflict of interest statement

The authors indicate no potential conflict of interest.

Acknowledgements

This study was supported in part by grants from the NationalNatural Scientific Foundation of China (NSFC Nos. 11202018 and81170905), the Postdoctoral Science Foundation of China(20110490269 and 2013T60055) and the Capital MedicalDevelopment Foundation (20091015).

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