Chondrocytes from congenital microtia possess an inferior capacity for in vivo cartilage regeneration to healthy ear chondrocytes

Abstract

The remnant auricular cartilage from microtia has become a valuable cell source for ear regeneration. It is important to clarify the issue of whether the genetically defective microtia chondrocytes could engineer cartilage tissue comparable to healthy ear chondrocytes. In the current study, the histology and cell yield of native microtia and normal ear cartilage were investigated, and the biological characteristics of derived chondrocytes examined, including proliferation, chondrogenic phenotype and cell migration. Furthermore, the in vivo cartilage-forming capacity of passaged microtia and normal auricular chondrocytes were systematically compared by seeding them onto polyglycolic acid/polylactic acid scaffold to generate tissue engineered cartilage in nude mice. Through histological examinations and quantitative analysis of glycosaminoglycan, Young's modulus, and the expression of cartilage-related genes, it was found that microtia chondrocytes had a slower dedifferentiation rate with the decreased expression of stemness-related genes, and weaker migration ability than normal ear chondrocytes, and the microtia chondrocytes-engineered cartilage was biochemically and biomechanically inferior to that constructed using normal ear chondrocytes. This study provides valuable information for the clinical application of the chondrocytes derived from congenital microtia to engineer cartilage. Copyright © 2016 John Wiley & Sons, Ltd.

Modeling Normal and Pathological Ear Cartilage in vitro Using Somatic Stem Cells in Three-Dimensional Culture

“…Discrepancies with previous studies may depend on the rather small number of patient samples they analyzed. Together, our analysis of microtic cartilage from five patients is more in agreement with observations by Gu et al (2018), suggesting abnormalities in perichondrium and lacunae organization, and support the view that at the cellular level microtic cartilage is not simply a smaller normal cartilage, but a cartilage that is unable to reach the maturity and organization of healthy auricular cartilage.…”

“…Many of these features are consistent with the hypotheses that in microtia ear cartilage maturation are arrested at an intermediate stage, and neural crest cell patterning into the first and second pharyngeal arch during ear development is defective, as previously suggested (Luquetti et al, 2012). Infiltration of collagen fibers from the perichondrium into the lacunar cartilage of microtic ears has been briefly mentioned only in one study (Gu et al, 2018), whereas other studies reported an overall good preservation of the microtic cartilage structure (Dahl et al, 2011;Pappa et al, 2014). Discrepancies with previous studies may depend on the rather small number of patient samples they analyzed.…”

“…Different degrees of reduction in size and malformed shape are observed among microtic ears depending on the severity of the malformation, with anotia and the most severe cases of microtia requiring surgical reconstruction. Development of tissue engineering approaches would circumvent the use of autologous rib cartilage, currently the most successful reconstructive approach, but associated with high morbidity and in some cases respiratory complications ( Ohara et al, 1997 ; Walton and Beahm, 2002 ; Kusuhara et al, 2009 ; Baluch et al, 2014 ; Pappa et al, 2014 ; Gu et al, 2018 ).…”

Tissue engineering applications in otolaryngology—The state of translation

“…Heatmap representing the proportion of publications by year that utilized specific translational research methodologies from construct characterization to human trial to investigate otologic tissue engineering 15,25‐35,38‐43,45,46,107‐144 …”

Creating Cartilage in Tissue-Engineered Chamber Using Platelet-Rich Plasma Without Cell Culture

“…20 Furthermore, chondrocytes from microtia cartilage showed inferior capacity to yield healthy ear chondrocytes. 21 Although many attempts have been made to slow dedifferentiation during passaging, including the use of hypoxic conditions, 22 threedimensional (3D) bioscaffolds, 23 high-density culture, 24 growth factors, 25 and varying temperatures, 24 no efficient methods have been developed to overcome these problems. 20 Alternatively, MSCs may represent a promising cell source owing to the chondrogenic differentiation ability of these cells.…”