Stem Cell Therapy in Injured Vocal Folds: A Three-Month Xenograft Analysis of Human Embryonic Stem Cells

Abstract

We have previously shown that human embryonic stem cell (hESC) therapy to injured rabbit vocal folds (VFs) induces human tissue generation with regained VF vibratory capacity. The aims of this study were to test the sustainability of such effect and to what extent derivatives of the transplanted hESCs are propagated in the VFs. The VFs of 14 New Zealand rabbits were injured by a localized resection. HESCs were transplanted to 22 VFs which were analyzed for persistence of hESCs after six weeks and after three months. At three months, the VFs were also analyzed for viscoelasticity, measured as dynamic viscosity and elastic modulus, for the lamina propria (Lp) thickness and relative content of collagen type I. Three months after hESC cell therapy, the dynamic viscosity and elastic modulus of the hESC treated VFs were similar to normal controls and lower than untreated VFs (p ≤ 0.011). A normalized VF architecture, reduction in collagen type I, and Lp thickness were found compared with untreated VFs (p ≤ 0.031). At three months, no derivatives of hESCs were detected. HESCs transplanted to injured rabbit VFs restored the vibratory characteristics of the VFs, with maintained restored function for three months without remaining hESCs or derivatives.

Collagen fibrillar structures in vocal fold scarring and repair using stem cell therapy: a detailed histological, immunohistochemical and atomic force microscopy study

“…In this connection, in our study we used a semiquantitative analysis by 11 criteria with the subsequent statistical processing, to objectively demonstrate the differences between the scars formed without treatment and those formed in the MSC presence. In such studies (Hertegård et al ., ; Cedervall et al ., ; Svensson et al ., ; Svensson et al ., ), a comparative analysis of the collagen type I content using immunohistochemistry was also performed for MSC‐treated scars. Estimation of collagen type I, as a basic component of a scar, is undoubtedly important; however, we believe that in the studies on vocal fold repair and restoration of its native morphology, the content of collagen type III is of no less importance.…”

Stem cell therapy for vocal fold regeneration after scarring: a review of experimental approaches

“…Such an approach is in agreement with the position of the European Medical Agency (EMA), established in the analytical document with the requirements on the quality of preclinical and clinical trials of medical products based on stem cells (EMA/CAT/571134/2009). The document states that, in order to prove a concept, the most suitable approach would be the use of human cells, since it is this product that will be potentially applied in the clinical practice [ 22 , 23 , 26 , 38 , 54 – 57 ].…”

Hyaluronan Hydrogels for the Local Delivery of Mesenchymal Stromal Cells to the Injured Vocal Fold

“…New Zealand white rabbits, with a body weight of 3-4 kg, were used for the pre-clinical in vivo experiments conducted as part of studies I (n=16), II (n=31) and III (n=18). We have previously developed this rabbit model of VF injury in house, and extensively validated its potential in studying VF injury and the effects of locally administered cell therapy in promoting tissue repair (55,74,160,161,189,206,227). Rabbits represent a good system, possessing large enough VFs to be able to successfully insert a laryngoscope and perform clinically relevant experiments.…”

“…This exploitation of species differences between ESC, MSCs and VF tissue, allowed us to use FISH as a measure of ESC and MSC persistence in the tissue after administration. This method had been previously established within our lab for this purpose in the rabbit VF injury model (55,160,161,189,206).…”