Assessment of the Bone Healing Process Mediated by Periosteum-Derived Mesenchymal Stem Cells' Secretome and a Xenogenic Bioceramic-An In Vivo Study in the Rabbit Critical Size Calvarial Defect Model.

Victor Martin,Gintaras Juodzbalys,Algirdas Kaupinis,Egidijus Šimoliūnas,Mindaugas Pranskunas,Algirdas Puisys,Pedro Sousa Gomes,Milda Alksne

doi:10.3390/ma14133512

Abstract

The mesenchymal stem cell (MSC) secretome has been considered an innovative therapeutic biological approach, able to modulate cellular crosstalk and functionality for enhanced tissue repair and regeneration. This study aims to evaluate the functionality of the secretome isolated from periosteum-derived MSCs, from either basal or osteogenic-induced conditions, in the healing of a critical size calvarial bone defect in the rabbit model. A bioceramic xenograft was used as the vehicle for secretome delivery, and the biological response to the established biocomposite system was assessed by clinical, histological, histomorphometric, and microtomographic analysis. A comparative analysis revealed that the osteogenic-induced secretome presented an increased diversity of proteins, with emphasis on those related to osteogenesis. Microtomographic and histological morphometric analysis revealed that bioceramic xenografts implanted with secretomes enhanced the new bone formation process, with the osteogenic-induced secretome inducing the highest bone tissue formation. The application of the MSC secretome, particularly from osteogenic-induced populations, may be regarded as an effective therapeutic approach to enhance bone tissue healing and regeneration.

Highlights

IntroductionMesenchymal stem cells (MSCs) are a self-renewable and multipotent heterogeneous population, with the ability to adhere to tissue culture plates expressing a spindle-shape morphology [1,2]
The local injection of mesenchymal stem cell (MSC) or the implantation of MSCs-loaded scaffolds significantly improved the bone healing process in several experimental and clinical models [7,8]. These therapies facilitated the vascular support through enhanced angiogenesis, diminished inflammation, and promoted a pro-osteogenic microenvironment at the healing site [8]
Despite the enhanced healing outcome, there is limited evidence of the in situ cellular engraftment and the MSC differentiation into the osteogenic lineage functionally contributing to the enhanced bone formation [9]

Summary

Introduction

Mesenchymal stem cells (MSCs) are a self-renewable and multipotent heterogeneous population, with the ability to adhere to tissue culture plates expressing a spindle-shape morphology [1,2]. These cells have been isolated and expanded from the stroma of distinctive tissues and anatomical locations, showcasing identifying features that reflect their individual and differential origin [3]. The local injection of MSCs or the implantation of MSCs-loaded scaffolds significantly improved the bone healing process in several experimental and clinical models [7,8] These therapies facilitated the vascular support through enhanced angiogenesis, diminished inflammation, and promoted a pro-osteogenic microenvironment at the healing site [8]. MSCs seem to induce a significant therapeutic activity via the production of distinct bioactive factors that support and enhance the healing process [10,11]

Objectives

Methods

Results