Combining Bone Collagen Matrix with hUC-MSCs for Application to Alveolar Process Cleft in a Rabbit Model.

Xue-Cheng Sun,Yu-Fang Yan,Hong-Fei Xia,Hu Wang,Xu Ma,Li-Qiang Yin,Dan Zhang,Jian-Hui Li

doi:10.1007/s12015-021-10221-y

Abstract

Most materials used clinically for filling severe bone defects either cannot induce bone re-generation or exhibit low bone conversion, therefore, their therapeutic effects are limited. Human umbilical cord mesenchymal stem cells (hUC-MSCs) exhibit good osteoinduction. However, the mechanism by which combining a heterogeneous bone collagen matrix with hUC-MSCs to repair the bone defects of alveolar process clefts remains unclear. A rabbit alveolar process cleft model was established by removing the bone tissue from the left maxillary bone. Forty-eight young Japanese white rabbits (JWRs) were divided into normal, control, material and MSCs groups. An equal volume of a bone collagen matrix alone or combined with hUC-MSCs was implanted in the defect. X-ray, micro-focus computerized tomography (micro-CT), blood analysis, histochemical staining and TUNEL were used to detect the newly formed bone in the defect area at 3 and 6months after the surgery. The bone formation rate obtained from the skull tissue in MSCs group was significantly higher than that in control group at 3months (P < 0.01) and 6months (P < 0.05) after the surgery. The apoptosis rate in the MSCs group was significantly higher at 3months after the surgery (P < 0.05) and lower at 6months after the surgery (P < 0.01) than those in the normal group. Combining bone collagen matrix with hUC-MSCs promoted the new bone regeneration in the rabbit alveolar process cleft model through promoting osteoblasts formations and chondrocyte growth, and inducing type I collagen formation and BMP-2 generation.

Highlights

An alveolar process cleft is a common clinical diagnosis of alveolar bone defects caused by birth defects, trauma, or inflammation, which severely affects a patient's facial and oral functions
Until tissue block was attached to the bottom of the cell culture dish, α-Minimal Essential Medium (α-MEM) culture medium containing 10% fetal bovine serum, 100 IU/mL penicillin, and 10 mg/mL streptomycin was added to the dishes and cultured in a carbon dioxide incubator
At 6 months after the surgery, the bone trabeculae in the damaged area of the MSCs group had connected to form bone tissue (Fig. 5 Ah1). These results indicate that the MSCs group shows better repair

Summary

Introduction

An alveolar process cleft is a common clinical diagnosis of alveolar bone defects caused by birth defects, trauma, or inflammation, which severely affects a patient's facial and oral functions. It greatly hinders the patient's subsequent denture repair. Studies have shown that human umbilical cord mesenchymal stem cells (hUC-MSCs) play an important role in inducing bone regeneration [7,8,9]. In this study, hUC-MSCs were inoculated into a bone collagen matrix to induce bone regeneration and repair. The mechanism by which combining a heterogeneous bone collagen matrix with hUC-MSCs to repair the bone defects of alveolar process clefts remains unclear

Methods

Results

Discussion

Conclusion