Cartilage Regeneration by Chondrogenic Induced Adult Stem Cells in Osteoarthritic Sheep Model

Chinedu C Ude,Norhamdan M Yahaya,Johan Ahmad,Aminuddin B Saim,Ng Min-Hwei,Ruszymah B H Idrus,Chen Hui-Cheng,Shamsul B Sulaiman,Chi Zhang

doi:10.1371/journal.pone.0098770

Abstract

ObjectivesIn this study, Adipose stem cells (ADSC) and bone marrow stem cells (BMSC), multipotent adult cells with the potentials for cartilage regenerations were induced to chondrogenic lineage and used for cartilage regenerations in surgically induced osteoarthritis in sheep model.MethodsOsteoarthritis was induced at the right knee of sheep by complete resection of the anterior cruciate ligament and medial meniscus following a 3-weeks exercise regimen. Stem cells from experimental sheep were culture expanded and induced to chondrogenic lineage. Test sheep received a single dose of 2×107 autologous PKH26-labelled, chondrogenically induced ADSCs or BMSCs as 5 mls injection, while controls received 5 mls culture medium.ResultsThe proliferation rate of ADSCs 34.4±1.6 hr was significantly higher than that of the BMSCs 48.8±5.3 hr (P = 0.008). Chondrogenic induced BMSCs had significantly higher expressions of chondrogenic specific genes (Collagen II, SOX9 and Aggrecan) compared to chondrogenic ADSCs (P = 0.031, 0.010 and 0.013). Grossly, the treated knee joints showed regenerated de novo cartilages within 6 weeks post-treatment. On the International Cartilage Repair Society grade scores, chondrogenically induced ADSCs and BMSCs groups had significantly lower scores than controls (P = 0.0001 and 0.0001). Fluorescence of the tracking dye (PKH26) in the injected cells showed that they had populated the damaged area of cartilage. Histological staining revealed loosely packed matrixes of de novo cartilages and immunostaining demonstrated the presence of cartilage specific proteins, Collagen II and SOX9.ConclusionAutologous chondrogenically induced ADSCs and BMSCs could be promising cell sources for cartilage regeneration in osteoarthritis.

Highlights

On-going findings indicate that stem cell therapy holds promise as a therapeutic option for many diseases
Osteoarthritis (OA), the most common degenerative joint disease comprises of a heterogeneous group of syndrome that affects all joint tissues; characterized by the degeneration of articular cartilages with loss of matrix, formation of fissures and complete loss of the cartilage surface [3]
Ethics approval was granted by Universiti Kebangsaan Malaysia (UKM) Animal Ethics Committee (PP/TEC/RUSZYMAH/25-NOV/342-DEC-2010JUN-2012) and Universiti Putra Malaysia (UPM) Animal Ethics Committee (RUJ: ACUC 07R6/JULY 07-DEC 09)

Summary

Introduction

On-going findings indicate that stem cell therapy holds promise as a therapeutic option for many diseases. The unique function and properties of cartilage are provided by their tissue’s extracellular matrix which is maintained by a population of cells known as chondrocytes (.5% by volume). Traditional efforts to treat articular cartilage damage include joint lavage, tissue debridement, and microfracture of the subchondral bone; abrasion arthroplasty or the transplantation of autologous or allogeneic osteochondral grafts [3] [4] [5]. Some of these procedures have yielded promising clinical results, they are generally not applicable to large degenerative diseases such as osteoarthritis [6]

Objectives

Methods

Results