Hyaluronic acid hydrogel encapsulated BMP-14-modified ADSCs accelerate cartilage defect repair in rabbits

Hao Liu,Yongjun Rui,Fandong Gao,Jun Liu,Yesheng Jin

doi:10.1186/s13018-021-02792-w

Abstract

BackgroundCartilage defect has a limited capacity to heal. In this context, we hypothesized that hyaluronic acid (HA) hydrogel encapsulated BMP-14-modified adipose-derived mesenchymal stem cells (ADSCs) could accelerate cartilage defect repair in rabbits.MethodsADSCs were isolated and identified by flow cytometry. ADSCs were treated with adenovirus vector encoding BMP-14 (Ad-BMP-14) or adenovirus vector encoding control (Ad-ctrl). Real-time PCR (RT-PCR) and western blot assay was performed to verify the transfection efficacy and chondrogenic differentiation markers (ACAN, Collagen II and SOX9). Rabbit cartilage defect model was performed and randomly divided into following groups: control group, HA hydrogel + ADSCs, ADSCs, HA hydrogel + Lv-ctrl-ADSCs, HA hydrogel + BMP-14 transfected ADSCs. At 6, 9 and 12 weeks after surgery, scanning electron microscopy, hematoxylin–eosin, Safranin-O/Fast Green and immunohistochemical staining for Collagen II were performed to determine the role of HA hydrogel encapsulated BMP-14-modified ADSCs in cartilage repair in vivo.ResultsADSCs were successfully isolated and positively expressed CD29, CD44 and CD90. Transfection efficacy of Ad-BMP-14 was verified by RT-PCR and western blot assay. Moreover, Ad-BMP-14 could significantly increased chondrogenic differentiation markers (ACAN, Collagen II and SOX9). The LV-BMP-14-ADSCs and HA hydrogel + LV-BMP-14-ADSCs groups revealed smoother surface cartilage repair that was level with the surrounding cartilage and almost complete border integration.ConclusionsHA hydrogel encapsulated BMP-14-modified ADSCs accelerate cartilage defect repair in rabbits. We need to further validate the specific mechanism of action of HA hydrogel encapsulated LV-BMP-14-ADSCs involved in the repairing cartilage damage in vivo.

Highlights

Cartilage defect has a limited capacity to heal
BMP‐14 overexpression increased chondrogenic differentiation markers The successful transfection of Bone morphogenetic protein-14 (BMP-14) was verified by quantitative real-time PCR (Fig. 3A)
We found that after transfected with LV-BMP-14, the chondrogenic differentiation markers (ACAN, Collagen II and SOX9) was significantly increased than control group (Fig. 3B–D)

Summary

Introduction

Cartilage defect has a limited capacity to heal. In this context, we hypothesized that hyaluronic acid (HA) hydrogel encapsulated BMP-14-modified adipose-derived mesenchymal stem cells (ADSCs) could accelerate cartilage defect repair in rabbits. $560–$635 billion annually, articular cartilage defects accounts for nearly 1–2.5% of GDP of the GDP [4, 5]. Articular cartilage defects cause a large socioeconomic burden. Articular cartilage has a limited ability to regenerate following injury due to its low cellularity, lack of vascularization and the low proliferative and migratory capacities of chondrocytes [6]. In order to solve this dilemma, transplantation of cultured chondrocytes or mesenchymal stem cells (MSCs) can regenerate cartilage tissue in cartilage defects [7].

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Conclusion