Autologous cell-coated particles for the treatment of segmental bone defects\u2014a new cell therapy approach

Dror Ben-David,Ephraim Tzur,Ora Burger,Nimrod Rozen,Shai Meretzki,Ilana Laevsky,Asaph Zaretsky,Bettina Fishman,Guy Rubin,Avinoam Kadouri,Yasmin Nishri Katz,Noam Bor,Atara Novak

doi:10.1186/s13018-019-1219-5

Abstract

BackgroundAdipose tissue-derived mesenchymal stem cells (AT-MSCs) are one of the most potent adult stem cells, capable of differentiating into bone, cartilage, adipose, muscle, and others. An innovative autologous AT-MSC-derived cell-based product (BonoFill-II) for bone tissue regeneration was developed to be suited as a bone graft for segmental bone defects.MethodsBonoFill-II was transplanted into 8 sheep with 3.2-cm full cortex segmental defect formed in the tibia. Bone regeneration was followed by X-ray radiographs for 12 weeks. At experiment termination, the healed tibia bones were analyzed by computed tomography, histology, and mechanical tests.ResultsOur results indicate that one dose of BonoFill-II injectable formula led to an extensive bone growth within the transplantation site and to a complete closure of the critical gap in the sheep’s tibia in a relatively short time (8–12 weeks), with no inflammation and no other signs of graft rejection. This new and innovative product opens new prospects for the treatment of long bone defects.ConclusionsInjection of BonoFill-II (an innovative autologous cell therapy product for bone tissue regeneration) into a critical size segmental defect model (3.2 cm), generated in the sheep tibia, achieved full bridging of the gap in an extremely short period (8–12 weeks).

Highlights

Bone defects due to trauma, infections, and skeletal diseases represent a major challenge to clinicians, from which, tibial fractures are the most common of all long bone fractures [1]
This stage takes place in a closed system, in which the Adipose tissue-derived mesenchymal stem cells (AT-Mesenchymal stem cells (MSCs)) are seeded on mineral particles and the culture incubation regime is changed to dynamic by a periodical stir of the system
Evaluation of advanced osteogenic differentiation capabilities of 3D-cultivated cells was done by exploring mineralization-related markers integrinbinding sialoprotein (IBSP) and osteopontin (SPP1)

Summary

Introduction

Bone defects due to trauma, infections, and skeletal diseases represent a major challenge to clinicians, from which, tibial fractures are the most common of all long bone fractures [1]. The gold standard solution is the use of autologous bone graft [3,4,5]. These grafts do not cause immunoreaction and act as live growing bone with all the osteoconductive and osteoinductive properties needed for healing. The autograft is typically obtained from either the anterior or posterior iliac crest, or when available, from the locally harvested bone Practically, this clinical practice is limited due to severe complications, such as donor site morbidity, limited mobility, and bone quantity and quality restrictions [5, 6]. An innovative autologous AT-MSCderived cell-based product (BonoFill-II) for bone tissue regeneration was developed to be suited as a bone graft for segmental bone defects

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Results

Discussion

Conclusion