Mesenchymal Stromal Cells Implantation in Combination with Platelet Lysate Product Is Safe for Reconstruction of Human Long Bone Nonunion

Narges Labibzadeh, Mohsen Emadedin, Roghayeh Fazeli, Fatemeh Mohseni, Seyedeh Esmat Hosseini, Reza Moghadasali, Soura Mardpour, Vajiheh Azimian, Maede Ghorbani Liastani, Ali Mirazimi Bafghi, Mohamadreza Baghaban Eslaminejad, Nasser Aghdami, Narges Labibzadeh, Mohsen Emadedin, Roghayeh Fazeli, Fatemeh Mohseni, Seyedeh Esmat Hosseini, Reza Moghadasali, Soura Mardpour, Vajiheh Azimian, Maede Ghorbani Liastani, Ali Mirazimi Bafghi, Mohamadreza Baghaban Eslaminejad, Nasser Aghdami

Abstract

Objective: Nonunion is defined as a minimum of 9 months since injury without any visible progressive signs of healing for 3 months. Recent literature has shown that the application of mesenchymal stromal cells is safe, in vitro and in vivo, for treating long bone nonunion. The present study was performed to investigate the safety of mesenchymal stromal cell (MSC) implantation in combination with platelet lysate (PL) product for treating human long bone nonunion.

Materials and methods: In this case series clinical trial, orthopedic surgeons visited eighteen patients with long bone nonunion, of whom 7 complied with the eligibility criteria. These patients received mesenchymal stromal cells (20 million cells implanted once into the nonunion site using a fluoroscopic guide) in combination with PL product. For evaluation of the effects of this intervention all the patients were followed up by taking anterior-posterior and lateral X-rays of the affected limb before and 1, 3, 6, and 12 months after the implantation. All side effects (local or systemic, serious or non-serious, related or unrelated) were observed during this time period.

Results: From a safety perspective the MSC implantation in combination with PL was very well tolerated during the 12 months of the trial. Four patients were healed; based on the control Xray evidence, bony union had occurred.

Conclusion: Results from the present study suggest that the implantation of bone marrow-derived MSCs in combination with PL is safe for the treatment of nonunion. A double blind, controlled clinical trial is required to assess the efficacy of this treatment (Registration Number: NCT01206179).

Keywords: Fractures Ununited; Mesenchymal Stromal Cells; Platelet Lysate.

Figures

Fig.1
Fig.1
Flow of patients through study. BM; Bone marrow, MSCs; Mesenchymal stromal cells, PL; Platelet lysate, HDL; High-density lipoprotein, LDL; Low-density lipoprotein, ALT; Alanine transaminase, AST; Aspartate aminotransferase, BUN; Blood urea nitrogen, TSH; Thyroid stimulating hormone, T4; Thyroxin, PT; Prothrombin time, PTT; Partial thromboplastin time, INR; International normalized ratio, HBS Ag; The surface antigen of the hepatitis B virus, HBS Ab; Hepatitis B antibody, HIV; Human immunodeficiency virus, and HTLV; Human T-lymphotropic virus or hu- man T-cell lymphotropic virus.
Fig.2
Fig.2
Lateral radiograph of a 32 years male non-united tibial fracture, arrow shows the fracture. A. Before intervention and B. 6 months after using MSCs in combination of platelet lysate product, arrow shows radiological signs of healing. MSCs; Mesenchymal stromal cells.
Fig.3
Fig.3
Characterization of passaged 1 human BM-derived MSCs. A. Phenotypic appearance and osteogenic differentiation potential of pas- saged one BM-derived MSCs (Alizarin red staining) and B. Representative flow cytometric analysis using WinMDI software indicated the expression of CD90, CD105, CD73, CD44 and CD45/CD34 surface markers (Red lines) on MSCs of both groups compared to isotype controls (Black lines). BM-MSCs; Bone marrow-mesenchymal stromal cells.

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