Treatment of Non Union of Long Bone Fractures by Autologous Mesenchymal Stem Cell

Effect of Bone Marrow-derived Mesenchymal Stem Cell Transplantation in Reconstructing Human Bone Defects

Treatment of nonunion, delayed union and malunion fractures of long bones remains problematic. The definition of nonunion is a failure of the fracture to heal in six months in a patient in whom progressive repair had not been observed radiographically between the third and sixth month after the fracture. First of all good surgical techniques are stable immobilization must be obtained and local sepsis excluded. Then stimulation of the callus is required. Numerous techniques have been developed ranging from invasive interventions (including internal fixation with the use of bone graft or bone graft substitutes) to non invasive procedures (ultrasound and pulsed electromagnetic fields).

Recently, autologous cell therapy was presented as an interesting approach. The concept of such therapies is based on the effect of stem cells presented in the bone marrow and able to be transformed in osteoblast cells. The purpose of this study is to find if mesenchymal stem cells can stimulate bone regeneration in nonunion and delayed union fractures to reduce later surgeries required to augment the healing process and to accelerate the time to healing.

Study Overview

• Status: Completed
• Conditions: Nonunion Fractures
• Intervention / Treatment: Biological: cell injection

Detailed Description

Treatment of nonunion, delayed union and malunion fractures of long bones remains problematic. The definition of nonunion is a failure of the fracture to heal in six months in a patient in whom progressive repair had not been observed radiographically between the third and sixth month after the fracture. Nonunion is a serious complication of a fracture, occurring in 2-10% of patients, as it is associated with high economic and health burden. Many cases are subsequently approached by multiple surgical and nonsurgical modalities. Various devices, under the name of "bone growth stimulators" have been used to enhance healing of the fracture. Recent studies, demonstrated the efficacy of mesenchymal stem cells in regeneration of bone and cartilage tissue. In this study percutaneous injection of mesenchymal stem cells to the site of fracture is performed as an outpatient procedure or during an operative exposure to evaluate its efficacy in enhancing bone regeneration. In the case of small size of bone gap, mesenchymal stem cells are injected into the callus of fracture site through an outpatient procedure under the guide of fluoroscopy. If there is a large bone gap, through a surgical management, mesenchymal stem cells seeded on bone matrix are placed at the site of fracture. Patients are followed by X-Ray examination 1,2,6, and 12 months after treatment.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Royan Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• Inclusion criteria:
• Both genders are eligible
• Nonunion or delayed union diagnosed with X-Ray examination.
• More than 4 cm distance to joint
• Provided written informed consent
• Exclusion criteria:
• Multiple major fracture or untreated major fracture
• Infected fracture
• HIV, hepatitis B or hepatitis C infection at the time of screening
• Pregnant or lactating women
• Diagnosis of cancer
• Active treatment with immunosuppressive drugs or anticoagulant agent
• Known allergic reaction to components of study treatment and/or study injection procedure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: non union; Patients with nonunion fracture of long bones	Biological: cell injection; Injection of mesenchymal cells in fractured zone; Other Names: Cell transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiological progression of bone fusion	callus formation in fracture zone	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of pain using VAS	Patients feel less pain during use of fractured limb	6 months
Cost analysis based on length of hospital stay	Cost benefit of cell transplantation by reduction of hospital admission time	6 months

Collaborators and Investigators

• Sponsor: Royan Institute
• Investigators: Study Chair: hamid gourabi, PhD, President of Royan Institute; Study Director: Mohammad reza Baghban Eslami Nejad, PhD, Sientific Board; Principal Investigator: Nasser Aghdami, MD,PhD, Head of Regenerative center; Principal Investigator: Ahmad Vosough, MD, Radiologist investigator

Publications and helpful links

General Publications

• Emadedin M, Labibzadeh N, Fazeli R, Mohseni F, Hosseini SE, Moghadasali R, Mardpour S, Azimian V, Goodarzi A, Ghorbani Liastani M, Mirazimi Bafghi A, Baghaban Eslaminejad M, Aghdami N. Percutaneous Autologous Bone Marrow-Derived Mesenchymal Stromal Cell Implantation Is Safe for Reconstruction of Human Lower Limb Long Bone Atrophic Nonunion. Cell J. 2017 Apr-Jun;19(1):159-165. doi: 10.22074/cellj.2016.4866. Epub 2016 Dec 21.
• Labibzadeh N, Emadedin M, Fazeli R, Mohseni F, Hosseini SE, Moghadasali R, Mardpour S, Azimian V, Ghorbani Liastani M, Mirazimi Bafghi A, Baghaban Eslaminejad M, Aghdami N. Mesenchymal Stromal Cells Implantation in Combination with Platelet Lysate Product Is Safe for Reconstruction of Human Long Bone Nonunion. Cell J. 2016 Fall;18(3):302-309. doi: 10.22074/cellj.2016.4557. Epub 2016 Aug 24.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: September 20, 2010
• First Submitted That Met QC Criteria: September 20, 2010
• First Posted (Estimate): September 21, 2010

Study Record Updates

• Last Update Posted (Estimate): December 14, 2011
• Last Update Submitted That Met QC Criteria: December 13, 2011
• Last Verified: June 1, 2008

More Information

Terms related to this study

• Keywords: nonunion fracture bone formation pain relief
• Additional Relevant MeSH Terms: Wounds and Injuries; Fractures, Bone; Fractures, Ununited
• Other Study ID Numbers: Royan-Bone-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No