Evaluation of Efficacy and Safety of Autologous MSCs Combined to Biomaterials to Enhance Bone Healing (OrthoCT1)

Institut National de la Santé Et de la Recherche Médicale, France

Status and phase

Completed

Phase 2

Conditions

Delayed Union After Fracture of Humerus, Tibial or Femur

Treatments

Procedure: Implantation of bone substitute plus autologous cultured mesenchymal cells

Study type

Interventional

Funder types

Other

Identifiers

NCT01842477

2011-005441-13 (EudraCT Number)

C11-12

Details and patient eligibility

About

Bone grafting is widely used in hospitals to repair injured, aged or diseased skeletal tissue. In Europe, about one million patients encounter a surgical bone reconstruction annually and the numbers are increasing due to our ageing population. Bone grafting intends to facilitate bone healing through osteogenesis (i.e. bone generation) at the site of damage, but this is only attained presently by including cells capable of forming bone into the augmentation.

Bone autograft is the safest and most effective grafting procedure, since it contains patient's own bone growing cells (to enhance osteogenesis) and proteins (to enhance osteoinduction), and it providing a scaffold for the new bone to grow into (osteoconduction). However, bone autograft is limited in quantity (about 20 cc) and its harvesting (e.g. from the iliac crest) represents an additional surgical intervention, with frequent consequent pain and complications.

We hypothesize that using autologous bone marrow cells expanded in GMP facility surgically implanted with synthetic bone substitutes contribute to the resolution of the health and socioeconomic complications of delayed union or non-union after diaphyseal and metaphyseal-diaphyseal fractures with safety and efficacy.

Full description

Tissue engineering combines bone marrow cells or mesenchymal stem cells (MSCs), synthetic scaffolds and molecular signals (growth or differentiating factors) in order to form hybrids constructs. For bone reconstruction purposes, human MSCs have been seeded and cultured on porous calcium phosphate ceramics in osteogenic media. Some clinical studies with low numbers of patients have been reported using this approach but the outcomes were inconsistent with low efficacy in bone regeneration. The reasons of the limited clinical success may be due to several bottlenecks in the multidisciplinary field of bone tissue engineering. The association in vitro of biomaterials and osteoprogenitor cells raises technical challenges and regulatory and ethic issues for the implementation of clinical trials, whereas the expansion of MSCs is now possible in GMP Facility.

The expected results are to obtain bone consolidation thus healing of delayed union or non-union, as proven by imaging techniques, without using bone graft. This will prove the efficacy of the proposed IMP based on pluripotent MSCs expanded in a GMP facility and mixed with granulated biphasic calcium phosphate in the surgical setting before implantation. No expected complications related to the procedure are expected. Changes in serum levels of bone turnover markers will be described.

Enrollment

30 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age 18 to 65, both sexes
Traumatic isolated closed or open Gustilo I and II humerus, tibial or femur diaphyseal or metaphyseal-diaphyseal fracture status delayed union or non-union
At least 3 months from acute fracture
Able to provide informed consent, and signed informed consent
Patients (by themselves) should have medical health care coverage to be included in a research study
Able to understand and accept the study constraints

Exclusion criteria

Pregnancy, breast feeding women and women who are of childbearing age and not practicing adequate birth control
Participation in another therapeutic trial in the previous 3 months
Delayed union or non-union related to iatrogeny
Segmental bone loss requiring specific therapy (bone transport, large structural allograft, megaprosthesis, etc)
Vascular or neural injury
Other fractures causing interference with weight bearing
Acute persistent chronic bacterial infections such as brucellosis, typhus, leprosy, relapsing fever, melioidosis and tularemia
Visceral injuries of diseases interfering with callus formation (cranioencephalic trauma, etc.)
History of bone harvesting on iliac crest contraindicating bone-marrow aspiration
Corticoid or immunosuppressive therapy more than one week in the three months prior to study inclusion
History of prior or concurrent diagnosis of HIV-, Syphilis, Hepatitis-B- or Hepatitis-C-infection (confirmed by serology or PCR)
History of neoplasia or current neoplasia in any organ
Subject legally protected, under legal guardianship, deprived of their liberty by judicial or administrative decision, subject of psychiatric care, or admission to a health facility.
Impossibility to meet at the appointments for the follow up
Insulin dependent diabetes
Obesity (BMI > 30)
Autoimmune inflammatory disease
Current treatment by biphosphonate or stopped in the three months prior to study inclusion.