Treatment Of Maxillary Bone Cysts With Autologous Bone Mesenchymal Stem Cells (MSV-H) (BIOMAX)
This trial pretends to validate for clinical use a bioengineered product composed of MSV cells (mesenchymal stem cells produced by IBGM, Valladolid, which have already been approved by the Spanish Regulatory Agency for three previous clinical trials) and a cross-linked matrix of autologous plasma patented by The Blood and Tissue Bank of Asturias (WO2008/ 119855) for bone maxillary cysts refilling. These two groups collaborate in the present project with the team of Maxillofacial Surgery of the Hospital Universitario del Río Hortega, who leads the clinical trial and deals with the medical aspects. The proposed trial is based on positive results obtained in previous animal studies performed by the present multidisciplinary team. The investigators propose a phase I / II clinical trial with 10 patients suffering from bone cysts in the maxillofacial region. Autologous mesenchymal stem cells isolated from a bone marrow sample will be seeded in the autologous plasma matrix and cultivated for 3 weeks. At this time, the cyst will be removed by surgery and the cavity filled with the protein matrix containing the mesenchymal cells. Checks will be conducted at 3 weeks, 3 and 6 months following the evolution of the cavity by panoramic radiography and computerized tomography scan.
Bone Loss of Substance
Other: Autologous Mesenchymal Stem Cells
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Regeneration of Maxillary Bone Cystic Cavities by Bio Implant of MSHV-H Cells Associated to a Cross-linked Serum Scaffold|
- To evaluate the feasibility and safety of the implementation of MSV in the treatment of maxillary cysts [ Time Frame: up to 6 months ] [ Designated as safety issue: Yes ]Clinical review and orthopantomograpy at different periods (0, 2 weeks, 2 months and 6 months) assessing evolution from baseline and possible complications.
- Indication of efficacy [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]Imaging exploration to evaluate effectiveness through development of criteria for orthopantomography and bone-CT quantitative bone regeneration Evolution at 2 and 6 months from intervention will be assessed.
|Study Start Date:||April 2011|
|Estimated Study Completion Date:||October 2015|
|Primary Completion Date:||May 2014 (Final data collection date for primary outcome measure)|
Experimental: MSV treatment
MSV-H autologous transplantation. Mesenchymal stem cells from bone marrow expanded by GMP-compliant procedure in IBGM cell production unit in autologous plasma scaffold and implanted in maxillary bone cavities after cyst removal
Other: Autologous Mesenchymal Stem Cells
Autologous maxillary bone marrow mesenchymal stem cells (MSV-H) collected from patient, mesenchymal cells isolation and expansion under GMP conditions following the IBGM-Valladolid protocol (MSV)
Other Name: H-MSV, Human Mesenchymal Stem Cells from Valladolid
The objective of this project is to provide a competitive clinical solution with an autologous product, a balanced cost and the possibility of extending use to other pathologies.
This protocol includes treatment of 10 patients with cystic disease of the jaws that meet all the inclusion criteria and none of the exclusion criteria.
For autologous cell preparation a sample of spongy bone from the maxillary tuberosity and 20 ml of serum are obtained from the patient in order to prepare the crosslinked protein matrix and the MSV-H cells. Cells are selected and expanded under GMP conditions according to the methodology used in previous trials (EudraCT 2005-005498-36, 2008-001191-68 and 2009-0170450-11 ). MSV-H cells are obtained directly from biopsy culture jawbone of the patient by cultivation techniques "in vitro" and differentiate for 21 days once conveyed in the matrix with osteogenic differentiation medium of the following composition: DMEM, 10% FBS, 1% P / E, 0.1 mM dexamethasone, 50 mM ascorbate 2-phosphate, 10 mM phosphate ßGlicerol. All differentiation factors have already been approved for clinical use. After the period of the product differentiation can be implanted to the patient.
The bioimplant is used to refill the bone defects after osteotomy and maxillary cyst enucleation, with 5-10 million cells per unit of 2 cm in diameter and 0.3 cm thick. The cavity is closed with the mucoperiosteal flap and sutured with reabsorbable material. The end point of the trial is to evaluate the feasibility, safety and indications of treatment efficacy according to both clinical criteria and objective imaging confirming the volumetric bone regeneration and maintenance over time. For this purposes orthopantomography exploration will be performed before and 2 and 6 months after intervention.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01389661
|Río Hortega University Hospital|
|Valladolid, Valladid, Spain, 47012|
|Instituto de Biologia y Genetica Molecular|
|Valladolid, Spain, 47003|
|Principal Investigator:||Luis M Redondo, MD, PhD||Oral and Maxillofacial Surgeon, Río Hortega University Hospital, SACYL, Valladolid, Spain|
|Study Director:||Ana Sánchez, MD, PhD||Instituto de Biología y Genética Molecular (IBGM), University of Valladolid, Spain|
|Study Director:||Javier García-Sancho, MD, PhD||University of Valladolid, Spain|