Code: OA-orMSCp-02

Title: Autologous bone marrow-derived mesenchymal stem cells seeded on a 3D scaffold in treatment of knee cartilage defects. Prospective open-label study to assess safety and feasibility.

Study Site: Department of Orthopedics, Masaryk Hospital, Usti nad Labem, Czech Republic

Principal Investigator: Pavel Neckar, M.D.

Rationale: The treatment of articular cartilage defects is relatively difficult; if untreated, the defect typically leads to onset of arthrosis, but methods aiming at structural repair of the hyaline cartilage are limited and their efficacy remains disputable.  Evidence accumulated during the last decade has shown that commonly used methods of cartilage treatment, such as the microfracturing technique, the application of osteochondral autografts or fresh osteochondral allografts, or even implantation of autologous cultivated chondrocytes, do not produce satisfactory clinical outcome. At the best, the defect is filled with fibrous or hyaline-like cartilage the biomechanical properties of which are markedly inferior compared to healthy hyaline cartilage, and normal function of the joint thus cannot be restored.

An alternative approach combines cellular and acellular elements in the surgical intervention: multipotent MSCs isolated from the patient´s bone marrow are expanded ex vivo under Good Manufacturing Practice (GMP) conditions and then implanted at the cartilage lesion site using commercially available 3D scaffold. The three-dimensional scaffolding material serves as the MSC suspension carrier but also is supposed to promote migration and differentiation of the stem cells that may result in a better healing of the cartilage defect.

Aims:

Primary: To assess the safety of a single dose of autologous MSCs seeded on a commercially available acellular 3D scaffold and fixed using autologous blood plasma in the repair of knee chondral lesions. 

Secondary: To collect preliminary efficacy data from patient administered questionnaires (VAS, KOOS and Lysholm-Tegner scoring scale) and X-ray. To evaluate feasibility of the treatment in the current clinical practice.


Phase: All patients have undergone the treatment, data collection is undergoing.

Code: BI-NTP-001 

Title: Healing of Acute Wounds Using Non-Thermal Plasma to Assess the Safety and the Efficacy. Case Studies.

Investigational Medical Device: Generator of non-thermal plasma (Plasmafor-M)

Study Site: Department of Burns and Reconstructive Surgery, University Hospital Brno-Bohunice, Brno, Czech Republic

Principal Investigator:  Bretislav Lipovy, M.D., Ph.D.

Sponsor: Institute of Experimental Medicine, Czech Academy of Sciences

CRO: Bioinova, s.r.o.

Rationale: For acute wounds, such as burns, it is characteristic that they are colonized with pathogenic microorganisms, having a negative influence on wound healing. For successful treatment of burn wounds, elimination of pathogenic bacteria and maintenance of the skin cells function is required.

Non-thermal plasma represents an effective tool for such elimination, especially in treating antibiotic-resistant infections as it has been shown that it has nonspecific antibacterial effect.

Favorable effect of non-thermal plasma on healing of chronic wounds has been presented in several preclinical and clinical studies.

Aims:

Primary: Safety: Absence of complications at the site of non-thermal plasma exposition or other treatment-emergent adverse events.

Sekundární cíl: Efficacy: Assessing pathogenic bacteria elimination.

Phase: The trial has been initiated.

Code: AMSC-BDT-001

Title: Utilization of Autologous Multipotent Mesenchymal Stem Cells in the Management of Large Skeletal Defects during Revision Total Hip Arthroplasty: a Prospective, Non-randomized, Open-Label Study to Assess the Safety and the Efficacy.

Study site: Department of Orthopedics, Medical Faculty of Charles University and Faculty Hospital in Hradec Kralove, Czech Republic

Principal Investigator: Pavel Sponer, M.D., Ph.D.

Sponsor: Medical Faculty of Charles University Hradec Kralove

Rationale: Revision total hip arthroplasty is one of the most frequently used surgical approaches in orthopedics. The use of autologous and allogenous bone grafts in reconstruction and healing of bone defects during this surgery is essential prerequisite for stability and long-term function of the re-implanted endoprosthesis. However, the amount of the autologous bone grafts is limited (particular in large bone defects), their harvesting prolongs the time of surgery and there are problems with donor site pain and morbidity. The main problem of allografts is risk of infectious disease transmission and the graft resorption. This risk is reduced in processed allografts but the processing itself adversely affects their mechanical and biological properties. To avoid limitations and complications of the autologous and allogenous bone grafts, combinations of synthetic beta-tricalcium phosphate biomaterial (acting as an osteoconductive matrix) and the patient’s own bone marrow stromal cells (supposed to significantly support and contribute to new bone formation) were used.

Aims:

Primary: Safety: To assess an absence of complications at the site of femoral bone defect.

Secondary: Safety: Incidence of other treatment - emergent adverse events. Overall safety. 

Efficacy: To assess the quality of healing of femoral bone defects measured according to Harris Hip Score, plain X-rays and densitometry.

The results of the clinical trial AMSC-BDT-001 have been published in Biomed .Res. Int. and Cell Transplantation journals (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838782/; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180724/)

Code: AMSC-DSD-001

Title: Utilization of Autologous Mesenchymal Cells in Posterolateral Spinal Fusion in Degenerative Spine Disease: a Prospective, Non-randomized, Open-Label Study to Assess the Safety and the Efficacy.

Study Site: Department of Spine Surgery, 2^nd Medical Faculty of Charles University and

 University Hospital Motol, Prague, Czech Republic

Principal Investigator: prof. Jan Stulik, M.D., CSc.

Rationale: Posterolateral fusion is one of the most frequently used surgical approaches in the therapy of degenerative spine diseases. During this surgery, an autologous bone implant obtained from the iliac crest is inserted between transverse processes of the spine. Disadvantages of this approach are frequent donor site morbidity and the insufficient quantity of the harvested bone, in particular for long, multi-level fusions.

A novel method which makes it possible to substitute the autologous bone graft consists in using an osteoinductive biomaterial based on calcium triphosphate mixed with the patient’s own bone marrow stromal cells cultivated for 3 passages. The goal of this trial was to assess the safety and the efficacy of osteoinduction in the fusioned spine segments using a calcium triphosphate foam biomaterial containing autologous mesenchymal stem cells. 

Aims:

Primary: Safety: To demonstrate absence of complications at the site of spinal fusion. or other treatment-emergent adverse events. Overall safety.

Secondary:Efficacy: To assess the quality of life determined by Oswestry Questionnaire and the quality of spinal fusion measured by X-rays and CT.

Code: AMSC-RC-001

Title: Utilization of Autologous Mesenchymal Cells to Enhance Rotator Cuff Repair - a Prospective Non-randomized, Open-Label Study to Assess the Safety and the Efficacy.

Study Site: Department of Orthopaedics and Traumatology, 2^nd Medical Faculty of Charles University and Univeristy Hospital Motol, Prague, Czech Republic

Principal Investigator: Vojtech Havlas, M.D., Ph.D.

Rationale: The rotator cuff is known to be a tissue with poor vascularization and a relatively low tendency to heal when torn. Post-operative complications, including surgical site infection, impaired healing, shoulder stiffness, and iatrogenic tendon injury, occur at a relatively low prevalence of 6–11 %, however the failure rate of the surgery is known to be relatively high due to poor quality of the tendon. Locally administered (injected) adult tissue-derived stem cells, known for their multipotent potential, have been shown to have a capability of differentiating and participating in the healing of various musculoskeletal tissues, including tendon. Bone marrow derived stromal cells and adipose tissue derived stromal cells were extensively tested in race horses with excellent results. Autologous expanded mesenchymal stem cells (seem to be very promising in the field of tendon repair, as they are able to repopulate the damaged tendons and produce growth factors supporting the tendon regeneration.

Aims:

Primary: Safety: To assess the safety and tolerability of treatment by autologous mesenchymal stem cells.

Secondary: Efficacy: To evaluate the effect of autologous mesenchymal stem cells (hAMSCs) applied during arthroscopic rotator cuff repair on rotator cuff healing.

The results of the clinical trial AMSC-RC-001 have been published in Acta Chir. Orthop. Traumatol. Cech. (http://www.achot.cz/detail.php?stat=751).

Code: AMSC-ALS-001

Title: A Prospective, Non-randomized, Open Label Study to Assess the Safety and the Efficacy of Autologous Multipotent Mesenchymal Stem Cells in the Treatment of Amyotrophic Lateral Sclerosis.

Study Site: Department of Neurology, University Hospital Motol, Prague, Czech Republic

Principal Investigator: Martin Bojar, M.D., CSc.

Rationale: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that targets motor neurons. Prognosis is invariably fatal within 3-5 years since manifestation of the disease. Despite improved understanding of the mechanisms underlying ALS, the treatment remains essentially only supportive and focused on symptoms relief. Over the past few years, stem cell research has expanded greatly as a tool for developing new therapies to treat incurable diseases. Stem cell therapy has been shown as promising in several animal ALS models and human clinical trials. 

Aims:

Primary: Safety: To assess an absence of complications at the site of intrathecal infusion and no new neurologic deficit (i.e. meningism, paraplegia, urinary incontinence) not attributed to the natural progression of the disease.

Secondary: Efficacy: To assess progress of the disease measured according to ALS functional rating scale (ALSFRS) and Norris scale and spirometry (FVC) after the AMSC treatment.

The results of the clinical trial AMSC-ALS-001 have been published in Cell Transplantation journal (http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-ct-1709_sykova_et_al).