Intravitreal autologous bone-marrow-derived mononuclear cell transplantation
Editor,
Based on the pioneering works by Friedlander and colleagues, who showed that the intravitreal application of bone-marrow-derived cells in animals can prevent retinal vascular degeneration (Otani et al. 2004; Smith 2004; Meyer et al. 2005; Harris et al. 2006), we conducted the present study to assess the effect of an autologous intravitreal application of bone-marrow-derived mononuclear cells in patients with end-stage macular degeneration and glaucoma.
Three patients were involved in the study, all of whom were fully informed about the experimental character of the treatment and provided informed consent. A 43-year-old pseudophakic patient suffered from end-stage diabetic retinopathy. After pars plana vitrectomy with panretinal endolaser coagulation and intravitreal silicone oil endotamponade, the retina was attached completely. The reason for a defective light projection was marked atrophy of the retina and optic nerve, with the retinal arteries mostly occluded. The second patient (age 78 years) suffered from large geographic atrophy caused by age-related macular degeneration without signs of exudation in both eyes. Visual acuity was hand movements. The third patient (age 72 years) showed absolute glaucomatous optic nerve damage in addition to a marked myopic maculopathy with an axial myopia of −15 dioptres. Visual acuity was defective light projection.
The patients’ bone marrow was harvested and mononuclear cells were separated via Ficoll density gradient sedimentation from the aspirate. All preparation procedures were carried out according to the current European Union Guidelines for Good Manufacturing Practice and under the corresponding manufacturing license (Cytonet Hannover GmbH, Hannover, Germany). The preparation was carried out 18 (patient 1) to 36 (patients 2 and 3) hr after the bone marrow harvesting. The white blood cell count in the three preparations ranged between 1.6 and 2.1 × 108 cells/ml, the viability between 94% and 99%, the haematocrit between 1.3% and 2.6%, the platelet count between 0.79 and 1.7 × 108 cells/ml, and the CD34+ cell count between 5.1 and 9.6 × 105 cells/ml. The colony-forming assay resulted in a growth clonogenicity of more than 10% in the final preparations of patients 1 and 3. A lower than 10% growth clonogenicity was observed in the final preparation of patient 2. An extensive sterility control beyond the requirements of the European Pharmacopoeia (Chapter 2.6.27) of the incoming bone marrow harvest and of the final product was carried out. Immediately after preparation, the cell product was delivered and the cell suspension of 0.5 ml was applied intravitreally.
In the first patient, the cell suspension was transsclerally injected into the intraocular silicone oil. The second and third patients underwent pars plana vitrectomy with the removal of the posterior vitreous cortex from the retinal surface. After a fluid–air exchange, the cell suspensions were dropped onto the macular region and the patients were asked to remain in supine position for several hours.
At the first postoperative day, a cluster of the injected cells was observed on the retinal surface in the inferior fundus periphery in the first patient. The two other patients showed an opaque vitreous cavity filled partially with air, partially with a fluid rich in cells. Polymorph cells were detected in the anterior chamber. For the first 4 weeks after the procedure, intraocular pressure ranged between 15 and 30 mm Hg. After that period, intraocular pressure normalized. At that time, all cell clusters on the retinal surface and in the anterior chamber had disappeared. At the end of follow-up, 12 months, 10 months and 2 months after the procedure, visual acuity was unchanged for all patients compared with the baseline findings. This finding confirms a previous report (Jonas et al. 2008).
This report suggests that an intravitreal injection of autologous bone-marrow-derived cells into the vitreous cavity is technically feasible. However, it remains unclear why the procedure did not result in an improvement of vision. Possible reasons for this include the end stage of the ocular diseases or enriched, concentrated and activated cell lines from the bone-marrow aspirate being more suitable. In view of the potential clinical indications of intravitreal autologous bone-marrow-derived mononuclear cell transplantations, further studies – particularly on higher-order animals – may be warranted.
