The recent report, published in Acta Neuropathologica, describes 2 cases of spinal tissue mass formation after local transplantation of autologous olfactory mucosa in patients with spinal cord injury. Both patients underwent cell translplantation 7- and 5 years ago in Portugal as part of clinical trial. Patients were evaluated at University of Michigan Medical Center for progressive neurological symptoms and were diagnosed with spinal cord mass. Surgical findings revealed “multiloculated mass with mucinous, septated compartments”. Histologic examination and immunofluorescence showed presence of olfactory epithelium-like, respiratory epithelium-like excessive tissues and immature neural cells. Stem cells were detected by positive staining for p63 and keratin 5 markers.
This is not the first case of spinal cord tissue mass formation at the site of local olfactory mucosa transplantation. Very similar case was reported in 2014. Mucus-producing epithelium and respiratory epithelium was found in excised masses in all 3 cases. In all cases, cells were freshly isolated, but not propagated in culture. These studies demonstrated that autologous olfactory mucosa-derived stem/ progenitor cells are persist for long time (5-8 years), proliferate and differentiate in the site of spinal cord injury. The presence of respiratory epithelium may indicate to metaplasia of olfactory mucosa-derived cells.
Olfactory mucosa contains neural stem/ progenitor cells and olfactory ensheathing cells, which are proved to be “therapeutically useful” in experimental models of spinal cord injury. The efficacy of olfactory mucosa-derived cell transplantation remain unclear, since no results of Phase 2/3 well designed controlled trials were reported to-date. As per my personal communication with the author of report, there was no clinical improvement observed after cell transplantation in both patients. Absence of any clinical benefit was also described in patient from 2014 report.
Excessive tissue formation is becoming quite common, but still rare complication of regenerative cell therapy. Since complication manifest many years after procedure, these patients should be followed-up for 5-15 years.