I continue to pick some reported findings from autopsies and biopsies of patients underwent cell therapy procedures. Today, I’d like to share with you the story of two fatal cases of ALS patients, traveled for cell therapy to Beijing (China).
The large number of patients with neurodegenerative disorders (stroke, ataxia, ALS, cerebral palsy…) traveled to China for cell transplantation treatment by so called “olfactory ensheathing cell (OEC)”. This type of cells derived from aborted fetuses, supposedly contain “neural progenitor cells” and should regenerate neural tissue and mitigate disease. The problem with this type of cell therapy is that Beijing clinic never reported long-term outcome of treated patients. They have report 2-8 weeks follow up in 1225 (!) patients with all neurodegenerative disorders and 4-months followup in 14 ALS patients in controlled study. So, seem like it is working for the first few months after procedure. Unfortunately, lack of long-term followup and observational studies, creates a lot of skepticism among neurologists.
The pathological studies of cell implantation sites usually assesses:
- – cell survival and integration in the site of implantation;
- exogenous (transplanted) and host cell proliferation;
- cell differentiation, fusion or identity changes;
- signs of tissue repair and changes in signs of disease;
- host tissue reaction – inflammation, scar formation, fibrosis;
- any other abnormal reactions.
Post-mortem analysis of two Italian ALS patients, returned from Beijing clinic after neurotransplantation, was recently reported. In both cases disease progressed few months after the procedure and caused fatal complications. Some pathological findings were the following:
Immediately below the entry site in the cortex, necrotic calcified material was found. It was surrounded by a prominent astroglial reaction with numerous hypertrophic astrocytes and an inflammatory reaction characterized by mononuclear cells and foamy macrophages. Perivascular cuffs of lymphocytes were also found in the cerebral cortex 1 mm–2 mm far from the needle track.
The role of the immune response in graft outcome is of utmost importance. The inflammatory signs observed in the two brains suggest that the implanted cells elicit a lifelong reaction; as they are derived from fetal CNS, their immunogenic properties are low, and inflammation is not very prominent but still persistent.
…the long-term fate of OECs transplanted into the human brain corresponds to the persistence of quiescent, undifferentiated cells within the needle track, encased by a prominent glial reaction; evidence of axonal regeneration, neuronal differentiation, myelination and neurotrophin expression was not seen. The surgical procedure of implantation is not permissive of a neurotrophic effect, and OEC transplantation did not modify the neuropathology of ALS.
Even given the methodological limitations of our study, the results do not support that the transplantation of fetal OECs into the frontal lobe can have any beneficial effect in ALS patients.
The authors saw the signs of cell survival, but nevertheless pointed out that “human brain is not inclined to integrate the exogenous cells”. Most importantly, like in other cases of neurotransplantation, there was NO any morphological signs of disease mitigation! In conclusion, as I said before – long-term outcome and morphological findings raises a question about future of this therapeutic approach.
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