Brain tumor after infusion of fetal liver-derived cells in patient with diabetes

by Alexey Bersenev on January 24, 2016 · 0 comments

in pathology and autopsy

I’m continuing to document of all clinical cases reports on complications of cell therapy with focus on regenerative medicine. I’m trying to capture all published autopsy or pathology reports. I believe, such database will equip professionals with a knowledge and allow to avoid mistakes in future translation of cell therapies. Today, I’m going to highlight the case, published online few days ago in Experimental Clinical Transplantation journal. You can find full text here. It was not the case of “stem cell tourism”, but IRB-approved clinical study (trial registry ID was not provided), conducted in academic medical center in Iran.

Briefly, 25 months after intravenous infusion of fetal liver-derived cells for experimental treatment of type 1 diabetes, patient was presented to neurologist with severe frontal headaches, vision disturbances and vomiting. Tumor-like mass was identified by CT in frontal lobe of the brain. Patients underwent neurosurgery and was diagnosed with transitional meningioma (benign tumor). Patient was discharged from the hospital 5 days after surgery. Tumor, patient’s blood and fetal liver cells were genetically tested:

Transplanted fetal HSCs, patient’s peripheral blood cells, and tumor cells were compared with a PCR using highly polymorphic microsatellite markers and PCR with specific primers for amelogenin homologous gene located on X and Y chromosomes. Genomic DNA was extracted from the patient’s blood samples and from the tumor tissue using standard protocols.

Unfortunately, the authors did not provide 100% evidence for tumor origin from transplanted fetal cells, but they have found DNA in the tumor, which was different from patient’s DNA:

Analysis of DNA obtained from the blood and tumor cells with 6 microsatellite markers which are listed in Table 1, demonstrated that the allele size for 5 markers were different from the DNA originated from the patient’s blood sample and the DNA extracted from the tumor. The number of alleles detected in the tumor originated from nonhost cells indicated the presence of more than 1 cell population in the tumor. Although the possibility of genomic instability in tumor remains as an alternative cause for these differences, it is more likely that the tumor had not originated from recipient cells.

The cell product was derived from 6-12-weeks aged aborted fetuses and cryopreserved for future infusions. The authors indicate that ~20% of cells were “recognized” as hematopoietic stem cells. Infused cell dose was 35-55 millions.

This is the first case report of tumorigenesis from systemically infused fetal cells. In previously reported cases, cells were delivered locally. I wish, more sophisticated genetic analysis would be performed for confirmation of tumor cell origin. I’d encourage you to read this report and discuss here. Also, you may be interested in contacting the authors about details of their genetic testing.

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