Friday, 10 January 2014

Researchers grow iPSCs from Alzheimer's biobanked brain tissue

Human Brain
Researchers at The New York Stem Cell Foundation (NYSCF) Research Institute, working in collaboration with scientists at the Columbia University Medical Center (CUMC), have generated for the first time induced pluripotent stem cell lines from non-cryoprotected brain tissue of patients with Alzheimer's disease.

These new stem cell lines will allow researchers to "turn back the clock" and observe how Alzheimer's develops in the brain, potentially revealing the onset of the disease at a cellular level long before any symptoms associated with Alzheimer's are displayed.

These reconstituted Alzheimer's cells will also provide a platform for drug testing on cells from patients that were definitively diagnosed with the disease. Until now, the only available method to definitively diagnose Alzheimer's disease that has been available to researchers is examining the brain of deceased patients. This discovery will permit scientists for the first time to compare "live" brain cells from Alzheimer's patients to the brain cells of other non-Alzheimer's patients.

NYSCF scientists successfully produced the stem cells from frozen tissue samples stored for up to eleven years at the New York Brain Bank at Columbia University.

This advance, published today in Acta Neuropathologica Communications , shows that disease-specific induced pluripotent stem cells (iPSCs) can be generated from readily available biobanked tissue that has not been cryoprotected, even after they have been frozen for many years. 

This allows for the generation of iPSCs from brains with confirmed disease pathology as well as allows access to rare patient variants that have been banked. In addition, findings made using iPSCs cellular models can be cross-validated in the original brain tissue used to generate the cells. The stem cell lines generated for this study included samples from patients with confirmed Alzheimer's disease and four other neurodegenerative diseases.

This important advance opens up critical new avenues of research to study cells affected by disease from patients with definitive diagnoses. This success will leverage existing biobanks to support research in a powerful new way.

iPSCs are typically generated from a skin or blood sample of a patient by turning back the clock of adult cells into pluripotent stem cells, cells that can become any cell type in the body. While valuable, iPSCs are often generated from patients without a clear diagnosis of disease and many neurodegenerative diseases, such as Alzheimer's disease, often lack specific and robust disease classification and severity grading.

These diseases and their extent can only be definitively diagnosed by post-mortem brain examinations. For the first time we will now be able to compare cells from living people to cells of patients with definitive diagnoses generated from their banked brain tissue.

Brain bank networks, which combined contain tens of thousands of samples, provide a large and immediate source of tissue including rare disease samples and a conclusive spectrum of disease severity among samples.

The challenge to this approach is that the majority of biobanked brain tissue was not meant for growing live cells, and thus was not frozen in the presence of cryoprotectants normally used to protect cells while frozen. NYSCF scientists in collaboration with CUMC scientists have shown that these thousands of samples can now be used to make living human cells for use in disease studies and to develop new drugs or preventative treatments for future patients.

References
- Sproul AA, Vensand LB, Dusenberry CR, Jacob S, Vonsattel JP, Paull DJ, Shelanski ML, Crary JF, & Noggle SA (2014). Generation of iPSC lines from archived non-cryoprotected biobanked dura mater. Acta neuropathologica communications, 2 (1) PMID: 24398250

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