prospects for cell-based therapies for ild · 2020-05-13 · • ‘stem cell transplants’ =...
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Prospects for cell-based therapies for ILD
Tushar Desai, MD, MPH
Stanford Medical School
Division of Pulmonary, Department of Internal Medicine
Institute for Stem Cell Biology and Regenerative Medicine
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• Pluripotent stem cells:
– Can generate cells of all types for any tissue (embryonic)
– Can now be made from any cell from an adult person (induced)
• Adult stem cells:
– Restricted to generating cell types for a specific tissue throughout life (normal adult physiology)
– Dysfunction can result in diseases of aging (lose activity) or cancer (overactive)
• Adult progenitor cells:
– Like adult stem cells but more limited capacity for making new cells
– Dysfunction can result in cancer (e.g., leukemia)
Stem cells produce new cells
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• Blood stem cell failure (myelofibrosis) anemia
• Blood progenitor cell ‘overactivity’ leukemias
• ‘stem cell transplants’ = blood stem cell transplants
• Mainstay of modern medicine
• Leukemia: purify patient’s own stem cells from blood, give chemotherapy to kill diseased progenitor and cancer cells, then infuse back blood stem cells
• Sickle cell anemia: collect blood stem cells from suitable donor, give chemotherapy to kill patient’s stem cells, then transfuse donor blood stem cells– ** Immune suppression to prevent immune cells generated by donor stem
cells from attacking patient tissues!
Stem cell diseases
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Donor blood stem cell transplant
+Immunosuppression
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• Immune system– Recognizes ‘non-self’ cells and attacks them
• Re-transplanting your own stem cells:– Ideal because no need to suppress your own immune response
– Sickle cell anemia purify patient stem cells, use gene-editing to correct mutation in DNA, use chemotherapy to kill residual patient stem cells, then transfuse in “corrected” stem cells
• Transplanting in donor stem cells from another person:– Blood stem cells: Suppress foreign immune cells generated by donor blood stem
cells from attacking you!
– Non-blood stem cells: Immune suppression needed to prevent your own immune cells from killing the donor cells (but no worry about donor cells attacking you)
Self versus Other
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Lung stem cells
Bronchial tube
Tubes forbringing airin and out
Sacs forexchangingOxygen and
Carbon dioxide
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Two types of cells in the air sacs
#1 Very thin barrier
#2 Detergent
Blood flow
Oxygen
C02
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• The good:
– Lung is easy to access (by bronchoscopy)
– Disease is very active, so even halting progression may be very helpful
– Stem cells could reduce severity of “flares”
• The bad:
– How to get rid of defective stem cells without making patients sick?
• The unknown:
– After engraftment, will they remain healthy and active?
– Which is more feasible, adult versus pluripotent derived cells and self versus other?
IPF may be a stem cell disease!
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Human lung stem cells grown in the lab
Human Lung Lobe ~1x1 mm
Peripheral FragmentsSubmerged
3D culture
Dissociation
~1cmExtracellular Matrix
Media
Salahudeen et al, Nature (in revision)
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Correcting cystic fibrosis airway stem cells for re-
transplantation
Airway stem cells
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Cells from an IPF patient’s lungs grown in lab!
Day 2 Day 5 Day 8
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Summary
• IPF may be a bona fide lung stem cell disease
• Hopefully coming down the pike!
• The best source of stem cells (pluripotent versus adult) is not clear
• Researchers are developing ways to collect and expand lung stem cells for transplantation