Stem cells and translational medicine

Question 1

Stem cells

Answer 1

Stem cells are undifferentiated cells that can differentiate into specialized cells and can proliferate to produce more stem cells.

Question 2

Stem cell types

Answer 2

• Totipotent: differentiation into embryonic and extraembryonic cell types. Such cells can construct a complete, viable organism.
• Pluripotent: differentiation into cells derived from any of the three germ layers, but only embryonic cell types.
• Multipotent: differentiation into a number of cell types (from a single germ layer)
• IPSCs -> differentiated cells from fibroblasts (mostly), reprogrammed with a genetic stimulus to became pluripotent. To be sure that they’re pluripotent: inject them into adult tissue, and they will create a kind of a teratoma.

Question 3

Two strategies used in regenerative medicine

Answer 3

• Cell therapy -> ethic and practical issues. Induced pluripotent stem cells are injected where the tissue needs to be regenerated: risk to implant a tumour.
• Stimulation of endogenous SCs -> identification of targets and drugs.

Question 4

Plerixafor

Answer 4

Specific factors involving stem cells niche in BM responsible for SCs homing.
CXCL12/CXCR4 interactions in the bone marrow: CXCL12 production by endosteal osteoblasts, endothelial cells and reticular is critical for the retention of CXCR4+ stem and progenitor cells in the bone marrow.
We can use an inhibitor (plerixafor) to mobilize these cells. Especially in autologous stem cells transplant, you mobilize their own SCs and then re-infuse.
Indications: neutropenia and mobilization of HSCs for leukapheresis collection

Question 5

Filgrastim

Answer 5

G-CSF, immunomodulant used as a treatment for neutropenia and for the mobilization of HSCs for leukapheresis collection.

Question 6

Different types of BM transplant based on different donors

Answer 6

• Allogenic (HLA-compatible)
• Syngeneic (twins) – not preferred over autologous bc the recurrence of leukaemia is higher.
• Autologous (myself)

Question 7

HSCs from chord blood

Answer 7

there is the possibility to store the HSCs of the chord blood in a biobank. Usually not really suggested for the patient itself. It might be useful especially if you don’t have HLA-compatible donors. Suggested to be collected for tx. Not suggested for yourself, because if you developed a leukaemia, you wouldn’t want to transplant your own cells, since they’re likely defective somehow.
Leukaemia in BM is often underlined by some sort of predispositions.

Question 8

BM transplant

Answer 8

• BM ablation
• Long period of immunodepression because to generate all lineages takes weeks. Patients are isolated
• HSCs injection

Question 9

BM transplant in rare genetic diseases.

Answer 9

They take out stem cells and by gene transfer correct the genetic defect and re-infuse the adjusted cells.

Question 10

Epithelial stem cells use

Answer 10

Regenerative therapy for the skin. Once placed in fibrin, they form nice epidermal layer.

Indicaions:

• burned patients (loss of tissue areas which are too big to be healed from the body itself. What they do: take a biopsy from the healthy tissue, culture the cells and create new skin layers).
• Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells

Question 11

Cornea regeneration

Answer 11

Limbus: portion in the eye next to the cornea, hosting stem cells. Any injury to the cornea will cause the conjunctiva to take over, which is not transparent, causing loss of vision.
Regenerative treatment: cut out the conjunctiva and insert SCs from the limbus of contralateral eye.
Holoclar: extremely costly treatment. From complete blindness to recovery.
Option of treatment from cadaver: not easy.