Biology of Stem Cells Exam III Flashcards
Using Mesenchymal Stem Cells as regenerative medicine:
A.) Uses of MSCs as drugs.
B.) Methods of receiving MSCs
C.) Cell issues to think about
D.) Efficacy and potency of these drugs
Outline of MSCs as drugs
Functions: tissue maintenance and repair
A.) Form skeletal tissues(bone, cartilage, adipose
B.) Regulate homeostasis
C.) Growth promoting effects
D.) Immunomodulation
Many functions of MSCs
Non skeletal uses:
Kidney, heart, liver, brain (neuron)
Skeletal uses:
Bone, cartilage, tendons, intervertebral discs
Tissue regeneration by MSCs
MSCs inhibit(prevent):
1.) inflammation by blocking the proliferation and differentiating of immune cells.
2.) Apoptosis=programmed cellular death
3.) organ fibrosis
MSCs stimulate/promote:
1.) cell proliferation by stimulating cell mitosis
2.) Angiogenesis of the tissue by secreting factors that induce the blood vessel formation.
Potential mechanisms to explain the therapeutic effects of MSC treatments in non-skeletal application
IV injection
surgical transplantation
injection directly into tissue
delivery of MSCs as drugs
Injected MSCS
Homing
A.) Site of injury
B.) Bone marrow: will the MSCs be able to differentiate into the cell type you need?
Trapped and die in the lungs
IV injection
MSCs: cells as drugs
Issues: IV injection requires homing to the injured tissues. There have been many good studies demonstrating that injected MSCs home to injured sites. It has been well demonstrated that the MSCs get trapped in the lungs. When the MSCs get to the proper site, will they properly differentiate into the cell type needed?
MSCs as drugs
Embryonic stem cells from the inner cell mass of pre-implantation blastocyst.
Pluripotent stem cell sources currently being used for therapy
Induced pluripotent stem cells created through somatic cell reprogramming.
pluripotent stem cell sources currently being used for therapy.
Somatic Cell Nuclear Transfer derived pluripotent stem cells are predicted to be pluripotent stem cell source for therapy in the future.
pluripotent stem cell sources currently being used for therapy
Must choose between making a baby or a stem cell line
Embryonic stem cells from the inner cell mass of the blastocyst
Reprogramming of somatic cells to a pluripotent state
induced pluripotent stem cells
Japanese researchers have had success in generating sperm and eggs from iPS cells. They created healthy mice from eggs that were generated entirely from iPS cells derived from skin. Potential fertility treatment as a source of artificial eggs.
Induced pluripotent stem cells
Tumor formation, especially teratomas
Issue related to the clinical use of embryonic stem cells
contamination with animal derived immunologic factors
Issue related to the clinical use of embryonic stem cell
Genetic and epigenetic changes to the cells from the extensive culture
Issue related to the clinical use of the embryonic stem cells
ethical issues related to the destruction of human embryos
issue related to the clinical use of embryonic stem cells
ES cell derived differentiated cells are “foreign” cells that will be recognized and destroyed by the patient’s immune system.
issues related to the clinical use of embryonic stem cells
poor efficiency of differentiation into specific cell types
issues related to the clinical use of embryonic stem cells
iPS cells share many of these issues, but not all. Which of these are not issues for iPS cells? Which of these is more likely to be a bigger issue for iPS as compared to ES cells?
Issues related to the clinical use of embryonic stem cells
undefined stem cell biology for differentiation
Additional issues related to the clinical use of embryonic stem cells
Undefined methods for use in tissue engineering
Additional issues related to the clinical use of embryonic stem cells
Undefined functionality of the engineered tissue
Additional issues related to the clinical use of embryonic stem cells.
Contamination with cells from different cell fates
Additional issues related to the clinical use of embryonic stem cells
Scale up of culture and differentiation for use
Additional issues related to the clinical use of embryonic stem cells
Feasibility and cost
safety and efficacy
additional issues related to the clinical use of embryonic stem cells
Dopamine secreting neurons to treat Parkinson’s
ES cells and iPS cells are pluripotent stem cells that can form every cell type in the body
Cardiomyocytes to treat heart damage
ES cells and iPS cells are pluripotent stem cells that can form every cell type in the body
For liver transplants
ES cells and iPS cells are pluripotent stem cells that can form every cell type in the bodyp
Insulin secreting cells to treat diabetes
ES ells and iPS cells are pluripotent stem cells that can form every cell type in the body
Insulin secreting cells to treat diabetes
ES ells and iPS cells are pluripotent stem cells that can form every cell type in the body
Embryoid body
Co-structure with stromal cells
Culture on extracellular matrix or growth factors or treat with drugs.
Do not use teratomas
Three general methods to differentiate ES cells
Adherent
Break up system cell via mechanical or enzymatic digestion
Plate pieces on non-adherent petri dishes and culture under differentiating conditions.
Floating in suspension
Induce 3D differentiation through Embryoid Body formation from human embryonic stem cells
With mouse embryoid bodies, we dissociated the cells into single cells with enzymes. Sometimes, enzymatic digestion is used on human ES cells too, but typically not single stem cells.
Induce 3D differentiation through embryoid body through embryoid body formation from human embryonic stem cells
With mouse embryoid bodies, we dissociated the cells into single cells with enzymes. Sometimes, enzymatic digestion is used on human ES cells too, but typically not single stem cells. Used for differentiation of several cell types including neural, cardiomyocyte, hematopoietic, B-like cells, hepatocytes, germ cell
induce 3D differentiation through embryoid body formation from human embryonic stem cells
each embryoid body is composed of thousands of differentiating ES cells
Embryoid bodies: produce most cell types, probably because they better mimic normal development, as different in a flat monolayer.
