Introduction
ESC | iPSC | SSC |
---|---|---|
Derived from inner cell mass of blastocyst | Derived from somatic cells | Isolated from postnatal adult tissue |
Allogenic material | Autologous or allogenic material | Autologous or allogenic material |
Pluripotent | Pluripotent | Multipotent |
Can differentiate in cell types of all three germ lineages | Can differentiate in cell types of all three germ lineages | Can differentiate in limited cell types depending on the tissue of origin |
Ability to form chimeras | Ability to form chimeras (maybe more difficult than for ESCs) | Cannot form chimeras |
Self-renewal | Self-renewal | Limited self-renewal |
Require many steps to drive differentiation into the desired cell type | Require many steps to manufacture (e.g. genetic modification) and to drive differentiation into the desired cell type | Difficult to maintain in cell culture for long periods |
High degree of proliferation once isolated | High degree of proliferation | Ease of access, yield and purification varies, depending on the source tissue |
Indefinite growth | Indefinite growth | Limited lifespan (population doublings) |
Production of endless number of cells | Production of endless number of cells | Production of limited number of cells |
Chromosome length is maintained across serial passage | Chromosomes tend to shorten with ageing | Chromosomes tend to shorten with ageing |
Significant teratoma risk | Significant teratoma risk | No teratoma risk |
Serious ethical issues | No ethical issues | No ethical issues |
Immuno-priviliged. Low level of MHC I and II (also in ESC-derived cells) | Not immuno-priviliged when derived from adult cells. Normal level of MHC I and II molecules. | MSC have low immunogenicity and are immunomodulatory. Not known for other somatic SC. |
Cell lines will be allogenic | Less chance immune rejection in case of HLA-matching | In case of autologous use, less chance of immune rejection, but immunogenicity in allogenic and non-homologous applications remains unpredictable |
Donor history may be unknown for 'old' cell lines (i.e. initially not intended for clinical application) | Targeted disease may still be present in stem cell in case of autologous use | Targeted disease may still be present in stem cell in case of autologous use |
Embryonal stem cells
Induced pluripotent stem cells
Somatic stem cells
Foetal stem cells
Mesenchymal stem cells
Risk factors
Risk factors or hazards | Identified risks | |
---|---|---|
Intrinsic factors | - Origin of cells (e.g. autologous vs. allogenic, diseased vs. healthy donor/tissue) | - Rejection of cells |
Cell characteristics | - Differentiation status | - Disease susceptibility |
- Tumourigenic potential | - Unwanted biological effect (e.g. in vivo differentiation in unwanted cell type) | |
- Proliferation capacity | - Toxicity | |
- Life span | - neoplasm formation (benign or malignant) | |
- Long term viability | ||
- Excretion patterns (e.g. growth factors, cytokines, chemokines) | ||
Extrinsic factors Manufacturing and handling | - Lack of donor history | - Disease transmission |
- Starting and raw materials | - Reactivation of latent viruses | |
- Plasma derived materials | - Cell line contamination (e.g. with unwanted cells, growth media components, chemicals) | |
- Contamination by adventitious agents (viral/bacterial/mycoplasma/fungi, prions, parasites) | - Mix-up of autologous patient material | |
- Cell handling procedures (e.g. procurement) | - neoplasm formation (benign or malignant) | |
- Culture duration | ||
- Tumourigenic potential (e.g. culture induced transformation, incomplete removal of undifferentiated cells) | ||
- Non cellular components | ||
- Pooling of allogenic cell populations | ||
- Conservation (e.g. cryopreservatives) | ||
- Storage conditions (e.g. failure of traceability, human material labelling) | ||
- Transport conditions | ||
Clinical characteristics | - Therapeutic use (i.e. homologous or non-homologous) | - Undesired immune response (e.g. GVHD) |
- Indication | - Unintended physiological and anatomical consequences (e.g. arrhythmia) | |
- Administration route | - Engraftment at unwanted location | |
- Initiation of immune responses | - Toxicity | |
- Use of immune supressives | - Lack of efficacy | |
- Exposure duration | - neoplasm formation (benign or malignant) | |
- Underlying disease | ||
- Irreversibility of the treatment |