Table 2 Overview of risk factors and risks associated with stem cell-based therapy

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