Stem and progenitor cells used for experimental and clinical studies have a certain features unique for each cell type. True neural stem cells (NSC) fulfill which of the following criteria?

• a)
  

  NSC can differentiate into the main types of cells in the CNS neurons and astrocytes

  
  
• b)
  

  NSC can differentiate into CNS oligodendrocytes

  
  
• c)
  

  NSC can differentiate into microglia

  
  
• d)
  

  NSC have the ability of self-renewal, to give rise to new NSC

  
  
• e)
  

  Transplanted NSC can replace any type of neurons in the adult central nervous system

In clinical trials of cell therapy for neurodegenerative diseases, such as ALS and Parkinson’s disease, cells are transplanted in the late stage of neurodegeneration, not the early stage. Which of the following is/are explanations for this?

• a)
  

  Patients in the early stage of neurodegeneration are almost never available for clinical trials in neurodegenerative diseases.

  
  
• b)
  

  There is not a substantial loss of neurons until the late stage of disease, therefore there is no possible benefit from transplanting cells in the early stage.

  
  
• c)
  

  It is not known if transplanted cells can have negative effects on the target tissue. To avoid the risk of worsening the patients’ situation, those with mild symptoms that live relatively normal lives are usually not recruited.

  
  
• d)
  

  In the early stage of neurodegenerative diseases, inflammation is the main cause of neuronal injury and death.

  
  
• e)
  

  Stem and progenitor cells do not affect inflammation, therefore cell therapy should be initiated at a late stage.

In Parkinson’s disease, patients have been treated with transplantation of intact embryonic/fetal tissue, pieces of the ventral mesencephalon injected into the basal ganglia. Concern has been raised about the appearance of negative side-effects in transplanted patients that may be a result of the transplanted tissue, and this is now addressed in on-going clinical trials. Which of the following is/are recognized side effects?

• a)
  

  The tissue gave rise to tumors in the brain of transplanted patients.

  
  
• b)
  

  Long-term evaluation of the patients showed that a large proportion were infected by the transplant since the source of tissue was often contaminated

  
  
• c)
  

  The transplantation procedure caused significant damage to the host basal ganglia at the time of injection, often worsening the Parkinsonian symptoms

  
  
• d)
  

  The transplantation procedure caused significant post injection damage to the host basal ganglia, often worsening the parkinsonian symptoms.

  
  
• e)
  

  The common side-effect of pharmacological treatment of Parkinson’s disease, dyskinesia, also occurred in transplanted patients.

Human neural cell therapy application in the laboratory or clinic involves ethical concerns that require which of the following?

• a)
  

  Adherence to ethical guidelines, study protocols and procedures approved by regulatory authorities

  
  
• b)
  

  Availability of residual human material

  
  
• c)
  

  Availability of GMP cell culture facilities

  
  
• d)
  

  Permission from the regional human ethical committee and informed consent from tissue donor and potential host

  
  
• e)
  

  Availability of potential host patients with neurological disease and/or lesions

The preferred route of administration of stem cell treatment in bronchopulmonary dysplasia is intra-tracheal because of which of the following?

• a)
  

  Systemic (intraperitoneal or intravenous) administration is too painful for a newborn infant.

  
  
• b)
  

  Engraftment of cells is better after local (intra-tracheal) administration.

  
  
• c)
  

  Intra-tracheal administration is already used for surfactant treatment in neonates.

  
  
• d)
  

  Cells will migrate towards the injured lung more efficiently than after systemic administration.

  
  
• e)
  

  The only currently available clinical trial used intra-tracheal administration.

The results indicating a neuroprotective effect of cell-based therapy in term hypoxic-ischemic encephalopathy can be directly translated to preterm brain injury because of which of the following?

• a)
  

  The cause of injury is similar.

  
  
• b)
  

  The pattern of distribution of injury is similar.

  
  
• c)
  

  Animal models for term and preterm brain injury are comparable.

  
  
• d)
  

  The main aim for cellular treatment is to prevent development of post-hemorrhagic hydrocephalus.

  
  
• e)
  

  Inflammatory damage is one of the major contributors to the pathogenesis of brain injury in both term and preterm infants

Maternal micro-chimerism (MMc) has been associated with which of the following autoimmune diseases?

• a)
  

  Systemic lupus erythematosus

  
  
• b)
  

  Biliary atresia

  
  
• c)
  

  Dermatomyositis

  
  
• d)
  

  Scleroderma

  
  
• e)
  

  Juvenile arthritis

Which of the following molecules are thought to be involved in the establishment and maintenance of immune tolerance to MMc in children?

• a)
  

  IL-2

  
  
• b)
  

  IL-1

  
  
• c)
  

  IL-10

  
  
• d)
  

  TGFβ

  
  
• e)
  

  PD1

The following statement(s) is/are true about in utero stem cell transplantation?

• a)
  

  The most important biological advantage is the potential for induction of fetal tolerance.

  
  
• b)
  

  Adult hematopoietic stem cells have a competitive advantage in the fetal environment.

  
  
• c)
  

  Mechanisms of central tolerance (clonal deletion) and peripheral T-regulatory suppression are important for fetal tolerance towards allo-antigen.

  
  
• d)
  

  Maternal donor cells are advantageous over paternal donor cells in IUHCT.

  
  
• e)
  

  The rationale for IUHCT applies only to disorders that impact fetal survival or organ function.

The following statement(s) is/are true about in utero gene therapy?

• a)
  

  Non-viral DNA delivery is as effective as viral vector based DNA delivery during fetal life

  
  
• b)
  

  Understanding of developmental events are critical for developing successful in utero gene therapy strategies

  
  
• c)
  

  The small size of the fetus is a major obstacle for fetal gene therapy

  
  
• d)
  

  Risks that are potentially increased for in utero gene therapy over postnatal gene therapy include insertional mutagenesis, developmental abnormalities, and germ line alterations.

  
  
• e)
  

  The development of gene editing technologies is unlikely to impact fetal gene therapy

Regarding pluripotent stem cells which of the following is/are true?

• a)
  

  They have the capacity to differentiate into any lineages of the three germ layers

  
  
• b)
  

  When produced chemically they are safer than iPS cells

  
  
• c)
  

  They can be produced via ectopic expression of a defined set of transcription factors

  
  
• d)
  

  They can form teratomas in vitro

  
  
• e)
  

  They can form teratomas in vivo

What is/are considered benefits of using fetal cells to produce iPS cells?

• a)
  

  Fetal cells have long telomeres

  
  
• b)
  

  Fetal cells have active telomerase

  
  
• c)
  

  They can be used for both prenatal and postnatal autologous and allogeneic applications

  
  
• d)
  

  They are easier to reprogram from younger developmental age

  
  
• e)
  

  They express higher levels of Ink4/arf

What is/are the main challenges of using differentiated iPS cells in the clinic setting?

• a)
  

  The capacity of the cells to functionally differentiate into a lineage of interest

  
  
• b)
  

  Expanding the cells to sufficient numbers

  
  
• c)
  

  Finding an appropriate HLA-match donor

  
  
• d)
  

  The generation of integration-free iPS cells

  
  
• e)
  

  Variation in specific tissues of origin to produce adequate cell numbers

Which gene is the most important for inducing pluripotency?

• a)
  

  DNMT3b

  
  
• b)
  

  SOX2

  
  
• c)
  

  OCT4

  
  
• d)
  

  NANOG

  
  
• e)
  

  SOX1

Human embryonic stem cells are used in ongoing clinical trials in which of the following conditions?

• a)
  

  Cartilage injuries

  
  
• b)
  

  Myocardial infarction

  
  
• c)
  

  Age-related Macula degeneration

  
  
• d)
  

  Spinal cord injury

  
  
• e)
  

  Brain injury

Human embryonic stem cell lines can be established:

• a)
  

  From aborted fetuses

  
  
• b)
  

  From the inner cell mass of supernumerary in vitro fertilization embryos

  
  
• c)
  

  From single isolated cells from 8-cell stage embryos 3 days after in vitro fertilization

  
  
• d)
  

  From chorio-villous samples for diagnosis of chromosomal conditions

  
  
• e)
  

  From coelocentesis samples

In the culture medium of human embryonic stem cells, the following constituents are needed:

• a)
  

  Human serum

  
  
• b)
  

  A chemically defined medium

  
  
• c)
  

  Conditioned medium from mouse embryonic stem cells

  
  
• d)
  

  Porcine serum extracts

  
  
• e)
  

  Cytoplasmic extraction from cultured hepatocytes

The placenta contains a heterogeneous population of cells. Current studies have shown which of the following?

• a)
  

  The types of cell populations originating from the placenta include the human amniotic epithelial cells (hAEC), human amniotic mesenchymal stromal cells (hAMSC) and chorionic mesenchymal stromal cells (hCMSC).

  
  
• b)
  

  The hematopoietic lineage appears to originate in the chorion, allantois and yolk sac.

  
  
• c)
  

  Mesenchymal lineage originates in the chorion and amnion

  
  
• d)
  

  Placental mesenchymal cells are not yet being tested in clinical trials

  
  
• e)
  

  Placental cells cannot differentiate into other cell types

Which of the following is/are true regarding placental stem cells?

• a)
  

  They have been reported to express pluripotency stem cell markers

  
  
• b)
  

  They have been known to form teratomas

  
  
• c)
  

  They have a similar expansion capacity, generation doubling time and proliferation rates to adult MSCs

  
  
• d)
  

  They are highly immunogenic

  
  
• e)
  

  They have no major ethical barriers to their procurement

The following is/are true regarding Human amniotic mesenchymal stromal cells (hAMSC) and chorionic mesenchymal stromal cells (hCMSC)?

• a)
  

  They appear to have similar patterns of adhesion molecules

  
  
• b)
  

  They can be maintained under GMP-grade culture

  
  
• c)
  

  They possess an immune-privileged profile

  
  
• d)
  

  They have the same properties whether they are derived from early or late pregnancy placenta

  
  
• e)
  

  They differ in their ability to differentiate into the three cell lineages

Placental mesenchymal stromal cells have which of the following typical characteristics?

• a)
  

  Bi-linear differentiation

  
  
• b)
  

  Short telomeres

  
  
• c)
  

  Augmented proliferative rates

  
  
• d)
  

  High clono-genicity

  
  
• e)
  

  Expression of markers associated with pluripotency

The following is/are true regarding bio-banking of placenta-derived cells?

• a)
  

  It is established only as a public-universal-donor model

  
  
• b)
  

  It is cheap and easily performed

  
  
• c)
  

  It does not require strict regulation

  
  
• d)
  

  It may not be an option for all women depending on their medical history

  
  
• e)
  

  It could be useful as a tool to screen drugs

Placental progenitor, stem and epithelial cells that have been shown to differentiate into which of the following tissue types?

• a)
  

  Adipose tissue

  
  
• b)
  

  Pancreatic cells

  
  
• c)
  

  Cardiac cells

  
  
• d)
  

  Pulmonary cells

  
  
• e)
  

  Osteogenic cells

The following is/are true regarding CD117 expressing amniotic fluid stem cells (AFSC):

• a)
  

  They have pluripotent potential similar to embryonic stem cells or induced pluripotent stem cells.

  
  
• b)
  

  They constitute the majority of live cells found in the amniotic fluid at all gestational ages.

  
  
• c)
  

  They can be expanded in non-tissue culture treated dishes at high serum conditions, and must be passaged to maintain confluence below 60% in order to ensure multi-potency.

  
  
• d)
  

  They can be converted to induced pluripotent stem cells with the addition of chemicals in the culture media.

  
  
• e)
  

  The beneficial effects of cell therapy with AFSC in animal models of necrotising enterocolitis and muscular dystrophy are mediated by similar mechanisms.

Which of the following is/are true regarding Amniotic fluid mesenchymal stem cells (AFMSC):

• a)
  

  They are isolated from amniotic fluid samples using appropriate culture conditions

  
  
• b)
  

  They are multipotent with mesodermal potential, and thus can differentiate to hepatocytes and neurons.

  
  
• c)
  

  They express mesenchymal (CD105, CDCD73, CD90) and hematopoietic markers (CD34, CD45).

  
  
• d)
  

  The beneficial effects of cell therapy with AFMSC in animal models of central and peripheral nervous system injury is mediated by release of neurotrophic factors at the site of injury and not by differentiation of AFMS into neurons.

  
  
• e)
  

  Pre-seeding of natural and/or synthetic scaffolds with AFMSC results in improved graft performance in vivo, in the setting of tracheal and bone tissue engineering.

The following statement(s) is/are true about WJ-MSC and AF-MSC?

• a)
  

  They are tumorigenic when transplanted in animals

  
  
• b)
  

  They express key embryonic markers, such as NANOG and SSEA3

  
  
• c)
  

  They are only collectable at term after caesarean section

  
  
• d)
  

  They express MHC class II molecules

  
  
• e)
  

  They can differentiate into cells of all three germ layers in vitro

WJ-MSC and AF-MSC have immunomodulatory capacities. Which of the following statement(s) is/are true?

• a)
  

  Tissue damage induced inflammation hampers the immunosuppressive effects of WJ-MSC and AF-MSC

  
  
• b)
  

  Immunomodulation only works through cell-cell contact

  
  
• c)
  

  IL-6, which is released by WJ-MSC, has immunosuppressive properties

  
  
• d)
  

  Resting AF-MSC have been shown to inhibit T cell proliferation

  
  
• e)
  

  BM-MSC are more immunosuppressive than WJ-MSC and AF-MSC

Zhang and co-workers evaluated the regenerative effects of WJ-MSC in a rat model of periventricular leukomalacia. They induced the brain damage in 7 days old rat pups by ligating the right common carotid artery, followed by the exposure to 8 % O ₂ for 3 hours, and made which of the following findings?

• a)
  

  The damage induction resulted in a primary damage in the frontal cortex

  
  
• b)
  

  The injection of WJ-MSC 72 hours post HI-injury was more effective on the behavioural outcome than treatment 24 hours upon damage. Thereby, it did not matter whether the cells were applied intra-venously or intra-peritoneally.

  
  
• c)
  

  Astrogliosis was lower when WJ-MSC were injected intra-peritoneally compared to by intra-venous injection

  
  
• d)
  

  Engrafted cells did not differentiate at the site of injury

  
  
• e)
  

  The co-administration of WJ-MSC and the ganglioside GM1 led to better behavioural recovery than the transplantation of WJ-MSC alone

For the future routine clinical use of WJ-MSC and AF-MSC several issues have to be clarified. To date which of the following issues is/are recognized?

• a)
  

  The cryopreservation of WJ-MSC is unproblematic, because it has no effect on the proteome

  
  
• b)
  

  AF-MSC keep their differentiation potential up to high passage numbers during large scale expansion

  
  
• c)
  

  Pre-eclampsia reduces the neuroglial commitment of WJ-MSC

  
  
• d)
  

  Cells isolated from AF are very homogenous, making AF an ideal source of MSC and autologous stem cell treatment

  
  
• e)
  

  Scaffolds may be used for the delivery of MSC together with soluble factors to the site of injury

What are the minimal phenotype criteria of MSC according the International Society of Cellular Therapy?

• a)
  

  Plastic adherence during culture expansion

  
  
• b)
  

  Surface expression of CD73, CD90, CD105

  
  
• c)
  

  Lack expression of the hematopoietic and endothelial markers CD14 CD34, CD45 or CD11b, CD19, CD79a and HLA-DR

  
  
• d)
  

  Tri-lineage differentiation to osteoblasts, chondroblasts and adipocytes

  
  
• e)
  

  Differentiation to endodermal and ectodermal cell lines