Totipotent and pluripotent cells

Following a body injury, bone marrow stem cells move to the site of damage and undergo cell differentiation.

Figure 5 shows how this differentiation occurs.

Suggest how SCFR is destroyed by a lysosome.

After a heart attack, cardiomyocytes (cardiac muscle cells) die, and become infarcted tissue. Infarcted tissue cannot contract.

Stem cells in bone marrow cannot move to the infarcted tissue and differentiate into cardiomyocytes. Scientists used laboratory rats to investigate if bone marrow stem cell transplants could be used to repair infarcted tissue resulting from a heart attack.

They split the rats into three groups.

• Control group did not get a transplant of bone marrow stem cells.

• c-KIT+ group got a transplant of bone marrow stem cells with a functioning c-KIT gene.

• c-KIT– group got a transplant of bone marrow stem cells with no functioning c-KIT gene.

After 9 days, the scientists measured the mean ventricular blood pressure of each of the three groups.

Figure 6 shows their results.

The differences between the groups were all statistically significant.

Using all of the information, suggest explanations for the results for the Control group and the c-KIT– group shown in Figure 6.

Nine days after transplantation, the c-KIT+ group showed that 68% of infarcted tissue was made up of new cardiomyocytes. The control group had no new cardiomyocytes.

Assuming that mean ventricular blood pressure is directly proportional to the number of cardiomyocytes, calculate the percentage of infarcted tissue that was made up of new cardiomyocytes in the c-KIT– group.

All new cardiomyocytes produced:

• Connexin-43, a channel protein that allows electrical impulses to pass between cardiomyocytes

• GATA-4, a transcriptional factor that stimulates the expression of genes for actin and myosin.

Suggest how production of Connexin-43 and GATA-4 could give the result seen in the c-KIT+ group in Figure 6 (on page 13).

Do not include details of transcription or translation in your answer.

Myelodysplastic syndromes (MDS) are a group of malignant cancers. In MDS, the bone marrow does not produce healthy blood cells.

Haematopoietic stem cell transplantation (HSCT) is one treatment for MDS. In HSCT, the patient receives stem cells from the bone marrow of a person who does not have MDS. Before the treatment starts, the patient’s faulty bone marrow is destroyed.

For some patients, HSCT is an effective treatment for MDS.

Explain how.

MDS can develop from epigenetic changes to tumour suppressor genes. In some patients, the drug AZA has reduced the effects of MDS. AZA is an inhibitor of DNA methyltransferases. These enzymes add methyl groups to cytosine bases.

Suggest and explain how AZA can reduce the effects of MDS in some patients.

Scientists investigated the effectiveness of AZA in patients with MDS. A total of 360 patients were randomised in the ratio of 1:1 to receive AZA or conventional drugs (control).

Figure 6 shows the scientists’ results.

The control patients were treated with conventional drugs.

Give two reasons why.

Use Figure 6 and the information provided to calculate the difference in the number of patients surviving at 10 months after treatment with AZA compared with conventional drugs.

Describe how the human immunodeficiency virus (HIV) is replicated once inside helper T cells (T_H cells).

HIV-1 is the most common type of HIV. HIV-1 binds to a receptor on T_H cells called

CCR5.

Current treatment for HIV-1 involves the use of daily antiretroviral therapy (ART) to stop the virus being replicated. Only 59% of HIV-positive individuals have access to ART.

Scientists have found that two HIV-1-positive patients (P and Q) have gone into remission (have no detectable HIV-1). This happened after a blood stem cell transplant (BSCT).

• Patient P was given two BSCTs, and patient Q was given one BSCT.

• All BSCTs came from a donor with T_H cells without the CCR5 receptor.

• In addition, patient P had radiotherapy, and patient Q had chemotherapy. Both of these treatments are toxic.

• Both patients (P and Q) stopped receiving ART 16 months after BSCT.

18 months after stopping ART, both patients had no HIV-1 RNA in their plasma, no HIV-1 DNA in their T_H cells and no CCR5 on their T_H cells.

Use the information given to evaluate the use of BSCT to treat HIV infections.

Alport syndrome (AS) is an inherited disorder that affects kidney glomeruli of both men and women. Affected individuals have proteinuria (high quantities of protein in their urine).

Suggest how AS could cause proteinuria.

AS results from a sex-linked mutation.

In a male with AS, where would the sex-linked mutation be located?

Tick () one box.

Scientists investigated the use of transplanted stem cells to treat AS in mice.

The scientists set up four experimental groups.

Group A – 40 wild type* mice Group B – 40 AS mice Group C – 40 AS mice that received stem cells from AS mice Group D – 40 AS mice that received stem cells from wild type mice

*Wild type mice are mice not affected by AS.

After 20 weeks, the scientists measured the quantity of protein in the urine using a scale from 0 (lowest quantity) to +++++ (highest quantity).

The results the scientists obtained are shown in Table 2.

Using all the information, evaluate the use of stem cells to treat AS in humans.

Answer space for this question continues on the next page

The scientists carried out further work to investigate how the transplanted stem cells developed after transplantation.

• The scientists transplanted stem cells from wild type male mice into AS female mice.

• After 20 weeks, they found that the quantity of protein in the urine of these female mice had significantly decreased.

• They examined cells from glomeruli in the female mice. Some of these cells contained a Y chromosome.

Suggest how the transplanted stem cells reduce proteinuria.

Sickle cell disease (SCD) is a group of inherited disorders. People with SCD have sickle-shaped red blood cells. A single base substitution mutation can cause one type of SCD. This mutation causes a change in the structure of the beta polypeptide chains in haemoglobin.

Explain how a single base substitution causes a change in the structure of this polypeptide.

Do not include details of transcription and translation in your answer.

Haematopoietic stem cell transplantation (HSCT) is a long-term treatment for SCD. In HSCT, the patient receives stem cells from the bone marrow of a person who does not have SCD. The donor is often the patient’s brother or sister. Before the treatment starts, the patient’s faulty bone marrow cells have to be destroyed.

Use this information to explain how HSCT is an effective long-term treatment for SCD.

A new long-term treatment for SCD involves the use of gene therapy.

Figure 2 shows some of the stages involved in this treatment in a child with SCD.

Some scientists have concluded that this method of gene therapy will be a more effective long-term treatment for SCD than HSCT. Use all the information provided to evaluate this conclusion.

Read the following passage.

Complete achromatopsia is a form of complete colour blindness. It is caused by having only rods and no functional cone cells. People with complete achromatopsia have difficulty in seeing detail. Complete achromatopsia is caused by an autosomal recessive allele and is usually very rare in populations with only one in 40 000 being affected. However on the Pacific 5 island of Pingelap ten percent of the population are affected.

One form of red-green colour blindness is caused by a sex-linked recessive allele which affects more men than women. People with this red-green colour blindness are unable to distinguish between red and green, and also between other colours. They have green-sensitive cones but the 10 photoreceptive pigment they contain does not function.

Scientists investigated the use of gene therapy to correct red-green colour blindness in monkeys. They injected viruses containing the gene for the green-sensitive pigment directly into the eyes of the monkeys. Although the monkeys maintained two years of colour vision, there is debate on whether 15 this form of gene therapy is worthwhile. No clinical trials of this procedure have been carried out on humans. Current research into the treatment of red-green colour blindness involves the use of induced pluripotent stem cells (iPS cells). The use of iPS cells could have advantages over the use of gene therapy. 20

Use the information in the passage and your own knowledge to answer the following questions.

People with complete achromatopsia have difficulty in seeing detail (lines 2–3).

Explain why.

Ten percent of the population on the Pacific island of Pingelap are affected by complete achromatopsia (lines 3–6).

Use the Hardy-Weinberg equation to calculate the percentage of this population who are heterozygous for this disorder. Show your working.

Red-green colour blindness affects more men than women (lines 7–8).

Explain why.

People with red-green colour blindness are unable to distinguish between red and green, and also between other colours (lines 8–10).

Explain why.

Current research into the treatment of red-green colour blindness involves the use of induced pluripotent stem cells (iPS cells) (lines 17–19).

Suggest how iPS cells could correct red-green colour blindness.

The use of iPS cells could have advantages over the use of gene therapy to correct red-green colour blindness (lines 19–20).

Using the information from the passage, suggest and explain reasons why.

Each year, a few people with type I diabetes are given a pancreas transplant. Pancreas transplants are not used to treat people with type II diabetes.

Give two reasons why pancreas transplants are not used for the treatment of type II diabetes.

The pancreas produces the hormone insulin.

Put a tick (✓) in the box next to the statement which describes incorrectly the action of insulin.

Scientists investigated the use of induced pluripotent stem cells (iPS cells) to treat type I diabetes in mice. The scientists used four transcription factors to reprogramme skin cells to form iPS cells. The scientists then stimulated the in vitro differentiation of iPS cells into pancreatic cells.

The scientists set up three experimental groups:

Group A – 30 mice with type I diabetes received pancreatic cell transplants derived from iPS cells.

Group B – 30 mice with type I diabetes were left untreated.

Group C – 30 mice without diabetes were left untreated.

The scientists measured the blood glucose concentration of all the mice on a weekly basis for 12 weeks.

The results the scientists obtained are shown in Figure 6.

Suggest how transcription factors can reprogramme cells to form iPS cells.

Using all the information provided, evaluate the use of iPS cells to treat type I diabetes in humans.