Making transplants last

This exercise is a part of Educator Guide: Transplant Tolerance / View Guide

These questions are based on the Science News (SN) article “Transplant tolerance.” As your students read the article, ask them to note where the article gives information about the experimental treatment methods that might reduce transplant rejection: (A) mixed chimeric or blended immune system, (B) facilitator cells, (C) regulatory T cells, (D) apoptotic cells and (E) stem cell–mobilizing drugs. You may assign students to groups to focus on one experimental treatment method after they have read the article.

1. What is the central idea of the article?

Possible student response: Some patients need organ transplants when one of their organs is failing. But patients’ own immune systems attack and try to destroy the transplanted organ. The standard approach to prevent patients’ immune systems from rejecting the transplanted organ has been for patients to take strong immune-suppressing drugs for the rest of their lives. Researchers are testing new ways to make patients’ immune systems more tolerant of transplanted organs.

2. What patient story is featured in the article?

Possible student response: Trent Jackson experienced sudden liver failure and received a liver transplant. He has to take many immune-suppressing drugs, has experienced side effects from those drugs and is still in serious danger of his immune system destroying the transplanted liver.

3. How common are organ transplants in the United States?

Possible student response: In the first eight months of 2018, 24,213 people in the United States received a donated organ. There are over 354,078 people living in the United States with transplanted organs as of June 29, 2018.

Based on the information in the article, answer the following questions about one experimental treatment method that researchers are testing to see if it could reduce transplant rejection without having to use immune-suppressing drugs. The potential treatments include: (A) mixed chimeric or blended immune system, (B) facilitator cells, (C) regulatory T cells, (D) apoptotic cells or (E) stem cell–mobilizing drugs.

4. What is the mechanism for the experimental treatment method?

Possible student responses:

A. Mixed chimeric or blended immune system: Bone marrow cells from the donor, and radiation that kills off some of the patient’s bone marrow cells to make room for the donated marrow.

B. Facilitator cells: Bone marrow stem cells, radiation and facilitator cells from the donor.

C. Regulatory T cells: Immune cells called B cells from a donor, plus immune cells called regulatory T cells (T regs) from the patient that have been specially treated.

D. Apoptotic cells: Specially treated apoptotic (dying) cells and possibly bone marrow stem cells from the donor.

E. Stem cell–mobilizing drugs: Drugs that encourage a patient’s stem cells to move to the new organ.

5. How does the experimental treatment method help prevent transplant rejection?

Possible student responses:

A. Mixed chimeric or blended immune system: The organ donor’s bone marrow, now in the patient’s body, produces donor immune cells that recognize the donated organ and hopefully tell the patient’s own immune cells not to attack it.

B. Facilitator cells: Facilitator cells help donor bone marrow stem cells grow better and last longer in the patient.

C. Regulatory T cells: T regs calm the patient’s other immune system cells and persuade them not to attack the transplanted organ.

D. Apoptotic cells: Apoptotic cells trick the immune system into treating the transplanted organ as a normal part of the body that it doesn’t need to attack. While it’s unclear how the cells do this, researchers have found that apoptotic cells attract phagocytes, which eat the dying cells and send signals to decrease the production of an inflammatory chemical called interferon alpha. Stomping out inflammation signals is important for the patient to tolerate a transplant. Apoptotic cells also attract to the organ protective cells that fend off immune system attacks.

E. Stem cell–mobilizing drugs: Stem cell–mobilizing drugs stimulate the patient’s bone marrow to send stem cells to the transplanted organ. There, the stem cells become new cells appropriate for that organ, and dissuade the patient’s immune system from attacking the organ.

6. What details does the article provide about the history of the experimental treatment method or researchers that are currently working on the method?

Possible student responses:

A. Mixed chimeric or blended immune system: Massachusetts General Hospital in Boston began combining kidney and bone marrow transplants in 1998. Massachusetts General Hospital, Stanford University, the University of Louisville in Kentucky and Northwestern University in Evanston, Ill., have been testing the method in small numbers of patients for over a decade.

B. Facilitator cells: Transplant surgeons Suzanne Ildstad at Regenerex, a pharmaceutical company in Rockville, Maryland, and the University of Louisville in Kentucky, and Joseph Leventhal at Northwestern University in Evanston, Ill. have been testing facilitator cells for about seven years.

C. Regulatory T cells: Sandy Feng, a transplant surgeon at the University of California, San Francisco, is studying T regs.

D. Apoptotic cells: Xunrong Luo, a transplant immunologist at Duke University, is studying apoptotic cells.

E. Stem cell–mobilizing drugs: Andrew Cameron, a transplant surgeon at Johns Hopkins University is studying stem cell–mobilizing drugs.

7. What have scientists achieved with the experimental treatment method?

Possible student responses:

A. Mixed chimeric or blended immune system: In 2005, Stanford researchers gave 29 patients bone marrow transplants along with kidneys from HLA matched living donors. Twenty three have been able to stop taking immune-suppressing drugs without rejecting the kidney for up to nine years so far. At Massachusetts General Hospital in Boston, 10 patients received bone marrow transplants plus HLA-mismatched kidneys. Seven patients were able to go for many years without taking immune-suppressing drugs, although eventually three of those patients had to go back on the drugs.

B. Facilitator cells: Among the 31 patients who got facilitator cells, bone marrow and a kidney from a living donor, 23 have kept the donor immune system, and 22 of those patients have not needed immune-suppressing drugs for eight months to nearly seven years. Among the seven patients who held on to the donor bone marrow for only a little while, five are down to a single low-dose medication.

C. Regulatory T cells: In patient studies, Sandy Feng and her colleagues are trying to persuade the body to eliminate the cells that would attack an organ while boosting T regs. The aim is to achieve a balance both the host and the donor organ can live with. No specific data from the studies is given.

D. Apoptotic cells: The method was demonstrated with published data on heart transplants in mice, and unpublished data on pancreatic islet cell transplants in monkeys. One small study in humans showed that apoptotic cells could help patients with bone marrow transplants avoid graft-versus-host disease.

E. Stem cell–mobilizing drugs: Rats and miniature pigs have gotten stem cell–mobilizing drugs in addition to kidney transplants. Pigs that had both kidneys removed, received one kidney from a donor pig and had no immune suppression died within about 10 days. Pigs that received one stem cell–mobilizing drug lived about 10 days to one month. Pigs that got two stem cell–mobilizing drugs lived three years and were still going strong when the study ended.

8. What are some disadvantages or dangers of the experimental treatment method?

Possible student responses:

A. Mixed chimeric or blended immune system: Donated bone marrow can die. Some of the patient’s own bone marrow must be destroyed by radiation to make room for the new bone marrow, which can have serious short term and long term side effects such as developing cancer.

B. Facilitator cells: The donated immune cells can become too strong, replacing most of the patient’s immune system and recognizing the donated organ but attacking the patient’s body — a potentially deadly condition known as graft-versus-host disease.

C. Regulatory T cells: T regs may not help enough to prevent transplant rejection.

D. Apoptotic cells: Researchers do not know why apoptotic cells help, or what other effects they might have.

E. Stem cell–mobilizing drugs: Stem cell–mobilizing drugs have side effects that are not mentioned. For example, the drugs may mobilize cells from the bone marrow that become cancerous. Other potential side effects include increased levels of white blood cells, decreased platelets and potentially enlarged spleens.

9. Are these experimental treatment methods currently being used to treat organ rejection?

Possible student responses: These methods have not been tested enough to be given to people as standard treatments for organ rejection. More research is needed, and even then, many may not turn out to be safe or effective enough to be used. Right now, the only non-experimental treatment for a person with a transplanted organ is to take immune-suppressing drugs.

10. What related work would you like to see researchers do in the future, or what work might you be able to do as a science fair project?

Student responses will vary.