Transplantable organs and tissues

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Transplantable organs and tissues may refer to both organs and tissues that are relatively often transplanted (here "major organs and tissues"), as well as organs and tissues which are relatively seldom transplanted (here "non-major organs and tissues"). In addition to this it may also refer to possible-transplants which are still in the experimental stage.[ citation needed ]

Contents

Major organs, tissues or cells

Heart

(Diagram illustrating the placement of a donor heart in an orthotopic procedure. Notice how the back of the patient's left atrium and great vessels are left in place). Heart transplant.jpg
(Diagram illustrating the placement of a donor heart in an orthotopic procedure. Notice how the back of the patient's left atrium and great vessels are left in place).

Heart transplantation is performed on patients with end-stage heart failure or severe coronary artery disease. The most common procedure is to take a working heart from a recently deceased organ donor (allograft) and implant it into the patient. The patient's own heart may either be removed (orthotopic procedure) or, less commonly, left in to support the donor heart (heterotopic procedure). It is also possible to take a heart from another species (xenograft), or implant a man-made artificial one, although the outcome of these two procedures has been less successful in comparison to the far more commonly performed allografts.[ citation needed ]

Lung

While lung transplants carry certain associated risks, they can also extend life expectancy and enhance the quality of life for end-stage pulmonary patients.

While the precise details of surgery will depend on the exact type of transplant, there are many steps which are common to all of these procedures. Prior to operating on the recipient, the transplant surgeon inspects the donor lung(s) for signs of damage or disease. If the lung or lungs are approved, then the recipient is connected to an IV line and various monitoring equipment, including pulse oximetry. The patient will be given general anesthesia, and a machine will breathe for them. [1]

It takes about one hour for the pre-operative preparation of the patient. A single lung transplant takes about four to eight hours, while a double lung transplant takes about six to twelve hours to complete. A history of prior chest surgery may complicate the procedure and require additional time. [1]

Heart-lung

A heart-lung transplant is a procedure carried out to replace both heart and lungs in a single operation. Due to a shortage of suitable donors, it is a rare procedure; only about a hundred such transplants are performed each year in the United States.[ citation needed ]

The patient is anesthetised. When the donor organs arrive, they are checked for fitness; if any organs show signs of damage, they are discarded and the operation cancelled. In order to avoid removal of recipient organs when donor organs are not viable, it is standard procedure that the patient is not operated on until the donor organs arrive and are judged suitable, despite the time delay this involves.

Once suitable donor organs are present, the surgeon makes an incision starting above and finishing below the sternum, cutting all the way to the bone. The skin edges are retracted to expose the sternum. Using a bone saw, the sternum is cut down the middle. Rib spreaders are inserted in the cut, and spread the ribs to give access to the heart and lungs of the patient.

The patient is connected to a heart-lung machine, which circulates and oxygenates blood. The surgeon removes the failing heart and lungs. Most surgeons endeavour to cut blood vessels as close as possible to the heart to leave room for trimming, especially if the donor heart is of a different size than the original organ.

The donor heart and lungs are positioned and sewn into place. As the donor organs warm up to body temperature, the lungs begin to inflate. The heart may fibrillate at first - this occurs because the cardiac muscle fibres are not contracting synchronously. Internal paddles can be used to apply a small electric shock to the heart to restore proper rhythm.

Once the donor organs are functioning normally, the heart-lung machine is withdrawn, and the chest is closed.

Kidney

The donor kidney is typically placed inferior of the normal anatomical location. Kidtransplant.svg
The donor kidney is typically placed inferior of the normal anatomical location.

Kidney transplantation is the organ transplant of a kidney in a patient with end-stage renal disease. Kidney transplantation is typically classified as deceased-donor (formerly known as cadaveric) or living-donor transplantation depending on the source of the recipient organ. Living-donor renal transplants are further characterized as genetically related (living-related) or non-related (living-unrelated) transplants, depending on whether a biological relationship exists between the donor and recipient.[ citation needed ]

Liver

Liver transplantation is the replacement of a diseased liver with a healthy liver allograft. The most commonly used technique is orthotopic transplantation, in which the native liver is removed and the donor organ is placed in the same anatomic location as the original liver. Liver transplantation nowadays is a well accepted treatment option for end-stage liver disease and acute liver failure.[ citation needed ]

Pancreas

A pancreas transplant involves implanting a healthy pancreas (one that can produce insulin) into a person who has diabetes. Because the pancreas performs functions necessary in the digestion process, the recipient's native pancreas is left in place, and the donated pancreas attached in a different location. In the event of rejection of the new pancreas, the recipient could not survive without the native pancreas still in place. The healthy pancreas comes from a donor who has just died or it may be a partial pancreas from a living donor. [2] Whole pancreas transplants from living donors are not possible, again because the pancreas is a necessary organ for digestion. At present, pancreas transplants are usually performed in persons with insulin-dependent diabetes who have severe complications.[ citation needed ]

Intestine

Currently, approximately half are pediatric recipients. [3] The most common indications in adults are ischemia (22%), Crohn's disease (13%), trauma (12%), and desmoid tumor (10%); and in pediatrics, gastroschisis (21%), volvulus (18%), and necrotizing enterocolitis (12%). Higher graft and patient survival rates are seen at the more experienced transplant programs. Within the last few years, 1-year graft and patient survival at more experienced centers have reached 60% to 70% and 65% to 80%, respectively. [4]

Cornea

Cornea transplant. Cornea transplant800.jpg
Cornea transplant.

Corneal transplantation is a surgical procedure where a damaged or diseased cornea is replaced by donated corneal tissue which has been removed from a recently deceased individual having no known diseases which might affect the viability of the donated tissue. The cornea is the clear part of eye in front of the iris and pupil. The surgical procedure is performed by ophthalmologists, medical doctors who specialize in eyes, and are often done on an outpatient basis (the patient goes home following surgery).[ citation needed ]

Skin

Walter Yeo, a British soldier, is assumed to be the first person to be benefited from plastic surgery employing tubed pedicle flaps, performed by Sir Harold Gillies in 1917. Before (left) and after (right) the operation. Walter Yeo skin graft.jpg
Walter Yeo, a British soldier, is assumed to be the first person to be benefited from plastic surgery employing tubed pedicle flaps, performed by Sir Harold Gillies in 1917. Before (left) and after (right) the operation.

Skin grafting is often used to treat:

Skin grafts are often employed after serious injuries when some of the body's skin is damaged. Surgical removal (excision or debridement) of the damaged skin is followed by skin grafting. The grafting serves two purposes: it can reduce the course of treatment needed (and time in the hospital), and it can improve the function and appearance of the area of the body which receives the skin graft.

Blood

Blood transfusion is the process of transferring blood or blood-based products from one person into the circulatory system of another. Blood transfusions can be life-saving in some situations, such as massive blood loss due to trauma, or can be used to replace blood lost during surgery. Blood transfusions may also be used to treat a severe anaemia or thrombocytopenia caused by a blood disease. People with hemophilia or sickle-cell disease may require frequent blood transfusions. Early transfusions used Whole Blood, but modern medical practice is to use only components of the blood.

Hematopoietic stem cells

Hematopoietic stem cell transplantation (HSCT) is the transplantation of blood stem cells derived from the bone marrow (that is, bone marrow transplantation) or blood. Stem cell transplantation is a medical procedure in the fields of hematology and oncology, most often performed for people with diseases of the blood, bone marrow, or certain types of cancer.

Stem cell transplantation was pioneered using bone-marrow-derived stem cells by a team at the Fred Hutchinson Cancer Research Center from the 1950s through the 1970s led by E. Donnall Thomas, whose work was later recognized with a Nobel Prize in Physiology and Medicine. Thomas' work showed that bone marrow cells infused intravenously could repopulate the bone marrow and produce new blood cells. His work also reduced the likelihood of developing a life-threatening complication called graft-versus-host disease. [5]

The first physician to perform a successful human bone marrow transplant was Robert A. Good.

With the availability of the stem cell growth factors GM-CSF and G-CSF, most hematopoietic stem cell transplantation procedures are now performed using stem cells collected from the peripheral blood, rather than from the bone marrow. Collecting peripheral blood stem cells [6] provides a bigger graft, does not require that the donor be subjected to general anesthesia to collect the graft, results in a shorter time to engraftment, and may provide for a lower long-term relapse rate.

Hematopoietic stem cell transplantation remains a risky procedure with many possible complications; it has traditionally been reserved for patients with life-threatening diseases. While occasionally used experimentally in nonmalignant and nonhematologic indications such as severe disabling auto-immune disease and cardiovascular disease, the risk of fatal complications appears too high to gain wider acceptance. [7] [8]

Non-major organs, tissues or cells

Penis

The penis may be an allograft from a human donor, or it may be grown artificially, though the latter is untested in humans.

Uterus

A uterine transplant is the replacement of a uterus which has undergone necrosis. Though the procedure has significant potential, it has been performed only a few times.

Thymus

Thymus transplantation can be used to treat infants with DiGeorge syndrome, which results in an absent or hypoplastic thymus, in turn causing problems with the immune system's T-cell mediated response. It is exclusively used in people with complete DiGeorge anomaly, which are entirely athymic. This subgroup represents less than 1% of DiGeorge syndrome patients. [9]

Heart valve

Biological valves are valves of animals, like pigs, which undergo several chemical procedures in order to make them suitable for implantation in the human heart. The porcine (or pig) heart is most similar to the human heart, and therefore represents the best anatomical fit for replacement. Implantation of a porcine valve is a type of Xenotransplantation, or Xenograft, which means a transplant from one species (in this case a pig) to another. There are some risks associated with a Xenograft such as the human body's tendency to reject foreign material. Medication can be used to delay this effect, but is not always successful.

Bone

Bone grafting is a surgical procedure that replaces missing bone with material from the patient's own body, an artificial, synthetic, or natural substitute. Bone grafting is used to repair bone fractures that are extremely complex, pose a significant health risk to the patient, or fail to heal properly.

Experimental transplants

The following is a list of possible-transplantations which are still in the experimental and research stage or have only been partially successful.

Face

A face transplant is a still-experimental procedure. In addition to skin, the transplant optimally includes bones, along with muscle, skin, blood vessels and nerves.

Hands

The operation is carried out in the following order: bone fixation, tendon repair, artery repair, nerve repair, then vein repair. The operation typically lasts 8 to 12 hours. By comparison, a typical heart transplant operation lasts 6 to 8 hours.

The recipient of a hand transplant needs to take immunosuppressive drugs, as the body's natural immune system will try to reject, or destroy, the hand. These drugs cause the recipient to have a weak immune system and react severely even from minor infections.

In 2008, surgeons in Munich transplanted two whole arms. [10] The long-term results remain to be seen.

According to legend, in the third century AD, Saints Cosmas and Damian miraculously transplanted the black leg of a dead slave onto an elderly servant. Fra Angelico 064.jpg
According to legend, in the third century AD, Saints Cosmas and Damian miraculously transplanted the black leg of a dead slave onto an elderly servant.

Leg

In ischiopagic conjoined twins, a healthy leg was transplanted from a dying conjoined twin to her sister. [11] There is no need for immunosuppression because of the identical genetic make-up of the donor and recipient.

The first leg transplant between genetically different people was performed in 2011, led by surgeon Pedro Cavadas. The procedure provided two legs to a double amputee, and recovery went well for about eight months. By then the man was able to stand up in a swimming pool. However, due to an unrelated illness, immunosuppressants had to be stopped, and the legs consequently needed to be amputated.

Ovary

Ovary transplantation, giving rise to successful pregnancies, will result in children who will have the genetic inheritance of the organ donor and not the recipient. It has so far only been carried out on identical twins, since the use of an ovarian transplant from a genetically identical donor prevents rejection of the donated organ. This bypasses the need for immune suppressants to maintain the function of the donated ovary, which is not vital for survival. [12] More significantly, many immunosuppressants, such as mycophenolate mofetil, may cause birth defects. [13]

Ovary transplants in non-genetically identical individuals have been attempted, however they have ultimately failed. One example of this is Lili Elbe who received an ovary transplant in the early 1930s but died shortly thereafter due to various complications. [14] [15] [16]

Islets of Langerhans

Islet cell transplantation has the possibility of restoring beta cells and curing diabetes.

The Chicago Project headed at University of Illinois at Chicago Medical Center is investigating ways to regenerate beta cells in vivo. With that being said, beta cells experience apoptosis early and thus are destroyed within a normal-functioning pancreas. The source of this seems to come from the transfer of Pander, a gene that works by attaching to RNA. [17] Pander, when active, causes the beta cells to be blocked at S phase, which induces apoptosis. This loss of beta cell mass eventually leads to a loss of most of the transplanted beta cells.

See also

Related Research Articles

Histocompatibility, or tissue compatibility, is the property of having the same, or sufficiently similar, alleles of a set of genes called human leukocyte antigens (HLA), or major histocompatibility complex (MHC). Each individual expresses many unique HLA proteins on the surface of their cells, which signal to the immune system whether a cell is part of the self or an invading organism. T cells recognize foreign HLA molecules and trigger an immune response to destroy the foreign cells. Histocompatibility testing is most relevant for topics related to whole organ, tissue, or stem cell transplants, where the similarity or difference between the donor's HLA alleles and the recipient's triggers the immune system to reject the transplant. The wide variety of potential HLA alleles lead to unique combinations in individuals and make matching difficult.

<span class="mw-page-title-main">Organ transplantation</span> Medical procedure in which an organ is removed from one body and placed in the body of a recipient

Organ transplantation is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organs may be transported from a donor site to another location. Organs and/or tissues that are transplanted within the same person's body are called autografts. Transplants that are recently performed between two subjects of the same species are called allografts. Allografts can either be from a living or cadaveric source.

<span class="mw-page-title-main">Liver transplantation</span> Type of organ transplantation

Liver transplantation or hepatic transplantation is the replacement of a diseased liver with the healthy liver from another person (allograft). Liver transplantation is a treatment option for end-stage liver disease and acute liver failure, although availability of donor organs is a major limitation. The most common technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomic position as the original liver. The surgical procedure is complex, requiring careful harvest of the donor organ and meticulous implantation into the recipient. Liver transplantation is highly regulated, and only performed at designated transplant medical centers by highly trained transplant physicians and supporting medical team. Favorable outcomes require careful screening for eligible recipients, as well as a well-calibrated live or deceased donor match.

<span class="mw-page-title-main">Transplant rejection</span> Rejection of transplanted tissue by the recipients immune system

Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient and by use of immunosuppressant drugs after transplant.

<span class="mw-page-title-main">Hematopoietic stem cell transplantation</span> Medical procedure to replace blood or immune stem cells

Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood, in order to replicate inside a patient and produce additional normal blood cells. HSCT may be autologous, syngeneic, or allogeneic.

<span class="mw-page-title-main">Graft-versus-host disease</span> Medical condition

Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants.

<span class="mw-page-title-main">Xenotransplantation</span> Transplantation of cells or tissue across species

Xenotransplantation, or heterologous transplant, is the transplantation of living cells, tissues or organs from one species to another. Such cells, tissues or organs are called xenografts or xenotransplants. It is contrasted with allotransplantation, syngeneic transplantation or isotransplantation and autotransplantation. Xenotransplantation is an artificial method of creating an animal-human chimera, that is, a human with a subset of animal cells. In contrast, an individual where each cell contains genetic material from a human and an animal is called a human–animal hybrid.

Allotransplant is the transplantation of cells, tissues, or organs to a recipient from a genetically non-identical donor of the same species. The transplant is called an allograft, allogeneic transplant, or homograft. Most human tissue and organ transplants are allografts.

<span class="mw-page-title-main">Kidney transplantation</span> Medical procedure

Kidney transplant or renal transplant is the organ transplant of a kidney into a patient with end-stage kidney disease (ESRD). Kidney transplant is typically classified as deceased-donor or living-donor transplantation depending on the source of the donor organ. Living-donor kidney transplants are further characterized as genetically related (living-related) or non-related (living-unrelated) transplants, depending on whether a biological relationship exists between the donor and recipient. The first successful kidney transplant was performed in 1954 by a team including Joseph Murray, the recipient's surgeon, and Hartwell Harrison, surgeon for the donor. Murray was awarded a Nobel Prize in Physiology or Medicine in 1990 for this and other work. In 2018, an estimated 95,479 kidney transplants were performed worldwide, 36% of which came from living donors.

<span class="mw-page-title-main">Regenerative medicine</span> Field of medicine involved in regenerating tissues

Regenerative medicine deals with the "process of replacing, engineering or regenerating human or animal cells, tissues or organs to restore or establish normal function". This field holds the promise of engineering damaged tissues and organs by stimulating the body's own repair mechanisms to functionally heal previously irreparable tissues or organs.

<span class="mw-page-title-main">Cell therapy</span> Therapy in which cellular material is injected into a patient

Cell therapy is a therapy in which viable cells are injected, grafted or implanted into a patient in order to effectuate a medicinal effect, for example, by transplanting T-cells capable of fighting cancer cells via cell-mediated immunity in the course of immunotherapy, or grafting stem cells to regenerate diseased tissues.

Autotransplantation is the transplantation of organs, tissues, or even particular proteins from one part of the body to another in the same person.

<span class="mw-page-title-main">Extramedullary hematopoiesis</span> Medical condition

Extramedullary hematopoiesis refers to hematopoiesis occurring outside of the medulla of the bone. It can be physiologic or pathologic.

Transfusion-associated graft-versus-host disease (TA-GvHD) is a rare complication of blood transfusion, in which the immunologically competent donor T lymphocytes mount an immune response against the recipient's lymphoid tissue. These donor lymphocytes engraft, recognize recipient cells as foreign and mount an immune response against recipient tissues. Donor lymphocytes are usually identified as foreign and destroyed by the recipient's immune system. However, in situations where the recipient is severely immunocompromised, or when the donor and recipient HLA type is similar, the recipient's immune system is not able to destroy the donor lymphocytes. This can result in transfusion associated graft-versus-host disease. This is in contrast with organ/tissue transplant associated GvHD, where matching HLA reduces the incident of the complication.

An amniotic epithelial cell is a form of stem cell extracted from the lining of the inner membrane of the placenta. Amniotic epithelial cells start to develop around 8 days post fertilization. These cells are known to have some of the same markers as embryonic stem cells, more specifically, Oct-4 and nanog. These transcription factors are the basis of the pluripotency of stem cells. Amniotic epithelial cells have the ability to develop into any of the three germ layers: endoderm, mesoderm, and ectoderm. They can develop into several organ tissues specific to these germ layers including heart, brain, and liver. The pluripotency of the human amniotic epithelial cells makes them useful in treating and fighting diseases and disorders of the nervous system as well as other tissues of the human body. Artificial heart valves and working tracheas, as well as muscle, fat, bone, heart, neural and liver cells have all been engineered using amniotic stem cells. Tissues obtained from amniotic cell lines show promise for patients with congenital diseases or malformations of the heart, liver, lungs, kidneys, and cerebral tissue.

MIRA is a multidisciplinary and complementary method for treating many chronic diseases. The MIRA Procedure is a result of combining efforts from different medical fields developed in the University of Chicago in 1992. It basically consists in medically grafting live rejuvenated tissue in the form of autologous adipose adult stem cells to a damaged organ in order to restore it and improve its function. This method is currently approved by the U.S. Food and Drug Administration (FDA).

<span class="mw-page-title-main">Intestine transplantation</span> Surgical replacement of the small intestine

Intestine transplantation is the surgical replacement of the small intestine for chronic and acute cases of intestinal failure. While intestinal failure can oftentimes be treated with alternative therapies such as parenteral nutrition (PN), complications such as PN-associated liver disease and short bowel syndrome may make transplantation the only viable option. One of the rarest type of organ transplantation performed, intestine transplantation is becoming increasingly prevalent as a therapeutic option due to improvements in immunosuppressive regimens, surgical technique, PN, and the clinical management of pre and post-transplant patients.

Organ donation is when a person gives their organs after they die to someone in need of new organs. Transplantation is the process of transplanting the organs donated into another person. This process extends the life expectancy of a person suffering from organ failure. The number of patients requiring organ transplants outweighs the number of donor organs available.

<span class="mw-page-title-main">Shimon Slavin</span> Israeli professor of medicine

Shimon Slavin is an Israeli professor of medicine. Slavin pioneered the use of immunotherapy mediated by allogeneic donor lymphocytes and innovative methods for stem cell transplantation for the cure of hematological malignancies and solid tumors, and using hematopoietic stem cells for induction of transplantation tolerance to bone marrow and donor allografts.

Tissue transplantation is a surgical procedure involving the removal of tissue from a donor site or the creation of new tissue, followed by tissue transfer to the recipient site. The aim of tissue transplantation is to repair or replace tissues that are missing, damaged, or diseased, thereby improving patients’ survival, functionality and quality of life.

References

  1. 1 2 "What Is the Surgical Procedure?". American College of Chest Physicians. October 2005. Archived from the original on 2006-09-25. Retrieved 2006-09-29.
  2. ↑ "diabetes FAQ: treatment (part 3 of 5)Section - Type 1 cures -- pancreas transplants". www.faqs.org.
  3. ↑ View Data Reports > National Data > Transplant, Intestine, & Transplant by Recipient Age] Retrieved 1 October 2010
  4. ↑ "Intestine Transplantation". www.medscape.com. Retrieved 1 October 2010.
  5. ↑ Thomas ED, Lochte HL, Lu WC, et al. (1957). "Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy". New England Journal of Medicine. 257 (11): 491–496. doi:10.1056/NEJM195709122571102. PMID   13464965.
  6. ↑ Cutler C, Antin JH (2001). "Peripheral blood stem cells for allogeneic transplantation: a review". Stem Cells . 19 (2): 108–17. doi: 10.1634/stemcells.19-2-108 . PMID   11239165.
  7. ↑ Tyndall A, Fassas A, Passweg J, et al. (1999). "Autologous haematopoietic stem cell transplants for autoimmune disease--feasibility and transplant-related mortality. Autoimmune Disease and Lymphoma Working Parties of the European Group for Blood and Marrow Transplantation, the European League Against Rheumatism and the International Stem Cell Project for Autoimmune Disease". Bone Marrow Transplant. 24 (7): 729–34. doi:10.1038/sj.bmt.1701987. PMID   10516675.
  8. ↑ Burt RK, Loh Y, Pearce W, et al. (2008). "Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases". JAMA. 299 (8): 925–36. doi: 10.1001/jama.299.8.925 . PMID   18314435.
  9. ↑ Markert ML, Devlin BH, Alexieff MJ, et al. (May 2007). "Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants". Blood. 109 (10): 4539–47. doi:10.1182/blood-2006-10-048652. PMC   1885498 . PMID   17284531.
  10. ↑ Tuffs, A. (2008). "Munich surgeons perform world's first transplantation of whole arms". British Medical Journal. 337 (aug05 22à): a1162. doi:10.1136/bmj.a1162. PMID   18682483. S2CID   35791291 . Retrieved 2009-03-30.
  11. ↑ Zuker, Ronald M.; Redett, Rick; Alman, Ben; Coles, John G.; Timoney, Norma; Ein, Sigmund H. (2006). "First Successful Lower-Extremity Transplantation: Technique and Functional Result". Journal of Reconstructive Microsurgery. 22 (4): 239–44. doi:10.1055/s-2006-939928. PMID   16783680.
  12. ↑ Woman to give birth after first ovary transplant pregnancy by James Randerson, science correspondent. guardian.co.uk, Sunday November 9, 2008 12.52 GMT.
  13. ↑ McKay DB, Josephson MA (2005). "Reproduction and Transplantation: Report on the AST Consensus Conference on Reproductive Issues and Transplantation". American Journal of Transplantation. 5 (7): 1592–1599. doi:10.1111/j.1600-6143.2005.00969.x. PMID   15943616. S2CID   32259645.
  14. ↑ Vaia Tsolas, Christine Anzieu-Premmereur, A Psychoanalytic Exploration of the Body in Today's World: On The Body (2017, ISBN   1351660284), page 234.
  15. ↑ "Lili Elbe Biography". Biography.com. A&E Television Networks. Retrieved December 11, 2015.
  16. ↑ Harrod, Horatia (8 December 2015). "The tragic true story behind The Danish Girl". The Telegraph. Retrieved 11 December 2015.
  17. ↑ Cao X, Gao Z, Robert CE, et al. (2003). "Pancreatic-derived factor (FAM3B), a novel islet cytokine, induces apoptosis of insulin-secreting beta-cells". Diabetes. 52 (9): 2296–303. doi: 10.2337/diabetes.52.9.2296 . PMID   12941769.
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