Regenerative Medicine Applications in Organ Transplantation

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Unique highlights from this book include the historical perspective offered by Joseph P Vacanti, Jean-Bernard Otte and Jason Wertheim in the first chapter. They cite examples of various advanced organisms such as the salamander and the sea cucumber regrowing appendages, suggesting a fascination with bioregeneration long before the rise of regenerative medicine as a major scientific field. Interestingly, the editor has elsewhere raised the question of why the mammal, which exhibits formidable regenerative abilities in utero , loses this capacity after birth and why simpler organisms throughout the plant and animal kingdoms retain this ability [ 1 ].

The authors trace transplantation and surgical reconstruction of each organ system to their respective origins and, in doing so, highlight that the endeavor to restore functional tissue long predated the rise of tissue engineering and regenerative medicine. Another notable section of this book deals with the possibility of immunosuppression-free transplantation offered by the regenerative medicine paradigm. As Sir Roy Calne, Emeritus Professor of Surgery at the University of Cambridge UK , notes in the preface, the introduction of cyclosporine immunosuppression following transplantation represented a watershed in organ transplantation due to the dramatic rise in survival rates.

If regenerative medicine enables transplantation to circumvent the need for immunosuppression via the manufacture of transplantable organs using autologous cells and scaffolding obtained from the patient, then we truly are on the brink of the next watershed in organ transplantation. The chapters presented in this context offer a rich scientific discourse on the nature of tolerance and on concepts such as immunomodulation and immune cloaking i. Fortunately, the technical and biomedical jargon that permeates most of the text is tempered by important ethical and economic considerations presented at the end of the book.

The era of regenerative medicine is coming and these chapters offer a small measure of preparedness for the inevitable. Nancy MP King, author of the ethics chapter, is a renowned bioethicist whose contribution to this edition is invaluable. She touches on several pertinent issues including the rights of human subjects during clinical trials and blurred distinction between research and treatment, which can lead to not only unreasonably high expectations of benefit from experimental intervention, but to unreasonable discounting of the risks involved with such interventions.

Judging by the goal of bridging the fields of organ transplantation and regenerative medicine, the editors and contributors in Regenerative Medicine Applications in Organ Transplantation ultimately succeed in providing an immersive discourse on the topic. Given the implications that a chronic shortage of organs has on public health and society, this book is a valuable resource for students and professionals seeking to do something about this problem by taking advantage of cutting-edge developments in one of those most dynamic scientific disciplines existing today, namely regenerative medicine.

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. More details about the book. Regenerative Medicine. Like 0 Comment. Traditionally, Muslims believe body desecration in life or death to be forbidden, and thus many reject organ transplant.

Applications of regenerative medicine in organ transplantation

The Organ Donor Registry maintains two types of information, firstly people of Singapore that donate their organs or bodies for transplantation, research or education upon their death, under the Medical Therapy, Education and Research Act MTERA , [94] and secondly people that object to the removal of kidneys, liver, heart and corneas upon death for the purpose of transplantation, under the Human Organ Transplant Act HOTA.

Organ transplantation in China has taken place since the s, and China has one of the largest transplant programmes in the world, peaking at over 13, transplants a year by One third of all heart transplants performed on Israelis are done in the People's Republic of China; others are done in Europe. Jacob Lavee, head of the heart-transplant unit, Sheba Medical Center, Tel Aviv, believes that "transplant tourism" is unethical and Israeli insurers should not pay for it.

Transplantation rates also differ based on race, sex, and income. A study done with people beginning long term dialysis showed that the sociodemographic barriers to renal transplantation present themselves even before patients are on the transplant list. Previous efforts to create fair transplantation policies had focused on people currently on the transplantation waiting list. In the United States nearly 35, organ transplants were done in , a 3.

About 18 percent of these were from living donors — people who gave one kidney or a part of their liver to someone else. But , Americans remain on waiting lists for organ transplants. Successful human allotransplants have a relatively long history of operative skills that were present long before the necessities for post-operative survival were discovered.

Rejection and the side effects of preventing rejection especially infection and nephropathy were, are, and may always be the key problem. Several apocryphal accounts of transplants exist well prior to the scientific understanding and advancements that would be necessary for them to have actually occurred.

The Chinese physician Pien Chi'ao reportedly exchanged hearts between a man of strong spirit but weak will with one of a man of weak spirit but strong will in an attempt to achieve balance in each man. Roman Catholic accounts report the 3rd-century saints Damian and Cosmas as replacing the gangrenous or cancerous leg of the Roman deacon Justinian with the leg of a recently deceased Ethiopian.

The more likely accounts of early transplants deal with skin transplantation. The first reasonable account is of the Indian surgeon Sushruta in the 2nd century BC, who used autografted skin transplantation in nose reconstruction, a rhinoplasty. Success or failure of these procedures is not well documented. Centuries later, the Italian surgeon Gasparo Tagliacozzi performed successful skin autografts; he also failed consistently with allografts , offering the first suggestion of rejection centuries before that mechanism could possibly be understood. He attributed it to the "force and power of individuality" in his work De Curtorum Chirurgia per Insitionem.

The first successful corneal allograft transplant was performed in in a gazelle model; the first successful human corneal transplant, a keratoplastic operation, was performed by Eduard Zirm at Olomouc Eye Clinic , now Czech Republic, in The first transplant in the modern sense — the implantation of organ tissue in order to replace an organ function — was a thyroid transplant in It was performed by the Swiss surgeon and later Nobel laureate Theodor Kocher.

In the preceding decades Kocher had perfected the removal of excess thyroid tissue in cases of goiter to an extent that he was able to remove the whole organ without the person dying from the operation. Kocher carried out the total removal of the organ in some cases as a measure to prevent recurrent goiter. By , the surgeon noticed that the complete removal of the organ leads to a complex of particular symptoms that we today have learned to associate with a lack of thyroid hormone.

Kocher reversed these symptoms by implanting thyroid tissue to these people and thus performed the first organ transplant. In the following years Kocher and other surgeons used thyroid transplantation also to treat thyroid deficiency that appeared spontaneously, without a preceding organ removal. Thyroid transplantation became the model for a whole new therapeutic strategy: organ transplantation.

After the example of the thyroid, other organs were transplanted in the decades around Some of these transplants were done in animals for purposes of research, where organ removal and transplantation became a successful strategy of investigating the function of organs. Kocher was awarded his Nobel Prize in for the discovery of the function of the thyroid gland.

At the same time, organs were also transplanted for treating diseases in humans. The thyroid gland became the model for transplants of adrenal and parathyroid glands , pancreas, ovary , testicles and kidney. By , the idea that one can successfully treat internal diseases by replacing a failed organ through transplantation had been generally accepted. Their skillful anastomosis operations and the new suturing techniques laid the groundwork for later transplant surgery and won Carrel the Nobel Prize in Physiology or Medicine.

From , Carrel performed transplant experiments on dogs. Surgically successful in moving kidneys , hearts , and spleens , he was one of the first to identify the problem of rejection , which remained insurmountable for decades. The surgery was done by Dr. Joseph Murray, who received the Nobel Prize in Medicine for his work. The reason for his success was due to Richard and Ronald Herrick of Maine. Richard Herrick was a in the Navy and became severely ill with acute renal failure.


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His brother Ronald donated his kidney to Richard, and Richard lived another 8 years before his death. Before this, transplant recipients didn't survive more than 30 days. The key to the successful transplant was the fact that Richard and Ronald were identical twin brothers and there was no need for anti-rejection medications, which was not known about at this point. Major steps in skin transplantation occurred during the First World War, notably in the work of Harold Gillies at Aldershot.

Among his advances was the tubed pedicle graft, which maintained a flesh connection from the donor site until the graft established its own blood flow. In , the first successful replantation surgery was performed — re-attaching a severed limb and restoring limited function and feeling. The donor was a convicted murderer, one Ilija Krajan, whose death sentence was commuted to 20 years imprisonment, and he was led to believe that it was done because he had donated his testis to an elderly medical doctor. Both the donor and the receiver survived, but charges were brought in a court of law by the public prosecutor against Dr.

Kolesnikov, not for performing the operation, but for lying to the donor. The first attempted human deceased-donor transplant was performed by the Ukrainian surgeon Yuri Voronyi in the s; [] [] but failed due to Ischemia. Joseph Murray and J. Hartwell Harrison performed the first successful transplant, a kidney transplant between identical twins , in , because no immunosuppression was necessary for genetically identical individuals. In the late s Peter Medawar , working for the National Institute for Medical Research , improved the understanding of rejection.

Identifying the immune reactions in , Medawar suggested that immunosuppressive drugs could be used. Cortisone had been recently discovered and the more effective azathioprine was identified in , but it was not until the discovery of cyclosporine in that transplant surgery found a sufficiently powerful immunosuppressive. There was a successful deceased-donor lung transplant into an emphysema and lung cancer sufferer in June by James Hardy at the University of Mississippi Medical Center in Jackson, Mississippi.

The patient John Russell survived for eighteen days before dying of kidney failure. Thomas Starzl of Denver attempted a liver transplant in the same year, but he was not successful until In the early s and prior to long-term dialysis becoming available, Keith Reemtsma and his colleagues at Tulane University in New Orleans attempted transplants of chimpanzee kidneys into 13 human patients.

Most of these patients only lived one to two months. However, in , a year-old woman lived for nine months and even returned to her job as a school teacher until she suddenly collapsed and died. It was assumed that she died from an acute electrolyte disturbance. At autopsy, the kidneys had not been rejected nor was there any other obvious cause of death. The heart was a major prize for transplant surgeons. But over and above rejection issues, the heart deteriorates within minutes of death, so any operation would have to be performed at great speed.

The development of the heart-lung machine was also needed. Lung pioneer James Hardy was prepared to attempt a human heart transplant in , but when a premature failure of comatose Boyd Rush 's heart caught Hardy with no human donor, he used a chimpanzee heart, which beat in his patient's chest for approximately one hour and then failed. Washkansky survived for eighteen days amid what many [ who?

The media interest prompted a spate of heart transplants. Over a hundred were performed in —, but almost all the people died within 60 days. Barnard's second patient, Philip Blaiberg , lived for 19 months. It was the advent of cyclosporine that altered transplants from research surgery to life-saving treatment.

In surgical pioneer Denton Cooley performed 17 transplants, including the first heart-lung transplant. Fourteen of his patients were dead within six months. By two-thirds of all heart transplant patients survived for five years or more. With organ transplants becoming commonplace, limited only by donors, surgeons moved on to riskier fields, including multiple-organ transplants on humans and whole-body transplant research on animals. On 9 March , the first successful heart-lung transplant took place at Stanford University Hospital.

The head surgeon, Bruce Reitz , credited the patient's recovery to cyclosporine-A. As the rising success rate of transplants and modern immunosuppression make transplants more common, the need for more organs has become critical. Transplants from living donors, especially relatives, have become increasingly common. However, there are still many problems that would need to be solved before they would be feasible options in people requiring transplants. Recently, researchers have been looking into means of reducing the general burden of immunosuppression.

Common approaches include avoidance of steroids, reduced exposure to calcineurin inhibitors, and other means of weaning drugs based on patient outcome and function. While short-term outcomes appear promising, long-term outcomes are still unknown, and in general, reduced immunosuppression increases the risk of rejection and decreases the risk of infection. The risk of early rejection is increased if corticosteroid immunosuppression are avoided or withdrawn after renal transplantation.

Many other new drugs are under development for transplantation. From year and forward, there have been approximately 2, lung transplants performed each year worldwide. From between and , the median survival period for lung transplant patients has been 5-and-a-half years, meaning half the patients survived for a shorter time period and half survived for a longer period.

One of the driving forces for illegal organ trafficking and for "transplantation tourism" is the price differences for organs and transplant surgeries in different areas of the world. Price disparities based on donor race are a driving force of attractive organ sales in South Africa, as well as in other parts of the world. In the United States of America, tissue transplants are regulated by the U. Food and Drug Administration FDA which sets strict regulations on the safety of the transplants, primarily aimed at the prevention of the spread of communicable disease.

Regulations include criteria for donor screening and testing as well as strict regulations on the processing and distribution of tissue grafts. Organ transplants are not regulated by the FDA. The donor was a year-old male, considered "high-risk" by donation organizations, and his organs transmitted HIV and Hepatitis C to four organ recipients. Experts say that the reason the diseases did not show up on screening tests is probably because they were contracted within three weeks before the donor's death, so antibodies would not have existed in high enough numbers to detect.

The crisis has caused many to call for more sensitive screening tests, which could pick up antibodies sooner. Currently, the screens cannot pick up on the small number of antibodies produced in HIV infections within the last 90 days or Hepatitis C infections within the last 18—21 days before a donation is made. NAT nucleic acid testing is now being done by many organ procurement organizations and is able to detect HIV and Hepatitis C directly within seven to ten days of exposure to the virus.

Both developing and developed countries have forged various policies to try to increase the safety and availability of organ transplants to their citizens. Austria, Brazil , France , Italy , Poland and Spain have ruled all adults potential donors with the "opting out" policy, unless they attain cards specifying not to be. However, whilst potential recipients in developing countries may mirror their more developed counterparts in desperation, potential donors in developing countries do not. The Indian government has had difficulty tracking the flourishing organ black market in their country, but in recent times it has amended its organ transplant law to make punishment more stringent for commercial dealings in organs.

It has also included new clauses in the law to support deceased organ donation, such as making it mandatory to request for organ donation in case of brain death. Other countries victimized by illegal organ trade have also implemented legislative reactions. Moldova has made international adoption illegal in fear of organ traffickers. China has made selling of organs illegal as of July and claims that all prisoner organ donors have filed consent. However, doctors in other countries, such as the United Kingdom, have accused China of abusing its high capital punishment rate.

Despite these efforts, illegal organ trafficking continues to thrive and can be attributed to corruption in healthcare systems, which has been traced as high up as the doctors themselves in China and Ukraine, and the blind eye economically strained governments and health care programs must sometimes turn to organ trafficking. Some organs are also shipped to Uganda and the Netherlands. This was a main product in the triangular trade in Starting on 1 May , doctors involved in commercial trade of organs will face fines and suspensions in China.

Regenerative Medicine Applications in Organ Transplantation - Google книги

Only a few certified hospitals will be allowed to perform organ transplants in order to curb illegal transplants. Harvesting organs without donor's consent was also deemed a crime. The Transplant Ethics Committee must approve living donor kidney transplants. Organ trading is banned in Singapore and in many other countries to prevent the exploitation of "poor and socially disadvantaged donors who are unable to make informed choices and suffer potential medical risks.

In an article appearing in the April issue of Econ Journal Watch , [60] economist Alex Tabarrok examined the impact of direct consent laws on transplant organ availability. Tabarrok found that social pressures resisting the use of transplant organs decreased over time as the opportunity of individual decisions increased. Tabarrok concluded his study suggesting that gradual elimination of organ donation restrictions and move to a free market in organ sales will increase supply of organs and encourage broader social acceptance of organ donation as a practice.

Artificial trachea built from scratch shows the promise of regenerative medicine.

The existence and distribution of organ transplantation procedures in developing countries , while almost always beneficial to those receiving them, raise many ethical concerns. Both the source and method of obtaining the organ to transplant are major ethical issues to consider, as well as the notion of distributive justice. The World Health Organization argues that transplantations promote health, but the notion of "transplantation tourism" has the potential to violate human rights or exploit the poor, to have unintended health consequences, and to provide unequal access to services, all of which ultimately may cause harm.

Regardless of the "gift of life", in the context of developing countries, this might be coercive. The practice of coercion could be considered exploitative of the poor population, violating basic human rights according to Articles 3 and 4 of the Universal Declaration of Human Rights. There is also a powerful opposing view, that trade in organs, if properly and effectively regulated to ensure that the seller is fully informed of all the consequences of donation, is a mutually beneficial transaction between two consenting adults, and that prohibiting it would itself be a violation of Articles 3 and 29 of the Universal Declaration of Human Rights.

Even within developed countries there is concern that enthusiasm for increasing the supply of organs may trample on respect for the right to life. The question is made even more complicated by the fact that the "irreversibility" criterion for legal death cannot be adequately defined and can easily change with changing technology. Surgeons, notably Paolo Macchiarini , in Sweden performed the first implantation of a synthetic trachea in July , for a year-old patient who was suffering from cancer.

Stem cells taken from the patient's hip were treated with growth factors and incubated on a plastic replica of his natural trachea. He allegedly made several trips to see Macchiarini for his complications, and at one point had surgery again to have his synthetic windpipe replaced, but Macchiarini was notoriously difficult to get an appointment with. According to the autopsy, the old synthetic windpipe did not appear to have been replaced.

Macchiarini's academic credentials have been called into question [] and he has recently been accused of alleged research misconduct. For example, former U. In year , about 3, ventricular assist devices were inserted in the United States, as compared to approximately 2, heart transplants. The use of airbags in cars as well as greater use of helmets by bicyclists and skiers has reduced the number of persons with fatal head injuries, which is a common source of donors hearts.

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An early-stage medical laboratory and research company, called Organovo , designs and develops functional, three dimensional human tissue for medical research and therapeutic applications. Organovo anticipates that the bioprinting of human tissues will accelerate the preclinical drug testing and discovery process, enabling treatments to be created more quickly and at lower cost. Additionally, Organovo has long-term expectations that this technology could be suitable for surgical therapy and transplantation.

A further area of active research is concerned with improving and assessing organs during their preservation. Various techniques have emerged which show great promise, most of which involve perfusing the organ under either hypothermic C or normothermic 37C conditions. All of these add additional cost and logistical complexity to the organ retrieval, preservation and transplant process, but early results suggest it may well be worth it. Hypothermic perfusion is in clinical use for transplantation of kidneys and liver whilst normothermic perfusion has been used effectively in the heart, lung, liver [] and, less so, in the kidney.

From Wikipedia, the free encyclopedia. Organ transplant Reenactment of the first heart transplant, performed in South Africa in Main article: Autotransplantation. Main article: Allotransplantation. Main article: Xenotransplantation. Main article: ABO-incompatible transplantation.

Main article: Transplantable organs and tissues. See also: Organ procurement. See also: Organ theft and Organ trade. Main articles: Ethics of organ transplantation and Declaration of Istanbul.

Fler böcker av Giuseppe Orlando

British Journal of Anaesthesia. The overall theme of the book is to provide insight into the synergy between organ transplantation and regenerative medicine. Recent groundbreaking achievements in regenerative medicine have received unprecedented coverage by the media, fueling interest and enthusiasm in transplant clinicians and researchers. Regenerative medicine is changing the premise of solid organ transplantation, requiring transplantation investigators to become familiar with regenerative medicine investigations that can be extremely relevant to their work.

Mayo Clinic Transplant Center Regenerative Medicine Consult Service

Similarly, regenerative medicine investigators need to be aware of the needs of the transplant field to bring these two fields together for greater results. Front Cover. Half Title Page. Title Page. Copyright Page.


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