Introduction

Tissue regeneration in living organisms represents a natural mechanism for preservation of life, which makes cells, organs, organisms, and the entire ecosystems resilient to changes in the environment that cause disturbances and damages. All living beings have the ability to regenerate their tissues, albeit to different extents. Some animals are very efficient in regenerating their entire organs, with typical examples found in jellyfish, lobsters, or lizards. Not only can they replace an organ lost due to an external force, but they can even take advantage of this ability to defend themselves from predators by shedding an organ to avoid capture and then regrowing a new one. Other animals, including humans, have a rather limited capacity for regeneration.

While most human beings are born with the potential to develop into fully functional adults, a subset of newborn babies is challenged by various genetic or congenital defects resulting in missing or dysfunctional tissues or organs. In addition, healthy adults sometimes lose (fully or partially) tissues or organs due to accidents or through contracting various diseases. Consequently, they can experience a failure of vital organs such as the heart, kidney, lungs, liver, etc. In the absence of medical intervention, death in such cases is unavoidable. Even with timely medical intervention, if the failed organ does not recover, the patient may lose independence and continue living only with the constant engagement of medical services.

Modern medicine has been investing a lot of effort in the development of strategies to help humans with missing organs or organ failures. The right approach to handling such health challenges could extend life, improve the quality and productivity of life, and decrease the health care burden. Since drug treatments are limited in such cases, other approaches have been developed, including organ transplantation and stem cell technology.

Organ Transplantation

Historically, one of the first strategies in tackling the issue of missing tissues or organs has been organ transplantation—surgically removing a dysfunctional/damaged organ and replacing it with a new one. The idea of organ transplantation has fascinated humans since ancient times. The first mention of a transplant took place in the remote sixteenth century BC, where skin grafting was described in the Ebers Papyrus—one of the oldest and most important of ancient Egypt’s medical papyri containing herbal knowledge of that period. Sushruta, the “father of surgery” from India, is believed to have performed the first skin transplantation around 600 BC (Nordham and Ninokawa 2022).

The first successful organ transplantation of the modern era happened in 1954 and was performed with a kidney from a living donor (Barker and Markmann 2013). The pioneering surgeons who made this grand achievement were Dr. Joseph Murray and Dr. David Hume from the Peter Brent Brigham Hospital in Boston. Eight years later, the first kidney transplantation from a deceased person (cadaveric transplantation) took place (Barkerk and Markmann 2013). By now, methods have been developed for successful transplantation of the lung, liver, heart, pancreas, intestines, cornea, bone marrow, etc. Organ transplantation has been shown to significantly extend life, increase the quality of life, and decrease treatment costs (Abouna 2003). For example, the average survival of a patient with a transplanted kidney is 20–40% longer than that of a patient undergoing dialysis. Some patients can live over thirty years after receiving a donated kidney. Of note, five years of dialysis costs three times more than a transplantation surgery.

Various sources of organ transplants exist. Apart from the aforementioned living or cadaveric organ donations from humans, it is also possible to transplant an organ from a nonhuman donor (xenotransplantation) or use artificially produced organs. Pigs are the most promising source of xenotransplants due to their genetic and physiological similarities to humans (Cooper 2012). Safe procedure would include growing pigs in a pathogen-free facility to avoid the transmission of diseases from animals to humans. Such pigs can be genetically modified to increase their genetic similarity and immune compatibility with humans. Some examples of such xenotransplantation are recent successful kidney and heart transplantations into brain-dead humans (Moazami et al. 2023; Montgomery et al. 2022).

Human-made, artificially produced organs are usually devices that get incorporated into the human body to replace a missing organ or a missing function (Duguet 2016). For example, a lost limb can be replaced by prosthesis. New technologies enable relatively high levels of integration of the prostheses into the human body so that the recipient can control such an artificial limb. A bionic eye with an incorporated mini-camera and an electronic interface can transmit basic visual information from the environment onto the retina and brain. Artificial pacemakers can augment or completely bypass the need for a natural living heart pacemaker. Almost fully functional artificial lungs have been designed to assist breathing in people with removed lungs. Various other organs can be replaced by artificial organs, including livers, kidneys, testes, etc. However, these artificial organs can only replace the function of the failed organs temporarily (Wang 2019). Interestingly, a fascinating and highly promising technology of 3D bioprinting organs is currently under development (Panja et al. 2022).

Even though organ transplantation has become a routine intervention in the past decades, it still poses significant risks for the patients—both the recipients and the living donors (Abouna 2003). Obvious risks are associated with the surgery itself and include potential infection and issues with anesthesia, especially in older patients. For a living donor, there may be consequences due to the loss of an organ. A serious common problem is rejection of the transplanted organ by the immune system of the recipient. This can happen because each person has a unique protein composition, with our immune system being built in a way that it ignores the “self” and attacks the “non-self.” “Self” is defined as a specific set of human leukocyte antigen (HLA) proteins on the surface of each cell. “Self” HLA proteins “tell” the immune system not to attack the HLA carrier cells. However, if cells or tissues that do not contain the “self” HLA set are introduced into the body, the immune system can recognize them as foreign and attack them. To avoid this problem, donor and recipient organs must be matched. The degree of similarity between HLAs of the donor and the recipient is called histocompatibility. Well-matched donor–recipient pairs have high histocompatibility, meaning their HLAs are sufficiently genetically similar. If the two organs match closely enough, a relatively tolerable immune response to the foreign organ will be induced. However, the only true match would be an organ derived from an identical twin. Interestingly, if the transplanted organ is immune-competent, it can attack the recipient’s tissues, causing a so-called “graft-versus-host reaction.” These problems can be reduced by a lifelong immunosuppressive therapy given to the recipient, but the therapy itself imposes an additional set of health risks.

A number of public health issues are associated with organ transplantation (Abouna 2003). One is a large gap between the demand and supply of organs. While the number of donors remains low, the lists of patients waiting for a transplant are rapidly increasing, with many patients dying while waiting for a transplant. Indeed, it is estimated that only 10% of the patients on the waiting lists eventually receive a transplant. The reasons for a shortage in organ supply differ for the living and cadaveric donations. While living donors are often not ready to risk their own health, cadaveric donations are hampered by a series of other issues, such as religious beliefs, family complaints, or lack of information. Public health systems have been attempting to increase the organ supply by employing several strategies. These include public education, promoting explicit consent, and a policy of presumed consent.

Public education is based on raising awareness among the general population about the merits of organ donation. In cases where explicit consent is needed, motivated individuals need to act upon their decision to provide a cadaveric transplant by registering into a database of donors. In many countries with such an opt-in policy, this wish is then stated on their driver’s license, personal ID, or organ donation card (Schulze Spuentrup 2024). However, these strategies have brought little success in increasing the number of potential donors. A policy of presumed consent (also called an opt-out policy) has proven much more successful. In this policy, society approves that every adult individual who dies is a potential organ donor (regardless of the opinion of the family) unless he or she has withdrawn their consent during their lifetime. Since a willingness to accept the default and tendency to avoid action is natural for humans, this policy has been very efficient in increasing the supply of organs. In countries that have introduced this policy, the number of potential donors has doubled in comparison with other countries. One argument defending this policy is that most major religions, including Christianity, Judaism, and Islam, do not object to this principle. This was pronounced by Pope John Paul II in 1992, by the Jewish Rabbinical Council of America in 1991, and even by the Islamic Fatwa Committee of Kuwait, which stated in 1979 that “organ transplantation can take place from a dead donor providing that there was a necessity to save a human life” and that “permission of the family is not required since human organs belong to God and not to the family” (Abouna 1984). However, few countries have adopted the presumed consent policy.

There are other significant ethical issues associated with organ transplantation, particularly in the case of living donation (Mamode et al. 2022). Usually, related family members are the most optimal organ donors, since genetic similarities decrease the chance of immunological rejection of an organ. These family members may encounter emotional pressure and coercion from other family members or from the recipients themselves. Unrelated family members such as spouses or in-laws may also endure pressure, since they can still provide their (non-matching) organs through donor exchange programs, wherein donor/recipient pairs are entered into a system, a match offer is eventually made, and then transplants are planned.

Risk–benefit ratio assessment is very important before donating an organ. Benefits of organ donation are often psychological and social, in terms of moral reward and earning respect from other community members, but also as contribution to a system that the donor himself can benefit from, if needed. Risks include the previously discussed health risks, as well as psychosocial and financial losses. In particular, even if everything goes smoothly health-wise, a donor must dedicate time for the surgery and recovery, which means absence from work, family duties and a necessity to secure appropriate caretaking during the recovery.

Another ethical issue is related to obtaining an informed consent from the donor prior to donation. Informed consent means that an individual is competent to comprehend relevant information and to give consent. If any of these two conditions is unmet, the individual becomes merely a source of an organ, rather than a real donor.

The equitable allocation of organs is a highly debated topic in the ethics of organ transplantation (Bunnik 2023). It is important that the criteria for prioritizing potential organ recipients are fair and unbiased. Questions such as “who is the sickest or most in need,” “who is most entitled to the organ,” “whose life is more worth saving,” and “who will benefit the most from organ transplantation” decide who will be the next recipient of an organ from a newly deceased person. In addition, not all donated organs are of equal quality—organs from younger and healthier donors with proper post-extraction handling will give better survival chances to the recipients. Another complicating issue is that some recipients are more difficult to match due to their rare HLA types, which lowers their chances of obtaining a compatible organ. All these issues contribute to the complexity of patient ranking. One simple way of ranking the patients is based on the waiting time, with advantage given to those who waited longer. However, this approach neglects many important parameters such as the age, fitness, and prospects of a patient. An alternative transplant allocation strategy has been developed with a goal of maximizing the longevity of transplanted organs. This can be achieved by giving the organs to younger and fitter individuals with high estimated post-transplantation survival. Robert Veatch weighs the eligibility of recipients based on who is worse off from an over-a-lifetime perspective. According to this principle, if there are two people with the same condition—one young and one old—the younger one would be more eligible for a transplant because they had lived less life so far and thus are worse off. Geography can also be an important factor. For example, it could be debated whether donors have the right to give preference to recipients from their local community, especially if their local community has a high number of donors in comparison to other, remote communities.

Finally, particularly concerning ethical issues in organ transplantation are organ trafficking and transplant tourism (Budiani-Saberi and Delmonico 2008; Akoh 2012; Bagheri and Delmonico 2013), both of which are driven by the gap in the demand and supply of organs, often in combination with social inequalities worldwide. Transplant tourism involves the movement of recipients and/or donors across borders to undergo transplantation surgery. Although transplant tourism does not necessarily pose ethical issues, the recipients are frequently well-off individuals traveling to developing countries where organ donation is poorly regulated by law and where they must provide significant financial compensation for the procedure. Tightly linked to transplant tourism is organ trafficking—an illegal trade of human organs. The most commonly traded organ is the kidney (Duguay et al. 2020), probably due to its bilateral nature, high demand on the organ market, relative ease of donor–recipient matching and relatively low impact on the donor’s post-transplantation life, at least when done appropriately. However, both the recipients and the donors are often exposed to suboptimal medical conditions and an absence of proper long-term medical follow-up. Many medical complications may happen, and the risks of losing the transplant or even of death are several times higher for recipients receiving an illegal transplant compared to a regular one.

Organ trafficking often involves illegal activities such as the exploitation of vulnerable humans and is thus considered a form of human trafficking. Organized crime groups exist in many developing countries, in particular in North and West Africa. These groups operate the complex logistics required for transplantation—the recruitment of donors and recipients, the organization of the entire networks of surgeons and other medical staff, and the running of the clandestine clinics and laboratories necessary for matching donors and recipients. Donors are usually the most vulnerable members of the population, such as those living in poverty, victims of other kinds of human trafficking, migrants, etc. They are sometimes coerced to donate their organs, especially if they initially accept the offer but later decide to opt out. Another problem is that even though these illegal transplants are extremely expensive—a kidney can cost up to US$120,000—an inappropriately small amount of money reaches the donor, usually no more than 10% of the total sum. The high cost of transplantation, which must be covered entirely out of pocket, means these organs are acquired mostly by wealthy individuals, which violates equitable allocation principles and the prohibition of financial gain for organ donors. Even though organ trafficking is forbidden by international law, its eradication has proven difficult to achieve.

Xenotransplantation has its own set of issues (Dooldeniya and Warrens 2003). One of them concerns the generally shorter lifespans of animals relative to humans. For instance, a pig, which is commonly used as an organ source, lives only twenty-seven years on average, which means its organs may age at a faster rate compared to human organs. It is thus questionable whether such an organ could survive long enough to sustain a human recipient until death. Also, the transmission of animal diseases to humans might pose a problem. This can be addressed by growing an animal source in a pathogen-free environment. Finally, activists object to xenotransplantation due to violation of animal rights.

Stem Cells in Regenerative Medicine

Regenerative medicine is a relatively new branch of medicine aiming to enable structural and functional restoration of specific tissues in patients suffering from severe injuries and chronic disease conditions. Diseases characterized by the disruption of various tissues include spinal cord injuries, type 1 diabetes, Parkinson’s disease, amyotrophic lateral sclerosis, Alzheimer’s disease, heart disease, stroke, burns, cancer, osteoarthritis, and many others. The main approach of regenerative medicine in the attempts to treat these diseases is mimicking the natural mechanisms of healing injuries. Natural regeneration happens on the molecular, cellular, and tissue levels and includes the activity of stem cells, which can serve as source material for the replacement of lost or dysfunctional tissues.

Stem cells are the body’s raw materials—unspecialized cells that can give rise to all other cells with specialized functions. Under the right conditions in the body or laboratory, stem cells divide to form more cells called daughter cells. During human development, and later, during aging, the number of stem cells and their differentiation potency generally declines. A newly fertilized egg or zygote is a totipotent cell with the highest differentiation potential. A zygote divides to produce more totipotent cells, thus evolving into a blastocyst, whose inner cell mass is composed of pluripotent cells with somewhat decreased differentiation potential, meaning they can differentiate into a limited number of cell types. Further divisions and differentiation of these cells lead to generation of multipotent, oligopotent, and terminally differentiated cells with gradually decreasing differentiation potential.

Decrease in number and inactivation of stem cells with aging is called stem cell exhaustion (López-Otín et al. 2023). It represents one of the major hallmarks of aging and is one of the key reasons for the limited regenerative potential of human bodies. Previously, scientists believed stem cells were present only at some restricted locations in the adult body. For instance, it has been known for a long time that bone marrow is rich in hematopoietic stem cells, which serve as an active source of new blood cells throughout the lifespan. However, recent research identified stem cells in almost all organs. Stem cells exist even in the brain, meaning new neurons can be produced in adult individuals, thus enabling neural plasticity. They are, however, found only in specific brain regions, including the hippocampus, olfactory bulbs, septum, striatum, and spinal cord (Zhao and Moore 2018). Importantly, these neural stem cells, as well as stem cells present in other organs, are mostly dormant. Finding ways to activate them pharmacologically is one of the major challenges in regenerative medicine.

Stem cell research is crucial for the advancement of regenerative medicine. Potential applications of stem cells are tremendous, and they include basic research, toxicological studies, drug discovery, diseases modeling, and cell therapy (Mahla 2016). This research requires using animal- or human-derived material to generate the appropriate experimental models. Multiple types of natural stem cells could be used, including adult, perinatal, and embryonic stem cells (ESCs). Adult stem cells derived from adult organisms are limited in number and application potential. Perinatal stem cells collected at birth from the amniotic fluid and umbilical cord blood are relatively abundant and more potent than the adult stem cells. The most potent stem cells are ESCs derived from embryos. Human ESCs (hESCs), first isolated in 1998 by James Thomson, can give rise to more than 200 cell types. However, despite their potency, application of hESCs has both medical and ethical limitations (Lo and Parham 2009; King and Perrin 2014). One example of such medical limitations is stem cell therapy for patients with dysfunctional or missing tissue. Similar to organ transplantation, the ESCs might be rejected by the recipient due to insufficient immunological compatibility with the donor. This can be circumvented by donor–recipient immunological matching or by somatic cell nuclear transfer, where the nuclei of the recipient’s somatic cells are transferred into the ESCs, making them genetically identical to the recipient, but with retained stem cell pluripotency.

The most serious ethical issue with hESCs is the necessity to destroy an unimplanted five-day old human embryo in order to harvest the cells. This issue has caused one of the most heated ethical debates in the history of medicine. The main point of disagreement is the moral status of an embryo or, more specifically, whether life begins at conception, at later a time point during the uterine life, or at birth. While the proponents of hESC research argue that an embryo does not have any moral status, others are utterly against any use of hESCs since they consider an embryo to be a person whose rights need to be protected. Between the two extremes are those who claim that the moral status of an embryo is limited and that the benefits of using hESCs outweigh the harm. The attitude towards the embryos varies depending on the origin of embryos. While the opposition to using embryos generated specifically for research purposes is generally quite strong, aborted embryos and those that are unused by-products of fertility treatments are tolerated better, since they would otherwise be discarded. The delicacy of these issues triggered the need to introduce tight regulation of hESC research and application. Thus, hESC research has been subjected to guidelines stating a strict set of rules and criteria for permissible and impermissible categories of such research. Embryonic stem cell research oversight committees have been established. Statements regarding the use of stem cells have been introduced in almost all grant applications, and funding of hESC research is strictly controlled.

Other ethical issues related to hESC research include informed consent and confidentiality. Informed consent was introduced as part of the Nuremberg Code—a set of principles for any human experimentation established in one of the Nuremberg trials following the Second World War. For unused frozen embryos that remained after fertility treatments, informed consent is needed from a woman or a couple donating the embryo. A debate exists about whether consent should also be mandatory when embryos are deidentified before any further use or for embryos created in a laboratory from donated gametes. Confidentiality of donors is also important—they should be entitled to protection of their identity to avoid unwanted publicity and potential harassment by opponents of the stem cell research. Confidentiality agreements can be signed with the donors, in which cases appropriate measures must be introduced to prevent leakage of such confidential information. Security measures for protecting donors’ identities include restricted access to the data, disconnecting storage computers from the internet, special background checks on the personnel that handle the data, etc.

One interesting case illustrating the ethical issues around perinatal stem cells happened in California in the 1990s. Parents of a girl affected by life-threatening leukaemia conceived through in vitro fertilization a second child as a source of bone marrow stem cells needed to save the life of their older daughter (The New York Times 1990). Although the newspaper story created a lot of public judgment, the action resulted in the rescue of the sick girl and a healthy and successful, now grown-up, donor sister (CBS News 2013).

Many of the ethical issues associated with hESCs have been circumvented by induced pluripotent stem cell (iPSC) technology (Moradi et al. 2019), which was established in 2006 by the Japanese scientists Kazutoshi Takahashi and Shinya Yamanaka (Takahashi and Yamanaka 2006). iPSCs are made from easily accessible somatic cells, which are then subjected to the process of in vitro de-differentiation in the laboratory to acquire stem cell-like properties.

A common source of the material for the production of iPSCs is terminally differentiated skin fibroblasts, or blood cells. These cells are subjected to a de-differentiation/reprogramming procedure, which reverts them back to their pluripotent, undifferentiated state. This is achieved by a set of pluripotency-associated transcription factors called Yamanaka factors. The introduction of these factors into cells was initially done using lentiviruses or retroviruses as Trojan horses to deliver genetic information for the production of Yamanaka factors into the host cells. These viruses can insert their genome into the host cell genome, thereby enabling stable production of the desired proteins (in this case, Yamanaka factors) by the host cells. However, since this insertion into the DNA is random, it can disturb the natural order of nucleotides in the host DNA, leading to mutagenesis in the recipient cell genome. Therefore, safer strategies for the delivery of Yamanaka factors into cells has been developed (Um 2012). These include episomal DNAs, adenovirus, Sendai virus, PiggyBac transposon, minicircles, recombinant proteins, synthetic modified mRNAs, or microRNAs.

iPSCs can be transformed into various terminally differentiated cells. Protocols have been developed for the differentiation of iPSCs into almost all cell types and subtypes, which usually takes several weeks of treating the cells with appropriate agents under laboratory conditions. Laboratory production of terminally differentiated cell types that are genetically identical to the genuine but inaccessible patient’s cells offers opportunities for personalized medicine approaches to studying and treating such patients. For instance, if a patient suffers from a neurodegenerative disorder such as Parkinson’s disease, it would be of great value to study their dopaminergic neurons affected by the disease. This is, however, not possible, since extracting dopaminergic neurons directly from the patient’s brain would require surgically opening the skull and operating on the living brain, which could jeopardize the integrity of the brain tissue. iPSC technology enables the production of dopaminergic neurons from the patient’s easily accessible skin cells; these iPSC-derived neurons can then be used as a proxy for the authentic patient’s neurons. Studying such neurons could provide information about patient-specific disease features, and testing various drugs on them could identify the most promising drug candidates for a given person. iPSC-derived neurons originating from a patient’s tissue represent a superior disease model over previously used neurons obtained from animal models of a disease.

Another illustration of the iPSCs’ value is the possibility to replace deteriorated tissues with grafts generated from the appropriately differentiated patient-derived iPSCs (Mahla 2016). In such an approach, the risk of immunological rejection of the graft would be minimized, since the iPSCs originate from the recipient tissue. This strategy is especially promising in cases of tissue degeneration caused by genetic mutations. Such mutations could be corrected in the iPSCs, which would then give rise to a healthy graft. Indeed, correction of genetic defects in the iPSCs represents one of the most exciting scientific achievements in the last couple of decades (Jang and Ye 2016). Several genome editing tools, such as zinc-finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic sequences (CRISPR) enable targeted correction of point mutations directly in the iPSCs. CRISPR-Cas9 system is currently preferred genome editing technique due to its low cost, high accuracy, and easy handling. It is an adaptation of a natural bacterial mechanism to destroy the genetic material of foreign, invading sources such as the viruses. CRISPR-Cas9 functions like a sort of molecular scissors where guide RNA recognizes the desired sequence in the cellular genome and guides Cas9 to that location in the DNA. Cas9, an enzyme specialized for cutting both DNA strands, cuts the DNA exactly where the editing should happen. Once the DNA is cut, natural DNA repair mechanisms are activated and introduce a desired change in the DNA in the process of fixing the damage.

Obviously, genetically corrected grafts can replace only a small part of the body. Since most cells in the body have the same genetic material, i.e., they carry the same inherited mutations, this strategy is only meaningful in cases where genetic defects have consequences restricted to a specific tissue. This is indeed often the case. For instance, there is a disease-specific selective vulnerability of a specific type of neuron in many familial forms of neurodegenerative diseases: dopaminergic neurons in the basal ganglia are affected in Parkinson’s disease, motor neurons in amyotrophic lateral sclerosis (ALS), striatal neurons in Huntington’s disease, etc. (Fu et al. 2018).

Although iPSCs are less controversial than hESCs, there are still many medical, ethical, legal, and social issues associated with iPSC application (Moradi et al. 2019). While the most serious obstacle to using iPSCs in vivo is their tumorigenicity upon injection (Lee et al. 2013), other issues are also not negligible. For instance, for the application of clinical-grade cells in humans, it would be necessary to standardize manufacturing conditions and the characterization of such cells, which poses a challenge when working with biological material. Furthermore, since these cells are derived from humans, concerns exist regarding the handling of genetic material and confidential personal information. Similar to organ donations, informed consent is needed from the donors. Nevertheless, since the iPSCs can be maintained in the laboratory for a long time, it is impossible to predict all future applications of these cells and hence give complete, accurate information to the donors. This may prevent donors from having full control over the fate of their cells in the long run. Genetic manipulations of the cells carry potential hazards and are ethically debatable. Furthermore, when iPSCs are used in basic or applied research, a question arises regarding intellectual property and patents, as well as the profits this research or application may bring.

Finally, since the production and maintenance of all stem cells entail significant costs, social justice could be violated if the benefits of stem cell technology become accessible only to a small, wealthy portion of the human population (Yap 2016). Such potential inequality in opportunities among patients should be prevented by policymakers.

Conclusions and Summary

Biomedical research and clinical practice have made tremendous progress in the past several decades by developing organ transplantation and stem cell technology as tools of regenerative medicine. Although significant medical and ethical issues around these approaches still exist, awareness about these issues is quite high. Much effort has been invested in resolving these issues. This has been achieved mostly by introducing legal measures and research control, improving existing technologies, and developing new ones. These efforts have realistic chances to allow the evolution of these approaches into safe and powerful tools that will improve the quality of life, resulting in increased healthy longevity and reduced suffering of humans.

In summary, this article presents current biomedical approaches to replacing missing or dysfunctional tissues or entire organs, including organ transplantation and stem cell technology. Emphasis is placed on ethical considerations around these approaches and the weighing of their benefits and drawbacks. The following key points have been presented or discussed here.

• Organ transplantation is the replacement of a missing or dysfunctional organ by an organ from a living or deceased human donor or animal source, or by an artificial organ. This surgical procedure can extend the life span, increase the quality of life, and decrease the health care burden.

• Issues around organ transplantation can include medical risks and multiple ethical issues. Medical risks can arise due to surgery complications or, later, potential immunological rejection of the transplanted organ by the recipient’s immune system. Ethical issues include a gap between the demand and supply of organs, equitable allocation of organs, exploitation of vulnerable populations in developing countries, and informed consent.

• Stem cells are undifferentiated cells that can divide and differentiate into any cell type. They represent a promising tool of regenerative medicine due to their tremendous application potential in basic research, disease modeling, and laboratory production of grafts that can replace missing tissues in patients. Various types of stem cells exist, including perinatal, adult, ESCs, and iPSCs.

• hESCs are derived from a pre-implantation human embryo and can give rise to almost all other cell types. To extract hESCs, it is necessary to destroy the embryo, which is why their use has become one the most debated ethical issues in modern biomedical research.

• iPSCs are stem cells produced in a laboratory by reprogramming somatic cells. Such cells are similar to ESCs, with the added value of reduced ethical issues and potential application in personalized medicine. They can also be genetically corrected using various genome editing tools.

• Issues around iPSCs include the standardization of manufacturing conditions for human application, confidentiality issues, informed consent, genetic manipulation of the cells, intellectual property, and patents.