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Tissue Transplantation

By Martin Hertl, MD, PhD, Harvard Medical School;Massachusetts General Hospital ; Paul S. Russell, MD, Harvard Medical School;Massachusetts General Hospital

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(See also Overview of Transplantation; for corneal transplantation, see Corneal Transplantation .)

Composite Transplantation (Hand, Extremity, Face)

Composite transplants involve multiple tissues, usually including skin and soft tissues and sometimes musculoskeletal structures. Many of these procedures are now possible because of advances in immunosuppressive therapy. However, the procedures are ethically controversial because they typically do not extend life, are very expensive and resource-intensive, and can potentially cause morbidity and mortality due to infections.

The first successful composite transplants were hand transplants. Since then, perhaps as many as 10 different structures have been replaced in about 150 patients, with varying functional success rates.

The first hand transplantation was done in 1998. Since then, double hand and upper-extremity transplantations have been done. Recovery of the hand function varies widely; some recipients regain enough function and sensitivity to do daily activities.

The first face transplantation was done in 2005. As of 2011, 17 such procedures have been done. To date, no graft failure has been reported, but the recipient of the first face transplant died in 2016. Ethical questions about face transplantation are even more prominent than those about extremity transplantation because the surgical procedure is extremely demanding and the immunosuppression required puts the recipient at considerable risk of opportunistic infections.

Immunosuppression usually consists of induction therapy (antithymocyte globulin [ATG] or IL-2 receptor blocker), followed by triple maintenance immunosuppression with a corticosteroid, an antiproliferative drug (eg, basiliximab), and a calcineurin inhibitor (see Table: Immunosuppressants Used to Treat Transplant Rejection). Sometimes topical creams containing calcineurin inhibitors or corticosteroids are used.

Skin grafts

Skin grafts may be

  • Autografts

  • Allografts

Skin autografts

Skin autografts use the patient's own intact skin as the source.

Split-thickness grafts are usually used; for these grafts, a thin layer of epidermis and some dermis are excised and placed on the recipient site. Such grafts are typically used for burns but may also be used to accelerate healing of small wounds. Because a significant amount of dermal elements remain at the donor site, the site eventually heals and can be harvested again.

Full-thickness grafts are composed of epidermis and dermis and provide better appearance and function than split-thickness grafts. However, because the donor site will not heal primarily, it must be a loose area of redundant skin (eg, abdominal or thoracic wall, sometimes scalp) so that the site can be sutured closed. Thus, full-thickness grafting is usually reserved for cosmetically sensitive areas (eg, face) or areas requiring a thicker, more protective skin layer (eg, hands). Because full-thickness grafts are thicker and more vascular, they do not have quite as high a survival rate as split-thickness grafts.

The patient's own skin cells may be grown in culture, then returned to a burned patient to help cover extensive burns. Alternatively, artificial skin, composed of cultured cells or a thin, split-thickness skin graft placed on a synthetic underlayer, may also be used.

Skin allografts

Skin allografts use donor skin (typically from cadavers). Skin allografts are used for patients with extensive burns or other conditions causing such massive skin loss that the patient does not have enough undamaged skin to provide the graft. Allografts can be used to cover broad denuded areas and thus reduce fluid and protein losses and discourage invasive infection.

Unlike solid organ transplants, skin allografts are ultimately rejected, but the resulting denuded areas develop well-vascularized granulations onto which autografts from the patient’s healed sites take readily.

Cartilage Transplantation

Cartilage transplantation is used for children with congenital nasal or ear defects and adults with severe injuries or joint destruction (eg, severe osteoarthritis). Chondrocytes are more resistant to rejection, possibly because the sparse population of cells in hyaline cartilage is protected from cellular attack by the cartilaginous matrix around them. Immunosuppression is therefore not indicated.

Bone Transplantation

Bone transplantation is used for reconstruction of large bony defects (eg, after massive resection of bone cancer). No viable donor bone cells survive in the recipient, but dead matrix from allografts can stimulate recipient osteoblasts to recolonize the matrix and lay down new bone. This matrix acts as scaffolding for bridging and stabilizing defects until new bone is formed.

Cadaveric allografts are preserved by freezing to decrease immunogenicity of the bone (which is dead at the time of implantation) and by glycerolization to maintain chondrocyte viability.

No postimplantation immunosuppressive therapy is used. Although patients develop anti-HLA antibodies, early follow-up detects no evidence of cartilage degradation.

Adrenal Autografting

Adrenal autografting by stereotactically placing medullary tissue within the CNS has been reported to alleviate symptoms in patients with Parkinson disease.

Allografts of adrenal tissue, especially from fetal donors, have also been proposed. Fetal ventral mesencephalic tissue stereotactically implanted in the putamen of patients with Parkinson disease has been reported to reduce rigidity and bradykinesia. However, with the ethical and political debates about the propriety of using human fetal tissue, a controlled trial large enough to adequately assess fetal neural transplantation appears unlikely.

Xenografts of endocrinologically active cells from porcine donors are being tested.

Fetal Thymus Implants

Fetal thymus implants obtained from stillborn infants may restore immunologic responsiveness in children with thymic aplasia and resulting abnormal development of the lymphoid system (DiGeorge syndrome).

Because the recipient is immunologically unresponsive, immunosuppression is not required; however, severe graft-vs-host disease may occur.

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