Skin Donors Positive for HBV Core Antibodies – to Bank or Not to Bank? An Overview from a Regional Tissue Bank

A prompt transplantation of skin allografts on patients with severe, large body area burns is a preferred treatment, but depends on a suitable supply of tissue donors. Limiting factors include donors' identification, families consent, and following the standards – exclusion due to assessed transmissible diseases. To increase the current rate of skin donations to our regional skin bank, we reviewed the data of all potential organ donors, identified at Soroka University Medical Center from October 1997 to December 2000 and evaluated the causes for exclusion, especially due to HBV serological profile. 114/168 (67.9%) patients did not meet the indicated standards for organ donation, among which 20/114 patients (17.5%) positive for anti-HBc (anti-HBc⁺). 54/168 persons were declared brain dead, with consents obtained from 21 families. To discuss the intriguing approval of skin from potential donors with anti-HBc⁺ serology, the literature was reviewed, specifically – the reported outcomes of organ transplants from anti-HBc⁺ donors, updates of HBV and skin, available tests, and finally a look for a safe commendable algorithm. The results suggested that HBV might be replicating in the skin, but proven communication of HBV has not been reported following grafting skin from anti-HBc⁺ donors. Unlike other procured organs and tissues, grafted banked skin is a temporary cover, storable up to six years, under appropriate conditions. Hence, banking of skin from anti-HBc⁺ donors might be considered for future grafting of patients with identical serological profiles, presumably immune to a subsequent HBV infection, until a further re-evaluation of the standards. This procedure is anticipated to increase the potential of organ and tissue donations, specifically skin.     

Analysis of Potential Causes of Positive Microbiological Cultures in Tissue Donors

The purpose of this statistical analysis is to determine what factors are the major contributors to bacterial contamination of recovered human cadaveric tissue. In this study we analyzed factors that could contribute to an increased bacterial bioburden from recovered tissues using the following independent variables: (1) the physical recovery environment; (2) recovery before or after an autopsy; (3) the length of time from death to recovery; (4) the cause of death; (5) the length of time to complete recovery; (6) the number of staff involved with the tissue recovery; and (7) the impact of organ and skin recovery on musculoskeletal contamination rates.In these analyses we used analysis of variance of main effects on data from seven tissue banks. The scale of the analysis included 1036 donors each having multiple cultures to better control for the inherent large variation in this type of data. We looked at several dependent variables. The dependent variable that was most useful was percent positive cultures.The results of the combined data differed from analyzing the tissue banks individually. The differences in each tissue bank's procedures and techniques were responsible for most of the variability. Depending on how the data was organized, statistically significant increases in bioburden were seen with: (1) recoveries after autopsy; (2) location of the recovery; (3) length of time taken for a recovery; (4) size of the recovery team; and (5) the impact of organ and skin recovery on musculoskeletal contamination rates.In conclusion, statistical analysis of recovery cultures can be a powerful tool that may be used to indicate problems within any bank's recovery procedures or techniques.     

The impact of the International Atomic Energy Agency (IAEA) program on radiation and tissue banking in Indonesia

In 1986, the National Nuclear Energy Agency (Batan) in Jakarta started the research and development for the setting up of a tissue bank (Batan Research Tissue Bank/BRTB) by preserving fresh amnion or fetal membranes by lyophilisation and then sterilising by gamma irradiation. During the period of 1990 and 2000, three more tissue banks were set up, i.e., Biomaterial Centre in Surabaya, Jamil Tissue Bank in Padang, and Sitanala Tissue Bank in Tangerang. In 1994, BRTB produced bone allografts. The banks established under the IAEA program concentrated its work on the production of amnion, bone and soft tissues allografts, as well as bone xenografts. These tissues (allografts and xenografts) were sterilised using gamma irradiation (about 90%) and the rest were sterilized by ETO and those products have been used in the treatment of patients at more than 50 hospitals in Indonesia. In 2004, those tissue banks produced 8,500 grafts and 5,000 of them were amnion grafts for eye treatment and wound dressing. All of those grafts were used for patients as well as for research. In 2006, the production increased to 9,000 grafts. Although the capacity of those banks can produce more grafts, we are facing problems on getting raw materials from suitable donors. To fulfill the demand of bone grafts we also produced bone xenografts. The impact of the IAEA program in tissue banking activities in Indonesia can be summarised as follows: to support the national program on importing substitutes for medical devices. The price of imported tissues are between US$ 50 and US$ 6,000 per graft. Local tissue bank can produce tissues with the same quality with the price for about 10–30% of the imported tissues.     

Tissue banking in Mexico

Introduction: Here, we describe our Tissue Banking experiences of 4 years of activity in Mexico. Methods: Data of allografts provided by our Bank and bone retrievals performed by our teams between February of 2001 and August of 2004 were included. Results: There were 100 bone donors, a total of 1107 tissues were obtained with an average of 11 tissues by retrieval, samples from all tissues were obtained during retrieval and cultured for bacterial contamination, 250 tissues were positives to bacterial growth with an average of 22.58% of bacterial contamination of tissue by retrieval. A total of 4493 allografts were provided and were utilized in 3643 patients. The allografts were used mainly by orthopedic surgeons (62%) and dentists (30%). The most used allografts were morcellized cancellous bone 31%, pulverized 25% and chips of cancellous bone 20%. Among orthopedic patients the most frequent procedures were related with spine degenerative diseases 39.09%, followed by non-pathological fractures and its complications 28.67% and bone tumors and cystic bone lesions 11.59%. Conclusions: Sustained increase of allograft utilization in Mexico reflects a great necessity for them in our country. The increase in public awareness about tissue donation has allowed an increase in tissue donations and retrievals.     

The value of autopsy and other histological examinations for the safety of tissue transplantation

Directive 2006/17/EC requires that all available medical information, including autopsy reports, is evaluated before releasing tissues for transplantation. The aim of this study was to investigate whether evaluation of results of autopsy and other histological examinations contributes to the safety of tissue transplantation. From the files of all deceased Dutch donors, from whom tissues were retrieved in a 6-month period, results of autopsy and other histological examinations (remnant heart after valve donation and biopsies obtained during retrieval) were evaluated for contraindications for transplantation. Of 758 donors at least one tissue was considered suitable for transplantation at initial assessment. 637 Donors donated corneas, 256 skin, 177 heart valves and 61 musculoskeletal tissues. On 220 donors (29.0%) autopsy was done. Of seven donors no autopsy results were requested, since a contraindication was detected earlier in the medical screening. In 19 donors with autopsy (8.9%) general or tissue-specific contraindications were detected. There were no differences in distribution of detected contraindications among donors who donated different tissues. For 136 donors (17.9%) results of histological examinations other than autopsy were available; results of examination of remnant hearts for all, brain autopsy for two (0.3%) and retrieval biopsy for four donors (0.5%). Contraindications were detected in nine of these donors with histology results other than autopsy (6.6%). For 402 donors (53%) no histological examinations were done. Evaluation of results of autopsy and other histological examinations improves the safety of tissue transplantation for all types of tissues. In donors without autopsy alternative histological examinations can contribute to enhance the safety of tissue transplantation.     

Are heart valves from donors over 65 years of age morphologically suitable for transplantation?

Since there is no upper age limit for general organ donation, unlike heart valve donation, and since a quarter of all organ donors are 65 years and older, we examined whether the heart valves from these donors are suitable as allografts. In the period 1999–2004 the aortic valve and pulmonary valve of 100 organ donors above 65 years of age were examined to establish whether they would have been suitable as valve grafts. To compare the valve grafts above and below the age limit of 65 years, we used data on the aortic and pulmonary valves of 380 organ donors below the age limit in the same time period. Examination of the 200 heart valves showed that – just like valves from donors below the age limit – 100 of them would have met the medical quality standards for transplantation, which discriminate among optimal, suitable and unsuitable tissue morphology. The morphological suitability of the aortic valves decreases rapidly during the 4th decade of life and near to the age limit only 6% of them are accepted as grafts. The rate of potentially acceptable aortic valve grafts from organ donors aged over 65 years of 15% is also small. By contrast, the pulmonary valves are not affected by age-related tissue changes that might reduce their transplantability. The predominant majority (85%) of potential pulmonary valve grafts from organ donors over 65 years of age fulfilled the acceptance criteria, half of them (48%) even showing good tissue quality. In light of these results the age limit was raised to 70 years in 2005.     

Brain grafts and Parkinson's disease

In animal models, grafts derived from several different tissues, principally fetal substantia nigra and adrenal medulla from young adults, have been found to be effective in alleviating some of the manifestations of lesions of the substantia nigra. It has been suggested that these grafts function by diffusely secreting dopamine, by exerting trophic effects on the host brain, or by producing a new innervation of the host corpus striatum. Evidence for each of these modes of action is briefly reviewed. Several brain tissue transplantation techniques have been described. Each of these techniques has significant limitations in animal models. The significance of these limitations for human application is described, and possibilities for improving the efficacy of brain tissue transplantation in animal models and for human application are discussed.     

Brain death and marginal grafts in liver transplantation

It is well known that most organs for transplantation are currently procured from brain-dead donors; however, the presence of brain death is an important risk factor in liver transplantation. In addition, one of the mechanisms to avoid the shortage of liver grafts for transplant is the use of marginal livers, which may show higher risk of primary non-function or initial poor function. To our knowledge, very few reviews have focused in the field of liver transplantation using brain-dead donors; moreover, reviews that focused on both brain death and marginal grafts in liver transplantation, both being key risk factors in clinical practice, have not been published elsewhere. The present review aims to describe the recent findings and the state-of-the-art knowledge regarding the pathophysiological changes occurring during brain death, their effects on marginal liver grafts and summarize the more controversial topics of this pathology. We also review the therapeutic strategies designed to date to reduce the detrimental effects of brain death in both marginal and optimal livers, attempting to explain why such strategies have not solved the clinical problem of liver transplantation.     

联合细胞培养在组织工程血管化中的应用

自从1987年正式提出组织工程这一概念来以来,培养具有生物学活性组织器官替代物始终是组织工程学的发展方向。目前,虽然一些工程化组织如皮肤、软骨等已被成功构建,并应用于临床,但其他工程化组织如心脏、骨骼肌、肝脏等体积大、功能复杂,移植后难以及时建立血液供应。而及时建立的血管网络对组织器官的存活与功能实现至关重要。为此,国内外一些实验室采用联合细胞培养的方法,观察不同细胞间的相互作用对血管形成的影响。结果表明,联合细胞培养在血管的形成、稳定和成熟方面起着重要作用。     

The impact of the International Atomic Energy Agency (IAEA) program on radiation and tissue banking in India

The banking of tissues such bone and skin began in India in the 1980s and 1990s. Although eye banking started in 1945 there was little progress in this field for the next five decades. As part of the IAEA/RCA program to use ionising radiation for the sterilisation of biological tissues in Asia and the Pacific Region, the Tata Memorial Hospital (TMH) in 1986 decided to set up a tissue bank in Mumbai funded by the Government of India. The TMH Tissue Bank became operational in January 1988, and stands as a pioneering effort in the country to provide safe, clinically useful and cost-effective human allografts for transplantation. It uses the IAEA International Standards on Tissue Banking. All the grafts are sterilised terminally by exposure to a dose of 25 kGy of gamma radiation, which has been validated as recommended by the IAEA Code of Practice for the Radiation Sterilisation of Tissues Allografts: Requirements for Validation and Routine Control. The TMH Tissue Bank is registered with the Maharashtra State Health Authorities, and in May 2004, it became India’s first Tissue Bank to receive ISO 9001:2000 certification of its Quality Management System. From 1989 to September 2007, the TMH Tissue Bank has supplied 11,369 allografts to 310 surgeons operating in 69 hospitals in Mumbai and 56 hospitals in other parts of India. These numbers have been limited by difficulties with the retrieval of tissues from deceased donors due to inadequate resources and tissue donation policies of hospitals. As the Government of India representative in the IAEA program, the TMH Tissue Bank has promoted and co-coordinated these activities in the country and the development of tissue banks using radiation sterilisation of tissue grafts. Towards this end it has been engaged in training personnel, drawing up project proposals, and supporting the establishment of a Tissue Retrieval Centre in Mumbai. Currently it networks with the Zonal Transplant Co-ordination Centre of the Government of Maharashtra, and the newly instituted National Deceased Donor Transplantation Network, which will work with the Government of India to set up rules and regulations for organ and tissue donation and transplantation.     

Cadaveric Tissue Supply to the Commercial Sector For Research: Collaboration between NHS Pathology and NBS Tissue Services in the U.K., Extending the Options for Donors

The Peterborough Hospital Human Tissue Bank (PHHTB) and National Blood Service Tissue Services (London and South East Zone) (NBSTS) operate within the U.K. National Health Service (NHS) and have a system in place to retrieve cadaveric tissues for commercial sector research. The collaboration meets the aims of PHHTB and NBSTS and is legal, ethical and safe. This paper presents the results of the first 20 successful retrievals referred from NBSTS to PHHTB. Cadaveric retrieval of tissue for research extends the options for donors and their relatives. The research option is particularly welcomed in cases where clinical retrieval for tissue transplantation is contraindicated. We believe the system is applicable to other centres.     

Corneal Donor Tissue Preparation for Descemet's Membrane Endothelial Keratoplasty

Descemet’s Membrane Endothelial Keratoplasty (DMEK) is a form of corneal transplantation in which only a single cell layer, the corneal endothelium, along with its basement membrane (Descemet''s membrane) is introduced onto the recipient''s posterior stroma³. Unlike Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK), where additional donor stroma is introduced, no unnatural stroma-to-stroma interface is created. As a result, the natural anatomy of the cornea is preserved as much as possible allowing for improved recovery time and visual acuity⁴. Endothelial Keratoplasty (EK) is the procedure of choice for treatment of endothelial dysfunction. The advantages of EK include rapid recovery of vision, preservation of ocular integrity and minimal refractive change due to use of a small, peripheral incision¹. DSAEK utilizes donor tissue prepared with partial thickness stroma and endothelium. The rapid success and utilization of this procedure can be attributed to availability of eye-bank prepared precut tissue. The benefits of eye-bank preparation of donor tissue include elimination of need for specialized equipment in the operating room and availability of back up donor tissue in case of tissue perforation during preparation. In addition, high volume preparation of donor tissue by eye-bank technicians may provide improved quality of donor tissue. DSAEK may have limited best corrected visual acuity due to creation of a stromal interface between the donor and recipient cornea. Elimination of this interface with transplantation of only donor Descemet''s membrane and endothelium in DMEK may improve visual outcomes and reduce complications after EK⁵. Similar to DSAEK, long term success and acceptance of DMEK is dependent on ease of availability of precut, eye-bank prepared donor tissue. Here we present a stepwise approach to donor tissue preparation which may reduce some barriers eye-banks face in providing DMEK grafts.     

Donor derived malignancy following transplantation: a review

Organ and tissue transplant is now the treatment of choice for many end stage diseases. In the recent years, there has been an increasing demand for organs but not a similar increase in the supply leading to a severe shortage of organs for transplant resulted in increasing wait times for recipients. This has resulted in expanded donor criteria to include older donors and donors with mild disease. In spite of implementation of more stringent criteria for donor selection, there continues to be some risk of donor derived malignancy. Malignancy after transplantation can occur in three different ways: (a) de-novo occurrence, (b) recurrence of malignancy, and (c) donor-related malignancy. Donor related malignancy can be either due to direct transmission of tumor or due to tumor arising in cells of donor origin. We will review donor related malignancies following solid organ transplantation and hematopoeitic progenitor cell transplantation. Further, we will briefly review the methods for detection and management of these donor related malignancies.     

Tissue Matching and Early Rejection of Cadaveric-Donor Renal Allografts: The Importance of Unidentified Donor Antigens

Tissue typing has been reviewed in a series of 100 technically successful cadaveric-donor kidney grafts. The criterion of transplant failure was immunological rejection causing total loss of function within three months of operation.No significant correlation was observed between matching grade and graft failure due to early acute rejection. This is attributed to the failure to detect at least one “LA” or “4” antigen (as defined in our laboratory), representing a potential incompatibility, in 89% of the grafts, and in the remaining 11% to the lack of an available recipient with identical “LA” and “4” typing. Undetected antigens on the donor are usually incompatible, and probably these incompatibilities unfavourably influence early graft survival.If the results of cadaveric-donor renal transplantation are to equal those of transplantation from well-matched living related donors it will be necessary to type with sera which can recognize individually all HL-A antigens, including those not yet identified, and to create an international pool of over 1,000 potential recipients.     

Bangkok Biomaterial Center: 15 Years Experience in Tissue Banking

Tissue banking is started in Thailand in 1979 at the Department of Orthopaedic Surgery, Siriraj Hospital, Bangkok. At that time tissues produced were freeze-dried bone allografts which were sterilized by ethylene oxide. In 1984, the freeze-dried tissue allograft project received an award from the National Research Council of Thailand. The Bangkok Biomaterial Center was officially inaugurated on December 6, 1984 under the Royal Patronage of H.R.H. Princess Galyanivadhana and is located inside the Siriraj Hospital. The Center is involved in the procurement, processing, storage and development of bone and tissue allografts. A variety of allografts including bone, cartilage, fascia lata, dura mater, cornea and also cardiovascular tissues have been procured and processed. Preservation and long-term storage are accomplished by freeze drying and deep freezing. Grafts prepared by the Center are supplied free of charge at the request of surgeons in hospitals throughout Thailand and in neighboring countries. The Center acts as the National Tissue and Allograft Bank of Thailand. From December 1984 to February 2000, the Center has processed a total of 20524 allografts: 16981 freeze-dried bones, 705 deep-frozen bones, 1838 freeze-dried amnion, 559 freeze-dried dura mater, 342 freeze-dried fascia lata, 46 costal cartilage, 18 corneas, 2 skin, 5 trachea, 22 fresh tendon and 6 bone substitutes. The allografts processed were used in 2049 patients by 223 surgeons in 53 hospitals in Thailand and 4 cases in neighboring countries. There have been 413 cadaveric donors, 619 living donors, 16 brain dead donors and 270 graveyard donors. There have been complications in 126 patients (6.14%) due to various clinical conditions. There have been production and application of 4 hydroxyapatite occular implant by the Center. The Center is in the process of establishing a full-fledged Research, Clinical and Cell Culture Laboratory.     

Tissue Banking in India: Gamma-Irradiated Allografts

In India, the procurement of tissues for transplantation is governed by the Transplantation of Human Organs Act, 1994. Although this law exists, it is primarily applied to organ transplantation and rules and regulations that are specific to tissue banking which have yet to be developed. The Tata Memorial Hospital (TMH) Tissue Bank was started in 1988 as part of an International Atomic Energy Agency (IAEA) programme to promote the use of ionising radiation for the sterilisation of biological tissues. It represents the Government of India within this project and was the first facility in the country to use radiation for the sterilisation of allografts. It is registered with the Health Services Maharashtra State and provides freeze-dried, gamma irradiated amnion, dura mater, skin and bone. The tissues are obtained either from cadavers or live donors. To date the TMH Tissue Bank has provided 6328 allografts which have found use as biological dressings and in various reconstructive procedures. The TMH Tissue Bank has helped initiate a Tissue Bank at the Defence Laboratory (DL), Jodhpur. At present these are the only two Banks in the country using radiation for the terminal sterilisation of preserved tissues. The availability of safe, clinically useful and cost effective grafts has stimulated innovative approaches to surgery. There is an increased demand for banked tissues and a heightened interest in the development of tissue banks. Inadequate infrastructure for donor referral programmes and the lack of support for tissue transplant co-ordinators however, continue to limit the availability of donor tissue.     

Setting up a Tissue Bank in India: The Tata Memorial Hospital Experience

In India, the procurement of tissues for transplantation is governed by the Transplantation of Human Organs Act, 1994. However, although this law exists, it is primarily applied to organ transplantation and rules and regulations that are specific to tissue banking have yet to be developed.The Tata Memorial Hospital (TMH) Tissue Bank was started in 1988 as part of an International Atomic Energy Agency (IAEA) programme to promote the use of ionising radiation for the sterilisation of biological tissues. It represents the Government of India within this project and was the first such facility in the country. It is registered with the Health Services Maharashtra State and provides lyophilised amnion, dura mater, skin and bone that have been terminally sterilised with exposure to 25 kGy of gamma radiation from a Cobalt 60 source. These are obtained either from cadavers or live donors.To date the TMH Tissue Bank has provided 6328 allografts for use as biological dressings or in various reconstructive procedures.The TMH Tissue Bank has helped initiate a Tissue Bank at the Defence Laboratory (DL), Jodhpur. At present these are the only two Banks in the country using radiation for terminal sterilisation of banked tissues.The availability of safe, clinically useful and cost effective grafts have resulted in changes in surgical treatment with a concomitant increase in demand for grafts and an interest in developing more tissue banks. The availability of donor tissue however, continues to be a major limitation.     

The impact of the International Atomic Energy Agency (IAEA) program on radiation and tissue banking in Asia and the Pacific and the Latin American regions

The technical assistance program of the International Atomic Energy Agency (IAEA) for its member states in the framework of the implementation of its program on radiation and tissue banking focuses on ensuring the availability of quality radiation-sterilised tissue grafts. The IAEA also helps its member states to develop quality control capabilities in order to ensure the safe use of the processed tissues in certain medical treatments. The majority of developing countries does not have such capacity, and must import expensive sterilised tissues from developed countries. The IAEA’s core contribution to its program on radiation and tissue banking in Asia and the Pacific and the Latin American regions is a technology for sterilisation by gamma radiation and a training program for tissue bank operators and medical personnel. The Agency develops capabilities for radiation sterilisation of tissue grafts, both for reducing the pre-processing bacterial load, and as a terminal sterilisation process. Sterilising tissue grafts offers a clear advantage in terms of safety. Moreover, compared to alternative sterilisation methods, radiation sterilisation is considered particularly safe in relation to environmental concerns, and the deposition of harmful residuals in the tissue, which occurs for example in the use of chemical such as ethylene oxide gas. Radiation sterilisation, thus, has become the method of choice for an increasing number of tissue banks. Radiation sterilisation of tissue grafts is a critical component in the chain connecting donors to recipients of high quality tissue grafts. Due to this fact, the IAEA has evolved as the only organisation in the UN System with expertise related to tissue banking.     

Exclusion of deceased donors post-procurement of tissues

The EU Tissues and Cells Directive (2004/23/EC, 2006/17/EC, 2006/86/EC) (EUTCD) provides standards for quality and safety for all aspects of banking of tissues and cells for clinical applications. Commission Directive 2006/17/EC stipulates that the complete donor record with all the medical information is assessed for suitability before releasing tissues for clinical use. The aim of this study was to investigate the medical reasons for post-procurement donor exclusion, to identify the various potential sources for gathering information about donors’ medical and behavioural history and to evaluate their contribution to maximising the safety of donations. Information was collected from the Tissue Services (TS) records of 1000 consecutive deceased donors submitted to National Health Service Blood and Transplant (NHSBT) medical officers for authorisation for release for subsequent tissue processing and then for transplantation. Of the 1000 donors 60 (6%) were excluded because they did not fulfil the donor selection requirements of the EUTCD and NHSBT donor selection guidelines. The main reasons for medical exclusion were the presence of significant local or systemic infection in 32 donors (53% of those excluded for medical reasons) and a history of past or occult malignancy in 9 donors (15% of those excluded for medical reasons) which was not identified prior to procurement. The information leading to post-procurement exclusion was obtained from autopsy reports in 35 of the 60 excluded donors for medical reasons (58%) and from the general practitioner for 10 donors (17% of those excluded for medical reasons). In summary, careful evaluation of complete donor records reduces the potential risk of disease transmission by tissue allografts and ensures compliance with regulations and guidelines. The findings may lead to changes in donor selection policies with the aim of improving efficiency without compromising safety.